Patients with cardiac failure have a generalized sympathetic vasoconstriction that may impair cardiac function and exercise tolerance. The ability of long-term alpha-receptor blockade and vasodilation with trimazosin (TMZ) to improve exercise capacity was studied in patients with chronic, stable heart failure of varying severity (functional exercise classes B to D). Exercise performance was monitored by respiratory gas exchange and air flow before and after patients were randomized to placebo (13 patients) or TMZ were then followed on treatment for up to 52 weeks. Significant (P less than 0.05) and sustained increases in exercise capacity, oxygen uptake, and oxygen pulse were observed with TMZ treatment in each Class B or C patient and in six of nine Class D patients, and were not observed during treatment with placebo.

Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospective, randomized, double-blind trial. One hundred forty-six patients received nine or more doses, had serial determinations of serum creatinine, and were evaluated for nephrotoxicity; 91 were able to cooperate with audiometry and were evaluated for auditory toxicity. Auditory toxicity developed in five of 47 (10 per cent) given gentamicin and five of 44 (11 per cent) given tobramycin. Nephrotoxicity developed in 19 of 72 (26 per cent) given gentamicin and nine of 74 (12 per cent) given tobramycin (P less than 0.025). The severity of the nephrotoxicity was not different; the mean increase in creatinine was 1.3 mg per 100 ml (114.9 mumol per liter) in both groups. Both the tobramycin and gentamicin groups had a similar mean age, initial serum creatinine level, total dose, serum aminoglycoside level, and duration of therapy. We conclude that tobramycin causes nephrotoxicity less frequently than does gentamicin.

To test the effectiveness of 6-mercaptopurine (6-MP) in the treatment of Crohn's disease, we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo. Crossover data showed that improvement occurred in 26 of 39 courses of 6-MP (67%) as compared with three of 39 courses of placebo (8%) (P less than 0.001). Non-crossover data likewise confirmed the superiority of 6-MP. The drug was more effective than placebo in closing fistulas (31 vs 6%) and in permitting discontinuation or reduction of steroid dosage (75 vs. 36%) (P less than 0.001). The onset of response to 6-MP was often delayed, with 32% of patients taking longer than three months to respond, and 19% taking longer than four months. Adverse side effects to 6-MP occurred in 10% of patients and were uniformly reversible. We conclude that 6-MP is an effective and useful agent in the management of Crohn's disease.

We evaluated the long-term effects of a five to 15-week course of chlorambucil and prednisone in 59 children with idiopathic nephrotic syndrome who had previously received prednisone alone and had had frequent relapses or steroid dependency or resistance. By actuarial analysis of 65 courses of dual therapy followed up for one to 12 years (mean, 5.0), we found that 95 per cent of patients were in remission at one year and 85 per cent at four years. All but two had remissions lasting longer than those induced by steroids alone, and only eight others had one or more relapses after therapy. Life-table analysis of two dosage schedules of chlorambucil at four years showed that 91 per cent of patients on low doses and 80 per cent of those on high doses were still in remission. Although immediate complications were minimal, the potential for long-term toxicity still requires careful selection of patients who receive chlorambucil. Prolonged use of chlorambucil in daily doses above 0.3 mg per kilogram of body weight per day or cumulative doses above 14 mg per kilogram is no longer warranted. Measured in terms of both the immediate and long-term responses, chlorambucil appears to lower the frequency of relapses in idiopathic nephrotic syndrome.

Physical exercise is known to improve glucose tolerance and diminish insulin requirements in patients with well-controlled diabetes mellitus. To ascertain whether these effects of exercise are associated with alterations in insulin receptors, we studied [125I]insulin binding to erythrocytes and monocytes in athletically untrained young men with insulin-treated diabetes during three hours of postprandial bicycle exercise (nine patients) and two hours of exercise during fasting (eight patients). Compared with control periods, postprandial exercise, as well as exercise during fasting, significantly increased insulin binding to erythrocytes and monocytes at an insulin-tracer concentration of 34 pmol per liter. We suggest that similar changes occur in working muscle cells and contribute to the improved glucose tolerance induced by exercise.

We studied the antiarrhythmic effect of a range of oral doses of encainide in 11 patients with stable high-frequency ventricular arrhythmias. Total suppression of arrhythmia was documented in 10 patients at a wide range of doses and plasma concentrations, and the suppression was subsequently verified in a placebo-controlled crossover study. Drug elimination was rapid (the half-life was 1.9 to 3.8 hours), but the margin between efficacy and side effects was sufficiently wide for therapy every six to 12 hours to be feasible in all 10 patients, with continuing outpatient treatment at six to 12 months. Marked prolongation of PR (mean, 44 per cent) and QRS (mean, 47 per cent) durations coincided with abolition of arrhythmia, but no evidence that these effects were detrimental was observed in radionuclide ventriculograms, exercise testing, or prolonged monitoring. A single patient whose arrhythmia and electrocardiogram were unchanged during therapy eliminated the drug much more slowly than the others and was the only patient in whom no O-demethyl form could be detected in plasma, suggesting that this metabolite may be active. In this study, encainide was a highly effective, well-tolerated antiarrhythmic agent.

To examine the effects of the Leboyer method of delivery, we randomly assigned 56 women to either a Leboyer or a conventional delivery and used a variety of clinical and behavioral measures to assess the outcome in mother and child. No differences were noted in maternal or newborn morbidity, in infant behavior in the first hour of life, at 24 or 72 hours post partum, or at eight months of age; or in maternal perceptions of her infant and the experience of giving birth, except that eight months after delivery, mothers who had used the Leboyer method were more likely to say that the event had influenced their child's behavior (P = 0.05). Women who expected a Leboyer delivery had shorter active labors (P = 0.03), suggesting that psychologic factors (expectations) influence physical outcomes in perinatal medicine. Our results suggest that the Leboyer procedure has no advantage over a gentle, conventional delivery in influencing infant and maternal outcomes.