Medical Specialties Commons^™

Lysosomal Abnormalities In Hereditary Spastic Paraplegia Types Spg15 And Spg11, Benoit Renvoise, Jaerak Chang, Rajat Singh, Sayuri Yonekawa, Edmond J. Fitzgibbon, Ami Mankodi, Adeline Vanderver, Alice B. Schindler, Camilo Toro, William A. Gahl, Don J. Mahuran, Craig Blackstone, Tyler Pierson

Neurology Faculty Publications

Objective

Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.

Methods

We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.

Results

Fibroblasts …

Implicit Sequence Learning In People With Parkinson's Disease, Katherine R. Gamble, Thomas J. Cummings, Steven E. Lo, Pritha T. Ghosh, James H. Howard, Darlene V. Howard

Neurology Faculty Publications

Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson’s disease (PD) have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these …

Concurrent Non-Ketotic Hyperglycinemia And Propionic Acidemia In An Eight Year Old Boy, Paul Kruszka, Brian Kirmse, Dina Zand, Kristina Cusmano-Ozog, Elaine Spector, John Hove, Kimberly A. Chapman

Pathology Faculty Publications

This is the first reported case of a patient with both non-ketotic hyperglycinemia and propionic acidemia. At 2 years of age, the patient was diagnosed with non-ketotic hyperglycinemia by elevated glycine levels and mutations in the GLDC gene (paternal allele: c.1576_1577insC delT and c.1580delGinsCAA; p.S527Tfs*13, and maternal allele: c.1819G>A; p.G607S). At 8 years of age after having been placed on ketogenic diet, he became lethargic and had severe metabolic acidosis with ketonuria. Urine organic acid analysis and plasma acylcarnitine profile were consistent with propionic acidemia. He was found to have an apparently homozygous mutation in the PCCB gene: c.49C …

Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis.

METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded …

Hemorrhagic Stroke In An Adolescent Female With Hiv-Associated Thrombotic Thrombocytopenic Purpura, Natella Rakhmanina, Edward C.C. Wong, Jeremiah C. Davis, Patricio E. Ray

Pediatrics Faculty Publications

HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIVTTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented …

Assessing Function And Endurance In Adults With Spinal And Bulbar Muscular Atrophy: Validity Of The Adult Myopathy Assessment Tool., Michael O. Harris-Love, Lindsay Fernandez-Rhodes, Galen Joe, Joseph A. Shrader, Angela Kokkinis, Alison La Pean Kirschner, Sungyoung Auh, Cheunju Chen, Li Li, Ellen Levy, Todd E. Davenport, Nicholas A. Di Prospero, Kenneth H. Fischbeck

Exercise and Nutrition Sciences Faculty Publications

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA).

Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer …

The Importance Of Early Identification And Treatment Of Childhood Onset Bipolar Disorder: Creating Specialty Care, Robert M. Post

Psychiatry and Behavioral Sciences Faculty Publications

No abstract provided.

Synthesizing Data And Models For The Spread Of Mers-Cov, 2013: Key Role Of Index Cases And Hospital Transmission, Gerardo Chowell, Seth Blumberg, Lone Simonsen, Mark A. Miller, Cecile Viboud

Global Health Faculty Publications

The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April–October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and …

Prescribing Multiple Neurostimulants During Rehabilitation For Severe Brain Injury., Amy A. Herrold, Theresa Louise-Bender Pape, Ann Guernon, Trudy Mallinson, Eileen Collins, Neil Jordan

Clinical Research and Leadership Faculty Publications

Background. Despite a lack of clear evidence, multiple neurostimulants are commonly provided after severe brain injury (BI). The purpose of this study is to determine if the number of neurostimulants received during rehabilitation was associated with recovery of full consciousness or improved neurobehavioral function after severe BI.

Method. Data from 115 participants were extracted from a neurobehavioral observational study database for this exploratory, retrospective analysis. Univariate optimal data analysis was conducted to determine if the number of neurostimulants influenced classification of four outcomes: recovery of full consciousness during rehabilitation, recovery of full consciousness within one year of injury, and meaningful …

The Ciliary Protein Cystin Forms A Regulatory Complex With Necdin To Modulate Myc Expression, Maoqing Wu, Chaozhe Yang, Binli Tao, Su Bu, Lisa Guay-Woodford

Pediatrics Faculty Publications

Cystin is a novel cilia-associated protein that is disrupted in the cpk mouse, a well-characterized mouse model of autosomal recessive polycystic kidney disease (ARPKD). Interestingly, overexpression of the Myc gene is evident in animal models of ARPKD and is thought to contribute to the renal cystic phenotype. Using a yeast two-hybrid approach, the growth suppressor protein necdin, known to modulate Myc expression, was found as an interacting partner of cystin. Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, …

