Internal Medicine Commons^™

Fine Mapping Seronegative And Seropositive Rheumatoid Arthritis To Shared And Distinct Hla Alleles By Adjusting For The Effects Of Heterogeneity, B. Han, D. Diogo, S. Eyre, H. Kallberg, A. Zhernakova, J. Bowes, L. Padyukov, Y. Okada, P. K. Gregersen, S. Raychaudhuri, +8 Additional Authors

Journal Articles

Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA(-) RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA(-) RA and observed independent associations for serine and leucine at position 11 in HLA-DRbeta1 (p = 1.4 x 10(-13), odds ratio [OR] = 1.30) and for aspartate at …

Genetics Of Rheumatoid Arthritis Contributes To Biology And Drug Discovery, Y. Okada, D. Wu, G. Trynka, T. Raj, C. Terao, K. Ikari, Y. Kochi, K. Ohmura, P. K. Gregersen, R. M. Plenge, +85 Additional Authors

Journal Articles

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating approximately 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico …

Genome-Wide Methylation Analyses In Glioblastoma Multiforme, R. K. Lai, Y. W. Chen, X. W. Guan, D. Nousome, C. Sharma, P. Canoll, J. Bruce, A. Lee, P. Gregersen, J. Barnholtz-Sloan, +8 Additional Authors

Journal Articles

Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery …

Integration Of Sequence Data From A Consanguineous Family With Genetic Data From An Outbred Population Identifies Plb1 As A Candidate Rheumatoid Arthritis Risk Gene, Y. Okada, D. Diogo, J. D. Greenberg, F. Mouassess, W. A. L. Achkar, R. S. Fulton, J. C. Denny, N. Gupta, P. K. Gregersen, R. M. Plenge, +38 Additional Authors

Journal Articles

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G. C (p.G755R) mutation at the PLB1 gene on …

Interferon Alpha On Nzm2328.Lc1r27: Enhancing Autoimmunity And Immune Complex-Mediated Glomerulonephritis Without End Stage Renal Failure, C. Dai, H. Y. Wang, S. S. J. Sung, R. Sharma, C. Kannapell, W. Han, Q. Wang, A. Davidson, F. Gaskin, S. M. Fu

Journal Articles

Interferon alpha (IFN alpha) may play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Recent literature suggests that IFN alpha does not correlate with disease activities and blockade of IFN alpha is not effective in treating SLE. This study aims to delineate further the role of IFN alpha in SLE. 12-week old NZM2328 and its congenic NZM2328.Lc1R27 (R27) female mice were challenged with adenovirus-IFN alpha (adeno-IFN alpha) or adenovirus-LacZ (adeno-LacZ). Only adeno-IFN alpha treated NZM2328 developed severe proteinuria and died of chronic glomerulonephritis (GN) and end stage renal disease. Adeno-IFN alpha treated R27 did develop immune complex-mediated GN but …

Pathogenetic Role Of Glomerular Cxcl13 Expression In Lupus Nephritis, K. Worthmann, F. Gueler, S. Von Vietinghoff, A. Davalos-Militz, F. Wiehler, A. Davidson, T. Witte, H. Haller, M. Schiffer, L. Schiffer, +1 Additional Author

Journal Articles

Podocytes maintain the structure and function of the glomerular filtration barrier. However, podocytes have recently been implicated in the innate immune response, and their function as non-haematopoietic antigen-presenting cells was highlighted. We have shown previously that excessive expression of the chemokine CXCL13 is a distinctive early event for nephritis in a murine model of systemic lupus erythematosus (SLE). Furthermore, we found that CXCL13 is elevated significantly in the serum of patients with SLE-nephritis. In this study, we were able to show for the first time that (i) CXCL13 is expressed locally in glomeruli in a model for SLE-nephritis in mice …

Biomechanical Comparison Of Hybrid Versus Non Locking Screw Fixation For Midshaft Clavicle Fractures, Joseph T. Cox, J Christopher Gayton, Matthew P. Noyes, Gregory C. Gould, Ronald J. Markert, Michael J. Prayson

