64 women with operable breast cancer were randomly allocated at the time of mastectomy to a group receiving immediate breast reconstruction or to a control group to whom breast reconstruction was offered 12 months later. The objective of the trial was to determine whether immediate breast reconstruction affected the psychosocial morbidity of mastectomy. Immediate reconstruction reduced the psychiatric morbidity assessed 3 months after operation, predominantly in women with unsatisfactory marriages. Women who underwent reconstruction had more freedom of dress and were less likely to be repulsed by their own naked appearance than women who did not undergo reconstruction. Sexual and social morbidity were not affected.

Atenolol was compared with placebo in a randomised and double-blind prospective study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest. Atenolol given once daily significantly reduced blood-pressure, prevented proteinuria, and reduced the number of hospital admissions. Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group, whose babies had a high morbidity. Respiratory distress syndrome occurred only in the placebo group. Intrauterine growth retardation, neonatal hypoglycaemia, and hyperbilirubinaemia occurred with the same frequency in the two groups. Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups. There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy. Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby.

42 obese women who lost at least 6 kg after 26 weeks on fenfluramine tablets had their treatment changed to either an equivalent dose of a sustained-release preparation of fenfluramine or matching placebo in double-blind fashion. Of the 21 given placebo all but 2 regained weight over the following year. Of the 21 crossed over to fenfluramine, 8 maintained their weight loss, 7 regained weight, and 6 had to be withdrawn for reasons other than weight gain. Plasma concentrations of fenfluramine and norfenfluramine taken before and 4 weeks after the crossover were similar in both responders and non-responders, but non-responders did not maintain their drug levels for as long as did the responders. Longer controlled administration of fenfluramine will prevent weight regain in some obese women but the hazards of prolonged use remain to be evaluated.

A 96 h infusion of epoprostenol (prostacyclin) or placebo was given as a treatment for rest pain to 28 patients with severe peripheral arterial disease. 24 h after the end of the infusion patients given epoprostenol had significantly less pain and took fewer analgesics tablets than did the controls. In some patients the epoprostenol effect lasted for over 1 month.

Two groups of outpatients (7 in each group) with Raynaud's syndrome, matched for severity of illness, were randomly allocated to receive at weekly intervals for three weeks either a 5 h intravenous infusion of buffer or epoprostenol (prostacyclin, PGI2) in buffer (7.5 ng/kg/min after the first hour). PGI2 reduced the frequency and duration of ischaemic attacks (both p less than 0.01). Hand temperature measurements with a thermocouple were significantly improved at 1 week; 6 weeks after the last infusion hand temperatures had returned to baseline. There was a corresponding loss of clinical response 8-10 weeks after the last infusion.

The effects on plasma proteins and haemostasis of haemotherapy with buffy-coat-poor red-cell concentrate and red cells suspended and stored in a new medium containing sodium chloride, adenine, glucose, and mannitol (SAGM) were studied in elective surgery. In patients with normal preoperative serum albumin levels no transfusion of plasma was necessary before 50% of blood volume had been lost. When three different types of haemotherapy were investigated in patients undergoing orthopaedic surgery, it was found that when whole blood was replaced by red-cell concentrate and, later, by red-cell suspension in SAGM medium, the peroperative bleeding pattern did not change. The volume of transfused plasma was reduced by 47% in the red-cell-concentrate series and by 72% in the red-cell-suspension series. No albumin preparations were given and the use of red cells was decreased by 26%. Haemotherapy with red cells suspended in SAGM was useful in elective surgery and saved plasma for other purposes.

Two patients with long-standing idiopathic chronic constipation, which responded only to large daily doses of laxatives and additional suppositories and enemas, were treated with the specific opioid antagonist, naloxone, on a single-blind crossover basis. Both patients responded to naloxone treatment, with increased passage of faeces and increased wet and dry faecal weight. Although naloxone is poorly absorbed after oral administration, there was a positive response during oral as well as intravenous treatment, suggesting that the primary effect of naloxone is at specific opiate receptor sites in the myenteric plexus and other neural and endocrine cells of the intestinal wall.

