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Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …

Safety And Immunogenicity Of Human Serum Albumin-Free Mmr Vaccine In Us Children Aged 12-15 Months., Maurice A. Mufson, Clemente Diaz, Michael Leonardi, Christopher J. Harrison, Stanley Grogg, Antonio Carbayo, Simon Carlo-Torres, Robert Jeanfreau, Ana Quintero-Del-Rio, Gisele Bautista, Michael Povey, Christopher Da Costa, Ouzama Nicholson, Bruce L. Innis

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: M-M-R(TM)II (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (Priorix(TM), GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States.

METHODS: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12-15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine …

Progressive Hearing Loss In Mice Carrying A Mutation In Usp53, Marcin Kazmierczak, Suzan L. Harris, Piotr Kazmierczak, Prahar Shah, Valentin Starovoytov, Kevin K. Ohlemiller, Martin Schwander

Open Access Publications

UNLABELLED: Disordered protein ubiquitination has been linked to neurodegenerative disease, yet its role in inner ear homeostasis and hearing loss is essentially unknown. Here we show that progressive hearing loss in the ethylnitrosourea-generated mambo mouse line is caused by a mutation in Usp53, a member of the deubiquitinating enzyme family. USP53 contains a catalytically inactive ubiquitin-specific protease domain and is expressed in cochlear hair cells and a subset of supporting cells. Although hair cell differentiation is unaffected in mambo mice, outer hair cells degenerate rapidly after the first postnatal week. USP53 colocalizes and interacts with the tight junction scaffolding proteins …

Cost Effectiveness Analysis Of Year 2 Of An Elementary School-Located Influenza Vaccination Program-Results From A Randomized Controlled Trial., Byung-Kwang Yoo, Sharon Humiston, Peter G. Szilagyi, Stanley J. Schaffer, Christine Long, Maureen Kolasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: School-located vaccination against influenza (SLV-I) has the potential to improve current suboptimal influenza immunization coverage for U.S. school-aged children. However, little is known about SLV-I's cost-effectiveness. The objective of this study is to establish the cost-effectiveness of SLV-I based on a two-year community-based randomized controlled trial (Year 1: 2009-2010 vaccination season, an unusual H1N1 pandemic influenza season, and Year 2: 2010-2011, a more typical influenza season).

METHODS: We performed a cost-effectiveness analysis on a two-year randomized controlled trial of a Western New York SLV-I program. SLV-I clinics were offered in 21 intervention elementary schools (Year 1 n = 9,027; …

‘The Thing Is Not Knowing’: Patients' Perspectives On Surveillance Of An Indeterminate Pulmonary Nodule, Renda Soylemez Wiener, Michael K. Gould, Steven Woloshin, Lisa M. Schwartz, Jack Clark

Dartmouth Scholarship

Background: The hundreds of thousands of patients found to have a potentially malignant pulmonary nodule each year are faced with tremendous uncertainty regarding what the nodule is and how it should be evaluated.

Objective: To explore patients' responses to the detection and evaluation of a pulmonary nodule.

Effect Of A Cognitive-Behavioral Prevention Program On Depression 6 Years After Implementation Among At-Risk Adolescents: A Randomized Clinical Trial., David A Brent, Steven M. Brunwasser Phd, Steven D Hollon, V Robin Weersing, Gregory N Clarke, John F Dickerson, William R Beardslee, Tracy R G Gladstone, Giovanna Porta, Frances L Lynch, Satish Iyengar, Judy Garber

College of Science & Mathematics Departmental Research

IMPORTANCE: Adolescents whose parents have a history of depression are at risk for developing depression and functional impairment. The long-term effects of prevention programs on adolescent depression and functioning are not known.

OBJECTIVE: To determine whether a cognitive-behavioral prevention (CBP) program reduced the incidence of depressive episodes, increased depression-free days, and improved developmental competence 6 years after implementation.

DESIGN, SETTING, AND PARTICIPANTS: A 4-site randomized clinical trial compared the effect of CBP plus usual care vs usual care, through follow-up 75 months after the intervention (88% retention), with recruitment from August 2003 through February 2006 at a health maintenance organization, …

Identification And Survival Outcomes Of A Cohort Of Patients With Cancer Of Unknown Primary In Ontario, Canada., Chong S Kim, Malek B Hannouf, Sisira Sarma, George B Rodrigues, Peter K Rogan, Salaheddin M Mahmud, Eric Winquist, Muriel Brackstone, Gregory S Zaric

Epidemiology and Biostatistics Publications

BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS).

MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. …

Potential Impact Of Prescribing Metformin According To Egfr Rather Than Serum Creatinine, Delphine S. Tuot, Feng Lin, Michael G. Shlipak, Vanessa Grubbs, Chi-Yuan Hsu, Jerry Yee, Vahakn Shahinian, Rajiv Saran, Sharon Saydah, Desmond E. Williams, Neil R. Powe

Nephrology Articles

OBJECTIVE: Many societies recommend using estimated glomerular filtration rate (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We examined the potential impact of these recommendations on metformin eligibility among U.S. adults.

RESEARCH DESIGN AND METHODS: Metformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999-2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if

RESULTS: Among adults with sCr above conventional cutoffs, MDRD eGFR ≥45 mL/min/1.73 m(2) was most common among men (adjusted odds ratio [aOR] 33.3 [95% CI 7.4-151.5] vs. women) and non-Hispanic …

Employment Status And Participation In Cardiac Rehabilitation: Does Encouraging Earlier Enrollment Improve Attendance?, Quinn R. Pack, Ray W. Squires, Claudia Valdez-Lowe, Mouhamad Mansour, Randal J. Thomas, Steven J. Keteyian

Cardiology Articles

PURPOSE: For patients hospitalized for a cardiac event, an earlier appointment to outpatient cardiac rehabilitation (CR) increases participation. However, it is unknown what effect hastening CR enrollment might have among employed patients planning to return to work (RTW).

METHODS: Using 2 complementary data sets from Henry Ford Hospital (HFH) and Mayo Clinic, we assessed when employed patients eligible for CR anticipated a RTW, the impact of an earlier appointment on CR enrollment, and the effect of employment status on the number of CR sessions attended. Patients at HFH attended CR at either 8 or 42 days (through randomization), whereas Mayo …

Identification Of Regions Of Normal Grey Matter And White Matter From Pathologic Glioblastoma And Necrosis In Frozen Sections Using Raman Imaging, Rachel Kast, Gregory Auner, Sally Yurgelevic, Brandy Broadbent, Aditya Raghunathan, Laila M. Poisson, Tom Mikkelsen, Mark L. Rosenblum, Steven N. Kalkanis

Neurosurgery Articles

In neurosurgical applications, a tool capable of distinguishing grey matter, white matter, and areas of tumor and/or necrosis in near-real time could greatly aid in tumor resection decision making. Raman spectroscopy is a non-destructive spectroscopic technique which provides molecular information about the tissue under examination based on the vibrational properties of the constituent molecules. With careful measurement and data processing, a spatial step and repeat acquisition of Raman spectra can be used to create Raman images. Forty frozen brain tissue sections were imaged in their entirety using a 300-µm-square measurement grid, and two or more regions of interest within each …

Repression Of Esophageal Neoplasia And Inflammatory Signaling By Anti-Mir-31 Delivery In Vivo., Cristian Taccioli, Michela Garofalo, Hongping Chen, Yubao Jiang, Guidantonio Malagoli Tagliazucchi, Gianpiero Di Leva, Hansjuerg Alder, Paolo Fadda, Justin Middleton, Karl J. Smalley, Tommaso Selmi, Srivatsava Naidu, John L. Farber, Carlo M. Croce, Louise Fong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Overexpression of microRNA-31 (miR-31) is implicated in the pathogenesis of esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary zinc deficiency. Using a rat model that recapitulates features of human ESCC, the mechanism whereby Zn regulates miR-31 expression to promote ESCC is examined.

METHODS: To inhibit in vivo esophageal miR-31 overexpression in Zn-deficient rats (n = 12-20 per group), locked nucleic acid-modified anti-miR-31 oligonucleotides were administered over five weeks. miR-31 expression was determined by northern blotting, quantitative polymerase chain reaction, and in situ hybridization. Physiological miR-31 targets were identified by microarray analysis and verified by luciferase reporter …

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 …

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 …

Microrna Circulating In The Early Aftermath Of Motor Vehicle Collision Predict Persistent Pain Development And Suggest A Role For Microrna In Sex-Specific Pain Differences., Sarah D. Linnstaedt, Margaret G. Walker, Joel S. Parker, Eunice Yeh, Robert L. Sons, Erin Zimny, Christopher A. Lewandowski, Phyllis L. Hendry, Kathia Damiron, Claire Pearson, Marc-Anthony Velilla, Brian J. O'Neil, Jeffrey Jones, Robert Swor, Robert Domeier, Scott Hammond, Samuel A. Mclean