Internal Medicine Faculty Publications

Objectives: Recent studies report nonunion rates of up to fifteen percent for nonoperative treatment of displaced, comminuted, or shortened midshaft clavicle fractures. Additionally, authors suggest operative treatment of these comminuted displaced midshaft clavicle fractures leads to a more satisfactory clinical outcome. Biomechanically, clavicle fracture plate fixation has been analyzed for locking versus non-locking screw use, but little evidence on hybrid screw use exists. We hypothesized that fixation of a comminuted midshaft clavicle fracture model with a pre-contoured hybrid screw-plate construct would increase stiffness and load-to-failure compared to a non-locking screw construct. Methods: Fourteen matched pairs of fresh frozen cadaveric clavicles …

Incidence And Risk Factors For Acute Myocardial Injury After Non-Cardiac Surgery At The Aga Khan University Hospital Nairobi, Salim Said Ahmed

Master of Medicine in Internal Medicine

Aim: To determine the incidence and risk factors for acute myocardial injury after non-cardiac surgery at Aga Khan University Hospital Nairobi. Design: Prospective cohort study Background: Myocardial injury is the most common major cardiovascular complication in patients undergoing non-cardiac surgery. Large numbers of intermediate-risk and high-risk cardiac patients will be undergoing surgery as the population grows older, and thus myocardial injury after non-cardiac surgery could be a rising problem. Patients and Setting: Adult participants undergoing intermediate and high risk non-cardiac surgery at the Aga Khan University Hospital Nairobi were evaluated for incidence and risk factors for myocardial injury after non-cardiac …

Comparison Of Cardiometabolic Risk Profile Between Hiv Patients On Art And Those Who Are Art Naïve, Erick Kimani Njenga

Master of Medicine in Internal Medicine

Background: Metabolic syndrome comprises of a set of aggregated risk factors that include: hypertension, central obesity, impaired fasting glucose, hypertriglyceridemia and low HDL-C (1)The is a noted increase in the prevalence of the metabolic syndrome cardiovascular risk factors in the HIV population. Methods: The study is a cross-sectional survey that enrolled 157 HIV positive patients over a 4 month period that were either newly diagnosed (HIV ART naïve) or were on ART from both the inpatient and outpatient setting. Data of their anthropometric, cardiovascular risk factors and clinical characteristics were collected with the aid of a standardized questionnaire and serum …

How Patients' Self-Disclosure About Sickle Cell Pain Episodes To Significant Others Relates To Living With Sickle Cell Disease, Valerian J. Derlega, Louis H. Janda, Jeannie Miranda, Ian A. Chen, B. Mitchell Goodman Iii, Wally Smith

Psychology Faculty Publications

Objectives: This cross-sectional study examines to whom and how fully sickle cell disease (SCD) patients talk to others about sickle cell pain, how helpful it is to talk with others about these pain episodes, and the association between talking to others about sickle cell pain episodes and patients' psychological adjustment and coping strategies in managing the disease.

Methods: A convenience sample of 73 African American patients with SCD (30 men and 43 women), were recruited from two SCD clinics at the time of routine medical visits. Most participants had been diagnosed with hemoglobin SS, and they reported an average number …

Prevalence And Clinical Characteristics Of Venous Thromboembolism At The Aga Khan University Hospital, Nairobi, Felix Mutuma Riunga

Master of Medicine in Internal Medicine

Aim: To determine the prevalence of venous thromboembolism in patients presenting to the Aga Khan University Hospital, Radiology Department for lower limb compression ultrasonography with doppler and CT pulmonary angiography. In those found to have venous thromboembolism, the distribution of risk factors as described by Wells, the pattern of clinical presentation, the pattern of initial therapy, the length of hospital stay, major bleeding episodes and in hospital mortality were described. Design: Prospective survey Background: Venous Thromboembolism is a major cause of morbidity and mortality worldwide and its occurrence locally, as well as its clinical characteristics needs to be described in …

High-Intensity Tasks With External Load In Military Applications: A Review, Eric K. O'Neal, Jared H. Hornsby, Kyle J. Kelleran

Human Movement Studies & Special Education Faculty Publications

This article provides a synopsis of the limited investigations examining the impact of external load (EL) on performance of high-intensity tasks under load (HITL), EL training intervention effects on HITL performance, and injuries from EL training. Repetitive lifting tasks and initiation of locomotion, such as rapidly moving from a prone position to sprinting appear to be more hindered by EL than maximal sprinting velocity and may explain why training with EL does not improve obstacle course or prolonged (200-300 yard shuttle) drills. EL training appears to offer very little if any benefit for HITL in lesser trained populations. This contrast …

