Université de Montréal

About: Université de Montréal is a education organization based out in Montreal, Quebec, Canada. It is known for research contribution in the topics: Population & Poison control. The organization has 45641 authors who have published 100476 publications receiving 4004007 citations. The organization is also known as: University of Montreal & UdeM.

Islet β cell failure in type 2 diabetes

Abstract: The major focus of this Review is on the mechanisms of islet beta cell failure in the pathogenesis of obesity-associated type 2 diabetes (T2D). As this demise occurs within the context of beta cell compensation for insulin resistance, consideration is also given to the mechanisms involved in the compensation process, including mechanisms for expansion of beta cell mass and for enhanced beta cell performance. The importance of genetic, intrauterine, and environmental factors in the determination of "susceptible" islets and overall risk for T2D is reviewed. The likely mechanisms of beta cell failure are discussed within the two broad categories: those with initiation and those with progression roles.

Risk alleles for multiple sclerosis identified by a genomewide study.

Abstract: �Background Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis. Methods We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis. Results A transmission disequilibrium test of 334,923 single-nucleotide polymorphisms (SNPs) in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P<1×10 −4 ); of these SNPs, 38 were selected for the second-stage analysis. A comparison between the 931 case subjects from the family trios and 2431 control subjects identified an additional nonoverlapping 32 SNPs (P<0.001). An additional 40 SNPs with less stringent P values (<0.01) were also selected, for a total of 110 SNPs for the second-stage analysis. Of these SNPs, two within the interleukin-2 receptor α gene (IL2RA) were strongly associated with multiple sclerosis (P = 2.96×10 −8 ), as were a nonsynonymous SNP in the interleukin-7 receptor α gene (IL7RA) (P = 2.94×10 −7 ) and multiple SNPs in the HLA-DRA locus (P = 8.94×10 −81 ).

Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial.

Abstract: ContextThe worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns.ObjectiveTo evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an α-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT).Design, Setting, and ParticipantsInternational, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years.InterventionPatients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714).Main Outcome MeasuresThe development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (≥140/90 mm Hg).ResultsThree hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P = .03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P = .02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P = .006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P = .02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P = .004) associated with acarbose treatment was still statistically significant.ConclusionThis study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma

Abstract: Background: Bone metastases are a common cause of morbidity in patients with prostate carcinoma. We studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases. Methods: Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a double-blind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months. Proportions of patients with skeletal-related events, time to the first skeletal-related event, skeletal morbidity rate, pain and analgesic scores, disease progression, and safety were assessed. All statistical tests were two-sided. Results: Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference = –11.0%, 95% confidence interval [CI] = –20.3% to –1.8%; P = .021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo = –5.8%, 95% CI = –15.1% to 3.6%; P = .222). Median time to first skeletalrelated event was 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg ( P= .011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg ( P= .491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P = .001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration. Conclusion: Zoledronic acid at 4 mg reduced skeletalrelated events in prostate cancer patients with bone metastases. [J Natl Cancer Inst 2002;94:1458–68]