Medicine and Health Sciences Commons^™

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, …

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 …

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 …

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 …

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.

Pediatric Palliative Care For Youth With Hiv/Aids: Systematic Review Of The Literature, Megan L. Wilkins, Ronald H. Dallas, Kathleen E. Fanone, Maureen E. Lyon

Pediatrics Faculty Publications

Improvement in treatment has led to decreased death in youth with human immunodeficiency virus (HIV) in developed countries. Despite this, youth with HIV are still at risk for increased mortality and morbidity compared with their uninfected counterparts. In developing countries, high numbers of youth die from acquired immune deficiency syndrome (AIDS)-related illnesses due to lack of access to consistent antiretroviral treatment. As a result, pediatric palliative care is a relevant topic for those providing care to youth with HIV. A systematic review was conducted to gather information regarding the status of the literature related to pediatric palliative care and medical …

Crystal Structure Of The N-Acetyltransferase Domain Of Human N-Acetyl-L-Glutamate Synthase In Complex With N-Acetyl-L-Glutamate Provides Insights Into Its Catalytic And Regulatory Mechanisms, Gengxiang Zhao, Zhongmin Jin, Norma M. Allewell, Mendel Tuchman, Dashuang Shi

Pediatrics Faculty Publications

N-acetylglutamate synthase (NAGS) catalyzes the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate (NAG), an obligate cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle. NAGS deficiency results in elevated levels of plasma ammonia which is neurotoxic. We report herein the first crystal structure of human NAGS, that of the catalyticN-acetyltransferase (hNAT) domain with N-acetyl-L-glutamate bound at 2.1 Å resolution. Functional studies indicate that the hNAT domain retains catalytic activity in the absence of the amino acid kinase (AAK) domain. Instead, the major functions of the AAK domain appear to be providing …

A Synthetic Model Of Human Beta-Thalassemia Erythropoiesis Using Cd34+ Cells From Healthy Adult Donors, Y. Terry Lee, Ki-Soon Kim, Colleen Byrnes, Jaira F. De Vasconcellos, Seung-Jae Noh, Antoinette Rabel, Emily Riehm Meier, Jeffrey L. Meier

Pediatrics Faculty Publications

Based upon the lack of clinical samples available for research in many laboratories worldwide, a significant gap exists between basic and clinical studies of beta-thalassemia major. To bridge this gap, we developed an artificially engineered model for human beta thalassemia by knocking down beta-globin gene and protein expression in cultured CD34+ cells obtained from healthy adults. Lentiviral-mediated transduction of beta-globin shRNA (beta-KD) caused imbalanced globin chain production. Beta-globin mRNA was reduced by 90% compared to controls, while alpha-globin mRNA levels were maintained. HPLC analyses revealed a 96% reduction in HbA with only a minor increase in HbF. During the terminal …

Is Adrenalectomy Necessary During Unilateral Nephrectomy For Wilms Tumor? A Report From The Children's Oncology Group., Kathleen Kieran, James R Anderson, Jeffrey S Dome, Peter F Ehrlich, Michael L Ritchey, Robert C Shamberger, Elizabeth J Perlman, Daniel M Green, Andrew M Davidoff

Pediatrics Faculty Publications

PURPOSE: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome.

METHODS: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy.

RESULTS: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially …

From Qualitative Work To Intervention Development In Pediatric Oncology Palliative Care Research, Terrah Foster Akard, Mary Jo Gilmer, Debra L. Friedman, Barbara Given, Verna L. Hendricks-Ferguson, Pamela S. Hinds

Pediatrics Faculty Publications

Qualitative methods can be particularly useful approaches to use with individuals who are experiencing a rare disease and thus who comprise a small sample (such as children with cancer) and are at points in care that few experience (such as end of life). This data-based methods article describes how findings from a qualitative study were used to guide and shape a pediatric oncology palliative care intervention. Qualitative data can lay a strong foundation for subsequent pilot intervention work by facilitating the development of an underlying study conceptualization, providing recruitment feasibility estimates, helping establish clinically meaningful inclusion criteria, establishing staff acceptability …

Characteristics Of Children With The Best And Poorest First- And Second-Year Growth During Rhgh Therapy: Data From 25 Years Of The Genentech National Cooperative Growth Study (Ncgs), Paul B. Kaplowitz, Dorothy I. Shulman, James W. Frane, Joan Jacobs, Barbara Lippe

Pediatrics Faculty Publications

Background

Models assessing characteristics contributing to response to recombinant human growth hormone (rhGH) response rarely address growth extremes in both years 1 and 2 or examine how children track from year to year. Using National Cooperative Growth Study (NCGS) data, we determined characteristics contributing to responsiveness to rhGH and the pattern of change from years 1 to 2.

Patients and methods

Height velocity standard deviation score (HV SDS) for 2 years for prepubertal children with idiopathic GH deficiency (IGHD) (n = 1899) and idiopathic short stature (ISS) (n = 1186) treated with similar doses for two years were computed. Group …

Age-Related Accumulation Of T Cells With Markers Of Relatively Stronger Autoreactivity Leads To Functional Erosion Of T Cells., Zohreh Tatari-Calderone, Milica Stojakovic, Ramita Dewan, Gama L. Bouder, Dragana Jankovic, Stanislav Vukmanovic

Pediatrics Faculty Publications

Background

Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases.

