Effect of chlorpropamide on glucose transport in rat adipocytes in the absence of changes in insulin binding and receptor-associated tyrosine kinase activity

In an attempt to elucidate the cellular mechanism(s) by which sulfonylureas exert their extrapancreatic hypoglycemic effects, various parameters of insulin action were examined in vitro, using rat adipocytes maintained in a biochemically defined medium. Cells were maintained for 20 hours in the absence or presence of 175 micrograms/mL chlorpropamide and insulin binding, hexose transport, glucose metabolism, and insulin receptor tyrosine kinase activity were compared. Chlorpropamide treatment had no effect on insulin binding, altering neither receptor number nor affinity. However, the sulfonylurea did enhance 2-deoxyglucose transport in both the absence (17%, P less than .01) and presence (20%, P less than .01) of insulin. Furthermore, glucose metabolism as measured by the conversion of glucose (0.2 mmol/L) to CO2 and total lipids was also significantly increased by chlorpropamide treatment in both the absence (30%, P less than .01) and presence (31%, P less than .05) of insulin. Potentiation of insulin-stimulated transport or metabolism was not explained by an increase in the basal state alone because the incremental responses to 40 ng/mL insulin were potentiated by 19% (P less than .01) and 25% (P less than .05), respectively. Activity of the insulin receptor kinase was unchanged as evaluated by autophosphorylation of partially purified receptors, phosphorylation of an artificial substrate and by phosphorylation of the receptor in situ. These studies demonstrate that the sulfonylurea, chlorpropamide, stimulates glucose transport and potentiates insulin's effect on this process by acting at a site(s) beyond insulin receptor binding and phosphorylation.     

Factors influencing vaccination compliance in peri-urban Gambian children

The vaccination status of 251 children aged 12-18 months in two peri-urban Gambian communities was determined from their health cards. Two subgroups were identified: children who were fully vaccinated, and those who had received less than half their vaccinations. The social and environmental circumstances of these children were investigated to detect factors which were associated with poor vaccination compliance. Mothers of well vaccinated children were more inclined to bring them for non-curative services. Mothers of poorly vaccinated children had a poorer knowledge of the diseases against which their children should be vaccinated and they also had a more superstitious view of disease causation. Those children who showed poor compliance came from larger families. In the poorly vaccinated group both parents were less well educated and there was a trend towards poorer literacy.     

Oxygen availability from the blood and the effect of phosphate replacement on erythrocyte 2,3-diphosphoglycerate and haemoglobin-oxygen affinity in diabetic ketoacidosis

Summary Eleven patients with diabetic ketoacidosis were given intravenous phosphate in doses (mean 118 mmol; range 83–320 mmol) adequate to maintain normal plasma phosphate, in addition to a standard treatment regime. Prevention of hypophosphataemia stimulated recovery of the initially low red-cell 2,3-diphosphoglycerate concentrations (10.6 ±5.8 (SD) mol/g Hb) after twenty-four hours. In ten control patients (initial concentration 8.1±4.4 mol/g Hb) treated without phosphate replacement, significantly lower red-cell 2,3-diphosphoglycerate concentrations were found between 2 and 6 days after admission (forty-eight hour value for control patients 14.6±1.6 and for phosphate-treated patients 18.9±4.1 mol/g Hb; p<0.01). However, no effect onin vivo p 50 or on the availability of oxygen from the blood resulted from the higher 2,3-diphosphoglycerate levels. Maintenance of normal plasma phosphate levels by intravenous phosphate is, therefore, not indicated to improve tissue oxygenation in diabetic ketoacidosis.     

Supported discharge service versus inpatient care evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm,functional impairment,and educational and clinical outcomes

Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. The aim of this study is to undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. 106 patients aged 12–18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomisation, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (five or more) of self-harm (OR = 0.18, 95% CI: 0.05–0.64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28.2–208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment.