Growth hormone treatment modulates active ghrelin levels in rats.

Introduction: Impairments in neuroendocrine regulation of food intake and postprandial satiety are leading causes to obesity. Ghrelin peptide is a GI hormone known to increase food intake partly through induction of growth hormone. The regulation of ghrelin production is still unknown.

Characterization of TtALV2, an essential charged repeat motif protein of the Tetrahymena thermophila membrane skeleton.

Alveolins are a recently described class of proteins common to all members of the superphylum Alveolata that are characterized by conserved charged repeat motifs (CRMs) but whose exact function remains unknown. We have analyzed the smaller of the two alveolins of Tetrahymena thermophila, TtALV2. The protein localizes to dispersed, broken patches arranged between the rows of the longitudinal microtubules.

Arginine butyrate: a therapeutic candidate for Duchenne muscular dystrophy.

As a strategy to treat Duchenne muscular dystrophy, we used arginine butyrate, which combines two pharmacological activities: nitric oxide pathway activation, and histone deacetylase inhibition. Continuous intraperitoneal administration to dystrophin-deficient mdx mice resulted in a near 2-fold increase in utrophin (protein homologous to dystrophin) in skeletal muscle, heart, and brain, accompanied by an improvement of the dystrophic phenotype in both adult and newborn mice (45 and 70% decrease in creatine kinase level, respectively; 14% increase in tidal volume, 30% decrease in necrotic area in limb and 23% increase in isometric force). Intermittent administration, as performed in clinical trials, was then used to reduce the frequency of injections and to improve safety.

Defining incidence, risk factors, and impact on survival of central line-associated blood stream infections following hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome.

Central line-associated blood stream infections (CLABSI) commonly complicate the care of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic stem cell transplantation (HCT). We developed a modified CLABSI (MCLABSI) definition that attempts to exclude pathogens usually acquired because of disruption of mucosal barriers during the vulnerable neutropenic period following HCT that are generally included under the original definition (OCLABSI). We conducted a retrospective study of all AML and MDS patients undergoing HCT between August 2009 and December 2011 at the Cleveland Clinic (N = 73), identifying both OCLABSI and MCLABSI incidence.

The role of vitamin D in chronic heart failure.

Purpose Of Review: Despite advanced medical and device-based therapies, congestive heart failure (CHF) remains a major medical problem, associated with significant morbidity and mortality. Vitamin D deficiency is prevalent in CHF and is associated with poor outcomes. In this manuscript we review the evidence linking vitamin D deficiency and CHF and discuss potential mechanisms involved, as well the clinical data on vitamin D supplementation in CHF patients.

Depression in heart failure.

Purpose Of Review: This review aims to provide a general overview of the recent advances in understanding of depression as it pertains to heart failure. The focus is to impart an up to date knowledge in this field.

Recent Findings: The mortality associated with heart failure remains high despite recent pharmacologic interventions that have improved survival.

Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling.

Background: Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) in explaining this differential response.

Methods: We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge.

The 2012 Canadian Cardiovascular Society heart failure management guidelines update: focus on acute and chronic heart failure.

The 2012 Canadian Cardiovascular Society Heart Failure (HF) Guidelines Update provides management recommendations for acute and chronic HF. In 2006, the Canadian Cardiovascular Society HF Guidelines committee first published an overview of HF management. Since then, significant additions to and changes in many of these recommendations have become apparent.

Laparoendoscopic transgastric histoacryl injection of gastric varices: a new surgical approach.

Background: Gastric varices (GVs) are a common finding in Egyptian patients with portal hypertension due to cirrhosis or schistosomal hepatic fibrosis. These patients present with an acute attack or history of hematemesis. Endoscopic histoacryl injection is the standard treatment in Egypt; however, because of technical difficulties it is possible to inject only a little amount of this material, as it may endanger the channels of the flexible endoscope.

Do high doses of AT(1)-receptor blockers attenuate central sympathetic outflow in humans with chronic heart failure?

In patients with CHF (chronic heart failure) sympathetic activity increases as cardiac performance decreases and filling pressures increase. We hypothesized that in patients with mild-to-moderate CHF, higher than conventional doses of an AT1-receptor [AngII (angiotensin II) type 1 receptor] antagonist would achieve greater central AT1-receptor blockade, resulting in diminished MSNA (muscle sympathetic nerve activity) and augmented MSNA variability, two indices of central effects on sympathetic outflow. In total, 13 patients with ischaemic cardiomyopathy [NYHA (New York Heart Association) class II-III] were weaned off all pharmacological RAS (renin-angiotensin system) modifiers, and then randomized to receive a low (50 mg/day) or high (200 mg/day) dose of losartan.

Effect of acute hypoxia on post-exercise parasympathetic reactivation in healthy men.

In this study we assessed the effect of acute hypoxia on post-exercise parasympathetic reactivation inferred from heart rate (HR) recovery (HRR) and HR variability (HRV) indices. Ten healthy males participated in this study. Following 10 min of seated rest, participants performed 5 min of submaximal running at the speed associated with the first ventilatory threshold (Sub) followed by a 20-s all-out supramaximal sprint (Supra).

Worsening renal function and prognosis in pulmonary hypertension patients hospitalized for right heart failure.

Increased central venous pressures have been associated with the development of worsening renal function (WRF), an important marker of prognosis. We sought to determine the incidence and prognostic significance of WRF in pulmonary hypertension patients (PH) with isolated right HF. A prospective study of PH clinic patients admitted to hospital for right HF.

Novel agents for the management of castration-resistant prostate cancer.

Purpose Of Review: Over the past 2 years, four new treatments have entered the treatment armamentarium for patients with castration-resistant prostate cancer (CRPC). Although these novel agents differ in their mechanism of action, they all face the same challenges: patient selection, timing of therapy and the cost/benefit of their use. In this review, we will discuss their development and implications when selecting treatment options for CRPC patients.

