The antihypertensive effect and metabolic side effects of bendroflumethiazide have been compared with those of propranolol in two randomly selected groups, of 53 previously untreated middle-aged men during 6 years' treatment for mild to moderately severe essential hypertension. The blood pressure-reduction was the same in the two groups. During the follow-up 1 man in the bendroflumethiazide group and 3 in the propranolol group died while 2, 1 on each treatment, became diabetic. None had gout but serum urate increased in both groups. Glucose tolerance improved significantly in both groups during the first year and this improvement was sustained for the follow-up period. Serum potassium did not differ in the two groups during the first 5 years but during the sixth year it decreased in the diuretic group. Total potassium was, however, unchanged in both groups. These results indicate that the frequency of metabolic side effects during diuretic treatment of mild to moderately severe essential hypertension is low and has been grossly exaggerated. Since the antihypertensive effect and side effects were equal with both drugs, and since the diuretics are cheaper, they should be the drug of first choice in this type of hypertension.

In the period 1968--78, 3161 children were enrolled in six studies of acute lymphoblastic leukaemia by participating institutions of the Childrens Cancer Study Group. In the first two studies, which did not include central-nervous-system (CNS) prophylaxis in the treatment programme, the outcome for male and female patients was very similar. In the following four studies, which included radiation prophylaxis to the CNS, a difference in outcome favouring females appeared consistently. This difference began about 6--12 months after initial remission and was further accentuated by withdrawal of therapy. Some of these studies also included a randomised trial of duration of therapy, studying 3 versus 5 years of maintenance treatment. Analysis of these studies suggests that sex group has implications both for duration of treatment and for optimum central-nervous-system prophylaxis.

A controlled trial of long term domiciliary oxygen therapy has been carried out in three centres in the U.K. The 87 patients, all under 70 years of age, who took part had chronic bronchitis or emphysema with irreversible airways obstruction, severe arterial hypoxaemia, carbon dioxide retention, and a history of congestive heart failure. The patients were randomised to oxygen therapy (treated) or no oxygen (controls). Oxygen was given by nasal prongs for at least 15 h daily, usually at 2 1/min. The two groups were well matched, both clinically and in terms of lung function and other laboratory findings. 19 of the 42 oxygen treated patients died in the five years of survival follow-up compared with 30 out of 45 controls: in the 66 men in this trial the survival advantage of oxygen did not emerge until 500 days had elapsed. Survival for the 12 female controls was surprisingly poor, 8 of them being dead at 3 years. Mortality was not easy to predict, though a summation of arterial carbon dioxide tension and red cell mass was helpful. Neither time spent in hospital because of exacerbations of respiratory failure nor work attendance were affected by oxygen therapy, but these patients were very ill at the start of the trial and many had already retired on grounds of age or ill-health. Physiological measurements suggested that oxygen did not slow the progress of respiratory failure in those who died early. However, in longer term survivors on oxygen, arterial oxygenation did seem to stop deterioration.

Hydrogen (H2) concentrations were measured in undiluted samples of intracolonic gas and in expired air in twenty patients undergoing colonoscopy after preparation with either mannitol or castor oil. Potentially explosive intracolonic H2 concentrations were present in six out of ten patients given mannitol, but in none given castor oil. This has important implications for colonoscopic, as well as for surgical, electrosurgery. H2 concentrations in expired air sampled preoperatively did not identify patients with potentially explosive intracolonic hydrogen levels.

Two levonorgestrel-releasing intrauterine devices (IUD) with different release rates of levonorgestrel and a 'Nova-T' copper-releasing device were compared in a randomised clinical performance study. 327 women had a levonorgestrel IUD and 156 women a nova-T device inserted postmenstrually. No statistically significant differences in the reasons for termination between the three devices were found in 12 months. The continuation rates for the two levonorgestrel IUDs were 84.1 and 81.4 and for the nova-T device 87.5. Duration of menstrual bleeding and spotting was highly significantly shorter with the levonorgestrel IUDs than with the nova-T device. There were no infections.

