Patients with very severe acne which had not responded to conventional treatment were given 13-cis retinoic acid (0.1 mg-1.0 mg/kg body-weight) in a double-blind dose response study. Sebum excretion rate was reduced by 75% at 4 weeks, and all patients had an 80% improvement in their acne severity after 4 months treatment. There were dose-related side-effects, particularly dryness of the skin and mucous membranes. No patient wished to stop treatment.

Behaviour therapy, pharmacotherapy, and a combination of the two were compared in 120 obese women and 14 obese men during six months of treatment for obesity and at one-year follow-up. Patients who received the appetite suppressant fenfluramine lost 14.5 kg and those who received the combined treatment lost 15.3 kg, both significantly more than those who received only behaviour therapy (10.9 kg). One-year follow-up of all living patients who completed treatment showed a striking reversal of these effects: behaviour-therapy patients regained only 1.9 kg, significantly less than pharmacotherapy patients (8.2 kg) and combined-therapy patients (10.7 kg). Weight changes of the 14 men did not differ from those of the women. Although pharmacotherapy produced more rapid initial weight loss than behaviour therapy, it was followed by more rapid weight gain after treatment. Addition of pharmacotherapy apparently compromised the long-term effects of behaviour therapy. Better maintenance of weight loss and lower costs favour behaviour therapy over pharmacotherapy for the treatment of obesity.

In a randomised double-blind multicentre clinical trial the effect of continued oral anticoagulant therapy after a myocardial infarction was assessed in a group of patients over 60 years of age. Half of the 878 patients who had been on anticoagulants ever since their primary myocardial infarction received placebos instead of the anticoagulant; the others continued anticoagulant therapy. All were followed for 2 years. The levels of hypocoagulability reached in the group on anticoagulants were such that, of the registered prothrombin times ('Thrombotest'), 72% were between 107 and 180 s. 2-year total mortality was 13.4% in the placebo group and 7.6% in the group treated with anticoagulants (p = 0.017. 2-year incidence of recurrent myocardial infarction was 15.9% in the placebo group and 5.7% in the anticoagulant treated group (p = 0.0001). The incidence of intracranial events was 5.6% in the placebo group and 3.1% in the group on anticoagulants (p = 0.18). Major haemorrhagic episodes were reported by 3 placebo patients and by 27 patients treated with anticoagulants. No fatal extracranial haemorrhages were seen. In this selected group of elderly patients, continuation of intensive and stable oral anticoagulant therapy substantially reduced the risk of recurrent myocardial infarction and thereby of cardiac death.

30 multiple sclerosis patients in a double-blind, controlled trial were given immunosuppressive treatment consisting of antilymphocyte globulin, prednisolone, and azathioprine, or placebo. After 15 months of treatment the immunosuppressed group had a reduction in the number of relapses and some retardation of the clinical course of the disease (p < 0.06). The beneficial effect was seen only in females.

Patients with acute myocardial infarction admitted to a coronary care unit were given either intravenous and oral disopyramide or matching placebo on admission and throughout their hospital stay. 199 patients entered the trial, and 138 were subsequently shown to have had a myocardial infarct. The placebo and study groups were well matched. There were no significant differences in mortality or observed arrhythmias between the two groups. These results do not confirm earlier observations that prophylaxis with disopyramide reduces mortality after acute myocardial infarction.

A 2-year prospective double-blind trial of the treatment of multiple sclerosis patients with the leucocyte extract, transfer factor (TF), obtained from leucocytes of relatives living with the patient, was conducted. 60 patients with definite MS, of whom 58 completed the trial, were divided into two equal groups, one of which received TF and the other placebo. The groups were evenly balanced with respect to sex ratios, disability, duration of disease, ratio of moderate to severe cases, and HLA phenotype. Neurological, electrophysiological, and immunological assessments were done at the start of the trial and every 6 months thereafter. The results indicated that (1) TF retarded but did not reverse progression of the disease; (2) a significant difference between treatment and placebo groups was not apparent with 18 months after the start of the trial; and (3) treatment was effective only in those patients with mild to moderate disease activity.

A study was undertaken to investigate whether toxin produced in the gut lumen contributes significantly to clinical illness and whether binding such toxin by GM1 ganglioside adsorbed onto charcoal could alter the clinical course of disease. 46 patients with severe cholera receiving standard intravenous therapy were randomly assigned to one of three groups: GM1 ganglioside-charcoal (16), charcoal alone (16), or water (14). The results demonstrated that patients were given sufficient GM1 ganglioside-charcoal to bind all luminal toxin produced by Vibrio cholerae in their intestines. Patients treated with GM1 ganglioside tended to have a greater reduction in purging than patients treated with either charcoal alone or water. This difference was statistically significant soon after beginning medication (8-15 h) and the reduction in fluid-loss was especially pronounced in patients with very severe initial purging who had been ill only for a short time before admission. These results suggest that toxin produced in the gut lumen increases fluid-loss early in cholera, but that later in the course of disease, toxin which is inaccessible to luminal binding agents in the major stimulus of purging.

