Pediatrics Commons^™

Metabolic Effects Of Acute Thiamine Depletion Are Reversed By Rapamycin In Breast And Leukemia Cells, Shuqian Liu, Sumitra Miriyala, Mignon A Keaton, Craig T. Jordan, Christina Wiedl, Daret K. St Clair, Jeffrey A. Moscow

Pediatrics Faculty Publications

Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently altered in cancer and therefore present cancer-relevant targets. We have previously shown that the recombinant enzyme thiaminase cleaves and depletes intracellular thiamine, has growth inhibitory activity against leukemia and breast cancer cell lines, and that its growth inhibitory effects were reversed in leukemia cell lines by rapamycin. Now, we first show further evidence of thiaminase therapeutic potential by demonstrating its activity against breast and leukemia xenografts, and against a primary leukemia xenograft. We therefore further explored the metabolic effects of thiaminase in combination with rapamycin in leukemia and breast cell lines. …

High Levels Of Dek Autoantibodies May Predict Early Flare Following Cessation Of Anti-Tnf Therapy In Juvenile Idiopathic Arthritis, Nirit Mor-Vaknin, Miguel Rivas, Maureen Legendre, Y. Yuanfang, Anne Johnson, Lawrence K. Jung, +12 Additional Authors

Pediatrics Faculty Publications

Introduction The nuclear oncoprotein DEK is a biochemically distinct, pro-inflammatory protein that is a chemoattractant for neutrophils and T-cells. High levels of DEK autoantibodies have been found in several autoimmune diseases including juvenile idiopathic arthritis (JIA), but their role in disease pathogenesis is unclear.

Objectives Since DEK and DEK autoantibodies can contribute to the development of immune complexes and joint inflammation, we suggest that DEK antibody levels can predict disease flare with discontinuation of anti-TNF therapy. Methods In 16 pediatric rheumatology centers, sera samples were collected from 137 children with polyarticular JIA on anti-TNF therapy. Therapy was stopped after 6 …

Animal Models Of In Utero Exposure To A High Fat Diet: A Review, L. Williams, Y. Seki, P. M. Vuguin, M. J. Charron

Journal Articles

The incidence of metabolic disease, including type 2 diabetes and obesity, has increased to epidemic levels in recent years. A growing body of evidence suggests that the intrauterine environment plays a key role in the development of metabolic disease in offspring. Among other perturbations in early life, alteration in the provision of nutrients has profound and lasting effects on the long term health and well being of offspring. Rodent and non-human primate models provide a means to understand the underlying mechanisms of this programming effect. These different models demonstrate converging effects of a maternal high fat diet on insulin and …

Greater Mortality And Morbidity In Extremely Preterm Infants Fed A Diet Containing Cow Milk Protein Products, S. A. Abrams, R. J. Schanler, M. L. Lee, D. J. Rechtman

Journal Articles

Background: Provision of human milk has important implications for the health and outcomes of extremely preterm (EP) infants. This study evaluated the effects of an exclusive human milk diet on the health of EP infants during their stay in the neonatal intensive care unit. Subjects and Methods: EP infants= 10% CM (p < 0.02). Conclusions: An exclusive human milk diet, devoid of CM-containing products, was associated with lower mortality and morbidity in EP infants without compromising growth and should be considered as an approach to nutritional care of these infants.

Effects Of Genetics And In Utero Diet On Murine Pancreatic Development, C. L. Lin, L. Williams, Y. Seki, H. Kaur, K. Hartil, A. Fiallo, A. S. Glenn, E. B. Katz, M. J. Charron, P. M. Vuguin

Journal Articles

Intrauterine (IU) malnutrition could alter pancreatic development. In this study, we describe the effects of high-fat diet (HFD) during pregnancy on fetal growth and pancreatic morphology in an 'at risk' animal model of metabolic disease, the glucose transporter 4 (GLUT4) heterozygous mouse (G4+/-). WT female mice mated with G4+/- males were fed HFD or control diet (CD) for 2 weeks before mating and throughout pregnancy. At embryonic day 18.5, fetuses were killed and pancreata isolated for analysis of morphology and expression of genes involved in insulin (INS) cell development, proliferation, apoptosis, glucose transport and function. Compared with WT CD, WT …

Dose And Outcomes In Primary Immunodeficiency Disorders, V. R. Bonagura

Journal Articles

No abstract provided.

