Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial

A multicenter, randomized placebo-controlled double-blind trial of nimodipine in poor-grade aneurysm patients was carried out in 17 Canadian hospitals. Of 188 patients enrolled in the trial, 32 were excluded for protocol violations and two were excluded due to statistical considerations, leaving 154 patients for valid outcome analysis. Nimodipine treatment was associated with a significantly better outcome (p less than 0.001): 21 (29.2%) of 72 nimodipine-treated patients had a good outcome at 3 months after subarachnoid hemorrhage (SAH) compared to eight (9.8%) of 82 placebo-treated patients. Delayed ischemic deficits from vasospasm alone were significantly less frequent in the nimodipine group (p less than 0.05) with permanent deficits occurring in five nimodipine-treated patients (6.9%) and in 22 placebo-treated patients (26.8%). Improvement in the good outcome rate and reduction in delayed ischemic deficits from vasospasm alone occurred in both Grade 3 and 4 patients, with no difference between nimodipine- and placebo-treated patients being found in Grade 5 patients. Repeat angiography after Day 4 was carried out in 124 patients. There was no significant difference in the incidence of moderate or severe diffuse spasm, which was seen in 64.3% of nimodipine-treated patients and 66.2% of placebo-treated patients. The authors conclude that nimodipine treatment in poor-grade patients with SAH results in an increase in the number of good outcomes and a reduction in the incidence of delayed neurological deterioration due to vasospasm. This effect occurs by a mechanism other than prevention of large-vessel spasm as visualized on angiography.     

Sir David Cuthbertson Medal Lecture. The impact of dietary protein restriction on insulin secretion and action

The goal of this review is to develop the hypothesis, and review the evidence, that protein restriction, through synergistic effects on multiple organ systems predisposes to loss of normal regulation of fuel homeostasis that plays the central role in the development of type 2 (non-insulin-dependent) diabetes mellitus. The ability of insulin to regulate glucose production and disposal varies between individuals. These differences, together with the various compensatory mechanisms that are invoked to attempt to normalize fuel homeostasis, are of fundamental importance in the development and clinical course of type 2 diabetes mellitus. Protein deprivation impacts on both insulin secretion and insulin action. These effects may persist even when a diet containing adequate protein is presented subsequently. Data are presented that suggest that protein restriction results in an impaired ability of pancreatic beta-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. This persistent impairment of insulin secretion resulting from protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of a diabetogenic challenge. This inability to maintain the degree of compensatory hyperinsulinaemia necessary to prevent loss of glucose tolerance may have relevance to the increased incidence of diabetes on changing from a nutritionally-poor diet to a Western diet, and to the hypothesis that some cases of type 2 diabetes in adulthood may be related to poor early nutrition.     

对发展中国家改善用药的10点建议

WHO建议改善药品管理的工作要在国家药物政策保障之下.在许多国家,执行国家药物政策的机制是实施国家基本药物计划,其要点是强调公共领域的药品选择、采购、流通与使用的合理性.不适当的处方使医疗质量降低并导致资源浪费.本文以探讨在国家药物政策范畴内鼓励更合理地使用药品的问题为重点,在已有证据的基础上,详细阐明基本药物计划内容中的合理用药问题.本文评述了在发展中国家改善用药状况的有效策略及最新知识,并为决策者与管理者提出达到改善用药目标的建议.     

Occupational Skin Allergies: Testing and Treatment (The Case of Occupational Allergic Contact Dermatitis)

Occupational contact dermatitis, including occupational allergic contact dermatitis, is one of the most common occupational diseases. Making a timely and accurate diagnosis is important to improving the outcome. Taking a work history and patch testing are essential elements in the diagnostic process. Management, based on an accurate diagnosis, must include both medical treatment to address the disease and workplace modifications as appropriate to reduce exposure the causative agents.     

Dexamethasone during late gestation exacerbates peripheral insulin resistance and selectively targets glucose-sensitive functions in beta cell and liver

We examined whether low-dose dexamethasone administration during late pregnancy modifies hepatic and/or peripheral insulin action or glucose-stimulated insulin secretion. Dexamethasone (100 microg/kg maternal body weight/d) was administered via an osmotic minipump from d 14--19 of gestation. Maternal glucose-insulin homeostasis was assessed on d 19 of pregnancy in the postabsorptive state. Insulin secretion and glucose tolerance was assessed after iv glucose, and insulin action examined during insulin infusion at euglycemia. Dexamethasone treatment during late pregnancy elicited fasting hyperinsulinaemia (by 88%; P < 0.001) and hyperglycaemia (by 20%; P < 0.05), and enhanced endogenous glucose production (by 29%; P < 0.001). Insulin secretion and rates of glucose disappearance after iv glucose were greatly impaired (by 44% and 39% respectively; P < 0.05). Suppression of endogenous glucose production by insulin was enhanced by dexamethasone treatment, but insulin's ability to promote glucose clearance was diminished. We demonstrate that excess maternal glucocorticoids during late pregnancy impairs glucose-stimulated insulin secretion and insulin-simulated glucose clearance but enhances insulin's ability to suppress endogenous glucose production. The data also indicate that elevated maternal glucocorticoids impair adaptations of the endocrine pancreas to pregnancy in vivo in that insulin hypersecretion in response to deteriorating peripheral insulin action is no longer apparent, leading to impaired glucose tolerance.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.