Medicine and Health Sciences Commons^™

Isosorbide Mononitrate In Heart Failure With Preserved Ejection Fraction., Margaret M. Redfield, Kevin J. Anstrom, James A. Levine, Gabe A. Koepp, Barry A. Borlaug, Horng H. Chen, Martin M. Lewinter, Susan M. Joseph, Sanjiv J. Shah, Marc J. Semigran, G. Michael Felker, Robert T. Cole, Gordon R. Reeves, Ryan J. Tedford, W.H. Wilson Tang, Steven E. Mcnulty, Eric J. Velazquez, Monica R Shah, Eugene Braunwald

Division of Cardiology Faculty Papers

BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients.

METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer …

Low-Dose Versus Standard-Dose Tissue Plasminogen Activator In Acute Ischemic Stroke In Asian Populations: A Meta-Analysis., Meng-Dong Liu, Wei-Dong Ning, Ren-Cong Wang, Wei Chen, Yang Yang, Yan Lin, Da-Hai Hu, Wayne Bond Lau, Yan Qu

Department of Emergency Medicine Faculty Papers

Recent studies have investigated the most efficacious dose of intravenous tissue plasminogen activator (IV-tPA) for acute ischemic stroke (AIS) patients. There remains no definitive consensus concerning the superior efficacious IV-tPA dose (standard- vs. low-dose), prompting us to perform a meta-analysis comparing the efficacy and safety profile of standard- versus low-dose IV-tPA.We identified relevant studies pertaining to the specific aim of our meta-analysis by searching PubMed and EMBASE (January 1990-September 2015) Either a fixed- or random-effects model was employed (dependent upon data heterogeneity) to analyze the efficacy and safety outcome.Ten cohort studies involving 4389 sum patients were included in the meta-analysis. …

Detection Of Sleep Disordered Breathing In Patients Hospitalized With Congestive Heart Failure, Sunil Sharma, Paul Mather

Department of Sleep Medicine Faculty Papers

OBJECTIVES: The purpose of this study was to evaluate the plethysmographic signal-derived oxygen desaturation index (ODI) as an inpatient screening strategy to identify sleep-disordered breathing (SDB) in patients with congestive heart failure (CHF).

BACKGROUND: SDB is highly prevalent among patients hospitalized with CHF but is widely underdiagnosed. We evaluated overnight photoplethysmography as a possible screening strategy for hospitalized patients with CHF.

METHODS: Consecutively admitted heart failure patients with high clinical suspicion of SDB and ODI ≥5 were offered outpatient polysomnography (PSG), which was completed within 4 weeks of discharge. PSG was considered positive if the apnea hypoxia index (AHI) was …

Emerging Immunopharmacological Targets In Multiple Sclerosis., Mojtaba Farjam, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami

Department of Neurology Faculty Papers

Inflammatory demyelination of the central nervous system (CNS) is the hallmark of multiple sclerosis (MS), a chronic debilitating disease that affects more than 2.5 million individuals worldwide. It has been widely accepted, although not proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell activation in the periphery and migration into the CNS, which subsequently triggers an inflammatory cascade that leads to demyelination and axonal damage. Virtually all MS medications now in use target the immune system and prevent tissue damage by modulating neuroinflammatory processes. Although current therapies such as commonly prescribed disease-modifying medications decrease the relapse rate …

Right Ventricular Dysfunction After Resuscitation Predicts Poor Outcomes In Cardiac Arrest Patients Independent Of Left Ventricular Function., Vimal Ramjee, Anne V. Grossestreuer, Yuan Yao, Sarah M. Perman, Marion Leary, James N. Kirkpatrick, Paul R. Forfia, Daniel M. Kolansky, Benjamin S. Abella, David F. Gaieski

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction.

METHODS: A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012.

PATIENTS: 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous …

Tools For Economic Analysis Of Patient Management Interventions In Heart Failure Cost-Effectiveness Model: A Web-Based Program Designed To Evaluate The Cost-Effectiveness Of Disease Management Programs In Heart Failure., Shelby D. Reed, Matthew P. Neilson, Matthew Gardner, Yanhong Li, Andrew H. Briggs, Daniel E E. Polsky, Felicia L. Graham, Margaret T. Bowers, Sara C. Paul, Bradi B. Granger, Kevin A. Schulman, David J. Whellan, Barbara Riegel, Wayne C. Levy

Department of Medicine Faculty Papers

BACKGROUND: Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable.

METHODS: We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying …

Enos Transfection Of Adipose-Derived Stem Cells Yields Bioactive Nitric Oxide Production And Improved Results In Vascular Tissue Engineering., Stephen Mcilhenny, Ping Zhang, Thomas Tulenko, Jason Comeau, Sarah Fernandez, Aleksandra Policha, Matthew Ferroni, Elizabeth J Faul, Gabor Bagameri, Irving Shapiro, Paul J. Dimuzio

Department of Surgery Faculty Papers

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels …

Migrated Avalon Veno-Venous Extracorporeal Membrane Oxygenation Cannula: How To Adjust Without Interruption Of Flow., Daizo Tanaka, Harrsion T. Pitcher, Nicholas C. Cavarocchi, Hitoshi Hirose

Department of Surgery Faculty Papers

The Avalon dual lumen cannula is presently the cannula of choice for veno-venous extracorporeal membrane oxygenation (VV-ECMO) via right internal jugular cannulation. This cannula establishes VV-ECMO with a single cannulation; however, it requires appropriate positioning to gain adequate oxygenation. Malposition of this cannula can cause inadequate ECMO flow, hypoxia, and structural injury. We have experienced two cases of migration: one into the hepatic vein and the other into the right ventricle. The former was repositioned using echocardiographic guidance without using a guidewire. The latter was repositioned using a guidewire from the femoral vein under fluoroscopy, without antegrade wire placement into …

Saving Life And Brain With Extracorporeal Cardiopulmonary Resuscitation: A Single-Center Analysis Of In-Hospital Cardiac Arrests., Graham Peigh, Nicholas C. Cavarocchi, Hitoshi Hirose

Department of Surgery Faculty Papers

OBJECTIVE: Despite advances in medical care, survival to discharge and full neurologic recovery after cardiac arrest remains less than 20% after cardiopulmonary resuscitation. An alternate approach to traditional cardiopulmonary resuscitation is extracorporeal cardiopulmonary resuscitation, which places patients on extracorporeal membrane oxygenation during cardiopulmonary resuscitation and provides immediate cardiopulmonary support when traditional resuscitation has been unsuccessful. We report the results from extracorporeal cardiopulmonary resuscitation at the Thomas Jefferson University.

METHODS: Between 2010 and June 2014, 107 adult extracorporeal membrane oxygenation procedures were performed at the Thomas Jefferson University. Patient demographics, survival to discharge, and neurologic recovery of patients who underwent extracorporeal …

Beyond The One-Locus-One-Mirna Paradigm: Microrna Isoforms Enable Deeper Insights Into Breast Cancer Heterogeneity., Aristeidis G Telonis, Phillipe Loher, Yi Jing, Eric R Londin, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

Here we describe our study of miRNA isoforms (isomiRs) in breast cancer (BRCA) and normal breast data sets from the Cancer Genome Atlas (TCGA) repository. We report that the full isomiR profiles, from both known and novel human-specific miRNA loci, are particularly rich in information and can distinguish tumor from normal tissue much better than the archetype miRNAs. IsomiR expression is also dependent on the patient's race, exemplified by miR-183-5p, several isomiRs of which are upregulated in triple negative BRCA in white but not black women. Additionally, we find that an isomiR's 5' endpoint and length, but not the genomic …

Dna-Repair Defects And Olaparib In Metastatic Prostate Cancer., Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula Mcgovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A'Hern, Amanda Swain, Lakshmi P Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J Lord, Alan Ashworth, Mark A Rubin, Karen E Knudsen, Felix Y Feng, Arul M Chinnaiyan, Emma Hall, Johann S De Bono

Department of Medicine Faculty Papers

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the …

A Piece Of My Mind. A Piece Of My Mind--Actually., Herbert M. Adler

Department of Psychiatry and Human Behavior Faculty Papers

No abstract provided.

Palbociclib In Hormone-Receptor-Positive Advanced Breast Cancer., Nicholas C Turner, Cynthia Huang Bartlett, Massimo Cristofanilli

Department of Medicine Faculty Papers

No abstract provided.

