Effect of streptozocin-induced diabetes on insulin-receptor tyrosine kinase activity in obese Zucker rats

We examined insulin binding, insulin-stimulated autophosphorylation, and phosphorylation of poly(Glu.Na,Tyr)4:1 by liver and skeletal muscle insulin receptor from lean, obese, and obese streptozocin-induced diabetic Zucker rats. Induction of diabetes with streptozocin (30 mg/kg) lowered the lasting insulin level from 11.4 to 3.8 ng/ml, which was not significantly greater than the lean control level. Autophosphorylation and tyrosine kinase activity of liver insulin receptors were increased 70-100% in the obese control group (relative to lean rats), but diabetes reversed this hyperresponsiveness to insulin. In muscle, obesity was associated with a 40-50% decrease in autophosphorylation and tyrosine kinase activity, which was also reversed in the diabetic state. Autophosphorylation and tyrosine kinase activity were significantly correlated in liver and muscle and were also correlated with fasting insulin levels. These data suggest that insulin-receptor tyrosine kinase activity is regulated differently in liver and muscle and that the abnormalities in kinase activity associated with the obese Zucker rat are at least partly secondary to hyperinsulinemia.     

Liver transplantation for severe Amanita phalloides mushroom poisoning

Amanita phalloides mushroom poisoning is an increasingly common and potentially lethal problem for which liver transplantation offers definitive therapy in selected patients. When significant liver dysfunction appears, early transfer to a liver transplant center is important to identify appropriate candidates and to begin the search for a donor organ. The clinical course of five severely poisoned patients, four of whom underwent liver transplantation, is reviewed. Indications for transplantation included primarily a markedly prolonged prothrombin time that was only partially correctable and a constellation of findings including metabolic acidosis, hypoglycemia, hypofibrinogenemia, and increased serum ammonia, following a marked elevation in serum aminotransferase levels. Unlike viral fulminant hepatic failure, grade III or IV hepatic encephalopathy, marked elevation of the serum bilirubin level, and azotemia were not indications for transplantation. Resected livers demonstrated hepatocyte viability of 0% to 30%. Manifestations of Amanita poisoning complicating preoperative and/or postoperative care included severe diarrhea, gastrointestinal hemorrhage, hypophosphatemia, bowel edema, and marrow suppression with lymphopenia, thrombocytopenia, and neutropenia. All five patients are well 1 year later. This largest experience with liver transplantation for Amanita poisoning further defines the early clinical and laboratory indications for, and the unique complicating features of, transplantation in this setting.     

Ectopic Pregnancy in Lower Segment Uterine Scar

Summary: A case of ectopic pregnancy in a lower uterine segment scar following previous Caesarean section is reported. A significant scar defect may result in deep implantation within the myometrium with the risk of persistent pain and bleeding followed inevitably by uterine rupture. In this report we discuss a number of management options. Except in the special situation of superficial implantation in a shallow scar defect where there is ultrasound evidence of continuity of the gestational sac with the uterine cavity we would strongly advise termination of the pregnancy.     

Child pedestrian injury 1978-87.

OBJECTS: to report the incidence of child pedestrian injury in New Zealand and review prevention strategies. METHODS: examination of National Health Statistics Centre mortality and public hospital morbidity data from 1978-87. RESULTS: over the ten year period, there was an annual average of 30 deaths (3.6/100,000 per year) and 411 hospitalisations (49.4/100,000 per year) for child pedestrian injury. There has been no significant reduction in the fatality or hospital morbidity rate over this time. Pedestrian fatality rates are highest for boys and for children in the youngest age groups. Hospitalisation rates are over 2.5 times higher for Maori children than for nonMaori children. CONCLUSIONS: child pedestrian injury is an important public health problem in New Zealand for which there are few established prevention strategies. Controlled studies aimed at the identification of modifiable environmental factors are required.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.