Medicine and Health Sciences Commons^™

Eculizumab For Gemcitabine-Induced Hemolytic Uremic Syndrome: A Novel Therapy For An Emerging Condition, Raphael Karkowsky, Md, Kinjal Parikh, Md

The Medicine Forum

Introduction

Atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy (TMA), is a disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment. Gemcitabine, a commonly used chemotherapy, is emerging as a cause of aHUS. Although rare, the morbidity and mortality can be significant. Few studies have explored the use of eculizumab, an anti-C5 monoclonal antibody as a potential therapy for gemcitabine-induced aHUS.

Case Presentation

A 45 year old Caucasian male with metastatic urothelial carcinoma was started on weekly gemcitabine (1000 mg/m2 per dose) to treat recurrent disease. During his seventh cycle, he was hospitalized for hypertension, acute kidney injury, and anemia. …

Chronic Idiopathic Intestinal Pseudo-Obstruction: A Working Diagnosis, Ankush Kalra, Md, Anthony Dimarino, Md

The Medicine Forum

Introduction

Chronic intestinal pseudo-obstruction (CIP) is a rare and disabling motility syndrome, yet one that demands an extensive review of digestive motility and peristaltic pathophysiology. Primarily a disorder of the small intestine, CIP was first described by Dudley and colleagues in 1958; it is defined by severe signs and symptoms of intestinal obstruction (abdominal pain and distention, nausea, vomiting, and constipation), in addition to radiographic evidence of dilated bowel in the absence of a true, mechanical obstruction. Symptoms are often slowly progressive and diagnosis requires the presence of symptoms for at least six months.1 A 2013 national survey in Japan …

Acute Respiratory Distress Syndrome From Tick-Borne Human Granulocytic Anaplasmosis Infection, Vedang Patel, Md

The Medicine Forum

Introduction

Tick-borne infections were first formally recognized over a century ago, but it was only in 1990 that the first case of human granulocytic anaplasmosis (HGA), a tick-borne infection caused by Anaplasma phagocytophilum, was identified.1,2 Like other tick-borne infections, HGA presents as a nonspecific febrile illness. The most common clinical features are fever, headache, myalgia and malaise.2 This case report presents a rare but serious complication of HGA – acute respiratory distress syndrome (ARDS).

CASE PRESENTATION

A 49-year-old female with no past medical history presented to her local emergency department with complaints of fevers, headache, neck pain, myalgia, and malaise. …

A Special Case Of A Broken Heart, Shuwei Wang, Md

The Medicine Forum

Introduction

Takotsubo cardiomyopathy (TC), also known as stress cardiomyopathy, and broken heart syndrome is characterized by transient left ventricular (LV) apical akinesis with symptoms mimicking acute coronary syndrome. The first case was described by Sato et al. in Japan.1 The Japanese word “takotsubo” translates to “octopus pot” describing the shape of the left ventricle during systole. TC can be triggered by a “broken heart” including death of a loved one, constant anxiety, surgery, or critical illness etc. Prevalence is around 2% to 3% with over 90% in postmenopausal women aged between 58 and 75. Its pathogenesis remains unclear. Some postulated …

A Case Of Ipilimumab Induced Hypophysitis, Eric Shiffrin, Md, Melinda Ukrainski, Md

The Medicine Forum

Introduction

Ipilimumab (Yervoy®) is a human monoclonal antibody that has been shown to significantly improve survival in cases of metastatic melanoma.1 Ipilimumab blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4), a protein receptor on the surface of T-cells, resulting in their activation, proliferation and an anti-tumor response.2,3,4 Commonly reported immune-related side effects of ipilimumab are enterocolitis, dermatitis, and hepatitis.5,6,7 However, different endocrinopathies, including autoimmune hypopituitarism, have become emerging clinical entities in patients taking ipilimumab. We present a case of ipilimumab induced hypophysitis in a 62-yearold male presenting with fatigue and hypotension.

Case Presentation

A 62-year-old male with a history of melanoma metastatic …

Table Of Contents

The Medicine Forum

Table of Contents for The Medicine Forum, Volume 16, 2014-2015.

From The Editors, Anusha G. Govind, Md, Loheetha Ragupathi, Md, Michael A. Valentino, Md, Phd

The Medicine Forum

We are excited to present you with the 16th annual edition of The Medicine Forum. This work is a culmination of months of effort on the part of medical students, residents, fellows and faculty to share clinical pearls from the last year of their experiences.