Effect Of Mycophenolate Mofetil On The White Blood Cell Count And The Frequency Of Infection In Systemic Lupus Erythematosus., Ananta Subedi, Laurence S. Magder, Michelle Petri

Department of Medicine Faculty Papers

Leukopenia is a common manifestation of SLE. Addition of immunosuppressive therapy in a SLE patient who is already leukopenic is a clinical concern. It could worsen leukopenia, increase the risk of infection, or both. The aim of this study was to analyze the immediate effect of mycophenolate mofetil on the white blood cell count and the rate of infection in SLE patients. Two hundred and forty-four patients within the Hopkins Lupus Cohort who were newly started on mycophenolate mofetil were included in the study. The white blood cell count and interval infection history on the day mycophenolate mofetil was started …

Racial Disparities In Intravenous Recombinant Tissue Plasminogen Activator Use Persist At Primary Stroke Centers., Hugo J. Aparicio, Brendan G. Carr, Scott E. Kasner, Michael J. Kallan, Karen C. Albright, Dawn O. Kleindorfer, Michael T. Mullen

Department of Emergency Medicine Faculty Papers

BACKGROUND: Primary stroke centers (PSCs) utilize more recombinant tissue plasminogen activator (rt-PA) than non-PSCs. The impact of PSCs on racial disparities in rt-PA use is unknown.

METHODS AND RESULTS: We used data from the Nationwide Inpatient Sample from 2004 to 2010, limited to states that publicly reported hospital identity and race. Hospitals certified as PSCs by The Joint Commission were identified. Adults with a diagnosis of ischemic stroke were analyzed. Rt-PA use was defined by the International Classification of Diseases, 9th Revision procedure code 99.10. Discharges (304 152 patients) from 26 states met eligibility criteria, and of these 71.5% were …

Motifs Of Vdac2 Required For Mitochondrial Bak Import And Tbid-Induced Apoptosis., Shamim Naghdi, Péter Várnai, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Voltage-dependent anion channel (VDAC) proteins are major components of the outer mitochondrial membrane. VDAC has three isoforms with >70% sequence similarity and redundant roles in metabolite and ion transport. However, only Vdac2(-/-) (V2(-/-)) mice are embryonic lethal, indicating a unique and fundamental function of VDAC2 (V2). Recently, a specific V2 requirement was demonstrated for mitochondrial Bak import and truncated Bid (tBid)-induced apoptosis. To determine the relevant domain(s) of V2 involved, VDAC1 (V1) and V2 chimeric constructs were created and used to rescue V2(-/-) fibroblasts. Surprisingly, the commonly cited V2-specific N-terminal extension and cysteines were found to be dispensable for Bak …

Segment And Fit Thresholding: A New Method For Image Analysis Applied To Microarray And Immunofluorescence Data., Elliot Ensink, Jessica Sinha, Arkadeep Sinha, Huiyuan Tang, Heather M. Calderone, Galen Hostetter, Jordan M. Winter, David Cherba, Randall E. Brand, Peter J. Allen, Lorenzo F. Sempere, Brian B. Haab

Department of Surgery Faculty Papers

Experiments involving the high-throughput quantification of image data require algorithms for automation. A challenge in the development of such algorithms is to properly interpret signals over a broad range of image characteristics, without the need for manual adjustment of parameters. Here we present a new approach for locating signals in image data, called Segment and Fit Thresholding (SFT). The method assesses statistical characteristics of small segments of the image and determines the best-fit trends between the statistics. Based on the relationships, SFT identifies segments belonging to background regions; analyzes the background to determine optimal thresholds; and analyzes all segments to …

A Phase 3 Trial Of 2 Years Of Androgen Suppression And Radiation Therapy With Or Without Adjuvant Chemotherapy For High-Risk Prostate Cancer: Final Results Of Radiation Therapy Oncology Group Phase 3 Randomized Trial Nrg Oncology Rtog 9902., Seth A. Rosenthal, Daniel Hunt, A. Oliver Sartor, Kenneth J. Pienta, Leonard G. Gomella, David Grignon, Raghu Rajan, Kevin J. Kerlin, Christopher U. Jones, Michael Dobelbower, William U Shipley, Kenneth Zeitzer, Daniel A. Hamstra, Viroon Donavanik, Marvin Rotman, Alan C. Hartford, Jeffrey Michalski, Michael Seider, Harold Kim, Deborah A. Kuban, Jennifer Moughan, Howard Sandler

Department of Urology Faculty Papers

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).

METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was …

Simple New Risk Score Model For Adult Cardiac Extracorporeal Membrane Oxygenation: Simple Cardiac Ecmo Score., Graham Peigh, Nicholas Cavarocchi, Scott W. Keith, Hitoshi Hirose

Department of Surgery Faculty Papers

BACKGROUND: Although the use of cardiac extracorporeal membrane oxygenation (ECMO) is increasing in adult patients, the field lacks understanding of associated risk factors. While standard intensive care unit risk scores such as SAPS II (simplified acute physiology score II), SOFA (sequential organ failure assessment), and APACHE II (acute physiology and chronic health evaluation II), or disease-specific scores such as MELD (model for end-stage liver disease) and RIFLE (kidney risk, injury, failure, loss of function, ESRD) exist, they may not apply to adult cardiac ECMO patients as their risk factors differ from variables used in these scores.

METHODS: Between 2010 and …

Characterization Of 1577 Primary Prostate Cancers Reveals Novel Biological And Clinicopathologic Insights Into Molecular Subtypes., Scott A. Tomlins, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Kasra Yousefi, Shuang Zhao, Zaid Haddad, Robert B. Den, Adam P. Dicker, Bruce J. Trock, Angelo M. Demarzo, Ashley E. Ross, Edward M. Schaeffer, Eric A. Klein, Cristina Magi-Galluzzi, R. Jeffrey Karnes, Robert B. Jenkins, Felix Y. Feng

Department of Radiation Oncology Faculty Papers

BACKGROUND: Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests.

OBJECTIVE: To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping.

DESIGN, SETTING, AND PARTICIPANTS: We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model …

Increased Expression Of Napdh Oxidase 4 In Systemic Sclerosis Dermal Fibroblasts: Regulation By Transforming Growth Factor Β., Sonsoles Piera-Velazquez, Alma Makul, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1).

METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc …

Caffeine And Progression Of Parkinson Disease: A Deleterious Interaction With Creatine., David K. Simon, Cai Wu, Barbara C. Tilley, Anne-Marie Wills, Michael J. Aminoff, Jacquelyn Bainbridge, Robert A. Hauser, Jay S. Schneider, Saloni Sharma, Carlos Singer, Caroline M. Tanner, Daniel Truong, Pei Shieen Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake.

METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from …

The Evolution Of Epilepsy Surgery Between 1991 And 2011 In Nine Major Epilepsy Centers Across The United States, Germany, And Australia., Lara Jehi, Daniel Friedman, Chad Carlson, Gregory Cascino, Sandra Dewar, Christian Elger, Jerome Engel, Robert Knowlton, Ruben Kuzniecky, Anne Mcintosh, Terence J O'Brien, Dennis Spencer, Michael R. Sperling, Gregory Worrell, Bill Bingaman, Jorge Gonzalez-Martinez, Werner Doyle, Jacqueline French

Department of Neurology Faculty Papers

OBJECTIVE: Epilepsy surgery is the most effective treatment for select patients with drug-resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities.

METHODS: We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers.

RESULTS: Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis …

Isoform-Specific Dynamic Translocation Of Pkc By Α1-Adrenoceptor Stimulation In Live Cells., Jin O-Uchi, Jaime Sorenson, Bong Sook Jhun, Jyotsna Mishra, Stephen Hurst, Kaleef Williams, Shey-Shing Sheu, Coeli M.B. Lopes

Center for Translational Medicine Faculty Papers

Protein kinase C (PKC) plays key roles in the regulation of signal transduction and cellular function in various cell types. At least ten PKC isoforms have been identified and intracellular localization and trafficking of these individual isoforms are important for regulation of enzyme activity and substrate specificity. PKC can be activated downstream of Gq-protein coupled receptor (GqPCR) signaling and translocate to various cellular compartments including plasma membrane (PM). Recent reports suggested that different types of GqPCRs would activate different PKC isoforms (classic, novel and atypical PKCs) with different trafficking patterns. However, the knowledge of isoform-specific activation of PKC by each …

Thromboembolism After Intramedullary Nailing For Metastatic Bone Lesions., Brandon Shallop, Alexandria Starks, Simon Greenbaum, David S Geller, Alan Lee, John Ready, Geno J Merli, Mitchell Maltenfort, Phd, John A Abraham

Rothman Institute Faculty Papers

BACKGROUND: The risk of venous thromboembolism (VTE) in patients undergoing intramedullary nailing for skeletal metastatic disease is currently undefined. The purpose of our study was to determine the risk of thromboembolic events, to define the risk factors for VTE, and to define the rate of wound complications in this population.

