30 insulin-dependent diabetic patients with background retinopathy were randomised to conventional treatment (UCT) or treatment with continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 1 year with fortnightly seven-sample home blood glucose measurements and retinal examinations every 6 months. Mean blood glucose and stable haemoglobin A1c during months 3-12 were significantly lower in the CSII than the UCT group. Retinal morphology deteriorated during the year with no significant differences between UCT and CSII groups. The frequency of deterioration was highest in the CSII group, especially among the 10 patients with best glycaemic control. Proliferative retinopathy developed in 3 patients--2 of these were CSII treated. Retinal function (oscillatory potential, macular recovery time, and posterior vitreous fluorophotometry) improved significantly with CSII treatment and deteriorated significantly with UCT. Changes in retinal function were most pronounced in patients with the best and the poorest regulated glycaemic control.

Thirty-four normocalcaemic women with multiple osteolytic bone metastases from breast cancer were randomly allocated to treatment with disodium dichloromethylene diphosphonate (Cl2MDP) 1600 mg/day orally (17) or placebo (17) for 3-9 months. Fasting urinary hydroxyproline/creatinine and calcium/creatinine ratios declined in the Cl2MDP group but not in the placebo group. Four patients in the placebo group died from hypercalcaemia. New bone metastases were more common in patients on placebo and these patients also required more analgesic drugs than those on Cl2MDP. Cl2MDP seemed to reduce bone pain and bone resorption and prevent the development of hypercalcaemia caused by osteolytic metastases. The formation of new bone metastases and the growth of old ones seemed to be retarded by Cl2MDP.

Flubendazole, an injectable benzimidazole drug, was compared with diethylcarbamazine (DEC) in a prospective double-blind study of the treatment of onchocerciasis. Nineteen Mexican men were randomly assigned to receive either flubendazole 750 mg intramuscularly once a week for 5 doses, or DEC 100 mg twice daily for 14 days, and they were then followed up for 12 months. Major systemic side-effects during the first 3 weeks were common in the DEC group but not in the flubendazole group in which there was considerable inflammation at the injection site instead. Ocular complications (limbitis, punctate keratitis, and uveitis) were also common in the DEC group, whereas in the flubendazole group they consisted only of one new punctate opacity at day 4 in one subject. One DEC patient also had several new areas of chorioretinal changes on day 2 but these had disappeared by 2 months. Skin microfilaria counts fell rapidly in the DEC group, but returned to the pretreatment levels. In contrast, skin microfilaria counts in the flubendazole group fell slowly, but by 6 and 12 months were lower than in the DEC group (at 12 months 0.2 vs 7.3 mf/mg, p less than 0.001). In addition, by 6 months none of the flubendazole subjects had intracorneal microfilariae, and only one had microfilariae in the anterior chamber, whereas the numbers of intraocular microfilariae in the DEC group had returned to pretreatment levels. The results suggest that flubendazole is safer and more effective than DEC in the treatment of onchocerciasis.

In a double-blind, placebo-controlled crossover study to compare the homoeopathic remedy Rhus tox. 6X with fenoprofen in osteoarthritis of the hip and knee, fenoprofen was shown to have beneficial analgesic and anti-inflammatory effects which differed significantly from those of placebo. The effects of Rhus tox. 6X and placebo did not differ significantly. Patient preference was for fenoprofen. Side-effects were not severe but were seen more frequently with fenoprofen. Similar results were seen in all patients regardless of whether they had been referred to and assessed by a homoeopathic physician or a rheumatologist.

Cigarette smoking reversed the inhibition of nocturnal gastric secretion produced by the H2-receptor antagonists cimetidine and ranitidine and by the phenothiazine derivative LM 24056. As a consequence of smoking, nocturnal secretion of acid increased by 91.5% and of pepsin by an average of 59% when compared with control studies when patients did not smoke. The inhibition of pentagastrin-stimulated gastric secretion produced by cimetidine or poldine was not affected by cigarette smoking. Since control of nocturnal secretion may be important in promoting ulcer healing and maintenance of remission, patients receiving antisecretory drugs should be advised not to smoke after having taken their nocturnal dose of the drug.

