Multidisciplinary teaching in a formal medical ethics course for clinical students

A successful feature of the 4th-year curriculum in the Medical Faculty of the Queen's University, Belfast has been the development of interdisciplinary teaching in a three-week joint course to which several clinical departments contribute...Co-ordinated teaching of topics of common interest in small groups included, until the academic year 1987/88, a three-hour session on medical ethics. In the spring of 1987 the authors approached the Department of Philosophy at Queen's; subsequently proposals for a formal multidiscipinary course in medical ethics for 4th-year clinical students in the Medical Faculty, for the academic year 1987/88, were approved by the Education Committee of the Medical Faculty.     

Memory T lymphocytes generated by Mycobacterium bovis BCG vaccination reside within a CD4 CD44lo CD62 ligand(hi) population

In the lungs of mice vaccinated with Mycobacterium bovis BCG, there was an accumulation of CD4 cells expressing the activated effector phenotype CD44hi CD62 ligandlo) (CD62Llo) which were capable of secreting gamma interferon. Upon cell transfer, however, cells expressing a resting/na?ve phenotype (CD44lo CD62Lhi) were capable of protecting the recipients from a virulent challenge infection, suggesting the emergence of T-cell memory from within this subset.     

Effects of a yearlong moderate-intensity exercise and a stretching intervention on sleep quality in postmenopausal women

STUDY OBJECTIVES: To examine the effects of a moderate-intensity exercise or stretching intervention and changes in fitness, body mass index, or time spent outdoors on self-reported sleep quality and to examine the relationship between the amount and timing of exercise and sleep quality. DESIGN: A randomized intervention trial. SETTING: A cancer research center in Seattle, Washington. PARTICIPANTS: Postmenopausal, overweight or obese, sedentary women not taking hormone replacement therapy, aged 50 to 75 years, and recruited from the Seattle metropolitan area. INTERVENTIONS: A yearlong moderate-intensity exercise (n=87) and a low-intensity stretching (n=86) program. MEASUREMENTS AND RESULTS: Among morning exercisers, those who exercised at least 225 minutes per week had less trouble falling asleep (odds ratio [OR]: 0.3, P < or = .05) compared with those who exercised less than 180 minutes per week. However, among evening exercisers, those who exercised at least 225 minutes per week had more trouble falling asleep (OR: 3.3, P < or = .05) compared to those who exercised less than 180 minutes per week. Stretchers were less likely to use sleep medication (OR = 0.4, P < or = .05) and have trouble falling asleep (OR: 0.7, P < or = .10) during the intervention period compared with baseline. A greater than 10% versus a 1% or less increase in maximum O2 consumption over the year was associated with longer sleep duration (P < or = .05), less frequently falling asleep during quiet activities (P < or = .05), and less use of sleep medication (P < or = .05). Reductions in body mass index and increases in time spent outdoors had inconsistent effects on sleep quality. CONCLUSIONS: Both stretching and exercise interventions may improve sleep quality in sedentary, overweight, postmenopausal women. Increased fitness was associated with improvements in sleep. However, the effect of moderate-intensity exercise may depend on the amount of exercise and time of day it is performed.     

Computer-generated dot maps as an epidemiologic tool: investigating an outbreak of toxoplasmosis

We used computer-generated dot maps to examine the spatial distribution of 94 Toxoplasma gondii infections associated with an outbreak in British Columbia, Canada. The incidence among patients served by one water distribution system was 3.52 times that of patients served by other sources. Acute T. gondii infection among 3, 812 pregnant women was associated with the incriminated distribution system.     

Adherence to antiretroviral medications in an inner-city population

Adherence to antiretroviral medications is essential for optimal treatment of HIV infection. We investigated nonadherence to antiretroviral medications in an inner-city population by using a confidential interview and a self-administered anonymous questionnaire. We estimated adherence on the day before and the month before the interview and asked reasons for nonadherence. Of 173 people who were taking antiretroviral medications, all participated in the confidential interview and 101 also completed the anonymous questionnaire. Results of the confidential interview and the anonymous questionnaire revealed rates of 6% and 28%, respectively, for nonadherence to any drug on the preceding day and of 11% and 39%, respectively, in the preceding month. The most common reasons for nonadherence in both methods were forgetfulness, inaccessibility of medications, and perceived or actual toxicity. On 12% of the anonymous questionnaires one reason for nonadherence was perceived or actual lack of drug efficacy: this reason was not given in any of the confidential interviews. Responses about the extent of nonadherence and the reasons for it may differ depending on the method of ascertainment. Interventions to improve adherence should focus on making medication dosages easier to remember, ensuring a continued supply of medications, and circumventing toxicities.     