The Impact Of A Large-Scale Power Outage On Hemodialysis Center Operations, Mahshid Abir, Sophia Jan, Lindsay Jubelt, Raina M. Merchant, Nicole Lurie

Emergency Medicine Faculty Publications

INTRODUCTION:

On June 29, 2012, mid-Atlantic storms resulted in a large-scale power outage affecting up to three million people across multiple (US) states. Hemodialysis centers are dependent on electricity to provide dialysis care to end-stage renal disease patients. The objective of thisstudy was to determine how the power outage impacted operations in a sample of hemodialysis centers in the impacted regions.

METHODS:

The sample consisted of all hemodialysis centers located in the District of Columbia and a total of five counties with the largest power losses in West Virginia, Virginia, and Maryland. A semi-structured interview guide was developed, and …

Clinical And Laboratory Features Distinguishing Juvenile Polymyositis And Muscular Dystrophy, Gulnara Mamyrova, James D. Katz, Robert V. Jones, Ira N. Targoff, Peter A. Lachenbruch, Olcay Y. Jones, Frederick W. Miller, Lisa G. Rider

Pathology Faculty Publications

OBJECTIVE:

To differentiate juvenile polymyositis (PM) and muscular dystrophy, both of which may present with chronic muscle weakness and inflammation.

METHODS:

We studied 39 patients with probable or definite juvenile PM and 9 patients with muscular dystrophies who were initially misdiagnosed as having juvenile PM. Differences in demographic, clinical, and laboratory results; outcomes; and treatment responses were evaluated by Fisher's exact and rank sum tests. Random forests classification analysis and logistic regression were performed to examine significant differences in multivariable models.

RESULTS:

Clinical features and serum muscle enzyme levels were similar between juvenile PM and dystrophy patients, except 89% of …

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …

Global Mortality Estimates For The 2009 Influenza Pandemic From The Glamor Project: A Modeling Study, Lone Simonsen, Peter Spreeuwenberg, Roger Lustig, Robert J. Taylor, Douglas M. Fleming, Madelon Kroneman, Maria D. Van Kerkhove, Anthony D. Mounts, W. John Paget

Global Health Faculty Publications

Background

Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries.

Methods and Findings

We obtained weekly virology and underlying cause-of-death mortality time series for 2005–2009 for 20 countries covering ~35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used …

Depression Is Associated With Repeat Emergency Department Visits In Patients With Non-Specific Abdominal Pain, Andrew C. Meltzer, Benjamin Bregman, Janice Blanchard

Emergency Medicine Faculty Publications

Introduction: Patients with abdominal pain often return multiple times despite no definitive diagnosis. Our objective was to determine if repeat emergency department (ED) use among patients with non-specific abdominal pain might be associated with a diagnosis of moderate to severe depressive disorder.

Methods: We screened 987 ED patients for major depression during weekday daytime hours from June 2011 through November 2011 using a validated depression screening tool, the PHQ-9. Each subject was classified as either no depression, mild depression or moderate/ severe depression based on the screening tool. Within this group, we identified 83 patients with non-specific abdominal pain by …

Severe Painful Vaso-Occlusive Crises And Mortality In A Contemporary Adult Sickle Cell Anemia Cohort Study., Deepika S. Darbari, Zhengyuan Wang, Minjung Kwak, Mariana Hildesheim, James Nichols, Darlene Allen, Catherine Seamon, Marlene Peters-Lawrence, Anna Conrey, Mary K. Hall, Gregory J. Kato, James G. Taylor Vi

Pediatrics Faculty Publications

BACKGROUND: Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

METHODS: Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations …

A Profile Of Children With Complex Chronic Conditions At End Of Life Among Medicaid Beneficiaries: Implications For Health Care Reform, Lisa C. Lindley, Maureen E. Lyon

Pediatrics Faculty Publications

Background: As the United States braces for full implementation of health care reform, the eyes of the nation are on Medicaid. The large number of newly eligible Medicaid beneficiaries may challenge health care resources and ultimately impact quality of care. This is a special concern among current Medicaid beneficiaries such as children with complex chronic conditions (CCCs) who have significant health care needs, especially at end of life (EOL). Yet, a comprehensive profile of these children is lacking.

Objective: To understand the demographic and health characteristics, health care utilization, and expenditures among Medicaid children with CCCs at EOL.

