Medical Specialties Commons^™

Magnetic Resonance Imaging/Angiography And Transcranial Doppler Velocities In Sickle Cell Anemia: Results From The Switch Trial, K. J. Helton, R. J. Adams, K. L. Kesler, A. Lockhart, B. Aygun, C. Driscoll, M. M. Heeney, S. M. Jackson, L. Krishnamurti, R. E. Ware, +3 Additional Authors

Journal Articles

The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over 7 years before enrollment. Standardized brain magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial Doppler (TCD) exams were performed at entry and exit, with a central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% >/=Grade 4); 31% had no vessel stenosis on either side. Baseline parenchymal injury was prevalent (85%/79% subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children had low or uninterpretable …

A New System For Naming Ribosomal Proteins, N. Ban, R. Beckmann, J. H. D. Cate, J. D. Dinman, F. Dragon, S. R. Ellis, D. L. J. Lafontaine, L. Lindahl, J. M. Lipton, M. Yusupov, +15 Additional Authors

Journal Articles

A system for naming ribosomal proteins is described that the authors intend to use in the future. They urge others to adopt it. The objective is to eliminate the confusion caused by the assignment of identical names to ribosomal proteins from different species that are unrelated in structure and function. In the system proposed here, homologous ribosomal proteins are assigned the same name, regardless of species. It is designed so that new names are similar enough to old names to be easily recognized, but are written in a format that unambiguously identifies them as 'new system' names.

Newborn Screening For Scid In New York State: Experience From The First Two Years, B. H. Vogel, V. Bonagura, G. A. Weinberg, M. Ballow, J. Isabelle, L. Diantonio, A. Parker, A. Young, C. Cunningham-Rundles, M. Caggana, +8 Additional Authors

Journal Articles

PURPOSE: To describe the process and assess outcomes for the first 2 years of newborn screening for severe combined immunodeficiency (SCID NBS) in New York State (NYS). METHODS: The NYS algorithm utilizes a first-tier molecular screen for TRECs (T-cell receptor excision circles), the absence of which is indicative of increased risk of immunodeficiency. RESULTS: During the first 2 years, 485,912 infants were screened for SCID. Repeat specimens were requested from 561 premature and 746 non-premature infants with low or borderline TRECs. A total of 531 infants were referred for diagnostic evaluation leading to identification of 10 infants with SCID and …

Newborn Screening For Severe Combined Immunodeficiency In 11 Screening Programs In The United States, A. Kwan, R. S. Abraham, R. Currier, A. Brower, K. Andruszewski, J. K. Abbott, M. Baker, M. Ballow, L. E. Bartoshesky, V. R. Bonagura, +70 Additional Authors

Journal Articles

IMPORTANCE: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. OBJECTIVES: To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN: Epidemiological and retrospective …

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 …

Comprehensive Analysis Of Human Cytomegalovirus Microrna Expression During Lytic And Quiescent Infection, Zhang-Zhou Shen, Xing Pan, Ling-Feng Miao, Han-Qing Ye, Stéphane Chavanas, Christian Davrinche, Michael Mcvoy, Min-Hua Luo

Pediatrics Publications

Background

Human cytomegalovirus (HCMV) encodes microRNAs (miRNAs) that function as post-transcriptional regulators of gene expression during lytic infection in permissive cells. Some miRNAs have been shown to suppress virus replication, which could help HCMV to establish or maintain latent infection. However, HCMV miRNA expression has not been comprehensively examined and compared using cell culture systems representing permissive (lytic) and semi-permissive vs. non-permissive (latent-like) infection.

Methods

Viral miRNAs levels and expression kinetics during HCMV infection were determined by miRNA-specific stem-loop RT-PCR. HCMV infected THP-1 (non-permissive), differentiated THP-1 (d-THP-1, semi-permissive) and human embryo lung fibroblasts (HELs, fully-permissive) were examined. The impact of …

Compliance With Referrals For Non-Acute Child Health Conditions: Evidence From The Longitudinal Asenze Study In Kwazulu Natal, South Africa, O. T. Uwemedimo, S. M. Arpadi, M. K. Chhagan, S. Kauchali, M. H. Craib, F. Bah, L. L. Davidson

Journal Articles

BACKGROUND: Caregiver compliance with referrals for child health services is essential to child health outcomes. Many studies in sub-Saharan Africa have examined compliance patterns for children referred for acute, life-threatening conditions but few for children referred for non-acute conditions. The aims of this analysis were to determine the rate of referral compliance and investigate factors associated with referral compliance in KwaZulu Natal, South Africa. METHODS: From September 2008-2010, a door-to-door household survey was conducted to identify children aged 4-6 years in outer-west eThekwini District, KwaZulu-Natal, South Africa. Of 2,049 identified, informed consent was obtained for 1787 (89%) children who were …

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. …

Clinical Profile Of Scrub Typhus In Children And Its Association With Hemophagocytic Lymphohistiocytosis, Saptharishi Lalgudi Ganesan, Naveen Sankhyan, Kandasamy Sasidaran, Anil Kanga, Sunit C. Singhi

Data and Test Instruments

No abstract provided.

