In man, the major function of calcitonin appears to be prevention of excessive or unwanted bone resorption. There is a striking sex difference in circulating levels, with a relative deficiency in women. Calcitonin secretion in young adults is increased by oestrogens and therefore long periods of oestrogen lack, such as after the menopause, may be associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of postmenopausal bone loss, especially since the latter may be due to excessive bone resorption. In a study of the effects of oestrogen treatment on circulating levels of calcitonin, parathyroid hormone, and vitamin-D metabolites in postmenopausal women, the most striking change was a sharp rise in plasma-calcitonin. Oestrogens prevent postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss. Its place in the treatment of postmenopausal osteoporosis warrants further evaluation.

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.

40 patients seen in general practice and psychiatric outpatient clinics who had taken lorazepam or diazepam alone in regular dosage for a mean period of 3.6 years had their benzodiazepine replaced by propranolol (60--120 mg/day) or placebo for two weeks under double-blind conditions. Depending on the criteria for the definition of an abstinence syndrome, 27--45% of the patients had withdrawal symptoms during the study. Propranolol did not affect the drop-out rate or the incidence of withdrawal symptoms but significantly reduced their severity in patients completing the study. The percentage fall in serum levels of desmethyldiazepam in patients who experienced withdrawal symptoms after stopping diazepam was significantly greater in patients with no withdrawal symptoms.

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.

Studies in fasting subjects have suggested that cimetidine therapy might lead to nocturnal hypochlorhydria, allowing bacterial overgrowth and the production of intragastric carcinogens. This hypothesis was investigated in normal subjects taking full-dose and maintenance cimetidine with food. Nocturnal hypochlorhydria wa rarely found and the incidence of bacterial overgrowth was correspondingly low; gastric-juice nitrite concentrations were rarely raised. These findings suggest that long term treatment with cimetidine is unlikely to promote gastric cancer as a result of bacterial metabolic activity.

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.