Medicine and Health Sciences Commons^™

Matrix Metalloproteinase Levels Identify Heart Failure Patients With Higher Burden Of Atrial Fibrillation, Toshimasa Okabe, Md, Avinash Chandra, Shaw R. Natan, Suzanne Adams, Jocelyn A. Sendecki, Melissa M. Mccarey, Reginald Ho, Md, Behzad B. Pavri, Md, Arnold J. Greenspon, Md, Daniel Frisch, Md

Department of Medicine Faculty Papers

Presented at ACC Mid-Atlantic conference in Washington DC.

INTRODUCTION/HYPOTHESIS

•Adverse cardiac remodeling and fibrosis provide an arrhythmic substrate for atrial fibrillation (AF), but the role of matrix metalloproteinases (MMPs) as a biomarker is not well understood. MMPs are zinc-dependent endopeptidases known to degrade substrates such as elastin, gelatin and collagen.

•In excised human atrial tissue, MMP 2 and 9 levels rise as the AF burden increases from sinus rhythm (“No AF”) to non-permanent AF (“Non-Prm AF”) to permanent AF (“PrmAF”). Higher plasma levels of MMPs are also associated with recurrent AF after cardioversion.

•This study sought to elucidate 1) the …

Sickle Cell Pain: A Critical Reappraisal., Samir K. Ballas, Kalpna Gupta, Patricia Adams-Graves

Department of Medicine Faculty Papers

Sickle cell pain includes 3 types: acute recurrent painful crises, chronic pain syndromes, and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the emergency department. It evolves through 4 phases: prodromal, initial, established, and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage, such as acute chest syndrome, multiorgan failure, and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation, and nociception. Aborting the acute …

Bandemia With Normal White Blood Cell Counts Associated With Infection., Marci Drees, Narrani Kanapathippillai, Marc T Zubrow

Department of Medicine Faculty Papers

OBJECTIVE: Measuring immature white blood cell forms ("bands") has been considered clinically unnecessary. We performed this study to determine whether elevated band counts, with normal total white blood cells on admission, were associated with infection or in-hospital death.

METHODS: We performed a retrospective cohort study including all patients admitted to the Christiana Care Health System 2-hospital, 1100-bed community-based academic health system in 2009 with normal white blood cells (3800-10,800 per mm(3)) on admission who had manual differentials performed. We defined our band groups as normal (≤10% bands and other immature cells), moderate (11%-19%), or high (≥20%). Via chart review, we …

Biosynthetic Pathways And The Role Of The Mas Receptor In The Effects Of Angiotensin-(1-7) In Smooth Muscles., Marcio Augusto Fressatto De Godoy, Larissa Pernomian, Ana Maria De Oliveira, Satish Rattan

Department of Medicine Faculty Papers

Ang-(1-7) is produced via degradation of Ang II by the human angiotensin converting enzyme, also known as ACE2. In the cardiovascular system, Ang-(1-7) has been shown to produce effects that are opposite to those of Ang II. These include smooth muscle relaxation and cardioprotection. While the roles of Ang-(1-7) in other systems are currently topic of intense research, functional data suggest a relaxation action in gastrointestinal smooth muscles in a way that corroborates the results obtained from vascular tissues. However, more studies are necessary to determine a relevant role for Ang-(1-7) in the gastrointestinal system. The Ang-(1-7) actions are mediated …

Drugs For Preventing Red Blood Cell Dehydration In People With Sickle Cell Disease., Srikanth Nagalla, Samir K Ballas

Department of Medicine Faculty Papers

BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs.

OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials …

Human Genome-Wide Association And Mouse Knockout Approaches Identify Platelet Supervillin As An Inhibitor Of Thrombus Formation Under Shear Stress., Leonard C. Edelstein, Elizabeth J. Luna, Ian B. Gibson, Molly Bray, Ying Jin, Altaf Kondkar, Srikanth Nagalla, Nacima Hadjout-Rabi, Tara C. Smith, Daniel Covarrubias, Stephen N. Jones, Firdos Ahmad, Moritz Stolla, Xianguo Kong, Zhiyou Fang, Wolfgang Bergmeier, Chad Shaw, Suzanne M. Leal, Paul Bray

Department of Medicine Faculty Papers

BACKGROUND: High shear force critically regulates platelet adhesion and thrombus formation during ischemic vascular events. To identify genetic factors that influence platelet thrombus formation under high shear stress, we performed a genome-wide association study and confirmatory experiments in human and animal platelets.

METHODS AND RESULTS: Closure times in the shear-dependent platelet function analyzer (PFA)-100 were measured on healthy, nondiabetic European Americans (n=125) and blacks (n=116). A genome-wide association (P

CONCLUSIONS: We show for the first time that (1) platelets contain supervillin; (2) platelet thrombus formation in the PFA-100 is associated with human SVIL variants and low SVIL expression; and (3) …

Cdo Patterns The Musculature Of The Esophagus And Is Required For Esophageal Motility In Mice, Anthony I. Romera, Jagmohan Singhb, Satish Rattan, Robert S. Krauss

Department of Medicine Faculty Papers

Introduction:

Cdo is a multifunctional cell surface co-receptor that promotes Hedgehog signaling during rostroventral midline development and cadherin-mediated signaling during skeletal myogenesis. We report here novel roles for Cdo in patterning of the murine esophageal musculature and esophageal motility disorders such as achalasia.

The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

Department of Medicine Faculty Papers

Limited data suggest anti-tumor necrosis factor (TNF) antibodies have equal efficacy but higher morbidity and mortality in older compared to younger inflammatory bowel disease (IBD) patients(1).

Gender-Sensitive Reporting In Medical Research., Shirin Heidari, Quarraisha Abdool Karim, Judith D Auerbach, Simone E Buitendijk, Pedro Cahn, Mirjam J Curno, Catherine Hankins, Elly Katabira, Susan Kippax, Richard Marlink, Joan Marsh, Ana Marusic, Heidi M Nass, Julio Montaner, Elizabeth Pollitzer, Maria Teresa Ruiz-Cantero, Lorraine Sherr, Papa Salif Sow, Kathleen Squires, Mark A Wainberg

Department of Medicine Faculty Papers

Sex and gender differences influence the health and wellbeing of men and women. Although studies have drawn attention to observed differences between women and men across diseases, remarkably little research has been pursued to systematically investigate these underlying sex differences. Women continue to be underrepresented in clinical trials, and even in studies in which both men and women participate, systematic analysis of data to identify potential sex-based differences is lacking. Standards for reporting of clinical trials have been established to ensure provision of complete, transparent and critical information. An important step in addressing the gender imbalance would be inclusion of …

Comprehensive Analysis Of Common Serum Liver Enzymes As Prospective Predictors Of Hepatocellular Carcinoma In Hbv Patients., Hie-Won Hann, Shaogui Wan, Ronald E Myers, Richard S Hann, Jinliang Xing, Bicui Chen, Hushan Yang

Department of Medicine Faculty Papers

BACKGROUND: Serum liver enzymes are frequently tested in clinics to aid disease diagnosis. Large observational studies indicated that these enzymes might predict cancer risk and mortality. However, no prospective study has reported on their relationships with the risk of HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the predictive values of four routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) in HCC risk in a prospectively enrolled clinical cohort of 588 Korean American HBV patients. For all four enzymes, the baseline level as well as the average and maximum levels during the …