Emergency Medicine Articles

BACKGROUND: Molecular mediators influencing the transition from acute to persistent musculoskeletal pain following common stress exposures such as motor vehicle collision (MVC) remain poorly understood. In this exploratory, proof of concept study, we compared circulating microRNA (miRNA) expression profiles in the early aftermath of MVC among individuals who did and did not subsequently develop persistent pain. Blood RNA samples were obtained from African American individuals (n = 53) who presented to the emergency department after MVC and were discharged to home after evaluation. The presence or absence of severe pain in the axial region, the most common and morbid region …

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 …

Workplace Safety Concerns Among Co-Workers Of Responder Returning From Ebola-Affected Country, Benjamin P. Chan, Elizabeth R. Daly, Elizabeth A. Talbot

Dartmouth Scholarship

We surveyed public health co-workers regarding attitudes toward a physician who returned to New Hampshire after volunteering in the West African Ebola outbreak. An unexpectedly large (18.0%) proportion of staff expressed discomfort with the Ebola responder returning to work. Employers should take proactive steps to address employee fears and concerns.

Sepsis In Hemodialysis Patients., Gilbert Abou Dagher, Elie Harmouche, Elsy Jabbour, Rana Bachir, Dina Zebian, Ralphe Bou Chebl

Emergency Medicine Articles

BACKGROUND: Bacterial infections are very common in End Stage Renal Disease (ESRD) patients. The diagnosis of sepsis in such patients is often challenging and requires a high index of suspicion. The aim of this study is to report on a series of patient with ESRD on hemodialysis (HD) diagnosed with sepsis.

METHODS: Single center retrospective study looking at ESRD on HD who presented to our tertiary hospital were retrieved. Inclusion criteria included a discharge diagnosis of sepsis, septic shock or bacteremia.

RESULTS: Our sample was composed of 41 females and 49 males, with a mean age of 70 ± 15 …

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 …

Validation Of Maximal Heart Rate Prediction Equations Based On Sex And Physical Activity Status, Stephen J. Roy, J.L. Mccrory

International Journal of Exercise Science

International Journal of Exercise Science 8(4): 318-330, 2015. The purpose of the study was to determine if measured maximal heart rate (HR_max) was affected by sex or aerobic training status, and to determine the accuracy of three common clinical age-prediction maximal heart rate regression equations used to predict HR_max: HR_max = 220 – age, HR_max = 226 – age, and HR_max = 208 – (0.7 ∙ age). Fifty-two participants in total, 30 of which were in the active group (15 M, 15 F) and 22 subjects in the sedentary group (9 M, …

Dynapenic Obesity And The Effect On Long-Term Physical Function And Quality Of Life: Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Dawna Pidgeon, Stephen J. Bartels

Dartmouth Scholarship

Obesity is associated with functional impairment, institutionalization, and increased mortality risk in elders. Dynapenia is defined as reduced muscle strength and is a known independent predictor of adverse events and disability. The synergy between dynapenia and obesity leads to worse outcomes than either independently. We identified the impact of dynapenic obesity in a cohort at risk for and with knee osteoarthritis on function.

Selective C1 Lesioning Slightly Decreases Angiotensin Ii Type I Receptor Expression In The Rat Rostral Ventrolateral Medulla (Rvlm)., Erick A Bourassa, Kristen A Stedenfeld, Alan F Sved, Robert Charles Speth

Faculty Articles

Cardiovascular homeostasis is regulated in large part by the rostral ventrolateral medulla (RVLM) in mammals. Projections from the RVLM to the intermediolateral column of the thoracolumbar spinal cord innervate preganglionic neurons of the sympathetic nervous system causing elevation of blood pressure and heart rate. A large proportion, but not all, of the neurons in the RVLM contain the enzymes necessary for the production of epinephrine and are identified as the C1 cell group. Angiotensin II (Ang II) activates the RVLM acting upon AT1 receptors. To assess the proportion of AT1 receptors that are located on C1 neurons in the rat …

Internship And Empathy: Variations Across Time And Specialties, Sameer K. Avasarala, Sarah Whitehouse, Sean Drake

Internal Medicine Articles

OBJECTIVES: To assess whether any differences exist in Interpersonal Reactivity Index (IRI) scores among postgraduate year 1 (PGY-1) residents across specialties.

