Medical Specialties Commons^™

Whole-Genome Sequencing And Disability In The Nicu: Exploring Practical And Ethical Challenges., Michael J. Deem

Manuscripts, Articles, Book Chapters and Other Papers

Clinical whole-genome sequencing (WGS) promises to deliver faster diagnoses and lead to better management of care in the NICU. However,several disability rights advocates have expressed concern that clinical use of genetic technologies may reinforce and perpetuate stigmatization of and discrimination against disabled persons in medical and social contexts. There is growing need, then, for clinicians and bioethicists to consider how the clinical use of WGS in the newborn period might exacerbate such harms to persons with disabilities. This article explores ways to extend these concerns to clinical WGS in neonatal care. By considering these perspectives during the early phases of …

Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield

Dartmouth Scholarship

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.

Hematologic Outcomes After Total Splenectomy And Partial Splenectomy For Congenital Hemolytic Anemia., Brian R Englum, Jennifer Rothman, Sarah Leonard, Audra Reiter, Courtney Thornburg, Mary Brindle, Nicola Wright, Matthew M Heeney, C Jason Smithers, Rebeccah L Brown, Theodosia Kalfa, Jacob C Langer, Michaela Cada, Keith T Oldham, J Paul Scott, Mukta Sharma, Andrew M Davidoff, Kerri Nottage, Kathryn Bernabe, David B Wilson, Sanjeev Dutta, Bertil Glader, Shelley E Crary, Melvin S Dassinger, Levette Dunbar, Saleem Islam, Manjusha Kumar, Fred Rescorla, Steve Bruch, Andrew Campbell, Mary Austin, Robert Sidonio, Martin L Blakely, Henry E Rice, Splenectomy In Congenital Hemolytic Anemia Consortium, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD).

Methods: The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin. We also compared laparoscopic to open splenectomy.

Results: The analysis included 130 children, with 62.3% (n=81) undergoing TS. For children with HS, all …

Introduction To Bioethics Special Supplement V: Ethical Issues In Genomic Testing Of Children., John D. Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Next-generation genome sequencing of children is one of the most promising and most challenging new technologies in pediatrics. On the one hand, it offers the hope that we will be able to diagnose rare conditions that were previously impossible to diagnose, which, in turn, might lead to new treatments. On the other hand, the technology for sequencing presents daunting problems of interpretation. It is problematic to conduct the research necessary to characterize the pathogenicity of those variants at the same time that we are using them to guide the clinical care of children who have complex medical problems. It is …

The Challenge Of Analyzing The Results Of Next-Generation Sequencing In Children., Isabelle Thiffault, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

In recent years, next-generation sequencing technologies have revolutionized approaches to genetic studies. Whole-exome or whole-genome sequencing allows diagnoses in many patients who have complex phenotypes and unusual clinical presentations. As genomic and exomic testing expands in both the research and clinical settings, pediatricians will need to understand the technology of next-generation sequencing and the complexity of interpreting genomic variants relevant to patient phenotypic features. This article briefly explains the technology by which genomes are sequenced and discusses some of the complexity related to interpreting genomic variants. We conclude with some thoughts on the clinical applications of such testing.

Slug Bug: Quality Improvement With Orchestrated Testing Leads To Nicu Clabsi Reduction., Anthony J. Piazza, Beverly Brozanski, Lloyd Provost, Theresa R. Grover, John Chuo, Joan R. Smith, Teresa Mingrone, Susan Moran, Lorna Morelli, Isabella Zaniletti, Eugenia K. Pallotto

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Reduce central line-associated bloodstream infection (CLABSI) rates 15% over 12 months in children's hospital NICUs. Use orchestrated testing as an approach to identify important CLABSI prevention practices.