Methods: Our …

Fixed Drug Eruption Associated With Sulfonamides Sold In Latino Grocery Stores — Greater Washington, Dc, Area, 2012–2013, Christine Yang, Audrey Green, Scott A. Norton

Dermatology Faculty Publications

No abstract provided.

Two-Category Place Representations Persist Over Body Rotations, Hyoun Kyoung Pyoun, Jesse Sargent, Stephen Dopkins, John W. Philbeck

Neurological Surgery Faculty Publications

We explored a system that constructs environment-centered frames of reference and coordinates memory for the azimuth of an object in an enclosed space. For one group, we provided two environmental cues (doors): one in the front, and one in the rear. For a second group, we provided two object cues: a front and a rear cue.For a third group, we provided no external cues; we assumed that for this group, their reference frames would be determined by the orthogonal geometry of the floor-and-wall junction that divides a space in half or into multiple territories along the horizontal …

An Assessment Of Hepatitis E Virus (Hev) In Us Blood Donors And Recipients: No Detectable Hev Rna In 1939 Donors Tested And No Evidence For Hev Transmission To 362 Prospectively Followed Recipients., Chenyu Xu, Richard Y. Wang, Cathy A. Schechterly, Shengxiang Ge, James W. Shih, Ning-Shao Xia, Naomi L. Luban, Harvey J. Alter

Pediatrics Faculty Publications

BACKGROUND:

Hepatitis E virus (HEV) infection has become relevant to blood transfusion practice because isolated cases of blood transmission have been reported and because HEV has been found to cause chronic infection and severe liver disease in immunocompromised patients.

STUDY DESIGN AND METHODS:

We tested for immunoglobulin (Ig)G and IgM antibodies to the HEV and for HEV RNA in 1939 unselected volunteer US blood donors. Subsequently, we tested the same variables in pre- and serial posttransfusion samples from 362 prospectively followed blood recipients to assess transfusion risk.

RESULTS:

IgG anti-HEV seroprevalence in the total 1939 donations was 18.8%: 916 of …

Second Messenger/Signal Transduction Pathways In Major Mood Disorders: Moving From Membrane To Mechanism Of Action, Part Ii: Bipolar Disorder, Mark Niciu, Dawn F. Ionescu, Daniel C. Matthews, Erica M. Richards, Carlos A. Zarate

Psychiatry and Behavioral Sciences Faculty Publications

The etiopathogenesis and treatment of major mood disorders have historically focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and amino acid [γ-aminobutyric acid (GABA), glutamate] receptors at the plasma membrane. Although the activation and inhibition of these receptors acutely alter local neurotransmitter levels, their neuropsychiatric effects are not immediately observed. This time lag implicates intracellular neuroplasticity as primary in the mechanism of action of antidepressants and mood stabilizers. The modulation of intracellular second messenger/signal transduction cascades affects neurotrophic pathways that are both necessary and sufficient for monoaminergic and amino acid–based treatments. In this review, we will discuss the evidence in …

Incidence Of Methicillin-Resistant Staphylococcus Aureus Infection In A Children's Hospital In The Washington Metropolitan Area Of The United States, 2003-2010, Xiaoyan Song, Joanthan Cogen, Nalini Singh

Pediatrics Faculty Publications

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major public health threat. In this retrospective cohort study, we included patients with laboratory-confirmed MRSA infections treated at Children’s National Medical Center in Washington, District of Columbia between July 2003 and December 2010. The secular trends in the incidence rates of skin/soft tissue and invasive MRSA infections were assessed. Molecular analyses were performed on a subset of patients with invasive infections whose MRSA isolates were available for genotyping. The study identified 3750 patients with MRSA infections. The incidence of MRSA infections peaked in 2007 (incidence rate: 5.34 per 1000 patient-visits) and subsequently …

Palliative Care For The Medically Complex Child, Melanie Anspacher, Neha H. Shah

E-Learning Modules

**From the AAMC website: Contains time-sensitive information that will likely be inaccurate, obsolete, or irrelevant by August 12, 2016**

Children with special health care needs are increasingly prevalent in US hospitals. The pediatric hospitalist is often the primary provider of inpatient care for these patients. The Complex Care Curriculum was developed to provide a multi-modal educational curriculum for providers with the overall goal of improving inpatient care for this population. The curriculum is composed primarily of a series of topic-specific learning modules. This particular resource was created to provide pediatricians with educational materials related to palliative care for the medically …

Peripheral Laser Iridoplasty Opens Angle In Plateau Iris By Thinning The Cross-Sectional Tissues, Ji Liu, Tania Lamba, David A. Belyea

