Medicine and Health Sciences Commons^™

Anti-Mog Antibodies Are Frequently Associated With Steroid-Sensitive Recurrent Optic Neuritis., Konstantina Chalmoukou, Harry Alexopoulos, Sofia Akrivou, Panos Stathopoulos, Markus Reindl, Marinos C. Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Predicting The Laterality Of Temporal Lobe Epilepsy From Pet, Mri, And Dti: A Multimodal Study., Dorian Pustina, Brian Avants, Michael R Sperling, Richard Gorniak, Xiaosong He, Gaelle Eve Doucet, Paul Barnett, Ms, Scott Mintzer, Ashwini Sharan Md, Joseph I Tracy

Department of Neurology Faculty Papers

Pre-surgical evaluation of patients with temporal lobe epilepsy (TLE) relies on information obtained from multiple neuroimaging modalities. The relationship between modalities and their combined power in predicting the seizure focus is currently unknown. We investigated asymmetries from three different modalities, PET (glucose metabolism), MRI (cortical thickness), and diffusion tensor imaging (DTI; white matter anisotropy) in 28 left and 30 right TLE patients (LTLE and RTLE). Stepwise logistic regression models were built from each modality separately and from all three combined, while bootstrapped methods and split-sample validation verified the robustness of predictions. Among all multimodal asymmetries, three PET asymmetries formed the …

Adiporon, The First Orally Active Adiponectin Receptor Activator, Attenuates Postischemic Myocardial Apoptosis Through Both Ampk-Mediated And Ampk-Independent Signalings., Yanqing Zhang, Jianli Zhao, Rui Li, Wayne Bond Lau, Yue-Xing Yuan, Bin Liang, Rong Li, Er-He Gao, Walter J. Koch, Xin-Liang Ma, Ya-Jing Wang

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) is a cardioprotective molecule. Its reduction in diabetes exacerbates myocardial ischemia/reperfusion (MI/R) injury. Although APN administration in animals attenuates MI/R injury, multiple factors limit its clinical application. The current study investigated whether AdipoRon, the first orally active molecule that binds APN receptors, may protect the heart against MI/R injury, and if so, to delineate the involved mechanisms. Wild-type (WT), APN knockout (APN-KO), and cardiomyocyte specific-AMPK dominant negative (AMPK-DN) mice were treated with vehicle or AdipoRon (50 mg/kg, 10 min prior to MI) and subjected to MI/R (30 min/3-24 h). Compared with vehicle, oral administration of AdipoRon to WT …

Mechanisms Of Activation Of Nucleus Accumbens Neurons By Cocaine Via Sigma-1 Receptor-Inositol 1,4,5-Trisphosphate-Transient Receptor Potential Canonical Channel Pathways., Jeffrey L. Barr, Elena Deliu, Gabriela Cristina Brailoiu, Pingwei Zhao, Guang Yan, Mary E. Abood, Ellen M. Unterwald, Eugen Brailoiu

College of Pharmacy Faculty Papers

Cocaine promotes addictive behavior primarily by blocking the dopamine transporter, thus increasing dopamine transmission in the nucleus accumbens (nAcc); however, additional mechanisms are continually emerging. Sigma-1 receptors (σ1Rs) are known targets for cocaine, yet the mechanisms underlying σ1R-mediated effects of cocaine are incompletely understood. The present study examined direct effects of cocaine on dissociated nAcc neurons expressing phosphatidylinositol-linked D1 receptors. Endoplasmic reticulum-located σ1Rs and inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) were targeted using intracellular microinjection. IP3 microinjection robustly elevated intracellular Ca(2+) concentration, [Ca(2+)]i. While cocaine alone was devoid of an effect, the IP3-induced response was σ1R-dependently enhanced by cocaine co-injection. Likewise, …

The Rise And Fall Of Poly(Adp-Ribose): An Enzymatic Perspective., John M. Pascal, Tom Ellenberger

Department of Biochemistry and Molecular Biology Faculty Papers

Human cells respond to DNA damage with an acute and transient burst in production of poly(ADP-ribose), a posttranslational modification that expedites damage repair and plays a pivotal role in cell fate decisions. Poly(ADP-ribose) polymerases (PARPs) and glycohydrolase (PARG) are the key set of enzymes that orchestrate the rise and fall in cellular levels of poly(ADP-ribose). In this perspective, we focus on recent structural and mechanistic insights into the enzymes involved in poly(ADP-ribose) production and turnover, and we highlight important questions that remain to be answered.