METHODS: Literature review, expert opinion, and benchmarking were used to develop clinical practice recommendations for central line care. Four existing CLABSI prevention strategies (tubing change technique, hub care monitoring, central venous catheter access limitation, and central venous catheter removal monitoring) were identified for study. We compared the change in CLABSI rates from baseline throughout the study period in 17 participating centers. Using orchestrated testing, centers were then placed into 1 of 8 …

Can Office Blood Pressure Readings Predict Masked Hypertension?, Mark M. Mitsnefes, Chris Pierce, Joseph Flynn, Joshua Samuels, Janis Dionne, Susan Furth, Bradley A. Warady, Ckid Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Studies in children with chronic kidney disease indicate a high prevalence of masked hypertension detected by ambulatory blood pressure monitoring (ABPM). However, it is not well known if the frequency of masked hypertension is related to the level of normal casual blood pressure (BP).

METHODS/RESULTS: We hypothesized that lower levels of normal casual BP are associated with a lower prevalence of masked hypertension. Data from the chronic kidney disease (CKiD) cohort were analyzed cross-sectionally across multiple visits. The majority of children with normal casual BP also had normal wake and sleep ABP (60 %), even at the highest percentiles …

Please Do Whatever It Takes To End Our Daughter's Suffering!, Stéphan Clément De Cléty, Marie Friedel, A A Eduard Verhagen, John D. Lantos, Brian S. Carter

Manuscripts, Articles, Book Chapters and Other Papers

What is the best way to care for a child with severe neurologic impairment who seems to be dying and is in intractable pain? Can we give sedation as we remove life support? Is it ethically permissible to hasten death? In the United States, 5 states have legalized assisted suicide (although only for competent adults). In Belgium and the Netherlands, euthanasia is legal for children under some circumstances. We present a case in which parents and doctors face difficult decisions about palliative care. Experts from Belgium, the Netherlands, and the United States then discuss how they would respond to such …

Nutritional Status And Tuberculosis Risk In Adult And Pediatric Household Contacts, Omowunmi Aibana, Xeno Acharya, Chuan-Chin Huang, Mercedes C Becerra, Jerome T Galea, Silvia S Chiang, Carmen Contreras, Roger Calderon, Rosa Yataco, Gustavo E Velásquez, Karen Tintaya, Judith Jimenez, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Studies show obesity decreases risk of tuberculosis (TB) disease. There is limited evidence on whether high body mass index also protects against TB infection; how very high body mass indices influence TB risk; or whether nutritional status predicts this risk in children. We assessed the impact of body mass index on incident TB infection and disease among adults and children.

METHODS AND FINDINGS: We conducted a prospective cohort study among household contacts of pulmonary TB cases in Lima, Peru. We determined body mass index at baseline and followed participants for one year for TB infection and disease. We used …

Atp-Site Binding Inhibitor Effectively Targets Mtorc1 And Mtorc2 Complexes In Glioblastoma, Jayson Neil, Craig Shannon, Avinash Mohan, Dimitri Laurent, Raj Murali, Meena Jhanwar-Uniyal

NYMC Faculty Publications

The PI3K-AKT-mTOR signaling axis is central to the transformed phenotype of glioblastoma (GBM) cells, due to frequent loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). The mechanistic target of rapamycin (mTOR) kinase is present in two cellular multi-protein complexes, mTORC1 and mTORC2, which have distinct subunit composition, substrates and mechanisms of action. Targeting the mTOR protein is a promising strategy for GBM therapy. However, neither of these complexes is fully inhibited by the allosteric inhibitor of mTOR, rapamycin or its analogs. Herein, we provide evidence that the combined inhibition of mTORC1/2, using the ATP-competitive binding …

Ethnic Differences In Maternal Adipokines During Normal Pregnancy, Xinhua Chen, Theresa O Scholl

