The integration of speaking and listening with twelfth-grade literature in Calais, Maine.

Thesis (Ed.M.)--Boston Universit

Does Digoxin Provide Additional Hemodynamic and Autonomic Benefit at Higher Doses in Patients With Mild to Moderate Heart Failure and Normal Sinus Rhythm?

AbstractObjectives. This study sought to examine the hemodynamic and autonomic dose response to digoxin.Background. Previous studies have demonstrated an increase in contractility and heart rate variability with digitalis preparations. However, little is known about the dose-response to digoxin, which has a narrow therapeutic window.Methods. Nineteen patients with moderate heart failure and a left ventricular ejection fraction <0.45 were studied hemodynamically using echocardiography and blood pressure at baseline and after 2 weeks of low dose (0.125 mg daily) and 2 weeks of moderate dose digoxin (0.25 mg daily). Loading conditions were altered with nitroprusside at each study. Autonomic function was studied by assessing heart rate variability on 24-h Holter monitoring and plasma norepinephrine levels during supine rest.Results. Low dose digoxin provided a significant increase in ventricular performance, but no further increase was seen with the moderate dose. Low dose digoxin reduced heart rate and increased heart rate variability. Moderate dose digoxin produced no additional increase in heart rate variability or reduction in sympathetic activity, as manifested by heart rate, plasma norepinephrine or low frequency/high frequency power ratio. In addition, we did not find that either low or moderate dose digoxin increased parasympathetic activity.Conclusions. We conclude that moderate dose digoxin provides no additional hemodynamic or autonomic benefit for patients with mild to moderate heart failure over low dose digoxin. Because higher doses of digoxin may predispose to arrhythmogenesis, lower dose digoxin should be considered in patients with mild to moderate heart failure.(J Am Coll Cardiol 1997;29:1206–13

Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: A randomized, double-blind, placebo-controlled study

AbstractObjectives. This study examined the of metoprolol on left ventricular performance, efficiency, neurohormonal activation and myocardial respiratory quotient in patients with dilated cardiomyopathy.Background.The mechanism by which beta-adrenergie blockade improves ejection fraction in patients with dilated cardiomyopathy remains an enigma. Thus, we undertook an extensive hemodynamic evaluation of this mechanism. In addition, because animal models have shown that catecholamine exposure may increase relative fatty acid utilization, we hypothesized that antagonism of sympathetic stimulation may result in increased carbohydrate utilization.Methods. This was a randomized, double-blind, prospective trial in which 24 men with nonischemic dilated cardiomyopathy underwent cardiac catheterization before and after 3 months of therapy with metoprolol (n = 15) or placebo (n = 9) in addition to standard therapy. Pressure-volume relations were examined using a micromanometer catheter and digital ventriculography.Results. At baseline, the placebo-treated patients had somewhat more advanced left ventricular dysfunction. Ejection fraction and left ventricular performance improved only in the metoprolol-treated patients. Stroke and minute work increased without an increase in myocardial oxgen consumption, suggesting increased myocardial efficiency. Further increases in ejection fraction were seen between 3 and 6 months in the metoprolol group. The placebo group had a significant increase in ejection fraction only after crossover to metoprolol. A significant relation the change in coronary sinus norepinephrine and myocardial respiratory quotient was seen, suggesting a possible effect of adrenergic deactivation on substrate utilization.Conclusions. These data demonstrate that in patients with cardiomyopthy, metoprolol treatment improves myocardial performance and energetics, and favorably alters substrate utilization. Beta-adrenergic blocking agents, such as metoprolol, are hemodynamically and energetically beneficial in the treatment of myocardial failure

A specific nanobody prevents amyloidogenesis of D76N \u3b22-microglobulin in vitro and modifies its tissue distribution in vivo

Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of \u3b22-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions. Here we compare the potency of two previously described inhibitors of wild type \u3b22-microglobulin fibrillogenesis, doxycycline and single domain antibodies (nanobodies). The \u3b22-microglobulin -binding nanobody, Nb24, more potently inhibits D76N \u3b22-microglobulin fibrillogenesis than doxycycline with complete abrogation of fibril formation. In \u3b22-microglobulin knock out mice, the D76N \u3b22-microglobulin/ Nb24 pre-formed complex, is cleared from the circulation at the same rate as the uncomplexed protein; however, the analysis of tissue distribution reveals that the interaction with the antibody reduces the concentration of the variant protein in the heart but does not modify the tissue distribution of wild type \u3b22-microglobulin. These findings strongly support the potential therapeutic use of this antibody in the treatment of systemic amyloidosis

Priority research questions in atopic dermatitis : an International Eczema Council eDelphi consensus

Recent advances in understanding the complex pathogenesis of atopic dermatitis (AD, also known as eczema or atopic eczema), coupled with the development of new treatments, have led to increased interest from multiple stakeholders. There is a need to prioritize areas for research to inform a coordinated approach to advancing science and patient care

The Effect of Plan Characteristics on the Cost of Pharmaceuticals in a Private Third-Party Prescription Program

This study used prescription claims data to evaluate whether average cost of pharmaceuticals differed among various plan characteristics after controlling for covariates and to examine the relationships among plan characteristics and cost of pharmaceuticals within various therapeutic categories. Data for the study were obtained from 1996 prescription claims information for a commercial population administered by a Rhode Island-based PBM. Six therapeutic categories were analyzed. Significant associations were found among plan characteristics and cost of pharmaceuticals. Average cost of pharmaceuticals differed among various plan characteristics such as copayment, mode of payment, formulary status, and pharmacy type after controlling for average wholesale price and days\u27 supply. © 2000, Informa UK Ltd All rights reserved: reproduction in whole or part not permitted. All rights reserved

Case report of tracheobronchial squamous cell carcinoma treated with radiation therapy and concurrent chemotherapy

Tracheobronchial tumors include primary malignant tumors, secondary malignant tumors, and benign tumors. Primary malignant tumors of the trachea are rare, representing only 0.1% to 0.4% of all malignant disease. Squamous cell carcinoma (SCC) and adenoid cystic carcinoma are the most common histological subtypes, making up approximately two-thirds of primary tracheal neoplasms.1 Such tumors have typically been treated with surgical resection and adjuvant radiation therapy (RT; Table 1). Medically inoperable tumors are usually treated with definitive RT, but because of the rarity of these tumors, there are no randomized trials to determine the optimal treatment regimen. A radiation dose of ∼60 Gy has been most commonly reported for external beam RT, with higher doses having significant toxicity of the tracheal and esophageal tissue using historical techniques. In contrast to definitive RT, the use of definitive RT with concurrent chemotherapy for tracheal SCC has been sparingly described in the literature. In this report, we describe our experience with 2 patients at our institution who received definitive RT using modern techniques with concurrent chemotherapy for tracheobronchial SCC