Optimization Of Chest Wall Hyperthermia Treatment Using A Virtual Human Chest Model, Dario B. Rodrigues, Mark D. Hurwitz, Paolo F. Maccarini, Paul R. Stauffer

Department of Radiation Oncology Faculty Papers

This work explores different coupling configurations (direct contact, air and water coupling) between a single 915 MHz waveguide applicator and human tissue in the setting of chest wall recurrence (CWR) of breast cancer. The objective is to treat chest wall tumours with microwave hyperthermia, while avoiding hot spots in critical areas such as scars and ribs. The best coupling configuration was a customized 24×29 cm water bolus developed by our team. It helps the applicator deliver an effective field size of 268 cm2 at 1 cm depth and a penetration depth of 2-3 cm. Water bolus thickness can be adjusted …

The Effect Of Aspirin On Bleeding And Transfusion In Contemporary Cardiac Surgery., Jordan E Goldhammer, Gregary D. Marhefka, Constantine Daskalakis, Mark W Berguson, John E Bowen, James Diehl, Jianzhong Sun

Department of Medicine Faculty Papers

OBJECTIVE: Despite evidence that preoperative aspirin improves outcomes in cardiac surgery, recommendations for aspirin use are inconsistent due to aspirin's anti-platelet effect and concern for bleeding. The purpose of this study was to investigate preoperative aspirin use and its effect on bleeding and transfusion in cardiac surgery.

METHODS: This retrospective study involved consecutive patients (n=1571) who underwent CABG, valve, or combined CABG and valve surgery at a single center between March 2007 and July 2012. Of all patients, 728 met the inclusion criteria and were divided into two groups: those using (n=603) or not using (n=125) aspirin within 5 days …

Stratification Of A Population Of Intracranial Aneurysms Using Blood Flow Metrics., Rohini Retarekar, Manasi Ramachandran, Benjamin Berkowitz, Robert E. Harbaugh, David Hasan, Robert H. Rosenwasswer, Christopher S. Ogilvy, Madhavan L. Raghavan

Department of Neurosurgery Faculty Papers

Indices of the intra-aneurysm hemodynamic environment have been proposed as potentially indicative of their longitudinal outcome. To be useful, the indices need to be used to stratify large study populations and tested against known outcomes. The first objective was to compile the diverse hemodynamic indices reported in the literature. Furthermore, as morphology is often the only patient-specific information available in large population studies, the second objective was to assess how the ranking of aneurysms in a population is affected by the use of steady flow simulation as an approximation to pulsatile flow simulation, even though the former is clearly non-physiological. …

Implementation Of Resident-Driven, Quality-Based Improvement Projects At A Single Academic Institution: Resident Value And Institutional Outcomes, Kathleen M. Lamb, Md, Randi E. Altmark, Rn, Bsn, Cnor, Adam P. Johnson, Md, Mph, Richard A. Burkhart, Md, Karen A. Chojnacki, Md, Facs, Scott W. Cowan, Md, Facs

Department of Surgery Faculty Papers

Significance

Finding a viable and sustainable methodology for resident involvement in surgical quality improvement is not only a GME requirement, but also imperative to patient care.

Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition In Inflammatory Breast Cancer Cells., Evan N Cohen, Hui Gao, Simone Anfossi, Michal Mego, Neelima G Reddy, Bisrat Debeb, Antonio Giordano, Sanda Tin, Qiong Wu, Raul J Garza, Massimo Cristofanilli, Sendurai A Mani, Denise A Croix, Naoto T Ueno, Wendy A Woodward, Raja Luthra, Savitri Krishnamurthy, James M Reuben

Department of Medical Oncology Faculty Papers

Inflammatory breast cancer (IBC) is the most insidious form of locally advanced breast cancer; about a third of patients have distant metastasis at initial staging. Emerging evidence suggests that host factors in the tumor microenvironment may interact with underlying IBC cells to make them aggressive. It is unknown whether immune cells associated to the IBC microenvironment play a role in this scenario to transiently promote epithelial to mesenchymal transition (EMT) in these cells. We hypothesized that soluble factors secreted by activated immune cells can induce an EMT in IBC and thus promote metastasis. In a pilot study of 16 breast …

Inflammatory Muscle Diseases., Marinos Dalakas

Department of Medicine Faculty Papers

No abstract provided.

