In a prospective study of insulin-dependent diabetic women who in the 1950s were involved in a drug trial, 13 (14%) of those who were still alive 27 years later were reported to have acquired thyroid disease or pernicious anaemia during the follow-up period. This suggests that their diabetes mellitus was a manifestation of a more generalised polyendocrine disorder. The pregnancy history of these 13 women differed strikingly from that of the other 82 insulin-dependent diabetic women: in the diabetic women who subsequently acquired other endocrine disease 69% of pregnancies resulted in a fetal or infant death, compared with 44% in other insulin-dependent diabetic women (p less than 0.01). This risk increased with pregnancy order, the odds ratio of an unfavourable outcome in women who later acquired thyroid disease or pernicious anaemia, compared with the other diabetic women, being 1.2 for the first pregnancy, 3.1 for the second pregnancy, 7.3 for the third pregnancy, and 14.0 for the fourth pregnancy. The mean birthweight of offspring of the women with other endocrine disease was substantially lower than the mean birthweight of offspring of other diabetic mothers (2977 g and 3430 g, respectively). These differences in birthweight and mortality could not be explained by the severity of the mothers' diabetes at the time of their pregnancies, and were evident even before the diabetes was diagnosed.

The study assessed the effect of screening for mental disorder by means of the General Health Questionnaire (GHQ) on the rate of detection of mental disorder by fourteen physicians in a primary-care clinic. After completing the GHQ, patients were randomised into control (722 patients) and experimental (730 patients) groups. GHQ results of the experimental group were made available to the physicians; those of the control group were not. Sociodemographic factors influenced the physicians' rate of diagnosis of mental disorders (rates were lower for men, students, and patients with at least a partial college education than in subjects who had a low income, less than 7 years of school, or were widowed) but there was no difference between control and experimental groups (16.8% vs 16.0%). Among patients with a prior diagnosis of a mental disorder, twice as many were found to have mental disorders by the physicians as by the GHQ (70% vs 33%).

55 postmenopausal women on established hormone replacement therapy were treated with either oestradiol and testosterone implants or placebo at the time of return of climacteric symptoms. Their response to therapy was assessed prospectively. The statistically highly significant levels of symptom relief that followed an oestradiol and testosterone implant were contrasted sharply with the lack of any significant relief with placebo. Despite the success of oestradiol and testosterone implants in relieving symptoms of the climacteric, symptoms returned once the treatment was stopped. Evidence is presented that it is the fall in hormone levels rather than the level itself that provokes the return of climacteric symptoms.

Preterm infants who were making expiratory efforts against ventilator inflation were randomised to be paralysed with pancuronium or to receive no paralysing agent during ventilation. Pneumothoraces developed in all 11 unparalysed babies but in only 1 of 11 (p less than 0.0004) of those managed with pancuronium, which had no serious side-effects. In 34 infants excluded from the trial because they were not breathing against the ventilator, no pneumothoraces developed.

A randomised controlled clinical trial was conducted to investigate the ability of nicotinic acid to reduce intestinal secretion in patients with severe cholera. Of the 62 adults investigated, 29 received either 1 or 2 g of nicotinic acid given orally in divided doses and 33 served as controls. Patients who received the 2 g dose had less fluid loss than did their controls during the first (p less than 0.01) and second (p less than 0.05) 8 h post-treatment periods. During the third and fourth 8 h periods, the rates were lower in the treatment groups, but not significantly so. The drug-specific stool reduction was 31%-47% during the first 16 h. Patients receiving 1 g consistently had lower rates of purging than had their controls during each 8 h observation period, but the differences were not significant. The effect of the 2 g dose was significantly better than that with the 1 g dose. The peak inhibition occurred 8-16 h after start of therapy. The drug was well tolerated, the only side-effect being transient flushing of the body in 1 patient.

In a three-year controlled trial of subcutaneous catheter tunnelling as a method of reducing total parenteral nutrition (TPN) catheter sepsis 99 silicone catheters (52 tunnelled, 47 untunnelled) were inserted into the subclavian (94%) or jugular (6%) veins under aseptic conditions. The influence of a nutrition nurse, who joined the nutrition team after 18 months, on catheter sepsis rate was also documented. Catheter sepsis was confirmed in 13 of 47 (28%) untunnelled catheters and only 6 of 52 (11.5%) tunnelled catheters (p less than 0.05). A nutrition nurse reduced sepsis rate from 33% (tunnelled 6, untunnelled 11) to 4% (0 tunnelled; 2 untunnelled) (p less than 0.001). There was no significant difference between tunnelled and untunnelled catheters in sepsis rates after the arrival of the nutrition nurse. Although 85% patients had concurrent internal sepsis, the pathogens implicated in catheter sepsis came from superficial sites in 16 of 19 cases (p less than 0.01). Rigorous aseptic nursing care is thus the most significant factor in the reduction of TPN catheter sepsis, but tunnelling can reduce sepsis rate when nursing care is suboptimum.

