Medicine and Health Sciences Commons^™

Comparison Of Response To 2-Years' Growth Hormone Treatment In Children With Isolated Growth Hormone Deficiency, Born Small For Gestational Age, Idiopathic Short Stature, Or Multiple Pituitary Hormone Deficiency: Combined Results From Two Large Observational Studies., Peter A Lee, Lars Sävendahl, Isabelle Oliver, Maithé Tauber, Oliver Blankenstein, Judith Ross, Marta Snajderova, Viatcheslav Rakov, Birgitte Tønnes Pedersen, Henrik Thybo Christesen

Department of Pediatrics Faculty Papers

BACKGROUND: Few studies have compared the response to growth hormone (GH) treatment between indications such as isolated growth hormone deficiency (IGHD), born small for gestational age (SGA), idiopathic short stature (ISS), and multiple pituitary hormone deficiency (MPHD). The aim of this analysis of data, collected from two large ongoing observational outcome studies, was to evaluate growth and insulin-like growth factor-I (IGF-I) response data for children of short stature with IGHD, MPHD, SGA, or ISS following two years of treatment with the recombinant GH product Norditropin® (Novo Nordisk A/S, Bagsværd, Denmark).

METHODS: Analysis of auxologic data from two ongoing prospective observational …

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 …

Treatment Options For Vasomotor Symptoms In Menopause: Focus On Desvenlafaxine., Elena M Umland, Laura Falconieri

College of Pharmacy Faculty Papers

Vasomotor symptoms (VMS), including hot flashes and night sweats, occur in as many as 68.5% of women as a result of menopause. While the median duration of these symptoms is 4 years, approximately 10% of women continue to experience VMS as many as 12 years after their final menstrual period. As such, VMS have a significant impact on the quality of life and overall physical health of women experiencing VMS, leading to their pursuance of treatment to alleviate these symptoms. Management of VMS includes lifestyle modifications, some herbal and vitamin supplements, hormonal therapies including estrogen and tibolone, and nonhormonal therapies …

Aisr Connections Fall 2012 (2012-2013 Orientation Issue), Aisr

The AC's Research Support Newsletter (Formerly AISR Connections)

Yearly publication of AISR Connections for 2012-2013.

Issue includes:

• Scott Library renovations
• New library catalog
• Clinical Resources Support
• Jefferson Digital Commons

The mission of Academic & Instructional Support & Resources (AISR) is to strengthen the educational, research and clinical activities of the Jefferson community by providing knowledge-based information, developing and managing instructional technologies and content, supporting and managing campus classroom technologies, and providing leadership in scholarly communication and publishing.

Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang

Department of Cancer Biology Faculty Papers

Altered lipid metabolism underlies several major human diseases, including obesity and type 2 diabetes. However, lipid metabolism pathophysiology remains poorly understood at the molecular level. Insulin is the primary stimulator of hepatic lipogenesis through activation of the SREBP-1c transcription factor. Here we identified cyclin-dependent kinase 8 (CDK8) and its regulatory partner cyclin C (CycC) as negative regulators of the lipogenic pathway in Drosophila, mammalian hepatocytes, and mouse liver. The inhibitory effect of CDK8 and CycC on de novo lipogenesis was mediated through CDK8 phosphorylation of nuclear SREBP-1c at a conserved threonine residue. Phosphorylation by CDK8 enhanced SREBP-1c ubiquitination and protein …

Colon Cancer Vaccine Study: Development Of A Decision Support Intervention For Study Recruitment, Evelyn Stevens

Summer Training Program in Cancer Immunotherapy

Focus: Identify factors that may influence trial participation.

28 PowerPoint slides

Colorectal Cancer Vaccine Clinical Trial: Internship Experience In Population Science, Shannel Ross, Baudelio Gutierrez, Jr.

Summer Training Program in Cancer Immunotherapy

Internship objectives:

1. Review the literature to identify factors that are likely to influence clinical trail participation.

2. Pretest vaccine trail scenario.

3. Conduct mock decision counseling session.

34 PowerPoint slides

Analytic Lymph Node Number Establishes Staging Accuracy By Occult Tumor Burden In Colorectal Cancer., Terry Hyslop, David S. Weinberg, Stephanie Schulz, Alan Barkun, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden.

METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category …

Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?, Fabian A. Mendoza, Md, Lynette L Keyes-Elstein, Sergio A. Jimenez

Scleroderma Center Faculty Papers

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should …

Two-Compartment Tumor Metabolism: Autophagy In The Tumor Microenvironment And Oxidative Mitochondrial Metabolism (Oxphos) In Cancer Cells., Ahmed F Salem, Diana Whitaker-Menezes, Zhao Lin, Ubaldo E. Martinez-Outshoorn, Herbert B Tanowitz, Mazhar Salim Al-Zoubi, Anthony Howell, Richard Pestell, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Previously, we proposed a new paradigm to explain the compartment-specific role of autophagy in tumor metabolism. In this model, autophagy and mitochondrial dysfunction in the tumor stroma promotes cellular catabolism, which results in the production of recycled nutrients. These chemical building blocks and high-energy "fuels" would then drive the anabolic growth of tumors, via autophagy resistance and oxidative mitochondrial metabolism in cancer cells. We have termed this new form of stromal-epithelial metabolic coupling: "two-compartment tumor metabolism." Here, we stringently tested this energy-transfer hypothesis, by genetically creating (1) constitutively autophagic fibroblasts, with mitochondrial dysfunction or (2) autophagy-resistant cancer cells, with increased …

Malignant Peripheral Nerve Sheath Tumor (Mpnst): An Overview With Emphasis On Pathology, Imaging And Management Strategies., Timothy C. Beer

Jefferson Hospital Staff Papers and Presentations

MPNSTs are rare malignancies that are classically associated with pre-existing plexiform neurofibromas in neurofibromatosis type 1 (NF-1) patients, but also occur in association with radiation as well as sporadically in patients with no known risk factors. The typical presentation of sporadic MPNST is a new painless enlarging mass. The typical presentation of MPNST in an NF-1 patient is rapid enlargement or new onset of pain associated with a pre-existing plexiform neurofibroma. Although both MPNST and benign neurofibromas share in common the absence of neurofibromin function due to loss of both NF-1 alleles, malignant transformation to MPNST requires several additional aberrations, …

B-Vitamin Deficiency In Patients Treated With Antiepileptic Drugs., Scott Mintzer, Christopher T Skidmore, Michael R Sperling

Department of Neurology Faculty Papers

Enzyme-inducing antiepileptic drugs (AEDs) produce many alterations in metabolism, including vitamin levels. Whether they produce clinically relevant deficiency of B vitamins has rarely been assessed. We obtained B-vitamin levels in patients who were being converted from an inducing AED (phenytoin or carbamazepine) to a non-inducing AED (levetiracetam, lamotrigine, or topiramate), with measurements both before and ≥ 6 weeks after the switch. A group of normal subjects underwent the same studies. Neither folate nor B12 deficiency was seen in any patient. Vitamin B6 deficiency was found in 16/33 patients (48%) taking inducers, compared to 1/11 controls (9%; p=0.031). After switch to …

A Refractive Surgery Candidate With Optic Nerve Head Cupping., Ivan Goldberg, L Jay Katz, Kaweh Mansouri, Mohammad Pakravan, Shahin Yazdani

Wills Eye Hospital Papers

No abstract provided.

The Use Of Epoetin-Α In Revision Knee Arthroplasty., Lawrence A Delasotta, Ashwin V Rangavajjula, Michael L Frank, Jamie L Blair, Fabio R Orozco, Alvin C Ong

Department of Surgery Faculty Papers

Introduction. To evaluate the efficacy of epoetin-α prior to revision total knee arthroplasty, we hypothesized that epoetin-α will reduce blood transfusion. Methods. Eighty-one patients were compared in this retrospective review; twenty-eight patients received our dosing regimen. All patients were mildly anemic. Epoetin-α to control (1 : 2) patient matching occurred so that one of two attending surgeons, gender, BMI, complexity of surgery, ASA score, and age were similar between groups. The clinical triggers for blood transfusion during or after the procedure were determined based on peri- and postoperative hemoglobin levels, ASA score, and/or clinical symptoms consistent with anemia. Blood salvage …

Department Of Radiology-Annual Executive Summary Report-July 1, 2011 To June 30, 2012, Vijay M. Rao, Md

Department of Radiology Administrative Documents and Reports

93 page Department of Radiology Annual Executive Summary Report, July 1, 2011 to June 30, 2012, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.

Table of Contents

Chairman, Vice Chairmen 1

Divisions and Directors 1

Committees and Chairmen 1

Radiology Department Faculty Rank 2

Faculty with Secondary Appointments 3

Clinical Divisions 4

Radiology Residents and Fellows 5

Department Organizational Chart 6

Department Administration Chart 7

State of the Department 8

Appendix I: Publications

Journal Articles 23

Books and Book Chapters 31

Abstracts 35

Appendix II: Formal Scientific Presentations 50

Appendix III: Honors, Editorial Activities, Service to Regional or National Organizations …

C1q/Tumor Necrosis Factor-Related Protein-3, A Newly Identified Adipokine, Is A Novel Antiapoptotic, Proangiogenic, And Cardioprotective Molecule In The Ischemic Mouse Heart., Wei Yi, Yang Sun, Yuexing Yuan, Wayne Bond Lau, Qijun Zheng, Xiaoliang Wang, Yajing Wang, Xiying Shang, Erhe Gao, Walter J Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

BACKGROUND: Obesity and diabetes mellitus adversely affect postischemic heart remodeling via incompletely understood mechanisms. C1q/tumor necrosis factor-related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation, similar to adiponectin. The aim of the present study was to determine whether CTRP3 may regulate postischemic cardiac remodeling and cardiac dysfunction, and, if so, to elucidate the underlying mechanisms.

