James A S Muldowney

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BACKGROUND The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. METHODS We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm(More)
OBJECTIVE Inflammation, insulin resistance and vascular dysfunction characterize obesity and predict development of cardiovascular disease (CVD). Although women experience CVD events at an older age, vascular dysfunction is evident 10years prior to coronary artery disease. Questions remain whether replacing SFA entirely with MUFA or PUFA is the optimal(More)
Thrombospondin-1 (THBS1) is a large extracellular matrix glycoprotein that affects vasculature systems such as platelet activation, angiogenesis, and wound healing. Increases in THBS1 expression have been liked to disease states including tumor progression, atherosclerosis, and arthritis. The present study focuses on the effects of thrombin activation of(More)
OBJECTIVE Drug eluting stents (DES) reduce the incidence of restenosis after coronary angioplasty. Enthusiasm has been tempered by a possible increased risk of in-stent thrombosis. We examined the effects of paclitaxel and rapamycin on the endothelial transcriptome to identify alterations in gene expression associated with thrombosis. METHODS AND RESULTS(More)
The C1166 variant, an A to C substitution polymorphism at the 1166 position of the angiotensin II type I (AT1) receptor, has been previously associated with hypertension in Caucasians. This study determines the frequency of the C1166 variant in an African American population. Normotensive African American (n = 99) and Caucasian (n = 100) subjects were(More)
Tissue-type plasminogen activator (t-PA) is a pivotal enzyme in the mammalian fibrinolytic system. It exerts its action by converting the zymogen plasminogen into the proteolytically active serine protease plasmin, which, in turn, degrades fibrin clots. Because of its affinity for fibrin, t-PA is the prototypic fibrin-specific plasminogen activator (1).(More)
The acute physiologic release of tissue-type plasminogen activator (t-PA) from the endothelium is critical for vascular homeostasis. This process is prostacyclin- and nitric oxide (NO)-independent in humans. It has been suggested that calcium signaling and endothelial-derived hyperpolarizing factors (EDHF) may play a role in t-PA release. G-protein-coupled(More)
Plasminogen activator inhibitor 1 (PAI-1), the primary inhibitor of fibrinolysis and C-reactive protein (CRP), is a predictor of myocardial infarction. Both are upregulated by tumor necrosis factor-alpha (TNF-α) within the obese population. This pilot study tested the hypothesis that TNF-α blockade with pentoxifylline lowers PAI-1 and high-sensitivity CRP(More)
Eplerenone is an aldosterone receptor antagonist indicated for the treatment of hypertension and congestive heart failure. Eplerenone contains an epoxy group, which offers greater mineralocorticoid receptor specificity. It is an effective antihypertensive that has been shown to reduce morbidity and mortality in individuals with left ventricular dysfunction(More)
STUDY OBJECTIVES Obstructive sleep apnea (OSA) is strongly associated with cardiovascular disease, including stroke and acute coronary syndromes. Plasminogen activator inhibitor-1 (PAI-1), the principal inhibitor of tissue-type plasminogen activator (t-PA), has a pronounced circadian rhythm and is elevated in both OSA and cardiovascular disease and may be(More)