Amongst the greatest strengths of medical professionals and patients alike is the ability to tell stories. Stories, and how they are told form the basis of medical care. The way in which a particular patient's story unfolds has a lasting impact on physicians, trainees, other medical staff, and perhaps most importantly, on future patients. Stories …

From The Desk Of The Residency Program Director, Gretchen Diemer, Md, Facp

The Medicine Forum

It is bittersweet to write my final Message from the Program Director for the Forum. This publication is one example of the passion, talent, creativity and scientific inquisitiveness of our Jefferson residents. As a completely resident run journal, what follows in this journal helps prove to me that the future of medicine is in good hands.

In my time as program director, we have seen many changes in the healthcare landscape, both nationally and locally at Jefferson. We have launched the Milestone evaluations in the Next Accreditation System for the ACGME and are embarking on major curricular reform at the …

Regulated Phosphorylation Of The K-Cl Cotransporter Kcc3 Is A Molecular Switch Of Intracellular Potassium Content And Cell Volume Homeostasis, Norma C. Adragna, Nagendra B. Ravilla, Peter K. Lauf, Gulnaz Begum, Arjun R. Khanna, Dandan Sun, Kristopher K. Kahle

Pharmacology and Toxicology Faculty Publications

The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K+ and Cl− efflux via activation of K+ channels, volume-regulated anion channels (VRACs), and the K+-Cl− cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the …

Potentiation Of Tonic Gabaergic Inhibition By Activation Of Postsynaptic Kainate Receptors, L Jiang, D Kang, J Kang

NYMC Faculty Publications

Presynaptic kainate-type glutamate ionotropic receptors (KARs) that mediate either the depression or the facilitation of GABA release have been intensively studied. Little attention has been given to the modulation of GABAA receptors (GABAARs) by postsynaptic KARs. Recent studies suggest that two GABAAR populations, synaptic (sGABAAR) and extrasynaptic (eGABAAR) GABAARs, mediate phasic and tonic forms of inhibition, respectively. Tonic inhibition plays an important role in the excitability of neuronal circuits and the occurrence of epileptic seizures. For this study, we are the first to report that the activation of postsynaptic KARs by the KAR agonist, Kainic acid (KA, 5 μM), enhanced …

Medicare At Fifty Needs To Grow, William H. Lane

English Faculty Publications

In America everybody has a healthcare story. A bill impossible to read, an inscrutable "additional" charge, trouble getting insurance, trouble keeping it, a friend or family member who's fallen between the coverage "cracks." [excerpt]

Aggregate And Event-Level Associations Of Substance Use And Sexual Behavior Among Gay And Bisexual Men: Comparing Retrospective And Prospective Data, H. Jonathan Rendina, Raymond L. Moody, Ana Ventuneac, Christian Grov, Jeffrey T. Parsons

Publications and Research

Background: Despite limited research, some evidence suggests that examining substance use at multiple levels may be of greater utility in predicting sexual behavior than utilizing one level of measurement, particularly when investigating different substances simultaneously. We aimed to examine aggregated and event-level associations between three forms of substance use—alcohol, marijuana, and club drugs—and two sexual behavior outcomes—sexual engagement and condomless anal sex (CAS).

Method: Analyses focused on both 6-week timeline follow-back (TLFB; retrospective) and 30-day daily diary (prospective) data among a demographically diverse sample of 371 highly sexually active HIV-positive and HIV-negative gay and bisexual men.

Results: …

King V Burwell: Subsidizing Us Health Insurance For Low- And Middle-Income Individuals, Lawrence O. Gostin, Mary C. Debartolo, Daniel Hougendobler

Georgetown Law Faculty Publications and Other Works

In King v. Burwell, the U.S. Supreme Court once again saved the Affordable Care Act (ACA) by upholding subsidies (tax credits) offered to low- and middle-income individuals for insurance bought on federal exchanges. A contrary opinion would have put at risk health insurance for 6.4 million Americans and threatened to destabilize insurance markets for millions more.

The ACA is supported by four interlocking reforms, each of which are necessary to realize its promise of expanding health care coverage: (1) guaranteed issue (prohibiting discrimination based on pre-existing conditions), (2) community rating (barring insurers from imposing higher premiums based on health …

Trna-Derived Short Non-Coding Rna As Interacting Partners Of Argonaute Proteins., Megumi Shigematsu, Yohei Kirino, Phd

Computational Medicine Center Faculty Papers

The advent of next-generation sequencing technologies has not only accelerated findings on various novel non-coding RNA (ncRNA) species but also led to the revision of the biological significance and versatility of fundamental RNA species with canonical function, such as transfer RNAs (tRNAs). Although tRNAs are best known as adapter components of translational machinery, recent studies suggest that tRNAs are not always end products but can further serve as a source for short ncRNAs. In many organisms, various tRNA-derived ncRNA species are produced from mature tRNAs or their precursor transcripts as functional molecules involved in various biological processes beyond translation. In …