From Infancy To Adolescence: Fifteen Years Of Continuous Treatment With Hydroxyurea In Sickle Cell Anemia, J. S. Hankins, B. Aygun, K. Nottage, C. Thornburg, M. P. Smeltzer, R. E. Ware, W. C. Wang

Journal Articles

Despite documented laboratory and clinical benefits of hydroxyurea for children with sickle cell anemia (SCA), the drug's long-term safety and efficacy remains poorly defined. The HUSOFT trial and extension study examined feasibility, toxicity, and hematological efficacy of hydroxyurea in infants with SCA.This report describes HUSOFT participants who have continued hydroxyurea therapy for 15 years. With IRB approval, medical records were reviewed for clinical, laboratory, and growth parameters.Twenty-eight infants enrolled in the original 2-year HUSOFT study received open-label liquid hydroxyurea at 20 mg/kg/day; 17 completed the extension study with dose escalation to 30 mg/kg/day. Eight of these 17 (6 girls and …

Immunizations In Children With Inflammatory Bowel Disease Treated With Immunosuppressive Therapy, Y. Lu, A. Bousvaros

Journal Articles

The vast majority of patients with inflammatory bowel disease (IBD) will receive immunosuppressive therapy at some point for their disease, whether for the short term (such as a course of corticosteroids) or long term (such as maintenance therapy with immunomodulators or biologics). The systemic immunosuppression places patients at increased risk for infections. Therefore, it is important that patients are up-to-date with immunizations to minimize vaccine-preventable infections. However, the literature shows that the rate of immunization in patients with IBD is low. Ideally, the vaccination status is checked at diagnosis, and patients are immunized with the vaccines they need. Drawing titers …

Outcomes After Hematopoietic Stem Cell Transplantation For Children With I-Cell Disease, T. C. Lund, S. S. Cathey, W. P. Miller, M. Eapen, M. Andreansky, C. C. Dvorak, J. H. Davis, J. D. Dalal, I. Sahdev, P. J. Orchard, +9 Additional Authors

Journal Articles

Mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. Although hematopoietic stem cell transplantation (HSCT) has been used to successfully treat some lysosomal storage diseases, only 2 cases have been reported on the use of HSCT to treat MLII. For the first time, we describe the combined international experience in the use of HSCT for MLII in 22 patients. Although 95% of the patients engrafted, overall survival was low, with only 6 patients (27%) alive at last follow-up. The most common …

Pediatric Crohn Disease Patients Exhibit Specific Ileal Transcriptome And Microbiome Signature, Y. Haberman, T. L. Tickle, P. J. Dexheimer, M. O. Kim, D. Tang, R. Karns, R. N. Baldassano, J. D. Noe, J. Markowitz, L. A. Denson, +14 Additional Authors

Journal Articles

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to …

Prevention And Control Of Haemophilus Influenzae Type B Disease: Recommendations Of The Advisory Committee On Immunization Practices (Acip), E. C. Briere, L. Rubin, P. L. Moro, A. Cohn, T. Clark, N. Messonnier

Journal Articles

This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of Haemophilus influenzae type b (Hib) disease in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians, public health officials, vaccination providers, and immunization program personnel as a resource. ACIP recommends routine vaccination with a licensed conjugate Hib vaccine for infants aged 2 through 6 months (2 or 3 doses, depending on vaccine product) with a booster dose at age 12 through 15 months. …

Pediatric Trainees' Engagement In The Online Nutrition Curriculum: Preliminary Results, K. O. Lewis, G. R. Frank, R. Nagel, T. L. Turner, C. L. Ferrell, S. G. Sangvai, R. Donthi, J. D. Mahan