Jdc Editor A 2015 Ir All-Star, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

JDC Editor Dan Kipnis has been recognized as a “2015 IR All-Star” in the DC Telegraph, a blog of the bepress Digital Commons community, for his outstanding promotion of the Jefferson Digital Commons. The JDC is Thomas Jefferson University’s institutional repository designed to enhance the visibility of Jefferson scholarship and to promote Jefferson authors. With more than 10,000 assets to date, the JDC recently exceeded 2 million downloads.

Sex Hormone-Dependent Trna Halves Enhance Cell Proliferation In Breast And Prostate Cancers., Shozo Honda, Phillipe Loher, Megumi Shigematsu, Juan P. Palazzo, Ryusuke Suzuki, Issei Imoto, Isidore Rigoutsos, Yohei Kirino, Phd

Computational Medicine Center Faculty Papers

Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER(-) breast cancer, AR(-) prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. …

Nf-Κb Regulation Of C-Flip Promotes Tnfα-Mediated Raf Inhibitor Resistance In Melanoma., Yongping Shao, Kaitlyn Le, Hanyin Cheng, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Targeted inhibitors elicit heterogeneous clinical responses in genetically stratified groups of patients. Although most studies focus on tumor intrinsic properties, factors in the tumor microenvironment were recently found to modulate the response to inhibitors. Here, we show that in cutaneous BRAF V600E melanoma, the cytokine tumor necrosis factor-α (TNFα) blocks RAF inhibitor-induced apoptosis via activation of NF-κB. Several NF-κB-dependent factors are upregulated following TNFα and RAF inhibitor treatment. Of these factors, we show that death receptor inhibitor cellular caspase 8 (FLICE)-like inhibitory protein (c-FLIP) is required for TNFα-induced protection against RAF inhibitor. Overexpression of c-FLIP_S or c-FLIP_L isoform decreased RAF …

Arthroscopic Transosseous Rotator Cuff Repair: A Prospective Study On Cost Savings, Surgical Time, And Outcomes, Luke S. Austin, Eric M. Black, Nicholas J. Lombardi, Matthew D. Pepe, Mark D. Lazarus

Rothman Institute Papers

Objectives: Health expenditures in the United States are outpacing national income, and affordability has become a major policy issue. Over 500,000 rotator cuff repairs (RCR) are performed annually in the United States making RCR a potential source of cost savings. Arthroscopic trans-osseous equivalent (TOE) repair using a double row of anchors has shown superior biomechanical strength compared to other techniques, but at a higher cost. The arthroscopic transosseous (TO) repair is a novel technique allowing arthroscopic rotator cuff repair to be performed without suture anchors. Arthroscopic TO repair may be a means to provide similarly excellent patient outcomes while lowering …

Achilles Tendons From Decorin- And Biglycan-Null Mouse Models Have Inferior Mechanical And Structural Properties Predicted By An Image-Based Empirical Damage Model., Joshua A. Gordon, Benjamin R. Freedman, Andrey Zuskov, Renato V. Iozzo, David E. Birk, Louis J. Soslowsky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Achilles tendons are a common source of pain and injury, and their pathology may originate from aberrant structure function relationships. Small leucine rich proteoglycans (SLRPs) influence mechanical and structural properties in a tendon-specific manner. However, their roles in the Achilles tendon have not been defined. The objective of this study was to evaluate the mechanical and structural differences observed in mouse Achilles tendons lacking class I SLRPs; either decorin or biglycan. In addition, empirical modeling techniques based on mechanical and image-based measures were employed. Achilles tendons from decorin-null (Dcn(-/-)) and biglycan-null (Bgn(-/-)) C57BL/6 female mice (N=102) were used. Each tendon …

Dna-Pkcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression And Metastasis., Jonathan F Goodwin, Vishal Kothari, Justin M Drake, Shuang Zhao, Emanuela Dylgjeri, Jeffry L. Dean, Matthew J. Schiewer, Christopher Mcnair, Jennifer K. Jones, Alvaro Aytes, Michael S. Magee, Adam E. Snook, Ziqi Zhu, Robert Den, Ruth C. Birbe, Leonard G. Gomella, Nicholas A. Graham, Ajay A. Vashisht, James A. Wohlschlegel, Thomas G. Graeber, R. Jeffrey Karnes, Mandeep Takhar, Elai Davicioni, Scott A. Tomlins, Cory Abate-Shen, Nima Sharifi, Owen N. Witte, Felix Y. Feng, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver …

Dumbbell-Pcr: A Method To Quantify Specific Small Rna Variants With A Single Nucleotide Resolution At Terminal Sequences., Shozo Honda, Yohei Kirino

Computational Medicine Center Faculty Papers

Recent advances in next-generation sequencing technologies have revealed that cellular functional RNAs are not always expressed as single entities with fixed terminal sequences but as multiple isoforms bearing complex heterogeneity in both length and terminal sequences, such as isomiRs, the isoforms of microRNAs. Unraveling the biogenesis and biological significance of heterogenetic RNA expression requires distinctive analysis of each RNA variant. Here, we report the development of dumbbell PCR (Db-PCR), an efficient and convenient method to distinctively quantify a specific individual small RNA variant. In Db-PCR, 5'- and 3'-stem-loop adapters are specifically hybridized and ligated to the 5'- and 3'-ends of …

Download Entire Issue Of The Medicine Forum, Volume 15, 2013-2014

The Medicine Forum

Download entire issue of The Medicine Forum, Volume 15, 2013-2014

Stay, Jennifer Alloo Hong, Md

The Medicine Forum

As an intern, I thought of myself as the member of the team who gets the things done. I took pride in prioritizing my long list of tasks and efficiently working through each item. I spent most of my time at the computer, on the phone, in front of the chart, or in a consultant’s office. My time with patients was so limited that I grew more comfortable thinking about their medical problems away from their bedside.

Swyer-James-Mcleod Syndrome, Esther Molnar, Md, Arun Matthew, Md

The Medicine Forum

Admission chest x-ray of an 81 year-old man admitted to the hospital for atrial fibrillation with rapid ventricular response is shown in Figure 1. The chest x-ray shows a unilateral hyperlucent lung, with paucity of peripheral vessels and decreased lung volume. Differential diagnosis for unilateral hyperlucent lung includes Swyer-James-McLeod syndrome (SJMS), centrilobular emphysema, allergic bronchopulmonary aspergillosis, congenital lobar over inflation, bronchial atresia and congenital interruption of pulmonary artery.1 High resolution CT imaging confirmed the diagnosis of SJMS in this patient.

Pyoderma Gangrenosum Associated With Acute Myelogenous Leukemia, Lekha Mikkilineni, Md, Aishah Ali, Md

The Medicine Forum

A 20-year-old man presented with a non-healing ulcer on the dorsum of the left foot that initially appeared after the patient fell and hit his left foot on the edge of a door. An ulcer had formed and grown in size over the past several weeks after repeated physical insults and despite home wound care, as seen in Figure 1. Additionally, the patient had a non-healing ulcer inferior to his left knee. He had a notable past medical history of acute myelogenous leukemia (AML) in remission after a haploidentical stem cell transplant, uncontrolled diabetes type 1, and graft-versus-host disease of …

Tb, Or Not Tb?, Michael A. Valentino, Md, Phd

The Medicine Forum

The patient is a 43-year-old African American male with a past medical history of hypertension, hyperlipidemia, and chronic low back pain who presented to the ER for worsening dyspnea and a 30-lb weight loss over the past 3 months. He also reported a nonproductive cough over this period of time as well as an eruption of small ~1cm flesh-colored nodules on his extremities and trunk. He denied any fevers, chills, or night sweats. In the ER, he had a chest x-ray performed (Figure 1) which showed diffuse centrilobular nodules visualized throughout the lung fields in a miliary pattern. He subsequently …

Technique For Safe Placement Of A Dobhoff Tube Without A Cortrak® Machine, Jon Chao, Md, Jennifer Alloo Hong, Md

The Medicine Forum

A 58 year old female with a history of end stage renal disease on hemodialysis, insulin dependent diabetes mellitus, ischemic cardiomyopathy, and adrenal insufficiency, presented from home with altered mental status and hypotension. She developed refractory hypotension requiring vasopressors and was admitted to the medical ICU for management of septic shock due to bacterial peritonitis. She was intubated and had an oro-gastric tube placed for enteral nutrition. However, significantly elevated gastric residuals developed secondary to delayed gastric emptying. We decided to place a post-pyloric Dobhoff tube as an alternative gastric access to continue enteral feeding. Since a Cortrak machine (an …