59 healthy, omnivorous subjects aged 25-63 years were randomly allocated to a control group, which ate an omnivorous diet for 14 weeks, or to one of two experimental groups, whose members ate an omnivorous diet for the first 2 weeks and a lacto-ovo-vegetarian diet for one of two 6-week experimental periods. Mean systolic and diastolic blood pressures did not change in the control group but fell significantly in both experimental groups during the vegetarian diet and rose significantly in the experimental group which reverted to the omnivorous diet. Adjustment of the blood-pressure changes for age, obesity, heart rate, weight change, and blood pressure before dietary change indicated a diet-related fall of some 5-6 mm Hg systolic and 2-3 mm Hg diastolic. Although the nutrient(s) causing these blood-pressure changes are unknown, the effects were apparently not mediated by changes in sodium or potassium intake.

A growth-hormone-releasing factor has been characterised and sequenced from a pancreatic tumour removed from a patient with acromegaly. It is a 40-residue linear peptide. Synthetic human pancreatic growth-hormone-releasing factor (hpGRF-40), 1 microgram/kg bodyweight, was administered as an intravenous bolus to six healthy men. hpGRF-40 selectively stimulated growth-hormone secretion. Serum growth-hormone concentrations were increased within 5 min, reaching a peak between 30 and 60 min (20 . 4 +/- 6 . 5 ng/ml compared with 2 . 1 +/- 0 . 1 ng/ml after placebo). Serum levels of prolactin, thyrotropin, luteinising hormone, and corticotropin (measured indirectly through plasma cortisol) were not increased after administration of hpGRF-40. Similarly, the concentrations of blood glucose, plasma insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, and somatostatin were unaffected by hpGRF-40. There were no changes in blood pressure, pulse rate, or body temperature, and no side-effects were noted. The characteristics of this peptide fulfil many of the criteria required of the hypophysiotropic growth-hormone-releasing hormone. hpGRF holds promise for a new approach to the diagnosis and treatment of various disorders of growth-hormone secretion.

The effects of intensive plasma exchange on the serological and clinical manifestations of mildly active systemic lupus erythematosus were evaluated in a controlled, double-blind trial. Twenty patients were randomised to receive either six 4-litre plasma exchanges or a seemingly identical control procedure over a 2-week period. Plasma exchange produced significant reductions in serum levels of IgG, IgM, IgA, and circulating immune complexes measured by an 125I-Clq binding assay. These serological measures returned to baseline 4 weeks after plasma exchange without a rebound above baseline values. Antibodies to DNA were reduced immediately after plasma exchange; however, they often returned to pre-treatment levels before the next procedure. No changes in any of the serological measures were observed in the control group. In sixteen of the eighteen patients who completed the clinical trial activity had either remained stable or improved; the frequency and degree of clinical improvement was the same in both plasma exchange and control groups.

Sodium DL-3-hydroxybutyrate was administered to obese subjects (more than 150% ideal body-weight) who were either receiving a 2 . 5 MJ (600 kcal) diet containing 34 g protein on one day with a total fast (water and vitamins only) on the next day, for 21 days, or were undergoing therapeutic starvation for 14 days. Both intravenous and oral hydroxybutyrate significantly reduced net body protein loss as measured by total urinary nitrogen and 3-methylhistidine excretion. Hydroxybutyrate administration did not significantly affect the rate of weight-loss but seemed to increase the fat/lean ratio of the tissue loss. The subjects experienced no untoward effects and none complained of hunger while receiving 3-hydroxybutyrate.

57 couples living in two communities of North Karelia, aged 30-50 years, were randomly allocated to three groups. After a 2-week baseline period group I followed a diet low in fat (23% of energy) with a high polyunsaturated/saturated (P/S) ratio (1 . 0), group II reduced daily salt intake from 192 mmol to 77 mmol, and group III (control group) continued the usual diet. After the 6-week intervention period groups I and II reverted to their usual diets. In group I systolic blood pressure declined from 138 . 4 to 129 . 5 mm Hg and diastolic blood pressure from 88 . 9 to 81 . 3 mm Hg during the intervention period; the values rose during switch-back. The fall was greater among hypertensive than among normotensive subjects. In groups II and III the mean blood pressure changed very little during the study.