The efficacy of high intrauterine insemination of a washed motile fraction of spermatozoa from men with poor quality semen on the day after the luteinising hormone (LH) surge was compared with that of natural intercourse based on symptothermal methods and a single act of intercourse timed on the day after the LH surge in the same 35 couples in a controlled and randomised trial of the three types of cycle. Each couple had been trying to conceive for at least 3 years, the woman being potentially fertile and the only detectable defect related to poor semen quality. After 39 intrauterine insemination cycles, 8 women conceived (all in their first insemination cycle); this procedure was significantly more successful than LH-timed intercourse (0/38; p less than 0.05) and natural intercourse timed by symptothermal methods (1/34; p = 0.022). The technique of intrauterine AIH, with a 'Tomcat' catheter, was simple, painless, and uncomplicated.

91 renal transplant candidates were randomised to receive Towne strain cytomegalovirus (CMV) vaccine or placebo at least 8 weeks before transplantation. The vaccine was well tolerated and there was no vaccine virus excretion. Serological and cellular immune responses developed in most vaccines but were lower in the transplant patients than in healthy volunteers and some of the seronegative patients failed to mount responses. CMV infection occurred in most of the seronegative vaccine-treated or placebo-treated patients who received kidneys from seropositive donors, but the illnesses were less severe in the vaccines than those in similarly exposed placebo-treated patients. Vaccine-treated patients who received kidneys from seronegative donors did not excrete virus, and therefore the vaccine virus was not reactivated from a putative latent state despite immunosuppression at the time of transplantation.

In a boarding school for boys, where routine influenza vaccination is carried out annually, 267 boys were given amantadine (100 mg daily) and 269 received no specific treatment during an influenza A (H1N1) outbreak. 3 boys receiving amantadine and 29 boys receiving no medication had laboratory-proven influenza A. There are circumstances when the prophylactic use of amantadine may be justified for the control of influenza A outbreaks in boarding schools and other institutions where high attack-rates are experienced.

In a randomised, controlled trial of the effectiveness of artificial surfactant therapy 100 babies of less than 34 weeks' gestation were intubated at birth and received manual ventilation. The 49 babies in the treated group also received 30 mg dipalmitoylphosphatidylcholine and 3 mg high-density lipoprotein in a 5 ml suspension. There were no significant differences in mortality or in the incidence or severity of respiratory distress syndrome between the surfactant-treated and control groups as a whole or between subgroups divided on the basis of sex or pulmonary maturity (as assessed by the lecithin-sphingomyelin ratio). However, there appeared to be a trend towards improved survival in treated babies of 27-29 weeks' gestation.

To investigate the value of maintenance chemotherapy after early consolidation treatment, an attempt was made to induce remission in 162 previously untreated patients, age-range 7-65 years (median 43). The 74 patients who were still in remission after early consolidation treatment (given for 3-5 months) were assigned to either maintenance chemotherapy every 8 weeks for 2 years or to observation only. After a median observation period of 44 months there was no difference between the groups in duration of remission or survival. Surprisingly, patients above 40 survived longer after early consolidation (median 4 years) than did patients aged 40 and below (median 1.6 years, p = 0.0002).

108 children with standard-risk acute lymphocytic leukaemia (ALL) were randomised to a post-induction treatment protocol including 15 doses of intermediate-dose methotrexate (1000 mg/m2) in addition to conventional oral therapy of mercaptopurine and low-dose methotrexate. After median follow-up of 26 months, 22 patients have had relapses. Among the 108 patients, rates of methotrexate systemic clearance ranged from 44.7 to 132 ml/min/m2. When the group was divided into three subgroups according to the patients' rates of methotrexate clearance, statistical analysis of the Kaplan-Meier curves estimating the probability of complete remission showed significant differences (p = 0.016) among the subgroups, patients with faster clearance having higher probability of relapse. Multivariate Cox's regression analysis incorporating other potential prognostic variables identified three significant variables influencing the risk of relapse--methotrexate clearance and white-blood-cell count and haemoglobin level at diagnosis (p = 0.0015). This study has demonstrated the potential clinical importance of the rate of drug clearance in children with ALL.

The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients. Half of the patients had major depression. There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients. Depression was measured by the Hamilton depression scale, Zung depression scale, present state examination, and an overall depression scale. Successfully treated patients had serum nortriptyline levels in the therapeutic range. Post-stroke depressions are common, severe, and longstanding, and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients.

Twenty-four patients with frequent drug-resistant seizures took part in a randomised double-blind placebo-controlled crossover trial of the GABA-transaminase inhibitor, gamma-vinyl GABA. It was added to their usual drug treatment in a dose of 3 g daily. The total number of seizures during the 9-week active treatment period was less than that in the placebo period (p less than 0.001, two-way analysis of variance). The greatest effect was on complex partial seizures. Mean weekly seizure frequency (complex partial and tonic-clonic) was 6.2 fits/week for the placebo period and 3.5 fits/week for the gamma-vinyl GABA period. Adverse effects, particularly drowsiness and mood changes, occurred more often during administration of active drug. Serum concentrations of phenytoin were lower during gamma-vinyl GABA treatment than during placebo (p less than 0.05), but the concentrations of other anticonvulsants given concomitantly did not change. These results suggest that gamma-vinyl GABA is an effective antiepileptic compound.

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%).

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.