Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy.

INTRODUCTION: Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin-converting enzyme inhibitor (ACE-I). MATERIALS AND METHODS: After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-I, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE-I, 5 mg/kg/day, n=7), or vehicle (n=7). RESULTS: In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44+7% and 59+8% respectively). ACE-I significantly decreased proteinuria (67+7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30+18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21+20% and 0%, respectively), ACE-I significantly lowered proteinuria (92+2%) and a focal glomerulosclerosis (69+1%) lowering trend was observed. CONCLUSION: These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage.     

Genetic factors for the span of apprehension test: a study of normal twins.

The Partial Report Span of Apprehension test has been found to detect cognitive deficits in some first degree relatives of schizophrenic patients. To assess the relative contribution of genetic vs. environmental factors on this measure, 19 monozygotic and 14 dizygotic female twin pairs, selected from a normal population, were tested on the Span of Apprehension test and an IQ test. Both Span of Apprehension test performance and IQ score had high heritabilities: 0.65 and 0.71, respectively. The mode of transmission for performance on the Span of Apprehension test appears to operate in a nonadditive manner. A multivariate behavioral-genetic model applied to the Span of Apprehension and IQ measures indicated that slightly less than half of the genetic effects important for the Span of Apprehension test are found in common with the genetic factors important for IQ. The phenotypic correlation between the Span of Apprehension and IQ measures can be attributed entirely to genetic factors. The influence of unique genetic components in the performance of the Span of Apprehension test in the general population heightens the promise of this measure as a genetic marker for schizophrenia.     

Impaired insulin receptor binding and postbinding defects of adipocytes from normal and diabetic pregnant women

To evaluate the relative contribution of insulin binding and postbinding defects of glucose utilization in peripheral tissue during normal and diabetic pregnancy, we have studied the in vitro insulin action of isolated adipocytes from eight nondiabetic pregnant women and nine pregnant women with insulin-dependent diabetes mellitus who were undergoing cesarian section. The pregnant women were compared with a matched group of normal nonpregnant women undergoing gynecologic surgery. Insulin binding to adipocytes measured at tracer insulin concentration was reduced by 45% (P less than 0.01) in normal pregnant women and by 30% (P less than 0.02) in pregnant women with diabetes. In contrast, no changes were found between the three groups in insulin binding to pure monocytes and erythrocytes. The glucose transport system in fat cells from both groups of pregnant women was characterized by impaired maximal (P less than 0.05) and half-maximal (P less than 0.05) response to insulin. When fat cell glucose metabolism was studied, pregnant diabetic women exhibited decreased basal lipogenesis (P less than 0.05) and decreased maximal responses of lipogenesis and glucose oxidation to insulin stimulation (P less than 0.05). Similar but less pronounced abnormalities were seen in glucose metabolism of adipocytes from nondiabetic pregnant women. In conclusion, both in late normal and diabetic pregnancy, insulin binding to adipocytes is significantly reduced and accompanied by decreased insulin sensitivity and reduced maximal insulin responsiveness of glucose transport and by impaired basal and maximally insulin-stimulated glucose metabolism.     

The ability of the SCORE high-risk model to predict 10-year cardiovascular disease mortality in Norway.

AIMS: To evaluate the predictive accuracy of the Systematic Coronary Risk Evaluation (SCORE) project high-risk function in Norway. METHODS AND RESULTS: We included 57 229 individuals screened in 1985-1992 from two population-based surveys in Norway (age groups 40-49, 50-59, and 60-69 years). The data have been linked to the Norwegian Cause of Death Registry. The SCORE high-risk algorithm for the prediction of 10-year cardiovascular disease (CVD) mortality was applied, and the risk factors entered into the model were age, sex, total cholesterol, systolic blood pressure, and smoking (yes/no). The number of expected events estimated by the SCORE model (E) was compared with the observed numbers (O). The SCORE low-risk algorithm was studied for comparison. In men, the observed number of CVD deaths was 718, compared with 1464 estimated by the SCORE high-risk function (O/E ratios 0.53, 0.53 and 0.45, for age groups 40-49, 50-59 and 60-69, respectively). In women, the observed and expected numbers were 226 and 547. The O/E ratios decreased with age (ratios 0.60, 0.45 and 0.37, respectively), i.e. the overestimation increased with age. The low-risk function predicted reasonably well for men (ratios 0.85, 0.92 and 0.79, respectively), whereas an overestimation was found for women aged 50-59 and 60-69 years (ratios 0.69 and 0.56, respectively). CONCLUSION: The SCORE high-risk model overestimated the number of CVD deaths in Norway. Before implementation in clinical practice, proper adjustments to national levels are required.     