After total mastectomy with partial axillary-lymph-node biopsy, patients with breast carcinomas with histologically positive lymph-nodes but without distant metastasis (N+, Mo) were allocated at random to receive either radiotherapy alone (384 patients) or radiotherapy plus levamisole 2.5 mg/kg/day for two consecutive days each week for 48 weeks (336 patients). At 1 year the levamisole-treated patients had a significantly higher recurrence rate than the radiotherapy-only group. They also had an unacceptably high incidence of side-effects, especially patients aged over 50. The frequency of levamisole-induced agranulocytosis was 3.6% and leucopenia 15-20%. These preliminary results suggest that adjuvant therapy with levamisole should not be used in patients with N+, Mo breast carcinoma.

473 patients with suspected acute myocardial infarction were entered into a randomised, double-blind, placebo-controlled comparison of disopyramide phosphate, 150 mg three times a day, and oxprenolol, 40 mg three times a day. When analysed on an intension-to-treat basis there was no significant difference in 6-week mortality between the groups, but patients who were able to continue on the active medications fared better than the patients who had to be withdrawn. The withdrawal rate because of heart failure in patients randomised to receive disopyramide was significantly increased. Patients receiving this agent also showed a reduced number of arrhythmic episodes on 24-h tape recordings but this trend did not achieve statistical significance. The results show that the early use of either oxprenolol or disopyramide phosphate in patients with suspected acute myocardial infarction is unlikely to improve mortality.

The effects of sulphinpyrazone on heart-rate and blood-pressure responses to exercise were assessed in 15 normal volunteers by a randomised double-blind crossover technique. Submaximal exercise tests were performed 1 and 2 hours after either sulphinpyrazone (SPZ) 200 mg orally or placebo. Heart-rate and blood-pressure responses were unchanged at rest and during exercise 1 hour after SPZ but after 2 hours there was a significant fall in the product of heart-rate and blood-pressure during exercise (peak 35.8 +/- 1.5 x 10(-3) mmHg beats/min, placebo: 33.0 +/- 1.3 x 10(-3) sulphinpyrazone, p < 0.005) and for the first 2 minutes of recovery. This was mainly due to a decreased exercise-induced rise in systolic blood-pressure with lesser effects on heart-rate. This haemodynamic effect of SPZ has a potentially protective oxygen-sparing effect on the normal myocardium during exercise and may explain its apparent benefit in reducing sudden cardiac death after myocardial infarction.

24-h whole-body retention (WBR) of diphosphonate (a sensitive indicator of skeletal metabolism) was measured in 37 oophorectomised women. 14 women had been prescribed oestrogen supplements and 3 of these had defaulted from therapy. For the study group there was a significant correlation between WBR and both the rate of bone loss as measured by photonabsorptiometry (r = 0.7, p ¿ 0.001) and urinary hydroxyproline (r = 0.53, p < 0.001). The oestrogen-treated group had significantly lower values for WBR and rate of bone loss than the untreated group (p < 0.01, p < 0.01 respectively) indicating suppressed skeletal metabolism. However, the highest values were found in those who had defaulted from oestrogen therapy suggesting a rebound period of accelerated skeletal metabolism and bone loss. There was a significant negative correlation between WBR and oestrogen dosage (r = 0.75, p < 0.02) suggesting that it may be possible to adjust the dosage for optimal skeletal metabolic activity. WBR of diphosphonate provides a simple and sensitive measure of skeletal metabolism which correlates well with conventional measurements of bone loss. WBR may be useful in the screening and identification of women who have increased bone turnover just after the menopause and who may subsequently be at risk of osteoporosis developing.

In 8 patients receiving intravenous isophosphamide 2 g/m2 at 2-week intervals for advanced bronchogenic carcinoma the protective effect of 2-mercaptoethane sulphonate sodium (mesnum) against isophosphamide-induced urothelial toxicity was tested in a single-blind crossover trial. With isophosphamide alone, 7 of the 8 patients developed either haematuria or symptoms of bladder irritation; when mesnum was given in addition, only 1 patient had microhaematuria and frequency, and this was in association with a urinary-tract infection. 5 patients then received fifteen courses of isophosphamide in increasing doses of 4 to 8 g/m2 i.v. with mesnum. In contrast to previous experience with isophosphamide at this high dosage, frank haematuria was never seen, microhaematuria was seen after only three courses, and mild dysuria after only one course. Pharmacokinetic studies showed that mesnum did not interfere with the metabolism of isophosphoramide or its active anti-tumour metabolite, isophosphoramide mustard. Mesnum therefore enhances the therapeutic ratio of isophosphamide and may thereby increase its clinical efficacy.