Medical Specialties Commons^™

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

Pediatrics Faculty Publications

No abstract provided.

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

Pediatrics Faculty Publications

Background

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

Methods

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

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

Pediatrics Faculty Publications

No abstract provided.

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

Pediatrics Faculty Publications

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

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

Pediatrics Faculty Publications

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

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

Pediatrics Faculty Publications

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

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

Pediatrics Faculty Publications

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

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

Pediatrics Faculty Publications

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

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

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

Pediatrics Faculty Publications

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

Teens Texting, Archana Srinivas, Megan White, Hatim A. Omar

Pediatrics Faculty Publications

In this chapter we summarize the current literature on texting use amongst adolescents. A brief overview will be presented on the prevalence of texting among teenagers, the use of texting for sexting and cyberbullying as well as the dangers of texting while driving. This chapter will serve as a brief overview of these topics in order to bring to light the emerging challenges that texting presents to the mental and physical well-being of adolescents in an effort to evoke further discussion regarding the need for increasing awareness and education to parents, educators, law makers and health care providers concerning these …

Adolescence And Human Sexuality, Donald E. Greydanus, Hatim A. Omar

Pediatrics Faculty Publications

Human sexuality is a complex phenomenon involving the interaction of biology, sex, core gender identity, and gender role behavior. Successful completion of normal stages of sexuality development is important for children and adolescents to allow for optimal life as an adult. Controversies arise for clinicians as they work with their pediatric patients regarding health care sexuality issues. It is important that clinicians help these patients in an unbiased and neutral manner. As adults, these children and adolescents will function in a number of sexuality roles, whether heterosexual, homosexual, or bisexual. This chapter reviews many of these complex and critical issues …

Emerging Biomarkers And Metabolomics For Assessing Toxic Nephropathy And Acute Kidney Injury (Aki) In Neonatology, M. Mussap, A. Noto, V. Fanos, John N. Van Den Anker

Pediatrics Faculty Publications

Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of …

Autosomal Recessive Polycystic Kidney Disease: The Prototype Of The Hepato-Renal Fibrocystic Diseases, Lisa Guay-Woodford

Pediatrics Faculty Publications

Autosomal recessive polycystic kidney disease (ARPKD) is a severe, typically early onset form of renal cystic disease. The care of ARPKD patients has traditionally been the purview of pediatric nephrologists for management of systemic hypertension and progressive renal insufficiency. However, the disease has multisystem manifestations and a comprehensive care strategy frequently requires a multidisciplinary team. In severely affected infants, the diagnosis often is first suspected by obstetricians when enlarged, echogenic kidneys and oligohydramnios are detected on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. …

Low-Dose Ketamine For Children And Adolescents With Acute Sickle Cell Disease Related Pain: A Single Center Experience, Caitlin M. Neri, Sophie R. Pestieau, Heather Young, Angelo Elmi, Julia C. Finkel, Deepika S. Darbari

Pediatrics Faculty Publications

Background: Opioids are the mainstay of therapy for painful vasoocclusive episodes (VOEs) in sickle cell disease (SCD). Based on limited studies, low-dose ketamine could be a useful adjuvant analgesic for refractory SCD pain, but its safety and efficacy has not been evaluated in pediatric SCD.

Procedure: Using retrospective chart review we recorded and compared characteristics of hospitalizations of 33 children with SCD hospitalized with VOE who were treated with low-dose ketamine and opioid PCA vs. a paired hospitalization where the same patients received opioid PCA without ketamine. We seek to 1) describe a single center experience using adjuvant low-dose ketamine …

Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced …

Characterization Of Cytomegalovirus Lung Infection In Non-Hiv Infected Children, Sonia M. Restrepo-Gualteros, Lina E. Jaramillo-Barberi, Monica Gonzalez-Santos, Carlos E. Rodriguez-Martinez, Geovanny F. Perez, Maria J. Gutierrez, Gustavo Nino

Pediatrics Faculty Publications

Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in …

Population Pharmacokinetics Of Ciprofloxacin In Neonates And Young Infants Less Than 3 Months Age, Wei Zhao, Helen Hill, Chantal Le Guellec, Tim Neal, Sarah Mahoney, Stephanie Paulus, Charlotte Castellan, Behrouz Kassai, John N. Van Den Anker, Gregory L. Kearns, Mark A. Turner, Evelyne Jacqz-Aigrain