METHODS AND RESULTS: Male adult mice were subjected to myocardial infarction (MI) via left anterior descending coronary artery occlusion. Both the effect of MI on endogenous CTRP3 expression/production and the effect of exogenous CTRP3 (adenovirus or recombinant CTRP3) replenishment on MI injury …

What's New In Spine Surgery., Keith H Bridwell, Paul A Anderson, Scott D Boden, Alexander R Vaccaro, Jeffrey C Wang

Rothman Institute Papers

No abstract provided.

Anatomical Relationships Of The Anterior Blood Vessels To The Lower Lumbar Intervertebral Discs: Analysis Based On Magnetic Resonance Imaging Of Patients In The Prone Position., Alexander R Vaccaro, Christopher K Kepler, Jeffrey A Rihn, Hidekazu Suzuki, John K Ratliff, James S Harrop, William B Morrison, Worawat Limthongkul, Todd J Albert

Rothman Institute Papers

BACKGROUND: Intra-abdominal vascular injuries are rare during posterior lumbar spinal surgery, but they can result in major morbidity or mortality when they do occur. We are aware of no prior studies that have used prone patient positioning during magnetic resonance imaging for the purpose of characterizing the retroperitoneal iliac vasculature with respect to the intervertebral disc. The purpose of this study was to define the vascular anatomy adjacent to the lower lumbar spine with use of supine and prone magnetic resonance imaging.

METHODS: A prospective observational study included thirty patients without spinal abnormality who underwent supine and prone magnetic resonance …

Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed …

Ctgf Drives Autophagy, Glycolysis And Senescence In Cancer-Associated Fibroblasts Via Hif1 Activation, Metabolically Promoting Tumor Growth., Claudia Capparelli, Diana Whitaker-Menezes, Carmela Guido, Renee Balliet, Timothy G Pestell, Anthony Howell, Sharon Sneddon, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Michael P. Lisanti, Federica Sotgia

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Previous studies have demonstrated that loss of caveolin-1 (Cav-1) in stromal cells drives the activation of the TGF-β signaling, with increased transcription of TGF-β target genes, such as connective tissue growth factor (CTGF). In addition, loss of stromal Cav-1 results in the metabolic reprogramming of cancer-associated fibroblasts, with the induction of autophagy and glycolysis. However, it remains unknown if activation of the TGF-β / CTGF pathway regulates the metabolism of cancer-associated fibroblasts. Therefore, we investigated whether CTGF modulates metabolism in the tumor microenvironment. For this purpose, CTGF was overexpressed in normal human fibroblasts or MDA-MB-231 breast cancer cells. Overexpression of …

Engrailed Cooperates Directly With Extradenticle And Homothorax On A Distinct Class Of Homeodomain Binding Sites To Repress Sloppy Paired., Miki Fujioka, Brian Gebelein, Zenobia C Cofer, Richard S Mann, James B Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Even skipped (Eve) and Engrailed (En) are homeodomain-containing transcriptional repressors with similar DNA binding specificities that are sequentially expressed in Drosophila embryos. The sloppy-paired (slp) locus is a target of repression by both Eve and En. At blastoderm, Eve is expressed in 7 stripes that restrict the posterior border of slp stripes, allowing engrailed (en) gene expression to be initiated in odd-numbered parasegments. En, in turn, prevents expansion of slp stripes after Eve is turned off. Prior studies showed that the two tandem slp transcription units are regulated by cis-regulatory modules (CRMs) with activities that overlap in space and time. …

Molecular Mechanisms Of Endothelial To Mesenchymal Cell Transition (Endomt) In Experimentally Induced Fibrotic Diseases., Sonsoles Piera-Velazquez, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Several recent studies have demonstrated that endothelial to mesenchymal transition (EndoMT), a newly recognized type of cellular transdifferentiation may be an important source of myofibroblasts during the development of experimentally induced pulmonary, cardiac and kidney fibrosis. EndoMT is a complex biological process induced by members of the transforming growth factor (TGF-β) family of regulatory polypeptides in which endothelial cells adopt a mesenchymal or myofibroblastic phenotype acquiring motile and contractile properties and initiating expression of mesenchymal cell products such as α smooth muscle actin (α-SMA) and type I collagen. Although these experimental studies provide compelling evidence for the participation of EndoMT …

Sudden Cardiac Death With Clozapine And Lorazepam Combination, Sriram Ramaswamy, Susan J. Boust, Prizada S. Sattar, Subhash C. Bhatia, Frederick Petty

Jefferson Journal of Psychiatry

Objective: To report a case of sudden cardiac death in a patient taking a combination of clozapine and lorazepam.