Tamoxifen ('Nolvadex'), an anti-oestrogen, has been evaluated as an adjunct to the local treatment of early breast cancer in a prospective randomised clinical trial. 1285 women (with pathological stage II premenopausal and pathological stage I and II postmenopausal disease) were treated by total mastectomy with either axillary node clearance or axillary node sampling and then randomised to receive either tamoxifen 10 mg twice daily for two years or no further treatment. Treatment failure (recurrent disease or death) at 21 months was reduced in patients receiving tamoxifen (14 X 2%) compared with controls (20 X 5%) (p = 0 X 01). This is equivalent to a prolongation of the disease-free interval from 21 months to 30 months at the mean follow-up time of 21 months. Subgroup analyses by menopausal, axillary lymph node, and oestrogen receptor status did not reveal a significantly different treatment effect in any of these subgroups. There has been no significant effect on mortality at this point in the study. This endocrine adjuvant therapy was well tolerated and treatment was discontinued in only 14 (2 X 2%) patients as a direct result of side-effects. Thus, tamoxifen significantly delays recurrence in early breast cancer. The magnitude of the effect is comparable with that associated with adjuvant cytotoxic chemotherapy at a similar follow-up time, but with minimal toxicity and excellent compliance.

The efficacy and safety of a single daily dose of sodium stibogluconate, 20 mg/kg body weight, given by deep intramuscular injection was compared with the conventional dose of 10 mg Sb/kg body weight in a randomised trial in Kenyan children and adults with visceral leishmaniasis. Splenic aspiration proved a safe and simple method for assessing parasitological response to treatment. In children the higher dose was associated with a faster clinical and parasitological response, and 100% were cured within 4 weeks, compared with 60% receiving the lower dosage. This difference is statistically significant by life-table analysis (x2 = 4.41, p less than 0.05). The superiority of the higher dose was not, however, seen in adults. In both children and adults the higher dose given daily for 2--4 weeks and in one patient for up to 7 weeks was found to be safe and well tolerated. It is likely, but not proven, that the use of sodium stibogluconate in a dose of 20 mg/kg bw daily for 4 weeks will reduce the relapse-rate in Kenyan children with visceral leishmaniasis.

74 insulin-dependent diabetic patients with background retinopathy were randomised to continue with usual diabetic care (group U) or to a more intensive programme (group A) using ultralente insulin as basal cover and soluble insulin at mealtimes. Group A attended the clinic more frequently, received closer dietary supervision, and were taught home blood glucose monitoring. Group A had a significantly lower mean glycosylated haemoglobin level during the study, although the mean level also fell in group U towards the end of year 2. Renal and sensory-nerve function were significantly better preserved in group A than in group U. Significant improvements were also seen in low-density-lipoprotein-cholesterol and whole-blood low-shear viscosity. The rate of progression of retinopathy was similar in both groups. It appears that a modest improvement in diabetic control, obtainable in most clinics, has been associated with a reduction in the progression of diabetic tissue damage.

30 insulin-dependent diabetic patients with background retinopathy were randomised to conventional treatment (UCT) or treatment with continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 1 year with fortnightly seven-sample home blood glucose measurements and retinal examinations every 6 months. Mean blood glucose and stable haemoglobin A1c during months 3-12 were significantly lower in the CSII than the UCT group. Retinal morphology deteriorated during the year with no significant differences between UCT and CSII groups. The frequency of deterioration was highest in the CSII group, especially among the 10 patients with best glycaemic control. Proliferative retinopathy developed in 3 patients--2 of these were CSII treated. Retinal function (oscillatory potential, macular recovery time, and posterior vitreous fluorophotometry) improved significantly with CSII treatment and deteriorated significantly with UCT. Changes in retinal function were most pronounced in patients with the best and the poorest regulated glycaemic control.