Tamsulosin oral controlled absorption system (OCAS) in the treatment of benign prostatic hypertrophy

The efficacy of tamsulosin at the cost of a relatively benign side effect profile has been attributed to receptor selectivity directed at the α1a and α1d adrenergic receptor subtypes. The oral-controlled absorption system (OCAS®) represents a drug delivery refinement that incorporates a matrix of gel-forming and gel-enhancing agents to promote a constant drug release independent of environmental food or fluid. There are clinical data to support the concept that drug peaks are lessened and that drug release continues throughout the alimentary tract due to the OCAS formulation. Furthermore this equates with less adverse effects on physiologic parameters. To date however improvements in cardiovascular symptoms such as dizziness, headache and syncope have not been demonstrated in healthy men. Ejaculatory dysfunction appears less problematic with the OCAS preparation. Tamsulosin OCAS may be of greatest benefit to men with cardiovascular co-morbidities taking anti-hypertensive medications that might predispose them to symptomatic hypotensive episodes. It will be necessary to evaluate this group of men more closely in further trials to determine what they stand to gain from changing medications, and then relate this to drug costs to draw a final conclusion as to the place of tamsulosin OCAS in contemporary urological practice

Myocardial dysfunction following ruptured abdominal aortic aneurysm repair, the role of tumour necrosis factor-Ã

grantor: University of TorontoRupture and repair of an abdominal aortic aneurysm, a combination of hemorrhagic shock and lower torso ischemia, is associated with a 50-70% mortality. Since myocardial dysfunction may contribute to the high mortality rate following aneurysm repair, the purpose of this thesis was to determine whether ruptured abdominal aortic aneurysm repair results in cardiac dysfunction, mediated by tumour necrosis factor-Ã (TNF-Ã). We modeled aortic rupture and repair in the rat by inducing hemorrhagic shock to a mean blood pressure of 50 mmHg for 1 hour followed by supramesenteric clamping of the aorta for 45 minutes. After 90 minutes of reperfusion, cardiac contractile function was assessed using an isolated heart perfusion apparatus. Myocardial TNF-Ã levels, myocardial energy stores (ATP and CP), neutrophil sequestration, markers of oxidant stress (F2-isoprostanes) and necrosis were measured. Cardiac function in the combined shock and clamp rats was significantly depressed compared to sham operated control rats, but was similar to that noted in animals subjected to shock alone. Myocardial TNF-Ã concentrations increased 10-fold in the combined shock and clamp rats compared to shams while there was no difference in myocardial ATP, CP, F2-isoprostanes and necrosis. Administration of a neutralizing anti-TNF-Ã antibody prior to shock improved cardiac function by 50% in the combined shock and clamp rats. Thus, Hemorrhagic shock is the primary insult inducing cardiac dysfunction in this model of ruptured abdominal aortic aneurysm repair and no synergistic effect between shock and aortic clamping was noted. An improvement in cardiac contractile function following immunoneutralization of TNF-Ã indicates that TNF-Ã mediates a significant portion of the myocardial dysfunction in this model.M.Sc

Safety and clinical efficacy of everolimus in the treatment of advanced renal cell carcinoma (RCC)

Rohan Shahani, Kevin G Kwan, Anil KapoorDivision of Urology, Department of Surgery, St. Joseph’s Healthcare Hamilton and McMaster University, Hamilton, Ontario, CanadaAbstract: Renal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies. Recently, there has been a paradigm shift in the management of advanced RCC. New targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been developed which have shown promising results in a patient population who otherwise had very few options for treatment. The first mTOR inhibitor, temsirolimus, an intravenous prodrug, has shown improved overall survival in poor prognosis patients. More recently, an oral mTOR inhibitor, everolimus (RAD 001), has been developed which has been shown to delay disease progression in patients with metastatic RCC who have progressed on other targeted therapies. Although a survival advantage in phase III trials is seen with everolimus, associated systemic toxicities, while generally well tolerated, are not insignificant. These include mucositis, hyperglycemia, hyperlipidemia, and pneumonitis. Despite the side effects, emerging evidence points to everolimus as the optimal second-line treatment for patients with advanced renal cell carcinoma.Keywords: metastatic renal cell carcinoma, everolimus, mTOR inhibitors, VEGF inhibitor