Acute cardiovascular effects of tranylcypromine: correlation with plasma drug, metabolite, norepinephrine, and MHPG levels

BACKGROUND: Recent case reports, small series, and uncontrolled, unblinded studies have suggested that tranylcypromine may produce pressor reactions in some patients. However, the physiologic mechanism underlying this cardiovascular change is unknown. METHOD: The authors studied the acute cardiovascular effects of tranylcypromine in 13 patients and attempted to correlate these changes with plasma measures of parent drug, possible pressor metabolites, norepinephrine, and 3-methoxy-4-hydroxyphenylglycol. RESULTS: Significant elevations in supine blood pressure occurred after administration of tranylcypromine and correlated with tranylcypromine dose. Similar changes were not observed in standing blood pressure measurements. In fact, an orthostatic decrease in blood pressure and increase in heart rate were observed. Amphetamine-like metabolites were not found. CONCLUSIONS: The authors speculate on possible mechanisms underlying these opposite cardiovascular effects.     

Single lung transplantation for severe chronic obstructive pulmonary disease. Washington University Lung Transplant Group

Single lung transplantation (SLT) has been considered physiologically inappropriate for patients with chronic obstructive pulmonary disease (COPD). It has been postulated that the high static compliance and elevated pulmonary vascular resistance of the native lung functioning in parallel with the more normal allografted lung could cause unacceptable ventilation-perfusion mismatching and/or overinflation of the native lung with encroachment on the expansion of the transplanted lung. While some degree of ventilation-perfusion imbalance may be physiologically obligatory after SLT for COPD, a significant disruption in gas exchange may not occur unless a complication, such as rejection or infection, arises in the transplanted lung. A 60-year-old man with COPD who underwent successful SLT is presented and discussed. In spite of scintigraphic evidence of ventilation-perfusion mismatching between the native lung and the allograft during the first six postoperative weeks, the recipient had normal resting gas exchange on room air after the second postoperative week. Fourteen weeks after transplantation, his maximum oxygen uptake was 37.3 percent of the predicted maximal value, and no evidence of ventilatory limitation was detected. His functional status and lifestyle have been markedly improved by SLT. The role of SLT for COPD should be reconsidered. It may be a reasonable transplantation alternative for selected patients with COPD who are not candidates for double lung transplantation (DLT).     

Acyclovir treatment of herpes simplex encephalitis: experience in a district hospital

Herpes simplex encephalitis may be underdiagnosed in Britain. We report eight patients treated at one hospital over three years. Fever, impaired consciousness or focal neurological signs were seen in all patients at presentation but herpes simplex encephalitis was rarely considered as the initial diagnosis. The electroencephalogram was the only initial investigation that was abnormal in each case and was the most useful test in establishing a clinical diagnosis. The diagnosis was confirmed by laboratory methods in each case. Following acyclovir treatment five patients were able to resume normal activities, one patient has moderate disability and two patients died. Three patients showed clinical evidence of relapse but two improved after further treatment with acyclovir. Herpes simplex encephalitis is a treatable condition and should be considered in all patients presenting with fever and neurological signs. The electroencephalogram is usually abnormal and the changes may be characteristic of the condition.     

The influence of rural physicians' perception on referral patterns to a university hospital.

The patient referral process is based on a complex set of social rewards and costs for the referring physician. For the physician or institution potentially receiving referrals, a key question is, why is one institution selected over other available choices? Factor analysis of a survey of rural physicians revealed five factors of reward and cost associated with the choice of where to refer patients. Further analysis of these factors suggested that the ability to have patients admitted and treated when necessary is central to the satisfaction of the referring physician and their willingness to continue the consultant relationship. Adequate information about the consultants was also important to satisfaction. Other factors have less influence. Further, “admissions when necessary” was the only reward/cost factor which predicted physicians who referred more to the university hospital than to other hospitals. If a university hospital wants to develop strategies to encourage referrals from rural physicians, it must be cognizant of these social reward-cost factors.     

Overexpressed Drosophila src 64B is phosphorylated at its carboxy-terminal tyrosine, but is not catalytically repressed, in cultured Drosophila cells.

Little is known about the regulation of non-receptor tyrosine kinases in invertebrates. We have studied the relationship between the phosphorylation state of the Drosophila src 64B (Dsrc) gene product, p62D, and its tyrosine kinase activity in Drosophila Schneider 2 cells, using wild-type and mutated Dsrc constructs that were overexpressed by transient transfection. Phosphopeptide mapping showed that the putative regulatory C-terminal tyrosine (Tyr-547) of p62D was phosphorylated in vivo. In contrast to vertebrate src family kinases overexpressed in fibroblasts, wild-type p62D overexpressed in Schneider 2 cells was phosphorylated at additional tyrosines outside of the C-terminus. These tyrosines corresponded to the major in vitro autophosphorylation sites. Overexpression of wild-type p62D or several catalytically active p62D mutants significantly increased the phosphorylation of numerous Schneider cell proteins on tyrosine, while expression of catalytically inactive mutants of p62D had no such effect. Thus, in contrast to the repression of src family kinase activity in fibroblasts, p62D is catalytically active when overexpressed in Drosophila cells, perhaps because of substoichiometric C-terminal tyrosine phosphorylation. These results raise the possibility that fly development will be sensitive to ectopic expression of p62D.     

Quality of life as outcome in the treatment of osteoporosis: The development of a questionnaire for quality of life by the European foundation for osteoporosis

The morbidity of osteoporosis is caused by fractures. Vertebral fractures lead to pain and disability and a decrease in quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with established vertebral osteoporosis. This questionnaire is intended for use in clinical trials. The questionnaire consists of questions and visual analogue scales in the following domains: pain, activities of daily living, jobs around the house, mobility, leisure and social activities, general health perception and mood. The questionnaire has been translated from English into French, German, Italian, Hebrew, Swedish and Dutch. The questionnaire is currently being validated in a multicentre study involving patients with stable osteoporosis and control subjects. Preliminary results indicate that the reproducibility is sufficient and that the questionnaire is able to discriminate between patients with vertebral osteoporosis and control subjects.     

A comparison of the insulinotropic and the insulin-inhibitory actions of gut peptides on newborn and adult rat islet cells

The objective of this study was to examine the release of insulin from cultured islet cells, taken from the pancreas of newborn and adult rats, in response to gastric inhibitory polypeptide (GIP), cholecystokinin-8 (CCK-8), calcitonin gene-related peptide (CGRP), and pancreastatin. GIP (10(-9)-10(-7) M) potentiated glucose-stimulated release of insulin in a dose-dependent fashion from both newborn and adult islet cells. CCK-8 (greater than 10(-8) M) also increased glucose-stimulated release of insulin from newborn islet cells, however its effect was not significant and not as strong as that observed with adult islet cells. Culture of newborn islet cells for 3 weeks with media containing high concentrations of glucose (16.7 mM) enhanced insulin release in response to CCK-8. CGRP did not affect the release of insulin from newborn islet cells, whereas at 10(-10) M, it reduced the release of insulin from adult islet cells by 66 +/- 4%. Pancreastatin (10(-9)-10(-8) M) did not affect the release of insulin from newborn islet cells when cells were incubated with 4.2 mM glucose, whereas it stimulated the release of insulin from adult islet cells in a dose-dependent fashion. When incubated with 16.7 mM glucose, pancreastatin inhibited the release of insulin from both newborn and adult islet cells. These results indicate that newborn islet cells experience developmental changes which render them responsive to enteric peptides.