A Case Of Body Packing: Internal Smuggling Of Illicit Drugs, Michael A. Valentino, Md, Phd

The Medicine Forum

The patient is a 27-year old Hispanic female who was brought to the ER from the airport by the Drug Enforcement Agency (DEA) on suspicion of “body packing” (illicit drug smuggling via ingestion). An abdominal X-ray (Figures 1a,b) was obtained in the ER which showed multiple radiopaque foreign bodies which were uniform in size measuring 5 cm x 2 cm throughout her colon. The patient then admitted to ingesting numerous heroin pellets. She subsequently had a CT Abdomen/Pelvis performed (Figure 2) which again showed numerous tubular radiopaque foreign bodies throughout the gastrointestinal tract. She was admitted to the medical intensive …

A Case Of Fanconi’S Syndrome In A Patient With Hiv, Mariam Kabir, Md, Phd, Christopher Miller, Md, Rakesh Gulati, Md, Mrcp, William R. Short, Md, Mph

The Medicine Forum

Introduction

Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue reverse transcriptase inhibitor (NtRTI), which blocks reverse transcriptase, an enzyme found in HIV. Since its approval for use in HIV by the FDA in 2001, it has contributed to effective treatment in numerous patients. The most common side effects include nausea, vomiting, diarrhea, asthenia, abdominal pain and hepatotoxicity. A less common side effect is nephrotoxicity leading to Fanconi’s syndrome. Here is an interesting case of Fanconi’s Syndrome caused by Tenofovir.

Case

A 50-year-old Caucasian female with a past medical history of HIV and Hepatitis C presented to the Emergency Department with …

A Case Of Septic Portal Vein Thrombosis (Pylephlebitis), Erin Carnish, Md, Andrew Garrett, Md, Mary Slome, Ms1

The Medicine Forum

INTRODUCTION

Pylephlebitis, defined as suppurative thrombosis of the portal vein often associated with bacteremia, is a rare and serious complication of intra-abdominal infections. Prior to antibiotics, the mortality rate of this disease approached 100%.1 The veins adjacent to the infection are the first to be involved, with later spread to the portal vein and possibly the mesenteric and splenic veins.2-3 Extension into the mesenteric veins can lead to bowel necrosis and increased morbidity and mortality.2-4

CASE PRESENTATION

A 63-year old male with a history of hypertension presented to the emergency department with one week of progressively worsening malaise, chills, severe …

Hepatitis C Therapy: Serendipitous Successes, Apeksha Shah, Md, Jonathan Fenkel, Md

The Medicine Forum

Introduction

Hepatitis C virus (HCV) infection is a growing epidemic worldwide, with about 170 million cases reported by 2011.1 New therapies have been introduced to the market, but the prior mainstay of therapy involves pegylated interferon-alpha (IFN) along with ribavirin (RBV).2 Treatment with the first generation direct-acting antiviral agent-containing regimens consisted of at least 24 weeks of therapy, with the goal of sustained viral response (SVR) – no detectable virus 24 weeks after treatment is completed. We report two cases in which therapy was terminated early due to the developed of severe infection, yet the patients still achieved SVR.

Case …

A Case Of Complete Heart Block Secondary To Anca-Associated Vasculitis, Krista Lim-Hing, Md

The Medicine Forum

INTRODUCTION

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are systemic autoimmune diseases that often present as non-specific prodromal symptoms such as fever, fatigue, headache, and weight loss.1 With modern treatment, the disease has changed from being universally fatal to being treatable. It can have a chronic relapsing and remitting course. Therefore, early diagnosis is necessary.2,3

CASE PRESENTATION

A 53-year-old male with a past medical history of chronic sinusitis and some epistaxis needing multiple courses of antibiotics and steroids, was admitted after being diagnosed with high-grade heart block at another institution. He was found to have a heart rate of 26 and …

An Unusual Atrial Mass: A Case Study, David F. Reilly, Bs, Christina Lindenmeyer, Md

The Medicine Forum

BACKGROUND

This case highlights the evolution of a broad differential diagnosis when presented with a rare and diagnostically enigmatic clinical finding.