Segregation analysis of peripheral neurofibromatosis (NF1).

Four studies of NF1 support a prevalence of 0.0003 and a carrier incidence at birth of 0.0004. The gene frequency (q) is therefore 0.0002, and the proportion of cases owing to fresh mutation is 0.56. The mutation rate (xq) is 10(-4), an unusually high value suggestive of a large gene. Penetrance among subjects examined is virtually complete, and there is no evidence of phenocopies or somatic mutations.     

Hanganutziu-Deicher antigen as a possible target for immunotherapy of melanoma

Hanganutziu-Deicher (H-D) antigen is classified as a heterophile antigen and chemically defined as a glycoconjugate which contains N-glycolylneuraminic acid. H-D antigens are absent from normal human tissues, but can be expressed on a variety of human malignant cells, including melanoma. Natural anti-H-D antibodies have been detected in man with and without malignancies, but in this study when the level of antibody was compared between healthy adults and patients with melanoma, elevated anti-H-D antibody levels were found more frequently in melanoma patients for both IgM (p = 0.0001) and IgG (p = 0.0001). The present study was designed to evaluate the significance of the H-D antigen-antibody system in melanoma suppression. Sera from melanoma patients containing anti-H-D antibody reacted strongly to H-D antigen expressed on melanoma by means of flow cytometry. In a complement-dependent cytotoxicity assay this antibody killed melanoma cells in vitro. In vivo significance of the antibody was assessed by evaluating the relationship between the antibody levels and the clinical course in patients with stage II melanoma. Antibody levels were measured by enzyme-linked immunosorbent assay using a H-D glycoprotein antigen isolated from bovine erythrocytes. A significantly higher level of IgG (p = 0.0640) and IgM (p = 0.0644) anti-H-D antibody was demonstrated in those patients who were free of disease more than 5 years after surgery than in those who relapsed within 2 years. This study provides a rational basis for immunotherapy targeting H-D antigen in human melanoma.     

Monitoring exercise stress by changes in metabolic and hormonal responses over a 24-h period

Summary Metabolic and endocrine responses of 14 subjects of varying levels of fitness to an intensive anaerobic interval training session were assessed before exercise and at 2 h, 4 h, 8 h and 24 h postexercise. The endocrine response of the same subjects to a control day, where they were required not to exercise, was also assessed and compared with the values obtained on the interval training day. Uric acid, urea, and creatine phosphokinase concentrations still remained elevated above pre-exercise values 24 h postexercise. Lactate, creatinine, testosterone and cortisol concentrations were significantly elevated above pre-exercise values immediately postexercise but these had reversed by 2 h postexercise. Over the remainder of the recovery period testosterone concentrations remained significantly lower than values measured at similar times on the control day. This was shown to be due directly to a change in testosterone as sex hormone binding globulin concentration remained constant throughout the recovery period. The data indicate that when comparisons of data were made to control (rest) days, imbalances in homeostasis, due to intensive training, are not totally reversed within the next 24-h. The data also demonstrate that the parameters measured undergo the same variations in subjects with a wide range of physical fitness, indicating that these parameters could be used to monitor exercise stress and recovery in athletes of a wide range of abilities. The more acute responses to exercise could be mistaken for overtraining if insufficient recovery time were not permitted between the final exercise session and taking blood samples, further emphasising the need to be able to recognise the difference between the fatigue associated with acute exercise and a state of chronic fatigue that may result from too little regeneration time within the training programme.     

Chest pain with nondiagnostic electrocardiogram in the emergency department: a randomized controlled trial of two cardiac marker regimens

BACKGROUND: Early detection of acute myocardial infarction (AMI) may save lives. In the emergency setting, it is unclear whether the early use of certain cardiac markers (myoglobin and cardiac troponin I [cTnI]) assists in making appropriate decisions whether to admit or discharge patients with chest pain of possible ischemic cause who have nondiagnostic electrocardiograms (ECGs). We performed a study to determine whether the addition of new cardiac markers in the emergency department results in improved clinical decisions. METHODS: A single-blind randomized controlled trial was conducted between June 1997 and June 1998 in a tertiary care emergency department in Kingston, Ont. Of 296 patients aged 30 years or more who presented to the emergency department with chest pain and nondiagnostic ECGs, 146 were randomly assigned to the intervention group (determination of baseline creatine kinase [CK] level, CK MB fraction and cTnI level, and myoglobin level at baseline and at 2 hours) and 150 to the control group (determination of baseline CK level and CK MB fraction). Outcome measures included the rate of admission to the inpatient cardiology service and length of stay in the emergency department. RESULTS: Of the 296 patients, 34 (11.5%) received a diagnosis of AMI in the emergency department, and 92 (31.1%) had chest pain of noncardiac cause. Patients in the intervention group were less likely than those in the control group to be admitted to the cardiology service (67 [45.9%] v. 81 [54.0%]). The absolute difference in the proportion (8.1% [95% confidence interval -3.3 to 19.5]), although potentially important clinically, was not statistically significant. The length of stay in the emergency department was essentially the same in the 2 study groups. At 30 days, the proportions of patients with a diagnosis of recurrent angina (58.2% in the intervention group and 58.0% in the control group) and AMI (12.3% and 14.7%) were also similar. INTERPRETATION: The optimal cardiac marker panel to be used in the emergency department remains unknown. The addition of serial testing of myoglobin with cTnI confirmation to the standard panel did not substantially change the clinical management or outcomes of patients presenting with chest pain and nondiagnostic ECGs.     

Clinical psychopharmacy consultations: acceptance of recommendations on an adult inpatient psychiatric unit

A retrospective chart review of consultations performed by a clinical pharmacist practicing in an adult psychiatric hospital was conducted. Data during the first 12 months of the service were collected from consultation reports, progress notes, physician's orders, laboratory data, and discharge summaries. Twenty-nine consultations were performed, resulting in a total of 135 recommendations. Of those, 125 were assessed and categorized. Of the recommendations, 113 (90.4%) were medication related and 12 (9.6%) were non-medication related. From the 125 recommendations, 99 (79.2%) were implemented and 26 (20.8%) were not. Particular categories of recommendations were also analyzed and had individual implementation rates ranging from 33.3% to 100%. Clinical pharmacists have previously documented their positive impact on patient care in a variety of settings, including psychopharmacy. The majority of recommendations made in this study were medication related with an overall implementation rate of 79%. This report illustrates the influence the clinical pharmacist has on the drug therapy of the psychiatric patient.     

Hydrolysis of the Prodrug, 2′, 3′, 5′ -Triacetyl-6-azauridine

Purpose. The purposes were to study the kinetics of hydrolysis of 2,3,5-triacetyl-6-azauridine ( 1 ) in aqueous solution (µ = 0.5) and to identify the main intermediates and products of the reaction. Methods. A stability indicating isocratic LC assay was used to study the rate of degradation of 1 A gradient LC assay was used to study the time courses of the degradants. The products of hydrolysis were isolated by preparative liquid chromatography and identified by ¹H-NMR and CI-MS. The pK_a value was obtained by potentiometric titration. Results. At 36.8°C, the pH-rate profile of 1 in water was adequately described by a four-term rate equation. The intermediates were identified as the primary and secondary di-acetates, and the primary and secondary mono-acetates. The final product was 6-azauridine. Conclusions. A simplified kinetic scheme could be used to describe the concentration-time profiles of 1, the intermediates and the final product.