Journal Articles

Background: The Pediatric Nutrition Series (PNS) consists of ten online, interactive modules and supplementary educational materials that have utilized web-based multimedia technologies to offer nutrition education for pediatric trainees and practicing physicians. The purpose of the study was to evaluate pediatric trainees' engagement, knowledge acquisition, and satisfaction with nutrition modules delivered online in interactive and non-interactive formats. Methods: From December 2010 through August 2011, pediatric trainees from seventy-three (73) different U. S. programs completed online nutrition modules designed to develop residents' knowledge of counseling around and management of nutritional issues in children. Data were analyzed using SPSS version 19. Both …

Use Of Menacwy-Crm Vaccine In Children Aged 2 Through 23 Months At Increased Risk For Meningococcal Disease: Recommendations Of The Advisory Committee On Immunization Practices, 2013, J. R. Macneil, L. Rubin, L. Mcnamara, E. C. Briere, T. A. Clark, A. C. Cohn

Journal Articles

During its October 2013 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM (Menveo, Novartis), as an additional option for vaccinating infants aged 2 through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the first quadrivalent meningococcal conjugate vaccine licensed for use in children aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is recommended for use in children aged 9 through 23 months who are at increased risk for meningococcal disease, and Hib-MenCY-TT (MenHibrix, GlaxoSmithKline) is recommended for use in children aged 6 weeks through 18 months at increased …

Safety Of Celecoxib And Nonselective Nonsteroidal Anti-Inflammatory Drugs In Juvenile Idiopathic Arthritis: Results Of The Phase 4 Registry, R. E. Sobel, D. J. Lovell, H. I. Brunner, J. E. Weiss, P. W. Morris, B. S. Gottlieb, E. C. Chalom, L. K. Jung, K. B. Onel, E. H. Giannini, +6 Additional Authors

Journal Articles

BACKGROUND: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). METHODS: Children aged >/=2 to-negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (

Utility Of Neutrophil Fcgamma Receptor I (Cd64) Index As A Biomarker For Mucosal Inflammation In Pediatric Crohn's Disease, P. Minar, Y. Haberman, I. Jurickova, T. Wen, M. E. Rothenberg, M. O. Kim, S. A. Saeed, R. N. Baldassano, J. Markowitz, L. A. Denson, +9 Additional Authors

Journal Articles

BACKGROUND: Neutrophil expression of the Fcgamma receptor I (CD64) is upregulated in adult patients with clinically active inflammatory bowel disease (IBD). We tested the relationship of CD64 with mucosal inflammation and clinical relapse in pediatric Crohn's disease (CD). METHODS: In a cohort of 208 newly diagnosed CD and 43 non-IBD controls, ileal expression of FcgammaRI/S100A9 was determined by RNA sequencing from biopsies obtained at ileocolonoscopy. In a second cohort, we tested for the peripheral blood polymorphonuclear neutrophil (PMN) CD64 index from 26 newly diagnosed CD, 30 non-IBD controls, and 83 children with established CD. RESULTS: Ileal FcgammaRIA mRNA expression was …

Pulse Oximetry: Fundamentals And Technology Update, M. Nitzan, A. Romem, R. Koppel

Journal Articles

Oxygen saturation in the arterial blood (SaO2) provides information on the adequacy of respiratory function. SaO2 can be assessed noninvasively by pulse oximetry, which is based on photoplethysmographic pulses in two wavelengths, generally in the red and infrared regions. The calibration of the measured photoplethysmographic signals is performed empirically for each type of commercial pulse-oximeter sensor, utilizing in vitro measurement of SaO2 in extracted arterial blood by means of co-oximetry. Due to the discrepancy between the measurement of SaO2 by pulse oximetry and the invasive technique, the former is denoted as SpO2. Manufacturers of pulse oximeters generally claim an accuracy …

Whole Exome Sequencing Identifies Novel Genes For Fetal Hemoglobin Response To Hydroxyurea In Children With Sickle Cell Anemia., V. A. Sheehan, J. R. Crosby, A. Sabo, N. A. Mortier, T. A. Howard, D. M. Muzny, S. Dugan-Perez, Banu Aygun, K. A. Nottage, J. M. Flanagan, +3 Additional Authors

Journal Articles

Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final …

A Pilot Academic-Community Partnership To Advance The D.C. Healthy Schools Act, Nisha Narayanan, Jonathan Tatum, Margarita Ramos, Jessica Kim, Nisha Punatar, Michele L. Mietus-Snyder

GW Research Days 2014

No abstract provided.

Mucopolysaccharidosis Iva (Morquio A Syndrome) And Vi (Maroteaux-Lamy Syndrome): Under-Recognized And Challenging To Diagnose, Ralph S. Lachman, Barbara K. Burton, Lorne A. Clarke, Scott Hoffinger, Shiro Ikegawa, Dong-Kyu Jin, Hiroki Kano, Ok-Hwa Kim, Christina Lampe, Nancy J. Mendelsohn, Renee Shediac, Pranoot Tanpaiboon, Klane K. White

Pediatrics Faculty Publications

OBJECTIVE:

Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux-Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI.

MATERIALS AND METHODS:

This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were …

Gauging Regional Differences In The Hiv Prevalence Rate Among Injection Drug Users In The U.S., Jichuan Wang, Brian Kelly

Pediatrics Faculty Publications

This article aims to introduce and demonstrate the application of the standardization and decomposition analysis (SDA) method to gauge differences in HIV prevalence rates among injection drug users (IDUs) across regions (Northeast, South, Midwest, and West) in the U.S. Using the SDA, the regional HIV prevalence rates were standardized and a rate difference between regions was decomposed into component effects, such as the “real” rate difference, and component effects attributed to differences in specific compositions of confounding factors. A total of 9,824 injection drug users (IDUs) retrieved from the national database of the National Institute on Drug Abuse’s Cooperative Agreement …

Superresolution Imaging Of Human Cytomegalovirus Vmia Localization In Sub-Mitochondrial Compartments, Shivaprasad Bhuvanendran, Kyle Salka, Kristen Rainey, Sen Chandra Sreetama, Elizabeth Williams, Margretha Leeker, Vidhya Prasad, Jonathan Boyd, George H. Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Pediatrics Faculty Publications

The human cytomegalovirus (HCMV) viral mitochondria-localized inhibitor of apoptosis (vMIA) protein, traffics to mitochondria-associated membranes (MAM), where the endoplasmic reticulum (ER) contacts the outer mitochondrial membrane (OMM). vMIA association with the MAM has not been visualized by imaging. Here, we have visualized this by using a combination of confocal and superresolution imaging. Deconvolution of confocal microscopy images shows vMIA localizes away from mitochondrial matrix at the Mitochondria-ER interface. By gated stimulated emission depletion (GSTED) imaging, we show that along this interface vMIA is distributed in clusters. Through multicolor, multifocal structured illumination microscopy (MSIM), we find vMIA clusters localize away from …

Perinatal Pharmacology, Karel M. Allegaert, V. Fanos, John N. Van Den Anker, Stephanie L. Läer

Pediatrics Faculty Publications

No abstract provided.

Rheumatic Heart Disease In Uganda: The Association Between Mhc Class Ii Hla Dr Alleles And Disease: A Case Control Study, Emmy Okello, Andrea Z. Beaton, Charles Mondo, Paul Kruszka, Noah Kiwanuka, Richard Odoi-Adome, Juergen Freers

Pediatrics Faculty Publications

Background

Rheumatic heart disease (RHD), the only long term consequence of acute rheumatic fever, remains a leading cause of morbidity and mortality among young adults in Uganda. An inherited susceptibility to acute rheumatic fever centers around the major histocompatibility class II human leucocyte antigens. However, there is paucity of data from sub-Saharan Africa. This study compares the frequency of HLA class II DR alleles between RHD cases and normal controls in Uganda.