Results

The phenotype of T cells …

Prenatal Diagnosis Of Long Qt Syndrome: Implications For Delivery Room And Neonatal Management, E. Anne Greene, Charles I. Berul, Mary T. Donofrio

Pediatrics Faculty Publications

This case describes the prenatal diagnosis and integrated peripartum management of a foetus with 2:1 atrioventricular block and torsade de pointes due to congenital long QT syndrome. The unique issues related to the detection of intrauterine conduction abnormalities and ventricular arrhythmias, along with the immediate postnatal care, have been described as an interesting teaching case with successful outcome.

Neuropsychiatric Effects Of Tenofovir In Comparison With Other Antiretroviral Drugs., Kathleen Ferrer, Natella Rakhmanina

Pediatrics Faculty Publications

Tenofovir is a widely used antiretroviral medication indicated to treat adults and children infected with HIV. Current guidelines for the management of HIV infection recommend tenofovir disoproxil fumarate (TDF) as a component of the preferred first-line combination antiretroviral therapy. The efficacy, tolerability, prolonged half-life allowing for once-daily administration, and availability as a component of several fixed-dose formulations make TDF an attractive choice for treatment-naive and treatment-experienced HIV-infected patients. TDF is also widely used as a component of postexposure prophylaxis in noninfected individuals. Most importantly, it has been recently approved for use as pre-exposure prophylaxis for noninfected adults and adolescents to …

Wound Care Challenges In Children And Adults With Spina Bifida: An Open-Cohort Study, Katherine Ottolini, Amy B. Harris, June K. Amling, Ann M. Kennelly, Leslie A. Phillips, Laura L. Tosi

Pediatrics Faculty Publications

Skin breakdown is a frequent concern for individuals with spina bifida. We explored wound incidence in patients with spina bifida and how it varies across a person's life span and functional neurologic level. We examined the settings in which skin breakdown most commonly occurred, looking for evidence of chronic, non-healing wounds. We also sought to develop criteria to improve wound monitoring. We identified reported wound episodes in an open-cohort study over a 13-year period, examining the hospital and outpatient clinical records of spina bifida patients at Children's National Medical Center (CNMC). Current age, age at wound presentation, sex, weight, functional …

The Association Of Cd81 Polymorphisms With Alloimmunization In Sickle Cell Disease, Zohreh Tatari-Calderone, Ryad Tamouza, Gama P. Lebouder, Ramita Dewan, Naomi L. Luban, Jacqueline Lasserre, Jacqueline Maury, Francois Lionnet, Rajagopal Krishnamoorthy, Robert Girot, Stanislav Vukmanovic

Pediatrics Faculty Publications

The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization. Given that a subset of SCD patients develop multiple RBC allo-/autoantibodies, while others do not in a similar multiple transfusional setting, we investigated a possible genetic basis for alloimmunization. Biomarker(s) which predicts (predict) susceptibility to alloimmunization could identify patients at risk before the onset of a transfusion program and thus may have …

Alloreactivity-Based Medical Conditions, Stanislav Vukmanovic, Margaret G. Petroff, Anne M. Stevens, Daniel Rukavina

Pediatrics Faculty Publications

No abstract provided.

Activation Of Human Herpesvirus Replication By Apoptosis, Alka Prasad, Jil Remick, Steven L. Zeichner

Pediatrics Faculty Publications

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 …

Oximetry Signal Processing Identifies Rem Sleep-Related Vulnerability Trait In Asthmatic Children, Geovanny F. Perez, Maria J. Gutierrez, Shehlanoor Huseni, Krishna Pancham, Carlos E. Rodriguez-Martinez, Cesar L. Nino, Gustavo Nino

Pediatrics Faculty Publications

Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA.

Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n=134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance level p ≤ 0.05).

Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, …

Low Plasma Citrulline Levels Are Associated With Acute Respiratory Distress Syndrome In Patients With Severe Sepsis, Lorraine B. Ware, Jordan A. Magarik, Nancy Wickersham, Gary Cunningham, Todd W. Rice, Brian W. Christman, Arthur P. Wheeler, Gordon R. Bernard, Marshall Summar

Pediatrics Faculty Publications

Introduction: The role of nitric oxide synthase (NOS) in the pathophysiology of acute respiratory distress syndrome (ARDS) is not well understood. Inducible NOS is upregulated during physiologic stress; however, if NOS substrate is insufficient then NOS can uncouple and switch from NO generation to production of damaging peroxynitrites. We hypothesized that NOS substrate levels are low in patients with severe sepsis and that low levels of the NOS substrate citrulline would be associated with end organ damage including ARDS in severe sepsis.

Methods: Plasma citrulline, arginine and ornithine levels and nitrate/nitrite were measured at baseline in 135 patients with severe …

Can Coronary Artery Involvement In Kawasaki Disease Be Predicted?, Sunil J. Ghelani, Neha Kwatra, Christopher F. Spurney

Pediatrics Faculty Publications

Background: Coronary artery involvement is seen in approximately 15–20% of children with Kawasaki disease. There is conflicting literature regarding the clinical and laboratory findings associated with coronary artery involvement. In this retrospective study, we attempt identification of predictive factors for coronary artery involvement at our institute and review the existing literature.

Methods and results: A review of 203 patients (65% males) with Kawasaki disease was performed, of whom 33 (16.3%) had coronary artery involvement. High erythrocyte sedimentation rate, high platelet count, low hematocrit, low albumin levels, and refractory Kawasaki disease showed significant association with coronary artery involvement. High …