Three sex and age matched groups of medical personnel, 20-40 individuals in each, received a course of hepatitis B vaccine: in one group the first dose of vaccine was given a month after injection of hepatitis B immune globulin; in the second, vaccine and immune globulin were given simultaneously; and, in the third, vaccine was given alone. The passively acquired antibody did not interfere with an active immune response to the vaccine. Both the timing of antibody appearance and the antibody titres were similar in the three groups, and the actively acquired antibody persisted for the 8 months of follow-up. Administration of the vaccine together with hepatitis B immune globulin will provide immediate protection, whereas people who receive vaccine alone may lack antibody for several months. This opens new possibilities for post-exposure prophylaxis.

LM24056, a tricyclic drug, weakly inhibited pentagastrin-stimulated gastric secretion but was a powerful inhibitor of nocturnal gastric secretion in 5 healthy volunteers. In 23 patients with duodenal ulcer, LM24056 at doses of 100,200, and 300 mg inhibited overnight acid output by 31%, 70%, and 81%, and overnight pepsin secretion by 15%, 50%, and 69%, respectively. In view of its gastric inhibitory effects, LM24056 warrants clinical evaluation in the treatment of peptic ulcer disease.

The Children's Cancer Study Group has organised two therapeutic clinical trials designed to evaluate the efficacy of various types and doses of CNS prophylaxis in the treatment of childhood acute lymphoblastic leukaemia. Of 478 previously untreated patients who subsequently achieved an initial marrow remission, 299 were randomised to receive 2400 rad craniospinal radiation therapy (RT) or 2400 rad cranial RT plus intrathecal methotrexate (i.t. MTX) while the remaining 179 patients were randomised between the same two regimens using a radiation dose of 1800 rad. All patients received identical induction and maintenance chemotherapy. Comparison of the two studies indicated that reduction of the dose of CNS radiation from 2400 rad to 1800 rad did not result in a significant increase in the frequency of CNS relapse, bone marrow relapse, or death. Moreover, no significant differences were observed when analyses were done within prognostic risk groups. Randomised trials with RT doses lower than 1800 rad or with i.t. chemotherapy alone should be considered to determine the most effective and least toxic forms of CNS prophylaxis.

The effect on forearm bone mineral content (BMC) of initiation and withdrawal of oestrogen/gestagen treatment was studied in a randomised trial in 94 healthy female volunteers six months to three years after the menopause. BMC was measured every three months for three years. BMC increased by 3.7% (p less than 0.001) during three years' hormone treatment and decreased by 5.7% (p less than 0.001) during three years' placebo treatment. The annual rate of bone loss after discontinuation of hormone therapy was identical with the bone loss in the placebo group. The present study indicates that even temporary hormone replacement therapy after the menopause will have a lasting beneficial effect on bone mass.

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in staff members from forty-eight French haemodialysis units where the risk of hepatitis B was high. Of 318 subjects who completed the protocol, 164 received three monthly injections of vaccine and 154 received corresponding injections of placebo. Hepatitis B infection was observed in 3.6% of the vaccine group and 12.3% of the placebo group (p less than 0.005). The 6 infections in the vaccine group all arose within 63 days from the first injections, whereas the 19 in the placebo group arose throughout the 12 months of follow-up. The rate of side-effects after injection did not differ in the two groups. 94% of the vaccine recipients had an immune response ( greater than 10 mIU/ml in at least 5 successive specimens). 4 months after the first injection the mean + or - 2 SE peak level of anti-HBs was 2433 + or - 1077 mIU/ml.

The effects of the hypothalamic 28 aminoacid peptide prosomatostatin (Pro-SS) on arginine-induced growth hormone (GH) and prolactin (PRL) release and blood glucose levels in man are compared with those obtained after an equimolar dose of somatostatin (SS). In comparison with SS, Pro-SS caused greater and more prolonged inhibition of GH release, a more marked reduction of the PRL response to arginine, and greater enhancement of the hyperglycaemic action of arginine. The greater potency and prolonged action of Pro-SS make it an interesting tool to study hormonal control mechanisms in a variety of physiological and pathological conditions.