Diethyldithiocarbamate causes nigral cell loss and dopamine depletion with nontoxic doses of MPTP

Although nontoxic when administered alone, diethyldithiocarbamate (DDC) is known to enhance the dopamine-depleting effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum. The purpose of the present study was twofold: (i) to carefully characterize the effects of DDC on MPTP-induced degeneration of dopaminergic neurons in substantia nigra pars compacta using unbiased, stereological cell counting techniques and (ii) to determine whether or not DDC can convert a nontoxic dose of MPTP into one which is clearly toxic on dopaminergic neurons in the substantia nigra. A single low dose of MPTP (15 mg/kg intraperitoneally (ip)) was used for these studies, which failed to induce any neurochemical or histological effects on the nigrostriatal system of C57BL/6 mice when administered alone. However, when animals were pretreated with DDC (400 mg/kg ip), the same dose of MPTP resulted in a 50% loss of neurons in the substantia nigra pars compacta, as well as a 70% reduction in striatal dopamine (DA). A 31% reduction of DA in the ventral mesencephalon was also seen. This combined regimen of DDC and MPTP was not significantly different from a maximally tolerated "toxic" dose of MPTP alone (15 mg/kg x 4, 1 h apart, ip). As expected, animals receiving DDC alone did not show any dopamine depletion nor nigral neuronal loss. The present study confirms previous work suggesting that DDC enhances MPTP-induced nigral cell loss and shows for the first time that DDC can "unmask" MPTP toxicity. These observations could have implications for theories on the cause of Parkinson's disease.     

A multiple locus analysis of the collaborative study on the genetics of alcoholism data set

Parametric and nonparametric statistical methods have been applied to the alcohol dependence data set collected in the Collaborative Study on the Genetics of Alcoholism (COGA). Our nonparametric linkage analyses (NPL) were based on the S(all) statistic of GENEHUNTER [Kruglyak et al., 1996] and the improved NPL statistic of GENEHUNTER-PLUS [Kong and Cox, 1997]. Based on likely regions for alcohol susceptibility genes identified from our nonparametric analyses, we reanalyzed the data using several two-locus models. We used the TMLINK program [Lathrop and Ott, 1990] in the LINKAGE package for these parametric analyses.     

NTP summary report on the metabolism, disposition, and toxicity of 1,4-butanediol (CAS No. 110-63-4)

1,4-Butanediol is an industrial chemical used in the manufacture of other organic chemicals. It was nominated by the National Cancer Institute and selected for evaluation by the NTP because of high production volume, the potential for worker exposure, the lack of adequate toxicological characterization, and the lack of evaluation for carcinogenic potential. As documented in the scientific literature, 1,4-butanediol is rapidly absorbed and metabolized to gamma-hydroxybutyric acid in animals and humans. A metabolism and disposition study conducted in F344/N rats by the NTP confirmed the rapid and extensive conversion of 1-[14C]-1,4-butanediol to 14CO2. Because of this rapid and extensive conversion, the toxicological profile of 1,4-butanediol reflects that of gamma-hydroxybutyric acid. gamma-Hydroxybutyric acid is a naturally occurring chemical found in the brain and peripheral tissues which is converted to succinate and processed through the tricarboxylic acid cycle. Although the function of gamma-hydroxybutyric acid in peripheral tissues is unknown, in the brain and neuronal tissue it is thought to function as a neuromodulator. gamma-Hydroxybutyric acid readily crosses the blood-brain barrier, and oral, intraperitoneal, or intravenous administration elicits characteristic neuropharmacologic responses. These same responses are observed after administration of 1,4-butanediol. The lactone of gamma-hydroxybutyric acid, gamma-butyrolactone, is also rapidly converted to gamma-hydroxybutyric acid by enzymes in the blood and liver of animals and humans. gamma-Butyrolactone was previously evaluated by the NTP in 14-day and 13-week toxicology studies and 2-year toxicology and carcinogenesis studies in F344/N rats and B6C3F1 mice. No organ-specific toxicity occurred in the toxicology studies. In the carcinogenesis studies, an equivocal response occurred in male mice, based on a marginal increase in the incidence of pheochromocytomas of the renal medulla. Because of the rapid and extensive conversion of gamma-butyrolactone to gamma-hydroxybutyric acid, the evaluation of gamma-butyrolactone was in fact an evaluation of gamma-hydroxybutyric acid. This summary report presents a review of the current literature which documents that both 1,4-butanediol and gamma-butyrolactone are rapidly metabolized to gamma-hydroxybutyric acid, and the pharmacologic and toxicologic responses to these chemicals are due to their metabolic conversion to gamma-hydroxybutyric acid. Because the toxicity and carcinogenicity of gamma-hydroxybutyric acid was fully evaluated in the NTP studies of gamma-butyrolactone, and a lack of organ-specific toxicity or carcinogenic potential was demonstrated, it is concluded that there is a high likelihood that 1,4-butanediol would be negative in a similar set of studies. For these reasons, it is the opinion of the NTP that 1,4-butanediol should be considered not carcinogenic in animals and no further evaluation of 1,4-butanediol is needed at this time.     

