22 cirrhotic patients with chronic encephalopathy were given oral zinc supplementation or placebo in a double-blind randomised trial. In the group which received zinc acetate 600 mg a day for 7 days, serum zinc had been restored to normal by day 8. On day 8 hepatic encephalopathy, as assessed by a trailmaking test, was improved in the supplemented group but not in the placebo group. There was also a significant increase in blood urea nitrogen in the supplemented group. Short-term oral zinc supplementation probably improved hepatic encephalopathy by correcting the zinc deficiency that compromises conversion of ammonia to urea. The duration of this improvement requires further investigation.

41 patients with pemphigoid entered a multicentre randomised study of the efficacy of plasma exchange. All patients received 0.3 mg/kg daily oral prednisolone, increased weekly if the disease remained active. 24 patients received plasma exchanges in addition (eight large-volume exchanges over 4 weeks), and 17 had prednisolone only. 4 patients, 2 in each group, were withdrawn from the study. The initial dose of prednisolone was effective in 13 of 22 patients receiving plasma exchange but in none of 15 patients receiving prednisolone only. Control of the disease was obtained with a mean daily prednisolone dose of 0.52 +/- 0.28 mg/kg in the plasma exchange group v 0.97 +/- 0.33 mg/kg in the other group and a mean cumulative dose of 1240 +/- 728 mg v 2770 +/- 1600 mg. This finding suggests that plasma exchange allows a substantial saving of corticosteroids in the management of pemphigoid. This sparing effect was observed whether or not serum anti-basement membrane antibodies had been detected before treatment.

The effect of specific H1 and H2 receptor antagonists on bronchial reactivity and increase in lung epithelial permeability in response to inhaled histamine was measured in 5 non-smoking men (age range 24-36 years). Inhaled histamine produced a short-lived but consistent increase in permeability to 99Tc-diethylenetriamine penta-acetate. An H1-receptor antagonist, terfenadine (60 mg), protected against the bronchoconstrictor effect but had no significant influence on the increase in permeability. The H2-receptor antagonist ranitidine (150 mg) significantly reduced the permeability response without having an effect on bronchial reactivity. These results demonstrate that the bronchoconstrictor effect of histamine is mediated by H1 receptors and permeability increase is mediated by H2 receptors. H2-receptor mediated increase in lung epithelial permeability may be important clinically.

A major assumption in current dietary advice for pregnancy is that the amount of energy expended on tissue maintenance increases by 36 000 kcal over the whole gestation period. In a group of rural Gambian women engaged in subsistence farming, the increase was much smaller and depended on maternal dietary status. In women having the customarily low food intake the net extra cost of tissue maintenance was just 1000 kcal; even in those given a dietary supplement in amounts previously shown to increase birthweight it was only 13 000 kcal. This finding partly explains why mothers, particularly those in the Third World, can apparently accomodate pregnancy without substantially increasing their dietary energy intake. The findings are of importance in the formulation of realistic dietary health strategies for such communities.

Of 28 788 women aged 40 to 74 registered at 28 university teaching practices in greater Belfast, half were randomly selected to receive a booklet on breast self-examination from their general practitioner at the start of the study and 1 year later. The frequency of breast abnormalities was identical in both groups (0.83%) during the 2-year follow-up. Early malignant breast cancers (stages TX, TO, Tla) were significantly more frequent in the intervention group (53.6%) than in the control group (24.3%). Among women in the intervention group with malignant lesions, 2 sites, left nipple and left inner/upper quadrant, were significantly less frequently involved. These findings in relation to staging and site were confirmed by multivariate comparisons. The intervention group also had a smaller average tumour size (24.0 mm compared with 32.6 mm) due to significantly smaller benign tumours and the absence of the relationship between delay and tumour size evident in the control group.

327 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after total mastectomy and axillary clearance, to receive either no additional treatment or oral cyclophosphamide 80 mg/m2 on days 1-14, intravenous methotrexate 32 mg/m2 on days 1 and 8, and intravenous fluorouracil 480 mg/m2 on days 1 and 8 (CMF), which was repeated every 28 days for twelve cycles. There was a significantly longer relapse-free survival (RFS) in patients treated with CMF. A prolonged RFS was seen in premenopausal patients, those with 1-3 nodes involved, and those with 4 or more nodes involved, but a similar trend in postmenopausal patients failed to reach statistical significance. RFS was greater in patients with CMF-induced amenorrhoea than in controls and in treated patients whose primary tumour contained progesterone receptors. Dose of chemotherapy did not have a significant effect on RFS. Survival was not influenced by treatment.

102 patients with endoscopically proven duodenal ulcers were randomly allocated to treatment with ranitidine either 150 mg twice a day or 300 mg every evening for 4 weeks in a prospective double-blind study. The two groups were similar. 48/57 (84%) healed on ranitidine 150 mg twice daily and 43/45 (96%) healed on 300 mg every evening (p = 0.9)--that is, ranitidine 300 mg as a single night time dose is as effective as 150 mg twice daily. The results also indicate the importance of overnight gastric acidity in the pathogenesis of duodenal ulcers.

510 of 1009 pregnant women in the Trondheim area (Norway) were randomly selected for ultrasound examination at the 19th and 32nd weeks of pregnancy in addition to routine antenatal care. Among the screened women, twins were diagnosed earlier and there were slightly fewer post-term inductions (2.8% versus 4.0%) and fewer low-weight births (2.2% versus 3.6% less than 2500 g), but none of these differences was statistically significant. There were no differences in the condition of the newborn. Small-for-gestational-age births were more often diagnosed antenatally in the screened group and the mothers received more active treatment. During pregnancy, screened women were admitted to hospital more often than unscreened women (15.5% versus 9.2%). The study revealed no adverse short-term biological effects from ultrasound. The cost of the screening programme, including associated costs such as extra hospital admissions, was about US$ 250 per pregnancy.

A double-blind, randomised, placebo-controlled, crossover trial of prednisolone (40 mg daily for 14 days) was carried out in 43 patients with chronic airflow limitation (mean age 60 years, mean FEV1 1.02 litres, FEV1/FVC ratio 43.7%). Several subjective and objective variables for response were measured. Significant improvements occurred with prednisolone in most variables measured, but improvements also occurred with placebo in some variables. The improvements with prednisolone in general wellbeing, 12 min walk distance, peak expiratory flow, FEV1, and relaxed vital capacity were significantly greater than those with placebo. Clinical assessment and assessment of atopic status did not reveal any feature of major predictive value for steroid responsiveness. A proportion of patients with chronic airflow limitation do improve on oral corticosteroids and the continued use of such trials in clinical practice is justified, though a placebo period should be included, and several variables for response should be measured.

In a longitudinal study designed to assess the impact of a massive-dose vitamin A programme on the incidence of keratomalacia, 50 000 preschool children in 450 slum areas in Hyderabad city (India) were given 200 000 IU of vitamin A once every 6 months. During the study period, the incidence of keratomalacia in areas covered by the programme decreased by about 80%, while in control areas the reduction was of the order of 20%. To test whether large doses of vitamin A supplements prevented keratomalacia, a case-control analysis was done, with patients with severe protein-energy malnutrition being used as controls. The high odds ratio clearly indicated that keratomalacia was more likely to occur in children not receiving supplements.

The hyperglycaemic effect of 20 g sucrose taken at the end of a regular mixed meal by diabetic patients was measured in six adult type 1 diabetics, C-peptide negative, controlled by the artificial pancreas, and twelve adult type 2 diabetics, with fasting plasma glucose levels below 7.2 mmol/l (130 mg/100 ml) and post-prandial plasma glucose levels below 10.0 mmol/l (180 mg/100 ml), treated by diet alone or with glibenclamide and/or metformin. All the patients were given on consecutive days, in random order, two mixed meals of grilled meat, green beans, and cheese, as well as a cake made either of rice, skimmed milk, and saccharine (meal A) or rice, skimmed milk, and 20 g sucrose (meal B). The meals contained equal amounts of calories and of carbohydrate. There was no difference between the meals in plasma glucose curves and plasma insulin or insulin infusion rate variations whether in peak values, peaking times, or areas under the curves, in either group of patients. Sparing use of sucrose taken during mixed meals might help well-controlled diabetic patients to comply with their daily dietary prescription while maintaining good blood glucose control.

56 patients with frequently recurring genital herpes were treated in a randomised double-blind trial with either oral acyclovir 200 mg four times a day or placebo for 12 weeks. 29 patients received the drug and 27 the placebo. The mean recurrence rate per month of treatment was 1.4 in the placebo-treated patients and 0.05 in the acyclovir group. Median time to the first recurrence after the start of therapy was 14 days in the placebo group compared with 100 days in the acyclovir group. After the end of treatment the recurrence rate was similar in the two groups. Prophylactic oral acyclovir seems to be an effective treatment for patients with frequently recurring genital herpes.