Alinidine is a new drug which reduces heart-rate in animals by an unknown mechanism. Oral administration of 40 and 80 mg significantly reduced an exercise tachycardia in healthy people, with small reductions in heart-rate in the standing and supine positions. Alinidine 80 mg reduced arterial pressure in the standing and supine positions. The reduction in exercise tachycardia produced by 80 mg alinidine was similar to that after 40 mg propranolol, but alinidine had no effect on an isoprenaline tachycardia. These observations indicate that alinidine reduces heart-rate without blocking beta-adrenoceptors and may be useful in patients with angina and in patients with tachyarrhythmias.

Spontaneous breathing during mechanical ventilation in newborn infants may damage the lung. To find out whether the prevalence of lesions which might be due to trauma was reduced by muscle relaxation, fifty infants who required mechanical ventilation of hyaline membrane disease were randomly assigned to treated and control groups. The treated infants were kept muscle relaxed with pancuronium bromide until they needed a FiO2 of 0.40 or less during ventilation. The mean birthweight, gestational age, age at entry to the trial, duration of intubation and ventilation, FiO2 during the acute phase of the illness, and ventilator pressures were closely comparable in the two groups. Two of twenty-six treated infants and one of twenty-four controls died. Four treated and five control infants acquired pneumothoraces and/or interstitial emphysema. The length of time that the treated infants required added oxygen was significantly less than in the control infants. All treated infants were breathing room air spontaneously by one month of age whereas seven control infants were still dependent on added oxygen, needing an average FiO2 of 0.35 to achieve a mean PaO2 of 6.5 kPa (49 mm Hg). These seven infants required added oxygen until they were 5-18 (mean 10) weeks old. Muscle relaxation during mechanical ventilation for hyaline membrane disease speeds recovery of the lungs, probably owing to a reduction in traumatic damage.

Three doses of inactivated hepatitis B vaccine were given at one-month intervals to Senegalese children aged less than two years. A control group received diphtheria/tetanus/polio vaccine. Of those HB vaccine recipients who were seronegative before immunisation, 94.5% had a specific anti-HBs response. Anti-HBs of maternal origin did not interfere with the active immunisation. HB vaccine was without ill-effects, irrespective of hepatitis B marker status before immunisation. After twelve months' follow-up, the incidence of the HBsAg carrier state was reduced by 85% in susceptible children (p less than 0.0001).

As part of a double-blind trial slow-release acetazolamide (500 mg daily) or placebo was given to 20 men ascending to 5000 m. In the 18 who attained this altitude, those on acetazolamide had fewer symptoms of acute mountain sickness (AMS) than those on placebo (p < 0.02). 10 of the men had been to 5400 m on a previous expedition. 5 of these men took acetazolamide and 5 took placebo. Those on the drug performed better than those on placebo (p < 0.005). Furthermore, the performance of the 5 men on acetazolamide during the second expedition had improved more than that of the men on placebo (p < 0.01). In the group as a whole the symptoms of AMS were negatively correlated with arterial oxygen tensions (p < 0.001) which were higher in the drug group (p < 0.001). Acetazolamide probably had its effect by causing a metabolic acidosis with a resultant increase in respiratory drive and arterial oxygen tension.

Five 6-month antituberculosis regimens, allocated at random to patients with acid-fast bacilli in their sputum on microscopy, were studied. Four, given three times a week from the start, contained isoniazid and rifampicin together with (1) streptomycin, pyrazinamide, and ethambutol, (2) streptomycin and pyrazinamide, (3) streptomycin and ethambutol, or (4) pyrazinamide and ethambutol. The fifth was daily isoniazid, rifampicin, pyrazinamide, and ethambutol. All 833 patients with drug-sensitive strains of bacilli before treatment had a favourable bacteriological response during chemotherapy, and the bacteriological relapse rates during 12 months after stopping chemotherapy were 2% or less for all regimens except thrice-weekly isoniazid, rifampicin, streptomycin, and ethambutol (the only regimen without pyrazinamide), which had a relapse rate of 8%. The results were equally good for the 138 patients with bacilli resistant to isoniazid, streptomycin, or both drugs initially. The incidence of potentially serious toxicity was low. The daily regimen is relevant to programmes in which patients self-administer their drugs, and the 3 pyrazinamide-containing intermittent regimens are relevant to fully supervised outpatient programmes.