Medical Specialties Commons^™

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 …

Effects Of Perinatal Oxycodone Exposure On The Cardiovascular Response To Acute Stress In Male Rats At Weaning And In Young Adulthood, Thitinart Sithisarn, Henrietta S. Bada, Richard J. Charnigo, Sandra J. Legan, David C. Randall

Pediatrics Faculty Publications

Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress.

Objectives: to determine the effects of POE on: (1) CV responses to acute stress and ability to discriminate using a classical conditioning paradigm; (2) changes in CV response to the paradigm and retention of the ability to discriminate from postnatal day (PD) 40 to young adulthood.

Methods: Pregnant rats were given i.v. OXY or vehicle (CON) daily. OXY and CON males …

Caveolar Fatty Acids And Acylation Of Caveolin-1, Qian Cai, Ling Guo, Haiqing Gao, Xiang-An Li

Pediatrics Faculty Publications

PURPOSE: Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane. Caveolae contain a variety of signaling proteins which provide platforms for signaling transduction. In addition to enriched with cholesterol and sphingolipids, caveolae also contain a variety of fatty acids. It has been well-established that acylation of protein plays a pivotal role in subcellular location including targeting to caveolae. However, the fatty acid compositions of caveolae and the type of acylation of caveolar proteins remain largely unknown. In this study, we investigated the fatty acids in caveolae and caveolin-1 bound fatty acids.

METHODS: Caveolae were isolated from Chinese hamster …

The Young And Suicide, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

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 …

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 …

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

Pediatrics Faculty Publications

No abstract provided.

The Impact Of The Internet On The Sexual Health Of Adolescents: A Brief Review, Julia Springate, Hatim A. Omar

Pediatrics Faculty Publications

The object of this review is to summarize the impact of the Internet on the sexual health of adolescents. This article examines the use of websites, blogs and chat rooms as sources for sexual health information for adolescents. The influence of Internet pornography on sexual behaviors and attitudes is addressed. The use of the Internet as a place to find sexual partners is also assessed. During a time of great physical, emotional and sexual change, the Internet is playing a huge role in the decisions adolescents are making, both positive and negative.

Neuromyelitis Optica In Child: Diagnostic And Therapeutic Challenges, Karolina Dembinski, Maria Gieron-Korthals, Carlos R. Martinez, Lisa Rodriguez

Pediatrics Faculty Publications

Neuromyelitis optica (NMO) is a rare syndrome of severe inflammatory demyelination of the central nervous system, causing attacks of optic neuritis and transverse myelitis. Although uncommon, attention should be given to the proper identification and management of the affected patients. We present a case of a 13-year-old girl with severe neuromyelitis optica. The patient’s initial presentation consisted of encephalopathy and optic neuritis. Approximately 2 months later, coinciding with the weaning of steroid treatment, she presented with ascending paralysis and respiratory failure. She was seropositive for NMO-IgG. Treatment included intravenous immune globulin, steroids, plasmapheresis, and rituximab and was complemented with proper …

Plac1 Expression Decreases In Chorionic Villi In Response To Labor, Yahdira M. Rodriguez-Prado, Xiaoyuan Kong, Michael E. Fant

Pediatrics Faculty Publications

PLAC1 (Placenta-Specific 1) is a recently described, trophoblast-expressed gene essential for normal placental development. The protein localizes to the microvillus membrane surface of the syncytiotrophoblast in direct proximity to the maternal compartment. Although its role has not been defined, increased circulating levels of human PLAC1 mRNA in maternal blood are associated with preeclampsia. Furthermore, PLAC1-null mice exhibit decreased viability in the peripartum period suggesting a role in pregnancy maintenance late in gestation. We examined PLAC1 gene expression in the human placenta during normal pregnancy and pregnancies associated with maternal diabetes and preeclampsia using quantitative, real time PCR (q-RT-PCR). Although …

Complex Cytogenetic Rearrangements At The Durs1 Locus In Syndromic Duane Retraction Syndrome, Hagit N. Baris, Wai-Man Chan, Caroline Andrews, Doron M. Behar, Diana J. Donovan, Cynthia C. Morton, Judith Ranells, Tuya Pal, Azra H. Ligon, Elizabeth C. Engle

Pediatrics Faculty Publications

No abstract provided.

A New Millennium: A New Age Of Behavioral Disorders?, Artemis Tsitsika, Mari Janikian, Donald E. Greydanus, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

The internet has become one of the most widely accessible media and is a significant part of everyday life in adolescence, offering opportunities for social networking and communication, education and entertainment. However, over the past decade a specific behavioral pattern has been researched in respect to Internet use, leading to isolation and neglect of everyday activities, social life –even personal health in general. The phenomenon has received increasing attention from the scientific community, describing it in various terms such as “excessive”, “problematic”, “pathological”, “addictive” use among others.

European research on Internet addictive behavior have been conducted in the past years …

Internet Addiction, Media Use, And Difficulties Associated With Sleeping In Adolescents, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

The objective of this review article is to summarize the current literature regarding Internet addiction; media use, and sleep disruption in adolescents. Design: Systematic review of current literature. Methods: The data was obtained through literature review of articles published in the last 10 years. Conclusion: Internet addiction and media use have the power to have great influence over the sleep of children and adolescents and it is important to take advantage of the positive effects of media while minimizing the potentially negative, but severe, consequence of sleep disruption.

Cyberbullying: A Brief Review, Amy L. Burnett, John A. Yozwiak, Hatim A. Omar

Pediatrics Faculty Publications

The objective of this review is to summarize the prevalence of Internet use among the adolescent population and the growing threat of cyberbullying. This manuscript also addresses the difference between cyberbullying and traditional bullying and the negative psychological effects that result from cyberbullying. Important intervention and prevention strategies for parents and school officials are noted as well.

Genomic Loss Of Tumor Suppressor Mirna-204 Promotes Cancer Cell Migration And Invasion By Activating Akt/Mtor/Rac1 Signaling And Actin Reorganization, Saadi J. Imam, Jason R. Plyler, Hima Bansal, Suresh Prajapati, Sanjay Bansal, Jennifer Rebeles, Jeffrey S. Dome, +12 Additional Authors

Pediatrics Faculty Publications

Increasing evidence suggests that chromosomal regions containing microRNAs are functionally important in cancers. Here, we show that genomic loci encoding miR-204 are frequently lost in multiple cancers, including ovarian cancers, pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced expression in several cancers and acts as a potent tumor suppressor, inhibiting tumor metastasis in vivo when systemically delivered. We demonstrated that miR-204 exerts its function by targeting genes involved in tumorigenesis including brain-derived neurotrophic factor (BDNF), a neurotrophin family member which is known to promote tumor angiogenesis and invasiveness. Analysis of primary tumors shows that increased expression …