Oxpentifylline (pentoxifylline), which is known to have pharmacological effects in animal models of respiratory distress syndrome, multiorgan failure, and shock, was tested in human beings after injection of endotoxin. Of ten healthy volunteers, nine met the inclusion criterion of a rise in body temperature of at least 1.0 degrees C after 100 ng endotoxin (Salmonella abortus equi) as a bolus injection. Serum levels of tumour necrosis factor alpha (TNF) and interleukin-6 (IL-6) were both significantly higher than baseline levels 2 h and 3 h after endotoxin injection. 3 weeks later the nine volunteers were again injected with 100 ng endotoxin and oxpentifylline (500 mg over 4 h) was also infused. There was no rise in TNF levels, though IL-6 levels rose in parallel with body temperature. These data suggest that oxpentifylline blocks the endotoxin-induced synthesis of TNF in man and, therefore, could possibly have beneficial effects in clinical endotoxaemia.

76 healthy women, who had been menopausal for less than 96 months and who had never received any form of treatment to prevent bone loss, were entered into a randomised double-blind study. For the first 6 months, half the patients received tiludronate 100 mg daily, while the others received placebo. During the second 6 months, all patients received placebo. Bone mineral density of the lumbar spine decreased significantly by 2.1% (SE 0.8%) in the placebo group and did not significantly change in the tiludronate group (+1.33 [0.8]%). The difference in response between the groups was significant, as were the differences between values for corrected urinary hydroxyproline and calcium. Treatment with tiludronate was not followed by increased secretion of parathyroid hormone. A 6 month course of oral tiludronate may counteract postmenopausal bone loss for at least a year by decreasing bone resorption.

In a study of the effect of a low-protein diet on the progression of renal disease 19 insulin-dependent diabetic patients with persistent clinical proteinuria were observed for 12-39 (mean 29) months while they were on a normal-protein diet (1.13 [0.06] g/kg per day), then for 12-49 (mean 33) months on a low-protein diet (0.67 [0.03] g/kg per day). The low-protein diet had no adverse effect on nutrition or glycosylated haemoglobin concentration. Mean supine blood pressure (BP) fell slightly on the low-protein diet and was probably due to the start or modification of antihypertensive medication in 9 patients. The mean rate of decline in glomerular filtration rate fell from 0.61 (SEM 0.14) ml/min per month with the normal-protein diet to 0.14 (0.08) with the low-protein diet, and this effect remained highly significant after adjustment for blood pressure, energy intake, and glycosylated haemoglobin. The rise in the fractional clearance of albumin during a normal-protein diet stopped with the low-protein diet, and there was a significant fall in albumin excretion from 467 (95% CI 234-895) micrograms/24 h on the normal-protein to 340 (138-719) on the low-protein diet. Thus, a low-protein diet, with its reduction in protein and possibly other dietary components such as phosphate or fat, seems to retard the rate of decline of glomerular filtration rate in diabetic nephropathy independently of blood pressure changes and glycaemic control.

To examine the value of vaccinating children against measles at age 4-5 months three groups of children in Togo were randomly assigned to receive high-dose Edmonston-Zagreb, high-dose Schwarz, or AIK-C vaccines at that age. Two other groups were vaccinated at age 8-10 months, with either the standard Schwarz vaccine or the same batch of AIK-C as for early immunisation. For the 55% of children who were seronegative before vaccination at age 4-5 months seroconversion rates were 96% with the AIK-C, 94% with the Edmonston-Zagreb, and 50% with the high-dose Schwarz. The immune response rates for children who were seropositive before vaccination were estimated to be around 50% with the high-dose Edmonston-Zagreb and AIK-C strains and 10% with the Schwarz strain. Seroconversion rates for vaccination at 8-10 months were 87% for the AIK-C and 68% for the Schwarz strains. Thus vaccination with the high-dose Edmonston-Zagreb or the AIK-C strain at 4-5 months was as good as vaccination with the AIK-C strain at 8-10 months and better than vaccination with the standard dose Schwarz strain at 8-10 months. These findings require confirmation by further investigations, particularly epidemiological studies, but they already provide evidence that the administration of AIK-C and high-dose Edmonston-Zagreb strains at 4-5 months is at least as effective as vaccination with the standard strains at 8-10 months.

An open paired randomised comparison of intramuscular chloroquine (3.5 mg base/kg every 6 h) and intramuscular quinine (20 mg salt/kg followed by 10 mg/kg every 12 h) was carried out in 50 Gambian children with severe falciparum malaria. 8 children died, 6 from the quinine-treated and 2 from the chloroquine-treated group. Chloroquine reduced parasitaemia significantly more rapidly than did quinine, but other measures of the therapeutic response were similar in the two groups. Quinine injections were painful. These findings do not support the proposition that quinine is intrinsically superior to chloroquine in the treatment of severe drug-sensitive falciparum malaria.

