Barrett's esophagus: a pre-cancerous condition approach to diagnosis and management.

Barrett's esophagus (BE) results from prolonged uncontrolled gastroesophageal reflux (GERD). Patients at risk for BE should be screened with upper endoscopy. Dysplasia is identified pathologically on endoscopic biopsy. The finding of low grade dysplasia indicates the need for more surveillance. High grade dysplasia warrants intervention with ablative techniques or surgery due to the extremely high rate of malignant transformation to esophageal adenocarcinoma. All patients should receive measures to control GERD (life-style modifications and acid suppression).

Effects of aging and atherosclerosis on endothelial and vascular smooth muscle function in humans.

BACKGROUND: Nitric oxide is an endothelium dependent dilator, which may protect against atherosclerosis. Several studies have shown a decrease in nitric oxide activity with aging, however none have assessed aging and atherosclerosis separately. We tested the hypothesis that aging blunts both basal and receptor-mediated endothelial nitric oxide release in humans. METHODS: We examined whether forearm blood flow responses to intra-arterial acetylcholine, and nitroprusside, were altered with aging, with and without co-infusion of an inhibitor of nitric oxide synthase (N(G)-mono-methyl-L-arginine) in three groups of human subjects; a group with clinical atherosclerotic vascular disease (n = 31, 21 M), otherwise healthy elderly (n = 17, 13 M), and healthy young controls (n = 15, 8 M). RESULTS: There was no difference in basal flows between the three groups. There was also no difference in the dilatation to either acetylcholine or nitroprusside responses between the AVD and the healthy elderly group; however, aging significantly decreased acetylcholine or nitroprusside responses when compared to the young controls (p < 0.02). Furthermore, the ratio between acetylcholine and nitroprusside, a marker of endothelial NO synthase activity, was significantly greater in the young volunteers (0.816 +/- 0.094% vs. 0.892 +/- 0.146 % vs. 1.389 +/- 0.2%, in atherosclerotic vascular disease, healthy elderly group, and young controls respectively). CONCLUSIONS: Forearm blood flow responses to endothelium dependent and independent stimuli are blunted with aging, independent of the presence of atherosclerotic disease. Moreover, the normal aging process may induce significant global vascular dysfunction (involving the endothelium and the vascular smooth muscle); to as great a degree as clinically manifest atherosclerosis.

The pivotal role of cholesterol absorption inhibitors in the management of dyslipidemia.

Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non HDL-C. Short term clinical trials have established the role of ezetimibe monotherapy and its use in combination with statins. Furthermore, ezetimibe and statin combination therapy increased the percentage of patients who achieved their LDL-C treatment goal. Studies using surrogate markers of atherosclerosis have suggested a possible role of ezetimibe in combating atherosclerosis. Ezetimibe provides an effective therapeutic strategy for the management of homozygous familial hypercholesterolemia (HoFH) and sitosterolemia. The lack of outcomes and long term safety data is attributed to the relatively recent introduction of this medication.