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Two adipokines (adiponectin and resistin) have opposite relations with insulin resistance and inflammation. Our major focus was to determine whether there were detectable ethnic differences in maternal adipokines during pregnancy. We also explored the correlation of the adipokines with maternal glucose homeostasis, blood pressure and anthropometric parameters. Pregnant women (n = 1634) were from a large prospective cohort study in Camden NJ (African-American 36.8%; Hispanic 47.6%; Caucasian 15.6%). Serum adiponectin and resistin were measured at entry (week 16.8) and the 3rd trimester (week 30.7) using the Luminex xMapTechnology. Significant differences were observed among ethnic groups, controlling for confounding variables. African …

The Happy Older Latinos Are Active (Hola) Health Promotion And Prevention Study: Study Protocol For A Pilot Randomized Controlled Trial, Daniel E. Jimenez, Charles F. Reynolds, Margarita Alegría, Philip Harvey, Stephen Bartels

Dartmouth Scholarship

Results of previous studies attest to the greater illness burden of common mental disorders (anxiety and depression) in older Latinos and the need for developing preventive interventions that are effective, acceptable, and scalable. Happy Older Latinos are Active (HOLA) is a newly developed intervention that uses a community health worker (CHW) to lead a health promotion program in order to prevent common mental disorders among at-risk older Latinos. This pilot study tests the feasibility and acceptability of delivering HOLA to older, at-risk Latinos.

Methods/Design: HOLA is a multi-component, health promotion intervention funded by the National Institute of Mental Health (NIMH). …

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 …

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

‘Much Clearer With Pictures’: Using Community-Based Participatory Research To Design And Test A Picture Option Grid For Underserved Patients With Breast Cancer, Marie-Anne Durand, Shama Alam, Stuart W. Grande, Glyn Elwyn

Dartmouth Scholarship

Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer.

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Silibinin-Mediated Metabolic Reprogramming Attenuates Pancreatic Cancer-Induced Cachexia And Tumor Growth., Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua J. Souchek, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Nagarajan, Nina V. Chaika, Fang Yu, Surendra K. Shukla

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic …

Effect Of Kidney Function On Drug Kinetics And Dosing In Neonates, Infants, And Children., Frederique Rodieux, Melanie Wilbaux, Johannes N. Van Den Anker, Marc Pfister

Pediatrics Faculty Publications

Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood …

Outcomes With As-Needed Ranibizumab After Initial Monthly Therapy: Long-Term Outcomes Of The Phase Iii Ride And Rise Trials., David S. Boyer, Quan Dong Nguyen, David M. Brown, Karen Basu, Jason S. Ehrlich

Journal Articles: Ophthalmology

PURPOSE: To determine whether the efficacy and safety achieved with monthly ranibizumab as treatment for diabetic macular edema (DME) can be maintained with less-than-monthly treatment.

DESIGN: Open-label extension (OLE) phase of randomized, sham-controlled phase III trials: RIDE (NCT00473382) and RISE (NCT00473330).

PARTICIPANTS: Five hundred of 582 adults who completed the 36-month randomized core studies elected to enter the OLE.

METHODS: All patients participating in the OLE were eligible to receive 0.5 mg ranibizumab according to predefined re-treatment criteria: Treatment was administered when DME was identified by the investigator on optical coherence tomography or when best-corrected visual acuity (BCVA) worsened by …

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 …

Banning The Handshake From Healthcare Settings Is Not The Solution To Poor Hand Hygiene, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Endometrial Stromal Sarcoma Metastatic From The Uterus To The Inferior Vena Cava And Right Atrium, Daniel Scher, William Nghiem, Salim Aziz, Rodeen Rahbar, Whitney Banks, Anthony Venbrux, Shawn Sarin

The Texas Heart Institute Journal

Endometrial stromal sarcoma metastases usually occur within the pelvis and rarely involve the great vessels or the heart. We present the case of a 55-year-old woman who was referred for endovascular therapy to treat presumed thrombosis of the inferior vena cava. The suspected thrombus was recalcitrant to endovascular removal with use of an AngioVac venous drainage device. Results of an intraprocedural transvenous biopsy revealed the mass to be the intravascular extension of an endometrial stromal sarcoma. The patient underwent surgical excision of the tumor, and, shortly thereafter, a hysterectomy and salpingo-oophorectomy. This complex case highlights both the rarity of malignancy …