Pediatrics Faculty Publications

Ciprofloxacin is used in neonates with suspected or documented Gram-negative serious infections. Currently, its use is off-label partly because of lack of pharmacokinetic studies. Within the FP7 EU project TINN (Treat Infection in NeoNates), our aim was to evaluate the population pharmacokinetics of ciprofloxacin in neonates and young infants <3 months of age and define the appropriate dose in order to optimize ciprofloxacin treatment in this vulnerable population. Blood samples were collected from neonates treated with ciprofloxacin and concentrations were quantified by high-pressure liquid chromatography-mass spectrometry. Population pharmacokinetic analysis was performed using NONMEM software. The data from 60 newborn infants (postmenstrual age [PMA] range, 24.9 to 47.9 weeks) were available for population pharmacokinetic analysis. A two-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that gestational age, postnatal age, current weight, serum creatinine concentration, and use of inotropes had a significant impact on ciprofloxacin pharmacokinetics. Monte Carlo simulation demonstrated that 90% of hypothetical newborns with a PMA of <34 weeks treated with 7.5 mg/kg twice daily and 84% of newborns with a PMA ≥34 weeks and young infants receiving 12.5 mg/kg twice daily would reach the AUC/MIC target of 125, using the standard EUCAST MIC susceptibility breakpoint of 0.5 mg/liter. The associated risks of overdose for the proposed dosing regimen were <8%. The population pharmacokinetics of ciprofloxacin was evaluated in neonates and young infants <3 months old, and a dosing regimen was established based on simulation.

Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis.

METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded …

Hemorrhagic Stroke In An Adolescent Female With Hiv-Associated Thrombotic Thrombocytopenic Purpura, Natella Rakhmanina, Edward C.C. Wong, Jeremiah C. Davis, Patricio E. Ray

Pediatrics Faculty Publications

HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIVTTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented …

Menarche, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Menarche is a female’s first menstrual period and a landmark event for females during puberty. Historically, menarche has been thought of as a time when women were “unclean.” However, cultural acceptance and scientific knowledge of menarche has greatly increased. Menarche occurs as part of the typical progression of puberty caused by rises in luteinizing hormone (LH), follicle stimulating hormone (FSH), and estrogen. The achievement of menstruation is associated with reproductive capability. Menarche that occurs earlier or later than expected should be evaluated by an experienced clinician and may signal a serious underlying problem. Currently, researchers are evaluating whether menarche is …

What We Are Not Talking About, Hatim A. Omar

Pediatrics Faculty Publications

Adolescents undergo significant physical and cognitive changes during their pubertal development. These changes contribute to and impact their future development. Educating adolescents at an early age about their expected development decreases the possible anxiety associated with this period of life and also helps adolescents make better choices in regards to their sexuality. In order to assess the degree of education regarding pubertal development and sexuality, we conducted a survey of late adolescents (median age 19 years) and parents of adolescents. A total of 409 adolescents (237 females, 172 males) and 124 parents completed the survey. 14.4% of teens (36.6% of …

Hyperparathyroidism Two Years After Radioactive Iodine Therapy In An Adolescent Male, Danielle L. Gomez, Dorothy I. Shulman

Pediatrics Faculty Publications

Primary hyperparathyroidism is a very rare complication following radioactive iodine therapy. There is typically a latency period of more than a decade following radiation exposure and, therefore, it is observed almost exclusively in adults. Consequently, pediatricians are not aware of the association. We present a case of primary hyperparathyroidism due to a solitary parathyroid adenoma occurring in an adolescent male two years following radioactive iodine treatment for papillary thyroid carcinoma. Periodic screening of serum calcium following ablative doses of radioactive iodine for thyroid cancer may be justified even in adolescents.

Fish Odor Syndrome: A Case Report Of Trimethylaminuria, Catherine A. Ulman, Julian J. Trevino, Marvin E. Miller, Rishi K. Gandhi

Pediatrics Faculty Publications

Trimethylaminuria is a rare, autosomal recessive, metabolic disorder that results in accumulation of trimethylamine (TMA), which smells like rotten fish. The chemical is excreted in sweat and urine owing to a deficiency in the enzyme flavin monooxygenase 3 (FMO3). We report a case of trimethylaminuria in a 12-year-old girl. The patient failed treatment with diet and hygiene modification, but achieved symptomatic improvement after a four-month course of metronidazole.

Factors For Recurrent Injuries In Victims Of Suspected Non-Accidental Trauma: A Retrospective Cohort Study, Katherine Deans, Jonathan D. Thackeray, Johnathan I. Groner, Jennifer N. Cooper, Peter Minneci

Pediatrics Faculty Publications

Background

Many children who are victims of non-accidental trauma (NAT) may be repeatedly evaluated for injuries related to maltreatment. The purpose of this study was to identify risk factors for repeated injuries in children with suspected NAT.

Methods

We conducted a retrospective cohort study using claims data from a pediatric Medicaid accountable care organization. Children with birth claims and at least one non-birth related claim indicating a diagnosis of NAT or skeletal survey in 2007–2011 were included. Recurrent events were defined as independent episodes of care involving an urgent/emergent care setting that included a diagnosis code specific for child abuse, …

Four-Month-Old Infant With Intussusception Presenting As Altered Mental Status, Luis Maldonado, Jennifer Takagishi

Pediatrics Faculty Publications

Objective: To remind pediatric care providers that an altered mental status can be the only presenting symptom for intussusception, a life-threatening diagnosis.

Method: A case report that presents a unique presentation of intussusception: a 4-month old boy with neurological findings after a reported head injury.

Conclusion: Diagnosis of intussusception in the pediatric population is highly dependent on its classical presenting signs and symptoms: sudden severe colicky abdominal pain, vomiting, and an abdominal mass in children between 3 months and 6 years of age. Consider that an altered mental status can be the only presenting symptom.

Firesetting And Maltreatment, Amy L. Burnett, Hatim A. Omar

Pediatrics Faculty Publications

In this chapter we try to determine if a link exists between firesetting offenders and a past history of maltreatment. A literature review was performed using research from various studies and populations. Firesetting is a significant problem that affects the world's youth today. Even though there is substantial loss of property and life from juvenile firesetters, there is not a great deal of research to provide insight into early identification of those at risk. In the literature review performed, 6 of 7 studies found a link with maltreatment and firesetting behaviors. There does seem to be a correlation between the …

Children, Violence And Bullying, Joav Merrick, Isack Kandel, Hatim A. Omar

Pediatrics Faculty Publications

Adolescent violence is a very visible phenomenon in our modern society, where you just have to open the newspaper or the television and you find yourself right in the middle of it. In order to understand the scope of the problem, we need to look at the epidemiology of global violence. Each year, more than 1.6 million people worldwide lose their lives to violence and for every person who dies as a result of violence, many more are injured and suffer from a range of physical, sexual, reproductive and mental health problems. Violence places a massive burden on national economies …

Adolescent Violence Prevention, Hatim A. Omar

Pediatrics Faculty Publications

Violence in adolescence has seen an increase since the 1990s with dramatic statistics on violent death and risk behaviors. School violence has been focused upon by a huge media coverage of especially violent cases that could have had some endemic consequences worldwide. We present a case of a 14 year old white male with change in school behavior, strategies for the case investigation, its results and long term prevention. Other research has shown that preventive measures during pregnancy, infancy and childhood can prevent adolescent and adult delinquency.

Prevention: Sexual Violence Against Adolescent And Young Adult Women, Kimberly K. Mcclanahan, Marlene B. Huff, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

A Grassroots Program For Youth Suicide Prevention, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Suicide is a major public health problem. It affects people of all ages. Youth, in particular, have a disturbingly high suicide rate. Suicide is the third leading cause of death for young people between the ages of 10 and 24 (1). Approximately 4600 young people die each year from a suicide attempt (1). The most common methods used in suicides are firearms (45%), suffocation (which may be in the form of hanging) (40%), and poisoning (8%) (1). However, more young people survive suicide attempts than actually die from the attempt. A national survey of youth in both private and public …