Clinical Features And Genetic Analysis Of 20 Chinese Patients With X-Linked Hyper-Igm Syndrome, Lin-Lin Wang, Wei Zhou, Wei Zhao, Zhi-Qing Tian, Wei-Fan Wang, Xiao-Fang Wang, Tong-Xin Chen

Pediatrics Publications

X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways. We retrospectively analyzed the clinical and molecular features of 20 Chinese patients diagnosed and followed up in hospitals affiliated to Shanghai Jiao Tong University School of Medicine from 1999 to 2013. The median onset age of these patients was 8.5 months (range: 20 days–21 months). Half of them had positive family histories, with a shorter diagnosis lag. The most common symptoms were recurrent sinopulmonary infections (18 patients, 90%), neutropenia (14 patients, 70%), oral ulcer (13 patients, 65%), and protracted diarrhea …

Metabolic Effects Of Acute Thiamine Depletion Are Reversed By Rapamycin In Breast And Leukemia Cells, Shuqian Liu, Sumitra Miriyala, Mignon A. Keaton, Craig T. Jordan, Christina Wiedl, Daret K. St. Clair, Jeffrey A. Moscow

Pediatrics Publications

Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently altered in cancer and therefore present cancer-relevant targets. We have previously shown that the recombinant enzyme thiaminase cleaves and depletes intracellular thiamine, has growth inhibitory activity against leukemia and breast cancer cell lines, and that its growth inhibitory effects were reversed in leukemia cell lines by rapamycin. Now, we first show further evidence of thiaminase therapeutic potential by demonstrating its activity against breast and leukemia xenografts, and against a primary leukemia xenograft. We therefore further explored the metabolic effects of thiaminase in combination with rapamycin in leukemia and breast cell lines. …

Cinacalcet Administration By Gastrostomy Tube In A Child Receiving Peritoneal Dialysis, Kristen R. Nichols, Chad A. Knoderer, Bethanne Johnston, Amy C. Wilson

Scholarship and Professional Work – COPHS

A 2-year-old male with chronic kidney disease with secondary hyperparathyroidism developed hypercalcemia while receiving calcitriol, without achieving a serum parathyroid hormone concentration within the goal range. Cinacalcet 15 mg (1.2 mg/kg), crushed and administered via gastrostomy tube, was added to the patient’s therapy. This therapy was effective in achieving targeted laboratory parameters in our patient despite instructions in the prescribing information that cinacalcet should always be taken whole.

Optimized Antimicrobial Dosing Strategies: A Survey Of Pediatric Hospitals, Chad A. Knoderer, Kristen R. Nichols, Elaine G. Cox

Scholarship and Professional Work – COPHS

Background

Extended-interval aminoglycoside (EIAG) and extended- and continuous-infusion β-lactam (EIBL and CIBL) dosing strategies are increasingly used in adults, but pediatric literature is limited.

Objective

The objective of this study was to describe the use of EIAG, EIBL, and CIBL dosing in pediatric hospitals in the USA.

Study Design, Setting, and Participants

A national survey of children’s hospitals was conducted. A single practitioner from each target hospital was identified through the Children’s Hospital Association. Practice-based survey questions identified whether hospitals utilize EIAG, EIBL, and CIBL dosing.

Main Outcome Measure

The main outcome measure was the percentage utilization of the dosing …

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 …

Research Annual Report Fy2014, Children's Mercy Hospital

Research Annual Reports

Annual report of the research at Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Graduate Medical Education 2013-2014 Annual Report, Children's Mercy Hospital

GME Annual Reports

Annual report of the Children's Mercy Hospital Graduate Medical Education department, including pediatric residency, internal medicine/pediatrics residency, fellowship programs, medical students, continuing medical education, and library services.

Improved Growth And Development In Premature Infants Managed With Nasal Continuous Positive Airway Pressure, Susan L. Flesher M.D., Renee S. Domanico M.D.

Pediatrics

Objective: Our goal was to assess the association between the use of nasal continuous positive airway pressure (NCPAP) vs. conventional ventilation (CV) in premature infants and its effects on: 1) growth in the NICU and at follow up visits 2) neurodevelopmental outcomes measured by Bayley Infant Neurodevelopmental Screener (BINS) 3) the incidence of retinopathy of prematurity (ROP) and chronic lung disease (CLD).