METHODS: A retrospective review of surgical databases at three National Cancer Institute (NCI)-designated cancer centers identified 287 patients with a total of 336 impending or pathologic long-bone fractures that were stabilized with intramedullary nailing between February 2001 and April 2013. Statistical analysis was performed utilizing multivariable logistic regression and Fisher …

The Fate Of Spacers In The Treatment Of Periprosthetic Joint Infection., Miguel M Gomez, Timothy L Tan, Jorge Manrique, Gregory K Deirmengian, Javad Parvizi Md

Rothman Institute Faculty Papers

BACKGROUND: Two-stage exchange arthroplasty remains the preferred method to treat periprosthetic joint infection. The aim of this study was to investigate the clinical course of periprosthetic joint infection following resection arthroplasty and insertion of a spacer.

METHODS: Our institutional database was used to identify 504 cases of periprosthetic joint infection (326 knees and 178 hips) treated with resection arthroplasty and spacer insertion as part of a two-stage exchange arthroplasty. A review of the patient charts was performed to extract information relevant to the objectives of this study that included the details of the clinical course following resection arthroplasty.

RESULTS: The …

Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery In Youth With Cerebral Palsy., M J Mulcahey, Mary D Slavin, Pengsheng Ni, Lawrence C Vogel, Scott H Kozin, Stephen M Haley, Alan M Jette

Department of Occupational Therapy Faculty Papers

BACKGROUND: The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent-reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP.

METHODS: This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed "Up & Go" test (TUG) before and after elective orthopaedic surgery in a convenience …

Gm1 Ganglioside In Parkinson's Disease: Pilot Study Of Effects On Dopamine Transporter Binding., Jay S. Schneider, Franca Cambi, Stephen M. Gollomp, Hiroto Kuwabara, James R. Brašić, Benjamin E. Leiby, Stephanie Sendek, Dean F. Wong

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: GM1 ganglioside has been suggested as a treatment for Parkinson's disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitudinally.

METHODS: Positron emission tomography (PET) imaging data were obtained from a subset of subjects enrolled in a delayed start clinical trial of GM1 in PD [1]: 15 Early-start (ES) subjects, 14 Delayed-start (DS) subjects, and 11 Comparison (standard-of-care) subjects. Treatment subjects were studied over a 2.5 year period while Comparison subjects were studied over 2 …

The Role Of Perlecan And Endorepellin In The Control Of Tumor Angiogenesis And Endothelial Cell Autophagy., Stephen Douglass, Atul Goyal, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

During tumor growth and angiogenesis there is a dynamic remodeling of tissue architecture often accompanied by the release of extracellular matrix constituents full of biological activity. One of the key constituents of the tumor microenvironment is the large heparan sulfate proteoglycan perlecan. This proteoglycan, strategically located at cell surfaces and within basement membranes, is a well-defined pro-angiogenic molecule when intact. However, when partially processed by proteases released during cancer remodeling and invasion, the C-terminal fragment of perlecan, known as endorepellin, has opposite effects than its parent molecule. Endorepellin is a potent inhibitor of angiogenesis by exerting a dual receptor antagonism …

Pkcε Is An Essential Mediator Of Prostate Cancer Bone Metastasis., Alvaro Gutierrez-Uzquiza, Cynthia Lopez-Haber University Of Pennsylvania, Danielle L. Jernigan, Alessandro Fatatis, Marcelo G. Kazanietz

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

UNLABELLED: The bone is a preferred site for metastatic homing of prostate cancer cells. Once prostate cancer patients develop skeletal metastases, they eventually succumb to the disease; therefore, it is imperative to identify key molecular drivers of this process. This study examines the involvement of protein kinase C epsilon (PKCε), an oncogenic protein that is abnormally overexpressed in human tumor specimens and cell lines, on prostate cancer cell bone metastasis. PC3-ML cells, a highly invasive prostate cancer PC3 derivative with bone metastatic colonization properties, failed to induce skeletal metastatic foci upon inoculation into nude mice when PKCε expression was silenced …