Pediatrics Commons^™

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 …

Children, Adolescents And Firesetting, Joav Merrick, Carrie Howell Bowling, Hatim A. Omar

Pediatrics Faculty Publications

The research of firesetting has been conducted in different ways and lacks a coherent, consistent and comprehensive set of empirical findings. A recent review concluded that despite a number of risk factors being repeatedly identified, an understanding of the etiology behind firesetting behavior and potential developmental trajectories remains theoretically rather than empirically based. Existing theories do not take sufficient account of the complexities of firesetting behavior and there is not yet a typology and accompanying assessment that has undergone thorough empirical testing and is of significant clinical utility. Due to the relationship between firesetting and antisocial behavior there is a …

Firesetting, Sexual Abuse And Long-Term Consequences, Lesley Davidson, Hatim A. Omar

Pediatrics Faculty Publications

In this chapter we summarize the limited studies on post-pubertal consequences of female childhood sexual abuse that includes both psychological distress and physiological stress. The characteristics of sexual abuse are discussed and determined to play a major role in the degree of trauma experienced and in the later effects. The concept of hormones and how disruptions in various endocrine systems can affect the development of these females are examined, especially during the pubertal period. Outcomes of interest included competence, in terms of cognitive, social, self-esteem, and locus of control, and psychopathology including depression, anxiety, dissociation, and hypersexuality. Direct physical results …

Firesetting Behavior And Psychiatric Disorders, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Firesetting behavior results in serious damage to lives and property every year. Firesetting has been linked to a number of comorbid psychiatric disorders including depression, substance abuse, conduct disorder, antisocial personality disorder, obsessive compulsive disorder, psychotic disorder, schizoid personality disorder, and schizophrenia. Psychiatric disorders differ by gender. In addition, juvenile firesetters have history of a separate set of psychiatric comorbidities. The strong correlation between psychiatric comorbidities and firesetting behavior illustrates the need for fire service and mental health collaboration.

Self-Reported Juvenile Firesetting, Carrie Howell Bowling, Hatim A. Omar

Pediatrics Faculty Publications

In this chapter we address gaps in existing research by examining the relationship between academic performance and attention problems with juvenile firesetting. Two datasets from the Achenbach System for Empirically Based Assessment (ASEBA) were used. The Factor Analysis Dataset (N = 975) was utilized and results indicated that adolescents who report lower academic performance are more likely to set fires. Additionally, adolescents who report a poor attitude toward school are even more likely to set fires. Logistic regressions were run to determine if attention problems predicted firesetting and the findings indicated that attention problems are predictive of self-reported firesetting. The …

Adolescent Bereavement, Leslie Robin, Hatim A. Omar

Pediatrics Faculty Publications

Depending on cognitive and emotional development, an adolescent may grieve very differently than a child or an adult. While mature enough to understand death's irreversibility, adolescents may not fully comprehend the enduring consequences of a loved one's death. As the desire to separate from their families and forge new intimate relationships with peers assumes increasing priority, adolescents can seem egocentric in their reaction to death, a response which often frustrates and perplexes adults. Because volatile behavior is characteristic of adolescence, health providers struggle to differentiate between normal and complicated bereavement. Here we review the commonly-accepted characteristics of normal and complicated …

Adolescent Health Issues, Joav Merrick, Ariel Tenenbaum, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

United States: Sexual Behavior In Association With Human Papilloma Virus Vaccination In Young Girls, Wafa R.R. Al Romaih, 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 preadolescents 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 …

Dating Violence In Adolescence, Anuja Bandyopadhyay, Amit M. Deokar, Hatim A. Omar

Pediatrics Faculty Publications

Adolescent dating violence is a health and social problem, worldwide. The objective of this chapter was to identify the risk factors and consequences of dating violence, assess the prevention measures taken to increase awareness regarding it and provide an overview of the screening and interventional tools used to support the teens involved in dating violence. Methods: A review of the literature, published in the last 29 years, was conducted and the content was clinically analyzed. Conclusions: There is an increasing trend of dating violence in a younger population. Consistent definitions, comprehensive assessment tools and focused screening are required to assess …

A Grassroots Program For Youth Suicide Prevention: An Overview Of Participant Comments Following Stop Youth Suicide Conference, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Disability And Women's Health, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Children, adolescents, and women with disabilities experience the same sexual development, pubertal changes, concerns, and desire to reproduce as their typically developing counterparts. However, society has tended to stigmatize women with disabilities as "asexual" and ignore this aspect of their health care. These women are less likely to receive gynecological exams, contraception, and evaluation of sexual dysfunction. Unfortunately, having a disability places women at risk for sexual exploitation and abuse as well as sexually transmitted infections. Therefore, reproductive health care for these women is imperative. A number of barriers to receiving reproductive care exist. However, with proper education and knowledge …

Family Environmental Health And Teen Outcomes, Lesley Davidson, Alissa Briggs, Hatim A. Omar

Pediatrics Faculty Publications

Understanding the impact of family dynamics on health has become an environmental health priority in the field of adolescent medicine. Family dynamics are much more complex than they were 60 years ago and so are behavioral outcomes. This transformation in the American family has led towards a large array of adolescent living situations. Rural Kentucky is a prime example of an area with a high rate of nontraditional family composition. Poor family dynamics may be associated with increased rates of high risk behaviors among teenagers. Among these behaviors are drug use, sexual activity, and depression. In this study, we evaluated …

Academic Predictors And Characteristics Of Self-Reported Juvenile Firesetting, Carrie Howell Bowling, Hatim A. Omar

Pediatrics Faculty Publications

The main purpose of this study was to address gaps in existing research by examining the relationship between academic performance and attention problems with juvenile firesetting. Two datasets from the Achenbach System for Empirically Based Assessment (ASEBA) were used. The Factor Analysis Dataset (N = 975) was utilized and results indicated that adolescents who report lower academic performance are more likely to set fires. Additionally, adolescents who report a poor attitude toward school are even more likely to set fires. Logistic regressions were run to determine if attention problems predicted firesetting and the findings indicated that attention problems are predictive …

Adolescence And Sexuality, Joav Merrick, Ariel Tenenbaum, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Obesity Reduces Left Ventricular Strains, Torsion, And Synchrony In Mouse Models: A Cine Displacement Encoding With Stimulated Echoes (Dense) Cardiovascular Magnetic Resonance Study, Sage P. Kramer, David K. Powell, Christopher M. Haggerty, Cassi M. Binkley, Andrea C. Mattingly, Lisa A. Cassis, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

BACKGROUND: Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV).

METHODS: Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on …