Multivariate Criteria Most Accurately Distinguish Cardiac From Noncardiac Causes Of Dyspnea, Mirza Nubair Ahmad, Syed Hasan Yusuf, Rafath Ullah, Mirza Mujadil Ahmad, Mary K Ellis, Haroon Yousaf, Timothy E Paterick, Khawaja Afzal Ammar

The Texas Heart Institute Journal

Cardiopulmonary exercise testing provides oxygen pulse as a continuous measure of stroke volume, which is superior to other stress-testing methods in which systolic function is measured at baseline and at peak stress. However, the optimal peak oxygen pulse criterion for distinguishing cardiac from noncardiac causes of exercise limitation is unknown.

In comparing several peak oxygen pulse criteria against the clinical standard of cardiopulmonary exercise testing, we retrospectively studied 54 consecutive patients referred for cardiopulmonary exercise testing. These exercise tests included measurement of oxygen consumption, carbon dioxide production, breathing reserve, arterial blood gases at baseline and at peak stress, exercise electrocardiogram, …

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. …

Tunneling A Pulmonary Artery Graft: A Simplified Way To Insert And Remove A Temporary Right Ventricular Assist Device, Pankaj Saxena, Silvana F Marasco

The Texas Heart Institute Journal

Right ventricular failure can occur early or late after left ventricular assist device implantation. Support with a right ventricular assist device is needed in patients whose right ventricular failure does not respond to conservative management. The use of a temporary right ventricular assist device can enable the recovery of right ventricular function and avoid the use of a more permanent biventricular assist device, which is associated with complications and higher costs. We present our technique of instituting temporary right ventricular assist device support in patients who have undergone left ventricular assist device implantation.

Microaxial Flow Left Ventricular Assist Device As A Bridge To Transplantation After Lvad Malfunction, Heidi J Reich, Aamir Shah, Babak Azarbal, Jon Kobashigawa, Jaime Moriguchi, Lawrence Czer, Fardad Esmailian

The Texas Heart Institute Journal

Evolving technology and improvements in the design of modern, continuous-flow left ventricular assist devices have substantially reduced the rate of device malfunction. As the number of implanted devices increases and as survival prospects for patients with a device continue to improve, device malfunction is an increasingly common clinical challenge. Here, we present our initial experience with an endovascular microaxial flow left ventricular assist device as a successful bridge to transplantation in a 54-year-old man who experienced left ventricular assist device malfunction.

The Creation Of A Model Pediatric Ward For African American Children In 1920s Kansas City., Jane F. Knapp, Robert Schremmer

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

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 …

Cyclin-Dependent Kinase Inhibitor P1446a Induces Apoptosis In A Jnk/P38 Mapk-Dependent Manner In Chronic Lymphocytic Leukemia B-Cells, Cody Paiva, J. Claire Godbersen, Ryan S. Soderquist, Taylor Rowland, Sumner Kilmarx

Dartmouth Scholarship

CDK (cyclin-dependent kinase) inhibitors have shown remarkable activity in CLL, where its efficacy has been linked to inhibition of the transcriptional CDKs (7 and 9) and deregulation of RNA polymerase and short-lived pro-survival proteins such as MCL1. Furthermore, ER (endoplasmic reticulum) stress has been implicated in CDK inhibition in CLL. Here we conducted a pre-clinical study of a novel orally active kinase inhibitor P1446A in CLL B-cells. P1446A inhibited CDKs at nanomolar concentrations and induced rapid apoptosis of CLL cells in vitro, irrespective of chromosomal abnormalities or IGHV mutational status. Apoptosis preceded inactivation of RNA polymerase, and was accompanied by …

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 …