Femoral shaft fractures in children

We report our experience with elastic stable intramedullary titanium nailing (ESIN) of femoral shaft fractures in children. From 1998 to 2001, we treated 31 children (20 boys), median age 6 (4-11) years, with ESIN for 29 closed and 2 grade I open femoral shaft fractures. We reviewed 30 children clinically after median 1.5 (1-3) years. Their median hospital stay was 6 (2-20) days. All fractures were radiographically united at a median of 7 (5-9) weeks. The nails were removed in 29 children after a median of 22 (6-38) weeks postoperatively. At follow-up, we found a leg-length discrepancy up to 1 cm in 6 children and 10 degrees of internal rotational deformity in 1 child. No angular deformity had occurred. Elastic stable intramedullary nailing seems to be a safe method for the treatment of femoral shaft fractures in children between 4 and 11 years of age.     

The effect of bone drilling on pain in gonarthrosis

Summary Seventy-seven patients with mild to moderate gonarthrosis of the knee were treated by subchondral bone drilling, and followed for from 2 to 7 years. Patients with generalised arthrosis benefited more than those with unicompartmental involvement. Pain, assessed by a visual analogue scale, was significantly reduced compared with a control group of 16 patients who had a diagnostic arthroscopy only. Drilling is a safe procedure with few complications and can be used in patients when more extensive surgery is not yet indicated or possible.

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Résumé Vingt-sept cas d'arthrose légère ou modérée du genou, diagnostiqués par arthroscopie et traités par forage, ont été revus avec un recul moyen de 4 ans (de 2 à 7 ans). La douleur, évaluée selon la cotation VAS, était diminuée pendant 24 mois en moyenne (1 à 76) dans les deux tiers des cas. Les résultats étaient meilleurs chez les patients présentant une arthrose globale que chez ceux atteints d'une arthrose uni-compartimentale. Ils étaient obtenus aussi bien dans les cas douloureux au repos (n=39) que dans ceux douloureux lors de la mobilisation du genou (n=14). Les complications ont été exceptionnelles (n=1). La douleur était diminuée dans une proportion significativement supérieure dans les genoux traités par forage que dans un groupe de contrôle de 16 cas, n'ayant subi qu'une arthroscopie à visée diagnostique (p=0.006). Le forage est un procédé sûr, n'entraînant que de rares complications. Il est indiqué dans le traitement des douleurs du genou chez les patients ayant une arthrose légère ou modérée, lorsque des interventions plus importantes ne sont ni nécessaires, ni réalisables.

     

Effect of nicotine, silver acetate, and ordinary chewing gum in combination with group counselling on smoking cessation.

Four hundred and ninety six smokers participated in a randomised comparison of the effect of silver acetate, nicotine, and ordinary chewing gum on smoking cessation. All were motivated to stop smoking abruptly and all had smoked at least 10 cigarettes a day for at least five years. Side effects and taste acceptability were related to outcome after six months. The participants attended nine meetings over a year, at which lectures, support, and advice about stopping smoking were given. Tobacco abstinence was confirmed by measurement of carbon monoxide in expired air. The chewing gums were used for 12 weeks. After 12 weeks there was a trend towards more abstainers in the nicotine group (59%) than in the silver acetate (50%) and ordinary (45%) chewing gum groups that was not quite significant (p = 0.07). At 26 and 52 weeks the number of cigarette abstainers was similar in the three treatment groups. Subjects in the nicotine chewing gum group had a longer mean time before relapse than those in the silver acetate and ordinary chewing gum groups. Mean success rates for all subjects combined at 12, 26, and 52 weeks were 52.8%, 39.7%, and 23.3%. The side effects of nicotine and silver acetate chewing gum were generally mild and transient, and unimportant except for mouth irritation from silver acetate, which had a negative effect on outcome, and the low taste acceptability of nicotine, which had a strong negative influence on the success rate. The results suggest a short term effect on nicotine chewing gum on smoking cessation, but the abstinence rates after one year were generally disappointing.