Methods

One hundred ninety-nine participants including 96 established RHD cases aged 5–60 years and 103 age and sex matched normal controls were recruited for participation. DNA was manually …

Preface Of The Special Issue: “Recent Cmv Research”, Kayla Dufrene, Roberta L. Debiasi, Anamaris M. Colberg-Poley

Pediatrics Faculty Publications

No abstract provided.

Expression Of A Secreted Fibroblast Growth Factor Binding Protein-1 (Fgfbp1) In Angioproliferative Kaposi Sarcoma, Patricio E. Ray, Ali Al-Attar, Xue-Hui Liu, Jharna R. Das, Elena Tassi, Anton Wellstein

Pediatrics Faculty Publications

Objective: Kaposi’s sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGFbinding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the …

Children's Hospital Association Consensus Statements For Comorbidities Of Childhood Obesity, Elizabeth Estrada, Ihuoma Eneli, Sarah Hampl, Michele L. Mietus-Snyder, Nazrat Mirza, Erinn Rhodes, Brooke Sweeney, Lydia Tinjaero-Deck, Susan J. Woolford, Stephen J. Pont

Pediatrics Faculty Publications

Background: Childhood obesity and overweight affect approximately 30% of US children. Many of these children have obesity-related comorbidities, such as hypertension, dyslipidemia, fatty liver disease, diabetes, polycystic ovary syndrome (PCOS), sleep apnea, psychosocial problems, and others. These children need routine screening and, in many cases, treatment for these conditions. However, because primary care pediatric providers (PCPs) often are underequipped to deal with these comorbidities, they frequently refer these patients to subspecialists. However, as a result of the US pediatric subspecialist shortage and considering that 12.5 million children are obese, access to care by subspecialists is limited. The aim of this …

Working Together For Global Health Goals: The United States Agency For International Development And Faith-Based Organizations, Clydette L. Powell

Pediatrics Faculty Publications

For many years, and before the term “FBO” was used for faith-based organizations, the United States Agency for International Development (USAID) has supported the work of FBOs in global health and development. The Agency has long recognized the impact of FBOs within that development space, because these organizations are often well positioned to reach the hard-to-reach and to go the last mile because of their strong ties to the community. Moreover, FBOs deliver a substantial percentage of the health services in some developing countries. Faith partners, whether Catholic, Protestant, Buddhist, Hindu, Muslim, or other, have an important role to play …

Proposed Guidelines For The Diagnosis And Management Of Methylmalonic And Propionic Acidemia., Matthias R Baumgartner, Friederike Hörster, Carlo Dionisi-Vici, Goknur Haliloglu, Daniela Karall, Kimberly A. Chapman, +19 Additional Authors

Pediatrics Faculty Publications

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100'000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA …

Aspirin Use And Knowledge In The Community: A Population- And Health Facility Based Survey For Measuring Local Health System Performance., Gregory A Roth, Catherine W. Gillespie, Ali A Mokdad, Danny D Shen, David W Fleming, Andy Stergachis, Christopher J L Murray, Ali H Mokdad

Pediatrics Faculty Publications

BACKGROUND: Little is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.

METHODS: The Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for …

Immunologic Special Forces: Anti-Pathogen Cytotoxic T-Lymphocyte Immunotherapy Following Hematopoietic Stem Cell Transplantation, Michael Keller, Catherine M. Bollard

Pediatrics Faculty Publications

Anti-pathogen adoptive T-cell immunotherapy has been proven to be highly effective in preventing or controlling viral infections following hematopoietic stem cell transplantation. Recent advances in manufacturing protocols allow an increased number of targeted pathogens, eliminate the need for viral transduction, broaden the potential donor pool to include pathogen-naïve sources, and reduce the time requirement for production. Early studies suggest that anti-fungal immunotherapy may also have clinical benefit. Future advances include further broadening of the pathogens that can be targeted and development of T-cells with resistance to pharmacologic immunosuppression.