Targeting Neddylation Induces Dna Damage And Checkpoint Activation And Sensitizes Chronic Lymphocytic Leukemia B Cells To Alkylating Agents, C Paiva, J C. Godbersen, A Berger, J R. Brown, A V. Danilov

Dartmouth Scholarship

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 …

Elevating Research: An Important Role For Nurse Leaders, Katreena Collette Merrill, Diane Andrews, Barbara B. Brewer, Diane Storer Brown

Faculty Publications

As leaders, we recognize the importance of professional scholarship to provide the evidence needed to transform practice. One key initiative for the American Organization of Nurse Executives (AONE) is the elevation of nursing research and AONE competencies for nurse executives emphasize utilization, dissemination and participation in studies. However, given our current healthcare climate and competing priorities, nurse leaders must often focus efforts on fiscal responsibility and operational effectiveness, making time and resources to support nursing research challenging. Initiatives that do not directly impact patient care, such as research, may be given a lower priority. Given today’s pressures, nurse leaders may …

Improving Early Infant Hiv Diagnosis In Kenya: Study Protocol Of A Cluster-Randomized Efficacy Trial Of The Hitsystem., Sarah Finocchario-Kessler, Kathy Goggin, Samoel Khamadi, Brad Gautney, Jacinda K. Dariotis, Charles Bawcom, An-Lin Cheng, Niaman Nazir, Catherine Martin, Andrea Ruff, Michael Sweat, Vincent Okoth

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Early infant diagnosis among human immunodeficiency virus (HIV)-exposed infants is a critical component of prevention of mother-to-child transmission programs. Barriers to early infant diagnosis include poor uptake, low retention at designated re-testing intervals, delayed test results, passive systems of communication, and poor linkage to treatment. This study will evaluate the HIV Infant Tracking System (HITSystem), an eHealth intervention that streamlines communication and accountability between the key early infant diagnosis stakeholders: HIV+ mothers and their HIV-exposed infants, healthcare providers, and central laboratory personnel. It is hypothesized that the HITSystem will significantly improve early infant diagnosis retention at 9 and 18 …

Nitric Oxide-Releasing Aspirin Suppresses Nf-Κb Signaling In Estrogen Receptor Negative Breast Cancer Cells In Vitro And In Vivo, Niharika Nath, Mitali Chattopadhyay, Deborah B. Rodes, Anna Nazarenko, Ravinder Kodela, Khosrow Kashfi

Publications and Research

Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model …

Mir-21 In Extracellular Vesicles Leads To Neurotoxicity Via Tlr7 Signaling In Siv Neurological Disease., Sowmya V. Yelamanchili, Benjamin G. Lamberty, Deborah A. Rennard, Brenda M. Morsey, Colleen G. Hochfelder, Brittney M. Meays, Efrat Levy, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Recent studies have found that extracellular vesicles (EVs) play an important role in normal and disease processes. In the present study, we isolated and characterized EVs from the brains of rhesus macaques, both with and without simian immunodeficiency virus (SIV) induced central nervous system (CNS) disease. Small RNA sequencing revealed increased miR-21 levels in EVs from SIV encephalitic (SIVE) brains. In situ hybridization revealed increased miR-21 expression in neurons and macrophage/microglial cells/nodules during SIV induced CNS disease. In vitro culture of macrophages revealed that miR-21 is released into EVs and is neurotoxic when compared to EVs derived from miR-21-/- knockout …

Burn Injury Alters The Intestinal Microbiome And Increases Gut Permeability And Bacterial Translocation, Zachary M. Earley, Suhail Akhtar, Stefan J. Green, Ankur Naqib, Omair Khan '15, Abigail R. Cannon, Adam M. Hammer, Niya L. Morris, Xiaoling Li, Joshua M. Eberhardt, Richard L. Gamelli, Richard H. Kennedy, Mashkoor A. Choudhry

Student Publications & Research

Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces …

Selective Involvement Of The Checkpoint Regulator Vista In Suppression Of B-Cell, But Not T-Cell, Responsiveness By Monocytic Myeloid-Derived Suppressor Cells From Mice Infected With An Immunodeficiency-Causing Retrovirus, Kathy A. Green, Li Wang, Randolph J. Noelle, William R. Green

Dartmouth Scholarship

Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ~50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness.

