Medical Specialties Commons^™

Neonatal Encephalopathic Cerebral Injury In South India Assessed By Perinatal Magnetic Resonance Biomarkers And Early Childhood Neurodevelopmental Outcome, Peter J. Lally, David L. Price, Shreela S. Pauliah, Alan Bainbridge, Justin Kurien, Neeraja Sivasamy, Frances M. Cowan, Guhan Balraj, Manjula Ayer, Kariyapilly Satheesan, Sreejith Ceebi, Angie Wade, Ravi Swamy, Shaji Padinjattel, Betty Hutchon, Madhava Vijayakumar, Mohandas Nair, Krishnakumar Padinharath, Hui Zhang, Ernest B. Cady, Seetha Shankaran, Sudhin Thayyil

Department of Pediatrics

Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR) biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India.

Anakinra And Related Drugs Targeting Interleukin-1 In The Treatment Of Cryopyrin-Associated Periodic Syndromes, Inessa Bachove, Christopher Chang

Department of Pediatrics Faculty Papers

Anakinra is an interleukin (IL) receptor antagonist that works by blocking the biological activity of IL-1 by competitively inhibiting binding of IL-1 to the type 1 interleukin receptor. IL-1 production is induced in response to inflammatory stimuli and mediates various physiological mechanisms, including inflammation and immunological reactions. Patients with neonatal onset multisystem inflammatory disease (NOMID) produce excess IL-1β, a major proinflammatory cytokine that regulates innate immune responses. Anakinra binds competitively and this results in a rapid reduction in disease severity. NOMID, also known as chronic infantile neurologic, cutaneous, articular syndrome, is the most severe clinical phenotype in the spectrum of …

Phase 2 Randomized, Flexible Crossover, Double-Blinded, Placebo-Controlled Trial Of The Farnesyltransferase Inhibitor Tipifarnib In Children And Young Adults With Neurofibromatosis Type 1 And Progressive Plexiform Neurofibromas, Brigitte C. Widemann, Eva Dombi, Andrea Gillespie, Pamela L. Wolters, Jean Belasco, Aerang Kim, +13 Additional Authors

Pediatrics Faculty Publications

Background

RAS is dysregulated in neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PNs). The activity of tipifarnib, which blocks RAS signaling by inhibiting its farnesylation, was tested in children and young adults with NF1 and progressive PNs.

Methods

Patients aged 3–25 years with NF1-related PNs and imaging evidence of tumor progression were randomized in a double-blinded fashion to receive tipifarnib (200 mg/m² orally every 12 h) or placebo (phase A) and crossed over to the opposite treatment arm at the time of tumor progression (phase B). PN volumes were measured with MRI, and progression was defined as ≥20% volume …

Rota Virus Diarrhea In Hospitalized Children, Muhammad Irfan Habib, Sayyeda Ghazala Kazi, Khalid Mehmood Ahmed Khan, Nukhba Zia

Department of Emergency Medicine

Objective: To determine the frequency and clinical features of Rota virus diarrhea in children presenting in a tertiary care hospital.

Study Design: A cross-sectional, observational study.

Place and Duration of Study: National Institute of Child Health, Karachi, from January to June 2007.

Methodology: A total of three hundred children of either gender aged 1 month to 5 years, who presented with diarrhea of < 7 days as a primary illness were enrolled. Children with bloody diarrhea or nosocomial gastroenteritis acquired duringhospitalization for other disease were not included. Detection of Rota virus in stool was done by enzyme linked immunoassay.

Results: Out of 300 children, 188 (63%) tested positive and 112 (37%) tested negative for Rota virus. Positive Rota virus cases in 7 – 12 months of age was (n = 34, 18.08%). Overall, 151 (80.3%) children …

Variation In Feeding Practices Following The Norwood Procedure., Linda M. Lambert, Nancy A. Pike, Barbara Medoff-Cooper, Victor Zak, Victoria L. Pemberton, Lisa Young-Borkowski, Martha L. Clabby, Kathryn N. Nelson, Richard G. Ohye, Bethany Trainor, Karen Uzark, Nancy Rudd, Louise Bannister, Rosalind Korsin, David S. Cooper, Christian Pizarro, Sinai C. Zyblewski, Bronwyn H. Bartle, Richard V. Williams, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II.

STUDY DESIGN: From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed.

RESULTS: Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only …

Testing The Prognostic Accuracy Of The Updated Pediatric Sepsis Biomarker Risk Model, Hector R. Wong, Scott L. Weiss, John S. Giuliano Jr., Mark S. Wainwright, Robert J. Freishtat, +20 Additional Authors

Pediatrics Faculty Publications

Background

We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort.

Objective

To test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort.

Methods

Study subjects were recruited from multiple pediatric intensive …

Consanguineous Marriage And Intellectual And Developmental Disabilities Among Arab Bedouins Children Of The Negev Region In Southern Israel: A Pilot Study, Hassan Abu Saad, Salman Elbedour, Eyad Hallaq, Joav Merrick, Ariel Tenenbaum

Pediatrics Faculty Publications

No abstract provided.

Zinc Deficiency-Associated Dermatitis In Infants During A Nationwide Shortage Of Injectable Zinc--Washington, Dc, And Houston, Texas 2012-2013, Duke Ruktanonchai, Michael Lowe, Scott A. Norton, Tiana Garrett, Lamia Soghier, Edward Weiss, June Hatfield, Jeffrey Lapinski, Steven Abrams, Wanda Barfield

Pediatrics Faculty Publications

No abstract provided.