A Gut Gone To Pot: A Case Of Cannabinoid Hyperemesis Syndrome Due To K2, A Synthetic Cannabinoid., Anene Ukaigwe, Paras Karmacharya, Anthony A. Donato

Reading Hospital Internal Medicine Residency

Cannabinoid Hyperemesis Syndrome (CHS) was first described in 2004. Due to its novelty, CHS is often unrecognized by clinicians leading to expensive workup of these patients with cyclical symptoms. It may take up to 9 years to diagnose CHS. CHS is characterized by cyclical nausea and vomiting, abdominal pain, and an unusual compulsion to take hot showers in the presence of chronic use of cannabinoids. Cannabicyclohexanol is a synthetic cannabinoid, popularly known as K2 spice. It is a popular marijuana alternative among teenagers and young adults since it is readily available as herbal incense. Unlike marijuana, many users know that …

Nanotechnology And Its Implication In Medical Science, Syed Ahsan Ali, M. Tariq

Department of Medicine

No abstract provided.

Mesenteric Vein Thrombosis In A Patient Heterozygous For Factor V Leiden And G20210a Prothrombin Genotypes., Paras Karmacharya, Madan Raj Aryal, Anthony A. Donato

Reading Hospital Internal Medicine Residency

Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia. The proportion of patients with primary (or idiopathic) MVT varies from 0% to 49%, with a decrease in frequency secondary to more recent availability of newer investigations for hypercoagulability. The presence of factor V Leiden (FVL) and prothrombin G20210A mutations (PGM) have been well documented in these cases. However, there have been scarce case reports describing MVT in heterozygotes of both these mutations occurring simultaneously and its implications on long term management. Our case …

Cholera Vaccination Campaign Contributes To Improved Knowledge Regarding Cholera And Improved Practice Relevant To Waterborne Disease In Rural Haiti, Omowunmi Aibana, Molly F Franke, Jessica E Teng, Johanne Hilaire, Max Raymond, Louise C Ivers

Faculty, Staff and Student Publications

BACKGROUND: Haiti's cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV) might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti.

METHODOLOGY/PRINCIPAL FINDINGS: We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811). An OCV campaign occurred from May-June 2012 after …

Clinical Reasoning And Dual Mental Processing In Diagnostic Competence., M. Tariq, Syed Ahsan Ali

Department of Medicine

No abstract provided.

Illuminating The Dark Side--Vitamin D Status In Different Localities Of Karachi, Romaina Iqbal, Lena Jafri, Ali Haroon, Aysha Habib Khan

Department of Medicine

This study was conducted to determine the association between place of residence (grouped into neighbourhoods), and 25-hydroxy D (25[OH]D) levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University (AKU), Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence (74%) of vitamin D deficiency (VDD) was observed. There was a significant difference (p-value < 0.01) between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification.

Effect Of Mobile Phone Short Message Service On Adherence Rates To Antihypertensives At The Family Medicine Clinic, Barbara Karau

Master of Medicine in Internal Medicine

Background: Systemic arterial hypertension is the main modifiable risk factor for development of cardiovascular disease, which is the number one cause of death in high income countries and is increasingly becoming a cause of concern in Sub-Saharan Africa (1). Awareness, management and overall control of hypertension in Sub-Saharan Africa is poor (2,3). Poor control stems from various causes; one being patient non-adherence with medication, a factor amenable to modification. The use of mobile health for behavioural change from low resource settings is gaining widespread use in management of communicable diseases (4,6). Mobile phone has the potential to significantly influence patients …

Unintentional Childhood Poisoning, Epidemiology And Strategies For The Prevention And Policy Change In Pakistan, Omer Ul Hassan, Hasana Qadri, Umer Mir, Bilal Ahmed

Department of Medicine

Poisoning is the fifth leading cause of unintentional injuries among young children. Agents most commonly ingested by young children include medicines, cleaning substances, hydrocarbons, pesticides and cosmetics. Children with less educated fathers, living in more crowded conditions and from lower income families are more predisposed to unintentional poisoning. Unsafe storage of medicines, chemicals and other hazardous substances is one of the leading reasons for childhood poisoning. Knowledge of parents and caregivers about prevention of poisoning may be the basis to prevent subsequent injuries. This paper is a review of the epidemiology of unintentional poisonings among young children (less than five …