The effect of metronidazole on anaerobic vaginosis (non-specific vaginitis) was assessed in a double-blind, placebo-controlled study of 40 women. 19 of 20 women given metronidazole 400 mg twice a day for seven days were clinically and microbiologically cured by the time they completed treatment. All 20 women given a placebo were treatment failures, but when they were given a single 2 g dose of metronidazole, 15 showed clinical and microbiological cure a week later. 14 of the responders showed a recurrence of infection a month after treatment; this was probably due to reinfection, although persistence of infection cannot be ruled out. Findings in the clinic correlated closely with subsequent microbiological results in 133 out of 140 patient-visits, which suggests that there is no need for expensive and time-consuming laboratory investigations in this condition.

In an open prospective half-side trial, creams containing 10% cholesterol or 10% urea were applied to lesions in 20 steroid-sulphatase-deficient male patients with recessive X-linked ichthyosis. In 18 there was a good response to the cholesterol cream. In 13 patients the response to cholesterol was better than that to urea. None showed a better response to urea than to cholesterol. A reduction in the cholesterol content of the stratum corneum may be responsible for abnormal cornification in recessive X-linked ichthyosis.

12 patients with troublesome hot flushes after orchidectomy (as a primary treatment for prostatic carcinoma) were treated with cyproterone acetate or placebo in a double-blind cross-over trial. The frequency of hot flushes was significantly reduced during the three weeks that cyproterone acetate (100 mg three times a day) was given. 5 patients complained of lassitude while on cyproterone acetate, but in none was it necessary to discontinue treatment.

The role of sclerotherapy in long-term management after oesophageal variceal bleeding was assessed by comparing repeated sclerotherapy by means of a rigid oesophagoscope in 37 patients with control medical management in 38 patients. Varices were eradicated in 21 of the 22 patients analysed (95%) in the sclerotherapy group, but recurred in 13 of the 21 patients (average 21.5 months). Varices persisted in 13 of 14 surviving controls. The sclerotherapy patients had fewer recurrent bleeds than control patients (43 versus 73); the majority occurred before variceal eradication and were mild. However, there was no difference in survival in the two groups. The commonest cause of death was liver failure (37 patients). 32 complications occurred in 24 patients during 258 injections. Repeated sclerotherapy failed to improve survival in this trial, although varices were eradicated and recurrent variceal bleeds were prevented with adequate follow-up.

The efficacy of a heat-inactivated hepatitis B vaccine, 3 micrograms of surface antigen (HBsAg), given at 0, 1, 2, and 5 months, was evaluated in 401 haemodialysis patients in 18 centres by a placebo-controlled, double-blind, randomised trial. The attack-rate of hepatitis B virus (HBV) infections in the control group was 18% over 435 days. The protective efficacy rate of the vaccine was 78% against all HBV infections in the entire study (p = 0.00016), and 94% against HBsAg-positive hepatitis more than 3 months after day 0. Those patients in whom HBV developed showed no evidence of vaccine-acquired anti-HBs. Among 152 similarly randomised staff members receiving three monthly injections, all 5 HBsAg-positive infections occurred in the placebo group (p = 0.022). The vaccine induced anti-HBs in 88% of the patients and 100% of the staff. Immediately after the fourth injection, anti-HBs levels were as high in responding patients as in staff. There were no serious side effects. In the four-dose schedule the vaccine provides dialysis patients with protection of the same order as that given by other hepatitis B vaccines to normal subjects.

Although osteomalacia is known to be common in some sections of the elderly population, the disease is often subclinical and there is uncertainty about the point at which treatment is necessary. Identification and treatment of osteomalacia are inseparably bound; the response of varying degrees of subclinical disease to treatment with vitamin D or alfacalcidol is described here. The response is assessed in relation to a simply derived reference range based on standard biochemical measurements together with a Jamshidi needle biopsy of the iliac crest. Although this technique does not define a truly normal range it identifies a treatable abnormality which could form the basis of further study of the problem of subclinical osteomalacia in the elderly.

Vasoactive intestinal peptide (VIP) caused significant bronchodilatation in seven asthmatic volunteers when given intravenously at the rate of 6 pmol/kg/min for 15 min during a double-blind study. Tachycardia and cutaneous flushing were observed during the infusion. VIP also ameliorated histamine-induced bronchoconstriction in all subjects. VIP may be an important natural bronchodilator in man and this has implications for the pharmacotherapy of asthma.