An alternative to intramuscular hydrocortisone self-injection was evaluated in healthy controls and in patients with adrenal insufficiency. Plasma cortisol concentrations were assayed after administration of 200 mg hydrocortisone by intramuscular injection (10 healthy subjects) or after insertion of an identical dose by rectal suppository (12 healthy subjects, 3 patients with adrenal failure). Plasma cortisol concentrations peaked at 1 hour (about 4000 nmol/l) following intramuscular injection and declined thereafter. After rectal administration, levels peaked at between 1 and 2 hours and persisted for 8 or more hours. Similar levels were achieved at 4 hours (about 1000 nmol/l) by both methods of administration. Self-treatment by rectal suppository may be useful in the prevention of Addisonian crises.

In a randomised parallel-block trial in thirteen European centres bromocriptine 2.5 mg twice a day was compared with placebo therapy for cyclical mastalgia. 272 patients were enrolled into the study. Linear analogue charts and diary pain cards were used for assessment of response. Reduction in breast pain, heaviness, tenderness, and serum prolactin after 3 and 6 months' therapy were significantly greater with bromocriptine than with placebo. Improvement in symptoms with bromocriptine was maintained for at least 6 months after therapy. Overall 29% of patients dropped out while on therapy, more from the bromocriptine than from the placebo group. Adverse effects, especially nausea and dizziness, were commoner among the bromocriptine-treated patients, but blood pressure was unaffected.

132 patients with advanced recurrent breast cancer were treated with four courses of mitozantrone 14 mg/m2 intravenously every 3 weeks (9 weeks). Patients showing disease stabilisation or objective response were randomised to stop chemotherapy or to continue until disease progression. At that stage 27% showed partial responses, 3% complete responses, and 10% disease stabilisation. 22 patients were randomised to continue chemotherapy and 21 to stop. There was no difference in time to disease progression, response duration, or survival between the two groups. Toxicity was mild during the first four courses of therapy. Thus, short courses of single-agent chemotherapy can produce similar therapeutic results to long-term chemotherapy, which has major implications for cost, resource allocation, and toxicity of therapy. Stopping chemotherapy early in responders did not cause rapid relapse. Since drug resistance apparently develops early during therapy, new approaches to modify resistance should be more useful than continuous chemotherapy.

The association between time to conceive reported by 2817 fertile women who had recently had a liveborn child and consumption of coffee, tea, and "cola" drinks has been investigated. No evidence for an adverse effect of caffeine was found. For levels of consumption ranging from less than one cup of coffee per week (501 mg caffeine per month) to more than two cups of coffee per day (7000 mg per month), the average time to conceive was similar. The fecundability ratio adjusted for known risk factors for time to conceive was 1.03 (95% confidence interval 0.92-1.16) between those who consumed more than 7000 mg caffeine per month and those who consumed 500 mg or less per month. Furthermore caffeine consumption was not associated with infertility in 1818 infertile women and their primiparous controls.

43 subfertile men with circulating antibodies to spermatozoa entered a double-blind crossover trial and received soluble prednisolone (20 mg twice daily on days 1-10 of the female partner's menstrual cycle, followed by 5 mg on days 11 and 12) or matching placebo tablets for 9 months each. 9 pregnancies were produced by men during prednisolone treatment, compared with 2 by men randomised to placebo (although only 1 was actually taking the placebo). No serious complications were produced, although 60% of those receiving prednisolone experienced mild side-effects.

The effects of gallium nitrate on bone turnover were evaluated in four patients with active Paget's disease. Treatment with gallium nitrate (100 mg/m2 daily for 5 days, intravenously in 5% glucose) significantly reduced serum calcium, serum phosphate, urinary calcium, and the ratio of maximum tubular reabsorption of phosphate to glomerular filtration rate in each patient. Serum parathyroid hormone levels rose. The findings suggest that the fall in serum calcium caused secondary hyperparathyroidism, resulting in a fall in serum phosphate. Serum alkaline phosphatase and urinary hydroxyproline levels fell substantially, showing that gallium effectively suppressed bone turnover. The fall in hydroxyproline excretion preceded that in serum alkaline phosphatase, suggesting that suppression of bone resorption by osteoclasts preceded that of bone formation by osteoblasts. Alkaline phosphatase levels remained low throughout follow-up (85-141 days), so the effect of gallium seems to be long-lasting.

Acute effects of a low-dose bradykinin infusion (30 ng/kg per min) on carbohydrate metabolism were studied in five patients after major burn injury. Peripheral glucose uptake was not affected but glucose oxidation and alanine flux were increased by 15% and 10%, respectively. These findings are compatible with an increase in glycolytic flux by an action of bradykinin. Nineteen patients who had undergone major gastro-intestinal surgery were studied in a randomised trial of chronic (6 day) bradykinin administration. Patients in the bradykinin group had a significantly improved rate of nitrogen retention (cumulative N balance, -0.014 [SE 0.064] vs -0.175 [0.048] g N/kg) in controls and significantly better nutritional indices. Manipulation of metabolism in surgical patients by bradykinin may have beneficial effects on nitrogen and protein dynamics, possibly mediated by improved aerobic and anaerobic glycolysis.

Eleven patients with chronic heart failure secondary to ischaemic heart disease (mean [SEM] age 63.0 [2.3] years; left ventricular ejection fraction 19 [8]% undertook 8 weeks of home-based bicycle exercise training and 8 weeks of activity restriction (rest) in a physician-blind, random-order, crossover trial. Training increased exercise duration from 14.2 (1.1) min to 16.8 (1.3) min and peak oxygen consumption from 14.3 (1.1) ml.min-1.kg-1 to 16.7 (1.3) ml.min-1.kg-1. Heart rates at submaximum workloads and rate-pressure products were significantly reduced by training, and there was also a significant improvement in patient-rated symptom scores. No adverse events occurred during the training phase. Thus home-based physical training programmes are feasible even in severe chronic heart failure and have a beneficial effect on exercise tolerance, peak oxygen consumption, and symptoms. The commonly held belief that rest is the mainstay of treatment of chronic heart failure should no longer be accepted.

In the absence of definitive medical treatment for severe fulminant hepatic failure, liver transplantation may be appropriate in selected patients. However, uniform and easily applicable criteria for diagnosis of severity and analysis of results are needed to prevent unnecessary transplantation and to ensure that patients who may benefit are appropriately treated. Previous regimens for treatment of fulminant hepatic failure were often advocated, on the basis of data from historical controls, for several years until controlled trials failed to show any benefit. To obtain reliable information more rapidly than achieved before, a controlled trial between specialist liver transplant units is needed to establish the role of emergency hepatic transplantation in patients with fulminant hepatic failure.

17 patients with New York Heart Association (NYHA) class IV congestive cardiac failure, refractory to conventional treatment, were additionally treated with oral metolazone (1.25-10 mg daily). 12 improved sufficiently to be discharged from hospital (NYHA class II or III, mean weight loss 8.3 kg), 1 of whom died at home 4 weeks later. The other 5 patients were treated with intravenous dobutamine for 72 h; 2 responded (average weight loss 4.4 kg), and 2 responded to subsequent reintroduction of metolazone. 4 of these 5 patients died, 2 in hospital of acute myocardial infarction. Overall, 15 patients with very severe refractory cardiac failure improved sufficiently to be discharged from hospital. Treatment was associated with mild transient hypokalaemia in 7 patients, and hyponatraemia and renal impairment in 1, for whom metolazone dosage had to be reduced. Failure to respond to the introduction of metolazone may indicate an especially poor prognosis.