METHODS: PGY-1 residents representing 11 specialties at our academic institution were invited to take a Web-based IRI survey at three time points. The specialties were condensed into several binary groups for analysis: internal medicine (IM) versus non-IM; primary care (IM, family medicine) versus nonprimary care; emergency medicine (EM, including the combined IM/EM) versus non-EM; surgical specialties (general surgery, obstetrics and gynecology, otolaryngology, orthopedics, urology) versus nonsurgical specialties (EM, family medicine, IM, neurology, pathology, and psychiatry); men versus women; and …

Rural Vs. Non-Rural Differences And Longitudinal Bone Changes By Dxa And Pqct In Men Aged 20-66 Years: A Population-Based Study, Bonny L. Specker, Howard E. Wey, Teresa L. Binkley, Tianna Beare, Maggie Minett, Lee A. Weidauer

Health and Nutritional Sciences Faculty Publications

The purpose of this research was to determine whether there were differences in estimated means and rates of change in BMC, bone area, BMD and measures of bone geometry among men (n=544) from three distinct populations (Hutterite [rural], rural non-Hutterite, non-rural), and whether activity levels or calcium intake explain these population differences. Men were enrolled in the South Dakota Rural Bone Health Study and followed for 7.5 years to estimate means and rates of change in bone mass, density, size and geometry. Femoral neck (FN) and spine measurements were obtained every 18 months by DXA and distal radius (4% 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 …

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 …

Protecting Ourselves From Harm: Voices Of Aging Farmers, Deborah B. Reed, Deborah T. Claunch

Nursing Faculty Publications

Senior farmers suffer the highest fatality risk of any age group in agriculture. The purpose of this exploratory study was to develop a "voice" for senior farmers by examining aging farmers' and their families' perspectives of farm work, associated injury risks, and methods to decrease those risks. Focus groups and personal interviews were used to collect data from 81 participants across seven U.S. states. The findings reflect the collective and verified voice of the study group. The Health Belief Model was applied and revealed differences between farmers and their family members; however, the need and desire to continue self-directed work …

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 …

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 …

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 …

Janus Kinase 2/Signal Transducer And Activator Of Transcription 3 Inhibitors Attenuate The Effect Of Cardiotrophin-Like Cytokine Factor 1 And Human Focal Segmental Glomerulosclerosis Serum On Glomerular Filtration Barrier., Mukut Sharma, Jianping Zhou, Jean-François Gauchat, Ram Sharma, Ellen T. Mccarthy, Tarak Srivastava, Virginia J. Savin

Manuscripts, Articles, Book Chapters and Other Papers

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) after renal transplantation is believed to be caused by a circulating factor(s). We detected cardiotrophin-like cytokine factor 1 (CLCF1), a member of the interleukin 6 family, in the plasma from patients with recurrent FSGS. We hypothesized that CLCF1 contributes to the effect of FSGS serum on the glomerular filtration barrier in vitro. Presently, we studied the effect of CLCF1 on isolated rat glomeruli using an in vitro assay of albumin permeability (P(alb)). CLCF1 (0.05-100 ng/mL) increased P(alb) and caused maximal effect at 5-10 ng/mL (P < 0.001). The increase in Palb was analogous to the effect of FSGS serum. Anti-CLCF1 monoclonal antibody blocked the CLCF1-induced increase in P(alb) and significantly attenuated the effect of FSGS serum (P < 0.001). The heterodimer composed of CLCF1 and cosecreted molecule cytokine receptor-like factor 1 (CRLF1) attenuated the increase in P(alb) caused by CLCF1 or FSGS serum. Western blot analysis showed that CLCF1 upregulated phosphorylation of signal transducer and activator of transcription 3 (STAT3) (Tyr705) in glomeruli. This effect was diminished by the heterodimer CLCF1-CRLF1. Janus kinase 2 (JAK2) inhibitor BMS-1119543 or STAT3 inhibitor Stattic significantly blocked the effect of CLCF1 or FSGS serum on P(alb) (P < 0.001). These novel findings suggest that when monomeric CLCF1 increases P(alb), the heterodimer CLCF1-CRLF1 may protect the glomerular filtration barrier. We speculate that albuminuria in FSGS is related to qualitative or quantitative changes in the CLCF1-CRLF1 complex, and that JAK2 or STAT3 inhibitors may be novel therapeutic agents to treat FSGS.