Ophthalmology Faculty Publications

Plateau iris syndrome has been described as persistent angle narrowing or occlusion with intraocular pressure elevation after peripheral iridotomy due to the abnormal plateau iris configuration. Argon laser peripheral iridoplasty (ALPI) is an effective adjunct procedure to treat plateau iris syndrome. Classic theory suggests that the laser causes the contraction of the far peripheral iris stroma, "pulls" the iris away from the angle, and relieves the iris-angle apposition. We report a case of plateau iris syndrome that was successfully treated with ALPI. Spectral domain optical coherence tomography confirmed the angle was open at areas with laser treatment but remained appositionally …

Neonatal Neurobehavioral Abnormalities And Mri Brain Injury In Encephalopathic Newborns Treated With Hypothermia, Maya B. Coleman, Penny Glass, Judy Brown, Nadja Kadom, Tammy Tsuchida, Joseph Scafidi, Taeun Chang, Gilbert Vezina, An Nguyen Massaro

Pediatrics Faculty Publications

Background

Neonatal Encephalopathy (NE) is a prominent cause of infant mortality and neurodevelopmental disability. Hypothermia is an effective neuroprotective therapy for newborns with encephalopathy. Post-hypothermia functional–anatomical correlation between neonatal neurobehavioral abnormalities and brain injury findings on MRI in encephalopathic newborns has not been previously described.

Aim

To evaluate the relationship between neonatal neurobehavioral abnormalities and brain injury on magnetic resonance imaging (MRI) in encephalopathic newborns treated with therapeutic hypothermia.

Study design

Neonates with hypoxic ischemic encephalopathy (HIE) referred for therapeutic hypothermia were prospectively enrolled in this observational study. Neurobehavioral functioning was assessed with the NICU network neurobehavioral scale (NNNS) performed …

Increased Reticulocytosis During Infancy Is Associated With Increased Hospitalizations In Sickle Cell Anemia Patients During The First Three Years Of Life, Emily Riehm Meier, Colleen Byrnes, Y. Terry Lee, Elizabeth C. Wright, Alan N. Schechter, Naomi L. Luban, Jeffrey L. Miller

Pediatrics Faculty Publications

Objective

Among older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60–180 days.

Study Design

Data from fifty-nine subjects who were followed at Children’s National Medical Center’s Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60–180 days and the clinical course of sickle cell anemia during infancy …

Ereply. Re: Balancing The Pulmonary Circulation In Tricuspid Atresia With An Aortopulmonary Window, Pranava Sinha, Syed Murfad Peer, Mary T. Donofrio

Pediatrics Faculty Publications

No abstract provided.

Appendicitis Is Like A Box Of Chocolates, Clint D. Cappiello, Phillip C. Guzzetta, Faisal G. Qureshi

Pediatrics Faculty Publications

Appendicitis is the most commonly encountered abdominal emergency in pediatric surgery. However, the presentation of acute appendicitis is as diverse as the patient population. We present here a case of appendicitis presenting as an intra-abdominal mass consistent with lymphoma. Our patient is a 3 year old male with an atypical presentation of acute appendicitis. Additionally, he was found to have malrotation at the time of surgery. A delayed presentation, coupled with anomalous laboratory findings and aberrant anatomy made for a difficult diagnosis and overall interesting case of appendicitis.

Analysis Of Lmnb1 Duplications In Autosomal Dominant Leukodystrophy Provides Insights Into Duplication Mechanisms And Allele-Specific Expression, Elisa Giorgio, Harshvardhan Rolyan, Laura Kropp, Anish Baswanth Chakka, Svetlana Yatsenko, Adeline Vanderver, +31 Additional Authors

Neurology Faculty Publications

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications …

Interests In High-Functioning Autism Are More Intense, Interfering, And Idiosyncratic Than Those In Neurotypical Development, Laura G. Anthony, Lauren Kenworthy, Benjamin E. Yerys, Kathryn F. Jankowski, Joette James, Madeline B. Harms, Alex Martin, Gregory L. Wallace

Psychiatry and Behavioral Sciences Faculty Publications

Although circumscribed interests are pathognomonic with autism, much about these interests remains unknown. Using the Interests Scale (IS), this study compares interests between 76 neurotypical (NT) individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched groupwise on age, IQ, and gender ratio. Participants and their parents/caregivers completed diagnostic measures (the Autism Diagnostic Interview—Revised and the Autism Diagnostic Observation Schedule; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale—Revised, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale), in addition to the IS. Consistent with previous research, HF-ASD and NT individuals did …