Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

Background

Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.

A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity

Adiponectin is a plasma protein expressed exclusively in adipose tissue. Adiponectin levels are linked to insulin sensitivity, but a direct effect of chronically elevated adiponectin on improved insulin sensitivity has not yet been demonstrated. We identified a dominant mutation in the collagenous domain of adiponectin that elevated circulating adiponectin values in mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and suppressed insulin-mediated endogenous glucose production. The induction of adiponectin during puberty and the sexual dimorphism in adult adiponectin values were preserved in these transgenic animals. As a result of elevated adiponectin, serum PRL values and brown adipose mass both increased. The effects on carbohydrate and lipid metabolism were associated with elevated phosphorylation of 5'-AMP-activated protein kinase in liver and elevated expression of peroxisomal proliferator-activated receptor gamma2, caveolin-1, and mitochondrial markers in white adipose tissue. These studies strongly suggest that increasing endogenous adiponectin levels has direct effects on insulin sensitivity and may induce similar physiological responses as prolonged treatment with peroxisomal proliferator-activated receptor gamma agonists.     

Left Ventricular Unloading During Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock

Background

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a widely used form of mechanical circulatory support in patients with refractory cardiogenic shock. A common drawback of this modality is a resultant increase in left ventricular afterload.

Streptozotocin,an O-GlcNAcase inhibitor,blunts insulin and growth hormone secretion

Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic beta-cells normally respond to glucose challenge by rapid insulin release (first phase insulin secretion), there is a loss of this acute response in virtually all of the type 2 diabetes patients with significant fasting hyperglycemia. Our previous studies demonstrated that irreversible intracellular accumulation of a glucose metabolite, protein O-linked N-acetylglucosamine modification (O-GlcNAc), is associated with pancreatic beta-cell apoptosis. In the present study, we show that streptozotocin (STZ), a non-competitive chemical blocker of O-GlcNAcase, induces an insulin secretory defect in isolated rat islet cells. In contrast, transgenic mice with down-regulated glucose to glucosamine metabolism in beta-cells exhibited an enhanced insulin secretion capacity. Interestingly, the STZ blockade of O-GlcNAcase activity is also associated with a growth hormone secretory defect and impairment of intracellular secretory vesicle trafficking. These results provide evidence for the roles of O-GlcNAc in the insulin secretion and possible involvement of O-GlcNAc in general glucose-regulated hormone secretion pathways.     

Immunoassay of human TSH using dried blood samples.

A sensitive, semi-quantitative radioimmunoassay method to screen for elevations of TSH concentration in blood is described. The method requires two 0.32 cm dots of dried blood-impregnated filter paper (equivalent to 3 mul plasma) and a 3-day incubation. Separation of bound and free is obtained using polyethylene glycol. The method can recognize TSH concentrations as low as 22 muU/ml using a highly sensitive antiserum developed by one of us (AFP). TSH in dried cord and newborn blood from 4 infants with congenital hypothyroidism was clearly higher than in normal infants. The method is suitable for use in a newborn screening program to confirm the suspicion of primary hypothyroidism in specimens with low T4 concentrations.     

Does obesity affect time to extubation in “fast track” cabg surgery?

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Gabapentin pharmacokinetics and feasibility in cardiac surgery

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -