Medicine and Health Sciences Commons^™

Deletion Of Glycogen Synthase Kinase-3Β In Cartilage Results In Up-Regulation Of Glycogen Synthase Kinase-3Α Protein Expression, J. R. Gillespie, V. Ulici, H. Dupuis, A. Higgs, A. Dimattia, S. Patel, J. R. Woodgett, Frank Beier

Paediatrics Publications

The rate of endochondral bone growth determines final height in humans and is tightly controlled. Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/β-catenin. The two GSK-3 proteins, GSK-3 and GSK-3β, display both overlapping and distinct roles in different tissues. Here we show that pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth, accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some, but not all, effects of phosphatidylinositide 3-kinase …

Rac1 Activation Induces Tumour Necrosis Factor-Α Expression And Cardiac Dysfunction In Endotoxemia, Ting Zhang, Xiangru Lu, Frank Beier, Qingping Feng

Paediatrics Publications

Induction of tumour necrosis factor-α (TNF-α) expression leads to myocardial depression during sepsis. However, the underlying molecular mechanisms are not fully understood. The aim of this study was to investigate the role of Rac1 in TNF-α expression and cardiac dysfunction during endotoxemia and to determine the involvement of phosphoinositide-3 kinase (PI3K) in lipopolysaccharide (LPS)-induced Rac1 activation. Our results showed that LPS-induced Rac1 activation and TNF-α expression in cultured neonatal mouse cardiomyocytes. The response was inhibited in Rac1 deficient cardiomyocytes or by a dominant-negative Rac1 (Rac1N17). To determine whether PI3K regulates Rac1 activation, cardiomyocytes were treated with LY294002, a PI3K selective …

Evaluation Of Kawasaki Disease Risk-Scoring Systems For Intravenous Immunoglobulin Resistance., Lynn A. Sleeper, L Luann Minich, Brian M. Mccrindle, Jennifer S. Li, Wilbert Mason, Steven D. Colan, Andrew M. Atz, Beth F. Printz, Annette Baker, Victoria L. Vetter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the performance of 3 risk scores from Japan that were developed to predict, in children with Kawasaki disease, resistance to intravenous immunoglobulin (IVIG) treatment.

STUDY DESIGN: We used data from a randomized trial of pulsed steroids for primary treatment of Kawasaki disease to assess operating characteristics of the 3 risk scores, and we examined whether steroid therapy lowers the risk of coronary artery abnormalities in patients prospectively classified as IVIG resistant.

RESULTS: For comparability with published cohorts, we analyzed the data of 99 patients who were not treated with steroids (16% IVIG-retreated) and identified male sex, lower …

Adolescent Medicine, Carol L. Watwood

DLPS Faculty Publications

No abstract provided.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, And Adenitis (Pfapa) Is A Disorder Of Innate Immunity And Th1 Activation Responsive To Il-1 Blockade., Silvia Stojanov, Sivia Lapidus, Puja Chitkara, Henry Feder, Juan C Salazar, Thomas A Fleisher, Margaret R Brown, Kathryn M Edwards, Michael M Ward, Robert A Colbert, Hong-Wei Sun, Geryl M Wood, Beverly K Barham, Anne Jones, Ivona Aksentijevich, Raphaela Goldbach-Mansky, Balu Athreya, Karyl S Barron, Daniel L Kastner

Department of Pediatrics Faculty Papers

The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in children. However, the pathogenesis is unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary periodic fevers (HPFs), and from healthy children and pediatric HPF patients. Gene expression profiling could clearly distinguish PFAPA flares from asymptomatic intervals, HPF flares, and healthy controls. During PFAPA attacks, complement (C1QB, C2, SERPING1), IL-1-related (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced (AIM2, IP-10/CXCL10) genes were significantly overexpressed, but T cell-associated transcripts (CD3, CD8B) were down-regulated. On the …

Does Improving Maternal Knowledge Of Vaccines Impact Infant Immunization Rates? A Community-Based Randomized-Controlled Trial In Karachi, Pakistan, Aatekah Owais, Beenish Hanif, Amna R. Siddiqui, Ajmal Agha, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: In Pakistan, only 59-73% of children 12-23 months of age are fully immunized. This randomized, controlled trial was conducted to assess the impact of a low-literacy immunization promotion educational intervention for mothers living in low-income communities of Karachi on infant immunization completion rates. Methods: Three hundred and sixty-six mother-infant pairs, with infants aged Results: Baseline characteristics among the two groups were similar. At 4 month assessment, among 179 mother-infant pairs in the intervention group, 129 (72.1%) had received all 3 doses of DPT/Hepatitis B vaccine, whereas in the control group 92/178 (51.7%) had received all 3 doses. Multivariable analysis …

Effect Of Preventive Zinc Supplementation On Linear Growth In Children Under 5 Years Of Age In Developing Countries: A Meta-Analysis Of Studies For Input To The Lives Saved Tool, Aamer Imdad, Zulfiqar Ahmed Bhutta

Woman and Child Health

Introduction:Zinc plays an important role in cellular growth, cellular differentiation and metabolism. The results of previous meta-analyses evaluating effect of zinc supplementation on linear growth are inconsistent. We have updated and evaluated the available evidence according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria and tried to explain the difference in results of the previous reviews.

Methods:

A literature search was done on PubMed, Cochrane Library, IZiNCG database and WHO regional data bases using different terms for zinc and linear growth (height). Data were abstracted in a standardized form. Data were analyzed in two ways i.e. weighted …

Impact Of Maternal Education About Complementary Feeding And Provision Of Complementary Foods On Child Growth In Developing Countries, Aamer Imdad, Mohammad Yawar Yakoob, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Childhood undernutrition is prevalent in low and middle income countries. It is an important indirect cause of child mortality in these countries. According to an estimate, stunting (height for age Z score < -2) and wasting (weight for height Z score < -2) along with intrauterine growth restriction are responsible for about 2.1 million deaths worldwide in children < 5 years of age. This comprises 21 % of all deaths in this age group worldwide. The incidence of stunting is the highest in the first two years of life especially after six months of life when exclusive breastfeeding alone cannot fulfill the energy needs of a rapidly growing child. Complementary feeding for an infant refers to timely introduction of safe and nutritional foods in addition to breast-feeding (BF) i.e. clean and nutritionally rich additional foods introduced at about six months of infant age. Complementary feeding strategies encompass a wide variety of interventions designed to improve not only the quality and quantity of these foods but also improve the feeding behaviors. In this review, we evaluated the effectiveness of two most commonly applied strategies of complementary feeding i.e. timely provision of appropriate complementary foods (+/- nutritional counseling) and education to mothers about practices of complementary feeding on growth. Recommendations have been made for input to the Lives Saved Tool (LiST) model by following standardized guidelines developed by Child Health Epidemiology Reference Group (CHERG).

Methods:

We conducted a systematic review of published randomized and quasi-randomized trials on PubMed, Cochrane Library and WHO regional databases. The included studies were abstracted and graded according to Study Design, limitations, intervention details and outcome effects. The primary outcomes were change in weight and height during the study period among children 6-24 months of age. We hypothesized that provision of complementary food and education of mother …

Impact Of Vitamin A Supplementation On Infant And Childhood Mortality, Aamer Imdad, Mohammad Yawar Yakoob, Christopher Sudfeld, Batool A. Haider, Robert E. Black, Zulfiqar Ahmed Bhutta

Woman and Child Health

Introduction:Vitamin A is important for the integrity and regeneration of respiratory and gastrointestinal epithelia and is involved in regulating human immune function. It has been shown previously that vitamin A has a preventive effect on all-cause and disease specific mortality in children under five. The Purpose of this paper was to get a point estimate of efficacy of vitamin A supplementation in reducing cause specific mortality by using Child Health Epidemiology Reference Group (CHERG) guidelines.

Methods:

A literature search was done on PubMed, Cochrane Library and WHO regional data bases using various free and Mesh terms for vitamin A …

Preventive Zinc Supplementation In Developing Countries: Impact On Mortality And Morbidity Due To Diarrhea, Pneumonia And Malaria, Mohammad Yawar Yakoob, Evropi Theodoratou, Afshan Jabeen, Aamer Imdad, Thomas P. Eisele, Joy Ferguson, Arnoupe Jhass, Igor Rudan, Harry Campbell, Robert E. Black, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation. Data sources/review methods: A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 …

An Evaluation Of The Emerging Interventions Against Respiratory Syncytial Virus (Rsv)-Associated Acute Lower Respiratory Infections In Children, Harish Nair, Vasundhara R. Verma, Evropi Theodoratou, Lina Zgaga, Tanvir Huda, Eric Af Simoes, Peter F. Wright, Igor Rudan, Harry Campbell

Dartmouth Scholarship

Background: Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization.

Methods: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed …

Effect Of Case Management On Neonatal Mortality Due To Sepsis And Pneumonia, Anita K. M. Zaidi, Hammad A. Ganatra, Sana Syed, Simon Cousens, Anne C. C. Lee, Robert Black, Zulfiqar A. Bhutta, Joy E. Lawn

Department of Paediatrics and Child Health

Background: Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-Patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST). Methods: We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where …

Evaluation Of The Reproductive And Developmental Risks Of Caffeine., Robert L Brent, Mildred S Christian, Robert M Diener

Department of Pediatrics Faculty Papers

A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the "pregnancy signal," which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine …

An Evaluation Of Hospital Breastfeeding Policies In The Philadelphia Metropolitan Area 1994-2009: A Comparison With The Baby-Friendly Hospital Initiative Ten Steps., Andrea Crivelli-Kovach, Esther K Chung

Department of Pediatrics Faculty Papers

OBJECTIVE: The purpose of this study was to describe current breastfeeding policies and practices among Philadelphia, PA metropolitan hospitals and changes in their policies and practices over time.

METHODS: In-person group interviews were conducted to obtain a composite picture of actual breastfeeding policies and practices. One questionnaire per hospital was completed based on responses from group consensus. Twenty-five hospitals providing maternity care were contacted. Information was obtained from personnel representing different areas of maternity services. Hospitals were classified according to the degree to which they were implementing the Ten Steps to Successful Breastfeeding.

RESULTS: Mean breastfeeding rates at suburban hospitals …

Gradenigo's Syndrome: Surgical Management In A Child, Hassan Nabeel Humayun, Shabbir Akhtar, Shakeel Ahmed

Section of General Surgery

Otits media is a common problem. Some of its complications that were seen frequently in the preantibiotic era are rare today. We report a case of an 8 year boy who presented with earache, retro-orbital pain and diplopia secondary to a sixth nerve palsy--Gradenigo's syndrome. In this syndrome infection from the middle ear spreads medially to the petrous apex of the temporal bone. Work-up includes CT scan of the temporal bones. Timely management with intravenous antibiotics (+ surgery) is needed to prevent intra-cranial complications.

Dual Chamber Pacemaker Implants--A New Opportunity In Pakistan For Children With Congenital And Acquired Complete Heart Block, Awais Ashfaq, Mansoor Ahmed Khan, Mehnaz Atiq, Muhammad Muneer Amanullah

Section of Cardiothoracic Surgery

Implantation of cardiac pacemakers has been practiced for at least five decades with continuous developments of the hardware. The invention of dual chamber pacemakers has initiated a debate concerning its superiority over single chamber ventricular pacemakers. Throughout the world, surgeons have been using dual chambered permanent pacemakers with successful follow ups. However, Pakistan has not yet taken the advantage of such pacemaker devices till now. We report three cases that underwent a dual chamber permanent pacemaker implantation for the first time in children less than 8 kg with successful follow ups.

Seeing The Unseen:Targeting Neonatal Mortality In Rural Vietnam., Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

No abstract provided.

Menstrual Bleeding Patterns In Adolescents Using Etonogestrel (Eng) Implant, Amit M. Deokar, Wendy Jackson, Hatim A. Omar

Pediatrics Faculty Publications

Background: Etonogestrel (ENG) implant is an effective method of contraception. The implant is designed to provide contraceptive efficacy for 3 years with a relatively quick return of fertility upon its removal. Menstrual irregularities are not uncommon on long-acting progestins and can often be the factor for discontinuation or removal. A retrospective chart analysis was done on 58 patients who chose to be on the ENG implant. Age ranged from 12 to 24 years. The cycle ranged from 1 to 17 months. The mean length of use of the implant was 10.9 months. Over the 20-month period, 13 ENG implants were …

The Pulmonologist's Role In Caring For Pregnant Women With Regard To The Reproductive Risks Of Diagnostic Radiological Studies Or Radiation Therapy., Robert Brent

Department of Pediatrics Faculty Papers

Radiography of the chest, head, neck, teeth, or extremity exposes the embryo or ovary to insignificant exposures of radiation except when radionuclides are utilized. In some instances, there is no exposure at all. Pulmonologists are fortunate with regard to the specific studies they request to provide clinical care because most of the diagnostic tests do not directly expose the uterus (embryo) or ovary. This article discusses radiation risks and their evaluation and pregnancy-related issues in diagnostic radiological studies.

Pediatric Ethics Guidelines For Hereditary Medullary Thyroid Cancer, M. Sara Rosenthal, Douglas S. Diekema

Internal Medicine Faculty Publications

Hereditary medullary thyroid cancer is an aggressive cancer for which there is no standard effective systemic therapy, but which can be prevented through genetic screening and prophylactic thyroidectomy. Although this cancer accounts for roughly 17% of all pediatric thyroid cancers, a significant percentage of affected families do not "accept" screening, while many gene carriers delay or refuse prophylactic thyroid surgery for their children. Current genetic screening practices in medullary thyroid cancer are inadequate; more than 50% of index patients with hereditary medullary thyroid cancer present with a thyroid mass; up to 75% have distant metastasis. These proposed pediatric ethics guidelines …

Human Spinal Cord Injury Causes Specific Increases In Surface Expression Of Beta Integrins On Leukocytes, Feng Bao, Christopher S. Bailey, Kevin R. Gurr, Stewart I. Bailey, M. Patricia Rosas-Arellano, Arthur Brown, Gregory A. Dekaban, Lynne C. Weaver

Paediatrics Publications

Spinal cord injury (SCI) activates circulating leukocytes that migrate into the injured cord and bystander organs using adhesion molecule-mediated mechanisms. These cells cause oxidative damage, resulting in secondary injury to the spinal cord, as well as injury to bystander organs. This study was designed to examine, over a 6-h to 2-week period, changes in adhesion molecule surface expression on human peripheral leukocytes after SCI (9 subjects), using as controls 10 uninjured subjects and 6 general trauma patients (trauma controls, TC). Both the percentage of cells expressing a given adhesion molecule and the average level of its expression was quantified for …

Hyperfiltration Affects Accuracy Of Creatinine Egfr Measurement, Shih Han S. Huang, Ajay P. Sharma, Abeer Yasin, Robert M. Lindsay, William F. Clark, Guido Filler

Paediatrics Publications

Background and objectives: Surrogate markers such as creatinine, cystatin C (CysC), and beta trace protein (BTP) have been used to estimate GFR (eGFR). The accuracy of eGFR may be altered with hyperfiltration and differences in filtration fraction (FF). It is hypothesized that the accuracy of creatinine for eGFR may be affected by hyperfiltration and different effective renal plasma flow (ERPF). Design, setting, participants, & measurements: A total of 127 pediatric patients with various renal diseases underwent simultaneous measurements of GFR using 51Cr-EDTA renal scan and ERPF ( 131I-hippurate clearance) to calculate the FF (FF = GFR/ERPF). The eGFRs were calculated …

Does Treatment Of Premature Labor With Terbutaline Increase The Risk Of Autism Spectrum Disorders?, Patricia Rodier, Richard K Miller, Robert L Brent

Department of Pediatrics Faculty Papers

Beta-adrenergic agents have been used in pregnant women for the treatment of premature labor and for the treatment of asthma. Concerns have been expressed that exposure to terbutaline, a beta-2 adrenergic agonist, may increase the risk of autism spectrum disorders (ASDs) in the offspring. This hypothesis deserves critical review, given the number of patients exposed to the drug in the last two decades. The results are important to both the obstetricians and patients who weigh the risks and benefits of interventions and to the pediatricians who counsel the families of affected children.

Serum 25-Hydroxyvitamin D Level And Acute-Phase Reaction Following Initial Intravenous Bisphosphonate., Tarak Srivastava, Hongying Dai, Connie J. Haney, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Continuous Ambulatory Peritoneal Dialysis (Capd) Associated Peritonitis In A Child: A Rare Case Of Peritonitis Caused By Sphingomonous Paucimobilis, Arwa Quresh Tambawala, Sadaf Hamid, Iqtidar Khan, Asad Ali

Department of Paediatrics and Child Health

First identified in 1977, Sphingomonous Paucimobilis has emerged as an opportunistic human pathogen. It is primarily known to cause a range of mostly nosocomial, non-life-threatening infections that typically are easily treated by antibiotic therapy. Sources of its isolation linked to clinical disease include blood, spinal fluid and leg ulcers. It has also been reported as a rare cause of peritonitis in patients on continuous ambulatory peritoneal dialysis. We present a case of a child with peritonitis due to this organism. Clinical features, bacteriology and treatment option and response have been discussed.

Safety Of Insulin Tolerance Test For The Assessment Of Growth Hormone Deficiency In Children, Saira Waqar Lone, Yasir Naqi Khan, Farah Qamar, Irum Atta, Mohsina Noor Ibrahim, Jamal Raza

Department of Paediatrics and Child Health

OBJECTIVE: To determine the safety of insulin tolerance test (ITT) for assessing growth hormone (GH) deficiency in children.

METHODS: This hospital based study was conducted at the National Institute of Child Health, Karachi from 1st November 2008 till 30th October 2009. All children suspected of growth hormone deficiency, were included after excluding all other causes of short stature. Verbal informed consent was taken from the parents. Children less than 2 years of age, weighing less than 10 kg, untreated/inadequately treated hypothyroidism or Addison's disease, epilepsy, having history of hypoglycaemic fits or cardiac disease were excluded. All children were subjected to …

Noncoronary Cardiac Abnormalities Are Associated With Coronary Artery Dilation And With Laboratory Inflammatory Markers In Acute Kawasaki Disease., Beth F. Printz, Lynn A. Sleeper, Jane W. Newburger, L Luann Minich, Timothy Bradley, Meryl S. Cohen, Deborah Frank, Jennifer S. Li, Renee Margossian, Girish S. Shirali, Masato Takahashi, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: We explored the association of noncoronary cardiac abnormalities with coronary artery dilation and with laboratory inflammatory markers early after Kawasaki disease (KD) diagnosis.

BACKGROUND: Left ventricular (LV) dysfunction, mitral regurgitation (MR), and aortic root dilation occur early after diagnosis; their associations with coronary artery dilation and inflammatory markers have not been well-described.

METHODS: Centrally interpreted echocardiograms were obtained at KD diagnosis and 1 and 5 weeks after diagnosis on 198 subjects in the National Institutes of Health-sponsored Pediatric Heart Network KD pulsed steroid trial. Regression models were constructed to investigate the relationships among early LV dysfunction, MR, and aortic …

Expedient Treatment Of A Collodion Baby, Michael Chung, Jaime Pittenger, Stuart Tobin, Andrew Chung, Nirmala Desai

Pediatrics Faculty Publications

Only ~270 cases of collodion babies have been reported in the literature since 1892. As the name suggests, the term "collodion baby" refers to a phenotype that can be characterized by a yellow, shiny, tight parchment-like membrane stretched over the skin. Although the collodion membrane is only an evanescent condition of the newborn, neonatal complications can occur in 45% of all collodion babies, leading to a mortality rate of ~11% in the first few weeks of life. Most children born as collodion babies will spontaneously desquamate within 2 weeks, but may be as long as 3 months. Eventually, these children …

No Significant Change In Sexual Behavior In Association With Human Papilloma Virus Vaccination In Young Girls, Wafa R.R. Al Romaih, Archana Srinivas, Said Shahtahmasebi, Hatim A. Omar

Pediatrics Faculty Publications

The first human Papilloma virus (HPV) vaccine was approved in the United States in 2006 with the potential to reduce cervical cancer and genital warts. Since then, its efficacy in preventing HPV-related cancers in both males and females has been promising. Despite CDC recommendations, opponents of the vaccine assert that vaccinating pre-adolescents and adolescents will increase their sexual activity, as well as overtly condone risky sexual behavior. We analyzed clinic data of 499 adolescents with a mean age of 16 years to explore whether vaccination led to change in sexual behavior after one year. Our results showed no statistically significant …

Efficacy Of Limited Cefuroxime Prophylaxis In Pediatric Patients After Cardiovascular Surgery, Chad A. Knoderer, Elaine G. Cox, Michelle D. Berg, Andrea H. Webster, Mark W. Turrentine

Scholarship and Professional Work – COPHS

Purpose The efficacy of limited cefuroxime prophylaxis in pediatric patients after cardiovascular surgery was evaluated.

Methods All patients age 18 years or younger who underwent cardiovascular surgery and received postoperative care from the cardiovascular surgery team between February and July 2006 (preintervention group) and between August 2006 and January 2007 (postintervention group) were eligible for study inclusion. Patients were excluded if they did not receive cefuroxime as postoperative prophylaxis, had a preexisting infection, underwent cardiac transplantation or extracorporeal membrane oxygenation, or underwent delayed sternal closure. The preintervention group received prolonged cefuroxime prophylaxis, and the postintervention group received 24 hours of …