Current treatment considerations in metastatic renal cell carcinoma.

In general, debulking neprhectomy is still considered for metastatic RCC patients with primary tumor in place, assuming good performance status. Initial systemic therapy should consider high-dose IL-2 for the highly select patient. One reason for initial consideration of this therapy is the less certain risk/benefit profile if employed after targeted therapy.

Usefulness of beta-blocker therapy and outcomes in patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a disorder in which pulmonary arterial remodeling and vasoconstriction progressively lead to right heart failure (HF), exercise intolerance, and high mortality. Beta-blockers have been shown to decrease mortality in left-sided HF, but their efficacy in isolated right HF associated with PAH is uncertain. Patients with PAH may have cardiac co-morbidities for which β-blocker therapy is indicated, and the relative risk benefit of this therapy remains to be proved.

Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up.

Imaging the failing right ventricle.

Purpose Of Review: This article will review the noninvasive modalities currently available for imaging the right ventricle, including two-dimensional echocardiography, cardiac magnetic resonance (CMR), multidetector computed tomography (MDCT), radionuclide ventriculography (RNV) and PET.

Recent Findings: Improvements in established imaging techniques, as well as development of newer imaging modalities, have shed light on the right ventricle's adaptation to pressure and volume overload states and have allowed better prognostication in patients with right ventricular failure (RVF).

Summary: As therapies are developed to alter the natural history of RVF, a better understanding of the imaging modalities for the assessment of right ventricular morphology and function is needed.

A phase I trial of adeno-associated virus serotype 1-γ-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C.

γ-Sarcoglycanopathy or limb girdle muscular dystrophy type 2C is an untreatable disease caused by autosomal recessively inherited mutations of the γ-sarcoglycan gene. Nine non-ambulatory patients (two males, seven females, mean age 27 years; range 16-38 years) with del525T homozygous mutation of the γ-sarcoglycan gene and no γ-sarcoglycan immunostaining on muscle biopsy were divided into three equal groups to receive three escalating doses of an adeno-associated virus serotype 1 vector expressing the human γ-sarcoglycan gene under the control of the desmin promoter, by local injection into the extensor carpi radialis muscle. The first group received a single injection of 3 × 10(9) viral genomes in 100 µl, the second group received a single injection of 1.

Recent advances in the management of chronic heart failure.

Purpose Of Review: This review will provide an overview of the recent advances in the management of chronic heart failure, with special focus on major publications in the past 2 years, 2010-2011.

Recent Findings: In the past 1-2 years, there have been a number of publications that promise to make a major difference in patient management and outcome in heart failure. These include two clinical trials in patients with less symptomatic heart failure, namely the use of cardiac resynchronization therapy (CRT) and eplerinone, an aldosterone receptor antagonist, and another study using ivabradine, which belongs to a new class of If channel blocking drugs used for heart rate reduction in patients with moderate heart failure.

Does FDG PET-assisted management of patients with left ventricular dysfunction improve quality of life? A substudy of the PARR-2 trial.

Background: Patients with left ventricular dysfunction whose management is directed by F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging may have a quality of life (QOL) benefit over standard care.

Methods: Among 430 patients randomized in the PET and Recovery Following Revascularization (PARR)-2 trial to FDG PET-assisted management vs standard, QOL scores were obtained using the European Quality of Life-5 Dimensions (EQ-5D) in 427 patients at baseline (FDG PET n = 216; standard n = 211) and 355 patients at 12-month follow-up (FDG PET n = 184; standard n = 171). EQ-5D scores between FDG PET and standard arms were compared using mixed model repeated measures (MMRM).

A critical role for the protein apoptosis repressor with caspase recruitment domain in hypoxia-induced pulmonary hypertension.

Background: Pulmonary hypertension (PH) is a lethal syndrome associated with the pathogenic remodeling of the pulmonary vasculature and the emergence of apoptosis-resistant cells. Apoptosis repressor with caspase recruitment domain (ARC) is an inhibitor of multiple forms of cell death known to be abundantly expressed in striated muscle. We show for the first time that ARC is expressed in arterial smooth muscle cells of the pulmonary vasculature and is markedly upregulated in several experimental models of PH.

Association of interleukin-10 gene promoter polymorphisms with chronic and aggressive periodontitis.

Objective: Interleukin-10 gene promoter polymorphisms have been associated with interleukin-10 decreased production, thereby playing a role in the pathogenesis of periodontitis. This study aimed to investigate whether interleukin-10 single nucleotide polymorphisms at positions -1087(G/A) and -597(C/A) are associated with generalised chronic periodontitis and localised aggressive periodontitis.

Methods: Genomic DNA samples were isolated from 276 unrelated Jordanian participants.

Effect of maturation on hemodynamic and autonomic control recovery following maximal running exercise in highly trained young soccer players.

The purpose of this study was to examine the effect of maturation on post-exercise hemodynamic and autonomic responses. Fifty-five highly trained young male soccer players (12-18 years) classified as pre-, circum-, or post-peak height velocity (PHV) performed a graded running test to exhaustion on a treadmill. Before (Pre) and after (5th-10th min, Post) exercise, heart rate (HR), stroke volume (SV), cardiac output (CO), arterial pressure (AP), and total peripheral resistance (TPR) were monitored.

Effect of daily cold water immersion on heart rate variability and subjective ratings of well-being in highly trained swimmers.

Purpose: We investigated the effect of daily cold water immersion (CWI), during a typical training week, on parasympathetic activity and subjective ratings of well-being.

Methods: Over two different weeks, eight highly trained swimmers (4 men; 19.6 ± 3.