Case summary: A 31-year-old white man with schizophrenia was found dead at his apartment. His medication regimen included clozapine 500 mg at bed time, lorazepam 0.5 mg three times daily and levothyroxine 75 mcg once a day. Autopsy studies revealed cardiac hypertrophy, pulmonary congestion and edema.

Discussion: Clozapine therapy may cause cardiomyopathy and reduction in heart rate variability (HRV) indices. Benzodiazepines can reduce vagal tone and increase sympathetic activity. This combination can have an enhanced potential for sudden cardiac death.

Conclusions: …

Using Transcranial Magnetic Stimulation (Tms) To Compare Cortical Excitability Among Depressed Patients, Sleep-Deprived Controls, And Rested Controls, Rajani Rajan, Paul A. Zarkowski, Pedro L. Delgado

Jefferson Journal of Psychiatry

Objective: To compare cortical excitability among sleep-deprived and rested controls, and depressed subjects.

Methods: 3 controls and 4 depressed patients (average HAM-D 19) wererecruited. Sleep-deprived controls were instructed to sleep <=4 hours the previous night. TMS-produced motor evoked potentials (MEPs) were measured before and after subjects engaged in sets of non-fatiguing manual exercise.

Results: Post-exercise MEP increased 71+1-19% for rested controls, 28+1-32% for sleep deprived controls, and 8+1-15% for depressed patients. This increase, "facilitation," was significantly greater in rested controls than in depressed patients (p=0.011). No significant difference in facilitation was found between sleep-deprived controls and depressed patients.

Conclusion: Sleep-deprivation may partially account for reduced cortical excitability in depressed patients.

Antidepressant Pharmacotherapy: Prescription Practices In Psychiatric Resident Care, Rachel Dew, W. Vaughn Mccall

Jefferson Journal of Psychiatry

Background: Research on treatment of depression has raised concerns regarding adequacy of medication trials and rationality of drug choice. Little data exists regarding pharmacotherapy by psychiatric residents. As practice habits begun in training will likely persist after graduation, examination of residents' antidepressant use may ultimately improve treatment by psychiatrists.

Methods: Charts of new patients presenting to the Wake Forest University Psychiatry Resident Clinic were reviewed. Survey was made of medications prescribed to 112 patients diagnosed with major depression, dysthymia, depressive disorder NOS, adjustment disorder with depressed mood, or bipolar disorder with a documented depression during the studied period. Drug choice …

The Duty To Warn/Protect Doctrine And Its Application In Pennsylvania, Clarence Watson

Jefferson Journal of Psychiatry

Despite the almost universal familiarity of mental health professionals with the Tarasoff case, many questions regarding its associated legal requirements often arise when evaluating potentially dangerous patients. The principles of the duty to warn/protect, while appearing nebulous at times, contain key concepts that the clinician must consider in the face of potential danger to third parties. This article reviews the landmark decision of the Tarasoff case and outlines its key concepts. In addition, given that state jurisdictions vary in treatment of Tarasoff-like cases, this article explores the Pennsylvania Supreme Court decision, Emerich v. Philadelphia Center for Human Development, Inc.

Editor's Note, Anika Vaughn-Cooke

Jefferson Journal of Psychiatry

No abstract provided.

Electroconvulsive Therapy: A Review Of Its Current Status, Tyler Kenning, Ranjnish Mago, Steven Huege, Kenneth Certa, Rodney Pelchat

Jefferson Journal of Psychiatry

This article presents an overview of the current knowledge and practice of ECT. It provides a brief history of the development of ECT followed by a discussion of the accepted indications for ECT in psychiatric practice, including major depression, bipolar disorder (mania and depression), and schizophrenia. Moreover, a description of the technique of performing ECT is given. Also examined are the use of ECT in medically ill patients and the risks associated with ECT. In conclusion, with the aid of advances in anesthesia and the delivery of ECT, electroconvulsive therapy is a safe and effective treatment of mood and psychotic …

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) …

Healthy Volunteer Registries And Ethical Research Principles, Erine A. Kupetsky-Rincon, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The dual enrolling of phase I volunteers is a potential risk to subjects. It can also distort study results, threaten study validity, and possibly cause harm to future patients. Existing subject registries differ in structure, funding, and governance. Although the choice of the ideal system is driven by the scope of the risk and the funding mechanism, and is ultimately a value judgment of freedom versus paternalism, none of the registries significantly impinges on the tenets of ethically based research.