Chronic treatment with exendin(9-39)amide indicates a minor role for endogenous glucagon-like peptide-1 in metabolic abnormalities of obesity-related diabetes in ob/ob mice

Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic hormone proposed to play a role in both the pathophysiology and treatment of type 2 diabetes. This study has employed the GLP-1 receptor antagonist, exendin-4(9-39)amide (Ex(9-39)) to evaluate the role of endogenous GLP-1 in genetic obesity-related diabetes and related metabolic abnormalities using ob/ob and normal mice. Acute in vivo antagonistic potency of Ex(9-39) was confirmed in ob/ob mice by blockade of the insulin-releasing and anti-hyperglycaemic actions of intraperitoneal GLP-1. In longer term studies, ob/ob mice were given once daily injections of Ex(9-39) or vehicle for 11 days. Feeding activity, body weight, and both basal and glucose-stimulated insulin secretion were not significantly affected by chronic Ex(9-39) treatment. However, significantly elevated basal glucose concentrations and impaired glucose tolerance were evident at 11 days. These disturbances in glucose homeostasis were independent of changes of insulin sensitivity and reversed by discontinuation of the Ex(9-39) for 9 days. Similar treatment of normal mice did not affect any of the parameters measured. These findings illustrate the physiological extrapancreatic glucose-lowering actions of GLP-1 in ob/ob mice and suggest that the endogenous hormone plays a minor role in the metabolic abnormalities associated with obesity-related diabetes.     

Do physicians provide counseling with HIV and STD testing at physician offices or hospital outpatient departments?

OBJECTIVES: To estimate the frequency of HIV/sexually transmitted disease (STD) counseling among patients tested for HIV or STD infection at physician offices and hospital outpatient departments and to describe the factors associated with HIV/STD counseling in private settings in the USA. DESIGN: Cross-sectional study of patients served by physicians in private settings in the USA. METHODS: We analyzed 1997-1998 data from two representative national surveys of ambulatory care visits in private settings by persons aged 18-64 years. RESULTS: During 1997-1998, 12.7 million ambulatory care visits included HIV or STD testing. HIV/STD counseling was documented in 35% of all visits and in 28% of visits by pregnant women at the time HIV or STD tests were done. Counseling was less common when only HIV tests (21%) or STD tests (37%) alone were carried out than when both HIV and STD tests (50%) were performed. Counseling was more common (65%) if the patient's reason for visit was related to HIV, STD, or genitourinary complaints than if the visit was for other reasons. CONCLUSIONS: Private physicians often counseled about HIV/STD when testing patients with symptoms. The proportion of other visits in which counseling accompanied HIV or STD tests was variable. This suggests the need for a better understanding of the reasons why clinicians in private settings decide whether to counsel patients about HIV and STD when they order testing, barriers to offering counseling, and interventions to increase counseling when appropriate.