Publications

The purpose of this study was to provide an analysis of gender-based disparities in hypertension and cardiovascular disease care in ambulatory practices across the United States. Using data from the 2005 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, we conducted a cross-sectional analysis of patient visits with their primary care providers and examined the association between gender and blood pressure control, use of any antihypertensive medication or initiation of new therapy for patients with uncontrolled hypertension, and receipt of recommended therapy for select cardiovascular conditions. Multivariable models were estimated to examine the association between gender and each outcome controlling for other variables. A total of 12 064 patient visits were identified (7786 women and 4278 men). Among patients with hypertension, women were less likely than men to meet blood pressure control targets (54.0% versus 58.7%; P<0.02). In multivariate analyses, women aged 65 to 80 years were less likely than men to have controlled hypertension (odds ratio: 0.62; 95% CI: 0.45 to 0.85). There was no association between gender and use of any antihypertensive medication or initiating a new therapy among patients with uncontrolled hypertension. In multivariate analyses, women were less likely than men to receive aspirin (odds ratio: 0.43; 95% CI: 0.27 to 0.67) and beta-blockers (odds ratio: 0.60; 95% CI: 0.36 to 0.99) for secondary prevention of cardiovascular disease. Our study highlights the persistent gender disparities in blood pressure control and cardiovascular disease management and also reveals the inadequate delivery of cardiovascular care to all patients.

The ATP-sensitive potassium (K(ATP)) channels couple intracellular metabolism to membrane potential. They are composed of Kir6.x and sulfonylurea receptor (SUR) subunits and are expressed in hypothalamic neurons that project to GnRH neurons. However, their roles in regulating GnRH secretion have not been determined. The present study first tested whether K(ATP) channels regulate pulsatile GnRH secretion, as indirectly reflected by pulsatile LH secretion. Ovariectomized rats received sc capsules containing oil, 17beta-estradiol (E(2)), progesterone (P), or E(2)+P at 24 h before blood sampling. Infusion of the K(ATP) channel blocker tolbutamide into the third ventricle resulted in increased LH pulse frequency in animals treated with E(2)+P but was without effect in all other groups. Coinfusion of tulbutamide and the K(ATP) channel opener diazoxide blocked this effect, whereas diazoxide alone suppressed LH. Effects of steroids on Kir6.2 and SUR1 mRNA expression were then evaluated. After 24hr treatment, E(2)+P produced a modest but significant increase in Kir6.2 expression in the preoptic area (POA), which was reversed by P receptor antagonism with RU486. Neither SUR1 in the POA nor both subunits in the mediobasal hypothalamus were altered by any steroid treatment. After 8 d treatment, Kir6.2 mRNA levels were again enhanced by E(2)+P but to a greater extent in the POA. Our findings demonstrate that 1) blockade of preoptic/hypothalamic K(ATP) channels produces an acceleration of the GnRH pulse generator in a steroid-dependent manner and 2) E(2)+P stimulate Kir6.2 gene expression in the POA. These observations are consistent with the hypothesis that the negative feedback actions of ovarian steroids on the GnRH pulse generator are mediated, in part, by their ability to up-regulate K(ATP) channel subunit expression in the POA.

The ultimate success of dendritic cell (DC) vaccination for the active immunotherapy of neoplasia is thought to be dependent on a very large number of variables, including DC generation protocol, loading methodology, dose, route of administration, and maturation method. Although the use of a maturation cocktail comprising interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, and prostaglandin E2 (ITIP) has recently appeared in the literature, much of the data in the basic and clinical literature have been generated using DCs matured with the single inflammatory cytokine TNF-alpha. Here, we demonstrate that DCs matured with TNF-alpha alone or in combination with CD40 agonism are highly deficient, both physiologically and functionally, in comparison with DCs matured with IL-1beta, TNF-alpha, IL-6, and prostaglandin E2. Empirically, the data suggest that DCs matured with these agents are deficient in the induction of type 1 T-helper responses. We further speculate that DCs matured by these methods might be suboptimal for the priming of naive responses.