Methods: A retrospective chart review of two groups of NICU patients was conducted. The first group was from 1/1999 – 12/2000 (n=140) and was managed by CV. The second group (n=168) was from 1/2003 – 12/2004 and was …

Choline Kinase Beta Is Required For Normal Endochondral Bone Formation, Zhuo Li, Gengshu Wu, Roger B. Sher, Zohreh Khavandgar, Martin Hermansson, Gregory A. Cox, Michael R. Doschak, Monzur Murshed, Frank Beier, Dennis E. Vance

Paediatrics Publications

Background Choline kinase has three isoforms encoded by the genes Chka and Chkb. Inactivation of Chka in mice results in embryonic lethality, whereas Chkb-/- mice display neonatal forelimb bone deformations. Methods To understand the mechanisms underlying the bone deformations, we compared the biology and biochemistry of bone formation from embryonic to young adult wild-type (WT) and Chkb-/- mice. Results The deformations are specific to the radius and ulna during the late embryonic stage. The radius and ulna of Chkb-/- mice display expanded hypertrophic zones, unorganized proliferative columns in their growth plates, and delayed formation of primary ossification centers. The differentiation …

The Role Of The Insula In Speech And Language Processing, Anna Oh, Emma G. Duerden, Elizabeth W. Pang

Paediatrics Publications

Lesion and neuroimaging studies indicate that the insula mediates motor aspects of speech production, specifically, articulatory control. Although it has direct connections to Broca's area, the canonical speech production region, the insula is also broadly connected with other speech and language centres, and may play a role in coordinating higher-order cognitive aspects of speech and language production. The extent of the insula's involvement in speech and language processing was assessed using the Activation Likelihood Estimation (ALE) method. Meta-analyses of 42 fMRI studies with healthy adults were performed, comparing insula activation during performance of language (expressive and receptive) and speech (production …

Measuring Physicians' Productivity: A Three-Year Study To Evaluate A New Remuneration System, Guido Filler, Vanessa Burkoski, Gary Tithecott

Paediatrics Publications

PURPOSE: To evaluate a new assessment tool measuring physicians' academic productivity and its use in a performance-based remuneration system. METHOD: The authors developed an assessment tool based on existing tools to measure productivity. Yearly, from 2008 to 2011, physicians at the University of Western Ontario received a score of up to three points for each of four components (impact, application, scholarly activity, mentorship) in each of four domains (clinical practice, education, research, administration). Scores were weighted by the percentage of time physicians spent on tasks in each domain. Year 1 scores were a baseline. In Years 2 and 3, scores …

Diagnosis By Peritoneal Scintigraphy Of Peritoneal Dialysis–Associated Hydrothorax In An Infant, M. Chavannes, A. P. Sharma, R. N. Singh, R. H. Reid, G. Filler

Paediatrics Publications

No abstract provided.

Chronic Abdominal Pain & Colonic Non-Fixation Case Report, Brett Howe, Andreana Butter

Paediatrics Publications

Abnormalities of intestinal rotation and fixation occur in one out of 500 live births and usually present within the first month of life. We report a case of a 14-year-old girl with lifelong, chronic abdominal pain. Despite treatment by multiple specialists and psychiatrists, her pain remained severe. A barium enema revealed that her left colon was located along her right paracolic gutter, suggesting a form of malrotation/ non-fixation. Laparoscopy, followed by laparotomy, demonstrated a complete lack of fixation of her entire colon. Due to the mobility of the colon, as well as its redundant mesentery, her entire small bowel was …

Low Birth Weight Male Guinea Pig Offspring Display Increased Visceral Adiposity In Early Adulthood., Ousseynou Sarr, Jennifer A Thompson, Lin Zhao, Ting-Yim Lee, Timothy Regnault

Paediatrics Publications

Uteroplacental insufficiency (UPI)-induced intrauterine growth restriction (IUGR) predisposes individuals to adult visceral obesity. We postulated that low birth weight (LBW) offspring, from UPI-induced IUGR pregnancies, would display a visceral adipose lipogenic molecular signature involving altered gene expression, phosphorylation status of proteins of the lipid synthesis pathway and microRNA (miR) expression profile, occurring in association with increased visceral adiposity. Normal birth weight (NBW) and LBW (obtained by uterine artery ablation) male guinea pig pups were fed a control diet from weaning to 145 days and sacrificed. Despite being lighter at birth, LBW pups displayed body weights similar to NBW offspring at …

Children's Mercy Hospital Annual Report 2013, Children's Mercy Hospital

Children's Mercy Annual Reports

Annual report for The Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

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 …