To assess the effectiveness of tunnelling the polyurethane venous catheter for parenteral nutrition in reducing the frequency of catheter microbial colonisation, and to investigate the routes taken by microorganisms colonising the central venous catheter, 109 patients were randomised to traditional subclavian catheterisation (58, group A) or to subcutaneous catheter tunnelling (51, group B). Samples were taken from patients and their nurse attendants to identify their indigenous flora. Cultures were also done of swabs from the catheter insertion site, blood, nutrient solution, segment of the catheter, and washings of the catheter hub. Intravascular segment colonisation was commoner in group A (18/58) than in group B patients (4/51), and bacterial migration from insertion site to intravascular segment was also commoner among group A (9/58) than among group B patients (1/51). Catheter hub contamination was responsible in 10 out of 22 cases of microbial colonisation; in 6 of these 10 the bacterium isolated was present on the skin of nurses who changed the bag. Contamination of the insertion site skin and of the CVC hub were equally responsible for the microbial colonisation of the intravenous segment of the catheter.

20 patients with mild hypertension (average supine blood pressure without treatment, 164/101 mm Hg) reduced their salt intake to 50 mmol (3 g) per day for a month. They then entered a 3 month double-blind randomised crossover study of three levels of sodium intake: 200, 100, and 50 mmol per day. Blood pressure was significantly reduced on the middle and lowest sodium intakes. The average fall in blood pressure from the highest to the lowest sodium intake was 16/9 mm Hg. Patients continued to restrict their sodium intake for a further year. In 16 of the 20 patients blood pressure remained well controlled with salt restriction alone. Supine blood pressure at 1 year was 142/87 (SE 3/2) mm Hg with a 24 h urinary sodium excretion of 54 (7) mmol. These results show a progressive blood pressure fall as salt intake is reduced and that, in many patients with mild essential hypertension, blood pressure can be controlled without the need for drug therapy.

In a randomised trial involving 13,079 liveborn children intrapartum care by electronic fetal heart rate monitoring, with scalp blood sampling when indicated, was associated with a 55% reduction in neonatal seizures. Reassessment, when aged 4, of the 9 children in the intensively monitored group and 21 in the control group who survived after neonatal seizures showed that 3 such children in each group had cerebral palsy. A fourth child in the intensively monitored group with cerebral palsy had had transient abnormal neurological signs during the neonatal period. 8 other children in the intensively monitored group and 7 in the control group who had not had abnormal neurological signs in the neonatal period also had cerebral palsy. 16 (78%) of the total of 22 cases of cerebral palsy had not shown clinical signs suggestive of intrapartum asphyxia. Thus, compared with intermittent intrapartum monitoring, intensive monitoring has little, if any, protective effect against cerebral palsy.

Endosonography, ultrasonography, and computed tomography (CT) were carried out prospectively in 52 patients with extrahepatic cholestasis. 35 patients had extrahepatic biliary obstructions (21 tumorous, 14 non-tumorous) and 17, with recent gallstone migration within the bile duct, had no extrahepatic obstruction at the time of investigation. The definitive diagnosis was established by surgery (in 39 patients), by transendoscopic sphincterotomy (11 patients), or by retrograde biliary opacification (2 patients). Endosonography was significantly more sensitive than ultrasonography or CT (100% vs 80% and 83%, respectively) in making a positive diagnosis of obstruction. Endosonography was also significantly more accurate than ultrasonography or CT (97% vs 49% and 66%) in diagnosing the cause of the obstruction and more effective in the assessment of the locoregional spread of tumorous obstructions (75% vs 38% and 62%). Thus, endosonography was superior to ultrasonography and CT in the diagnosis and staging of biliary obstructions.

Three intravenous bisphosphonates were compared in the treatment of cancer-associated hypercalcaemia. 48 patients were randomly allocated to one of three treatment groups (each with 16 subjects)--30 mg pamidronate or 600 mg clodronate, both as single intravenous infusions; or etidronate as three infusions of 7.5 mg/kg per day for three consecutive days. Patients were rehydrated with normal saline before bisphosphonate treatment. All three bisphosphonates lowered serum calcium by inhibiting bone resorption; pamidronate was the most potent in this respect. By comparison with the other groups, more patients in the pamidronate group became normocalcaemic, and the effect on serum calcium was apparent sooner and lasted longer.