Full-Range Public Health Leadership, Part 2: Qualitative Analysis And Synthesis, Erik L. Carlton, James W. Holsinger Jr., Martha C. Riddell, Heather Bush

Preventive Medicine and Environmental Health Faculty Publications

Public health leadership is an important topic in the era of U.S. health reform, population health innovation, and health system transformation. This study utilized the full-range leadership model in order to examine the public health leadership. We sought to understand local public health leadership from the perspective of local health department leaders and those who work with and for them. Public health leadership was explored through interviews and focus groups with directors (n = 4) and staff (n = 33) from local health departments. Qualitative analytic methods included reflexive journals, code-recode procedures, and member checking, with analysis facilitated …

Characteristics Of A Novel Treatment System For Linear Accelerator–Based Stereotactic Radiosurgery, Ning Wen, Haisen Li, Kwang Song, Karen Chin-Snyder, Yujiao Qin, Jinkoo Kim, Maria Bellon, Misbah Gulam, Stephen Gardner, Anthony Doemer, Suneetha Devpura, James Gordon, Indrin Cherry, Farzan Siddiqui, Munther Ajlouni, Robert Pompa, Zane Hammoud, Michael Simoff, Steven Kalkanis, Benjamin Movsas, M. Salim Siddiqui

Internal Medicine Faculty Publications

The purpose of this study is to characterize the dosimetric properties and accuracy of a novel treatment platform (Edge radiosurgery system) for localizing and treating patients with frameless, image-guided stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various components of the system, such as a comprehensive assessment of the dosimetric properties of the flattening filter-free (FFF) beams for both high definition (HD120) MLC and conical cone-based treatment, positioning accuracy and beam attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test, and integrated end-to-end accuracy tests, have been performed. The end-to-end test of the …

Inferring Interaction Type In Gene Regulatory Networks Using Co-Expression Data, Pegah Khosravi, Vahid H. Gazestani, Leila Pirhaji, Brian Law, Mehdi Sadeghi, Bahram Goliaei, Gary D. Bader

Publications and Research

Background

Knowledge of interaction types in biological networks is important for understanding the functional organization of the cell. Currently information-based approaches are widely used for inferring gene regulatory interactions from genomics data, such as gene expression profiles; however, these approaches do not provide evidence about the regulation type (positive or negative sign) of the interaction.

Results

This paper describes a novel algorithm, “Signing of Regulatory Networks” (SIREN), which can infer the regulatory type of interactions in a known gene regulatory network (GRN) given corresponding genome-wide gene expression data. To assess our new approach, we applied it to three different benchmark …

Neuronal Interferon Signaling Is Required For Protection Against Herpes Simplex Virus Replication And Pathogenesis, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Interferon (IFN) responses are critical for controlling herpes simplex virus 1 (HSV-1). The importance of neuronal IFN signaling in controlling acute and latent HSV-1 infection remains unclear. Compartmentalized neuron cultures revealed that mature sensory neurons respond to IFNβ at both the axon and cell body through distinct mechanisms, resulting in control of HSV-1. Mice specifically lacking neural IFN signaling succumbed rapidly to HSV-1 corneal infection, demonstrating that IFN responses of the immune system and non-neuronal tissues are insufficient to confer survival following virus challenge. Furthermore, neurovirulence was restored to an HSV strain lacking the IFN-modulating gene, γ34.5, despite its expected …

Toll-Like Receptors And Dectin-1, A C-Type Lectin Receptor, Trigger Divergent Functions In Cns Macrophages, John C. Gensel, Yan Wang, Zhen Guan, Kyle A. Beckwith, Kaitlyn J. Braun, Ping Wei, Dana M. Mctigue, Phillip G. Popovich

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid …

Editorial: Phosphoinositides And Their Phosphatases: Linking Electrical And Chemical Signals In Biological Processes, Susy C. Kohout, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

No abstract provided.

Nurse Driven Volume Based Feeding, Megan Chernega Bsn, Rn, Jillian Michael Bsn, Rn, Maciej Nawracaj Bsn, Rn

Patient Care Services / Nursing

No abstract provided.

Critical Burn Patient Skin Breakdown Prevention Protocol, Kara Kohler Bsn, Rn, Kara Perini Bsn, Rn

Patient Care Services / Nursing

No abstract provided.

Empowerment Of Graduate Nurses, Madison Gumpper Bsn, Rn, Rachel Hughes Bsn, Rn, Yekaterina Korotchuk Bsn, Rn, Ashley Otto Bsn, Rn

Patient Care Services / Nursing

No abstract provided.