An Efficient, Free-Breathing Protocolf For Mr Right Heart Catheterization, Jonathan R. Mazal, Toby Rogers, Anthony Z. Faranesh, Peter Kellman, William H. Schenke, Annette M. Stine, Laurie P. Grant, Kanishka Ratnayaka, Robert J. Lederman

Pediatrics Posters and Presentations

No abstract provided.

Technologist Primer For Mri Right Heart Catheterization: The Nih And Cnmc Experience, Jonathan R. Mazal, Kendall O'Brien, William Schenke, Annette Stine, Laurie Grant, Anthony Z. Faranesh, Kanishka Ratnayaka, Robert J. Lederman

Pediatrics Posters and Presentations

No abstract provided.

Quantification Of Right Ventricular Function From Short-Axis Displacement-Encoded Images, Jonathan D. Suever, Gregory J. Wehner, Linyuan Jing, David K. Powell, Christopher M. Haggerty, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Presentations

Background

Right ventricular (RV) function is important in many disease states, but is difficult to quantify from routine MR imaging. Previous work has shown that long-axis deformation/strain is the most critical contributor to global RV function; however, short-axis datasets allow for better coverage of the RV. Thus it would be ideal to be able to quantify RV long-axis function using short-axis slice orientations. We hypothesized that a stack of three-dimensional (3D) displacement encoded (DENSE) images could reliably quantify longitudinal deformation of the RV to overcome the need for acquiring additional long-axis views of the RV.

Methods

A contiguous stack of …

Assessment Of Intra- And Inter-Ventricular Cardiac Dyssynchrony In Patients With Repaired Tetralogy Of Fallot: A Cardiac Magnetic Resonance Study, Linyuan Jing, Christopher M. Haggerty, Jonathan D. Suever, Ashwin Prakash, Frank Cecchin, Oskar Skrinjar, Tal Geva, Andrew J. Powell, Brandon K. Fornwalt

Pediatrics Presentations

Background

Patients with repaired tetralogy of Fallot (TOF) frequently have right bundle branch block. However, the contribution of cardiac dyssynchrony to dysfunction remains controversial. To better understand this phenomenon and ultimately study therapies, we developed a method to quantify left (LV), right (RV) and inter-ventricular cardiac dyssynchrony using standard cine CMR.

Methods

30 patients with repaired TOF (age 28 ± 16, 46% female) and 17 healthy controls (age 29 ± 7, 12% female) underwent cine CMR. Patients were imaged twice to assess inter-test reproducibility. Circumferential strain vs time curves were generated with a custom feature tracking algorithm for 12 LV …

Two-Dimensional Estimates Of Left Ventricular Strains Are Significantly Affected By Through-Plane Motion, Jonathan D. Suever, Gregory J. Wehner, Linyuan Jing, David K. Powell, Christopher M. Haggerty, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Presentations

Background

Advanced measures of cardiac mechanics such as left ventricular (LV) strains can be used in conjunction with classical biomarkers to gauge cardiovascular health and improve prediction of patient outcomes. Several imaging techniques, including displacement-encoded magnetic resonance imaging (DENSE), are used to non-invasively assess cardiac mechanics. These data are predominantly acquired in two dimensions (2D) due to simplified post-processing and shorter acquisition times; however, this type of acquisition and subsequent analysis cannot account for through-plane motion caused by longitudinal contraction of the left ventricle. We hypothesized that through-plane motion has a significant effect on 2D strain estimates.

Methods

Cine DENSE …

Characterizing The Temporal Evolution Of Altered Cardiac Mechanics In Diet-Induced Obese Mice Using Cine Dense Cmr, Christopher M. Haggerty, Andrea C. Mattingly, Cassi M. Binkley, Sage P. Kramer, David K. Powell, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Presentations

Background

Obesity and metabolic syndrome are associated with increased risk of cardiovascular disease. Research suggests that altered cardiac mechanics (i.e., reduced strains, torsion, and synchrony of contraction) are present in obesity; yet, the causes of this mechanical dysfunction and its relationship to other sequelae of obesity (e.g., hypertension and elevated blood glucose) are not well understood. We hypothesize that diet-induced obesity in mice leads to reductions in measures of left ventricular (LV) mechanics, which develop in acute response to the onset of hyperglycemia, hypertension, and ventricular remodeling.

Methods

Twenty 4-week-old C57BL/6J mice were randomized (n = 10 per group) to …

Sodium-Coupled Neutral Amino Acid Transporter 1 (Snat1) Modulates L-Citrulline Transport And Nitric Oxide (No) Signaling In Piglet Pulmonary Arterial Endothelial Cells, Anna Dikalova, Angela Fagiana, Judy L. Aschner, Michael Aschner, Marshall Summar, Candice D. Fike

Pediatrics Faculty Publications

Rationale

There is evidence that impairments in nitric oxide (NO) signaling contribute to chronic hypoxia-induced pulmonary hypertension. The L-arginine-NO precursor, L-citrulline, has been shown to ameliorate pulmonary hypertension. Sodium-coupled neutral amino acid transporters (SNATs) are involved in the transport of L-citrulline into pulmonary arterial endothelial cells (PAECs). The functional link between the SNATs, L-citrulline, and NO signaling has not yet been explored.

Objective

We tested the hypothesis that changes in SNAT1 expression and transport function regulate NO production by modulating eNOS coupling in newborn piglet PAECs.

Methods and Results

A silencing RNA (siRNA) technique was used to assess the contribution …

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 …