Medicine and Health Sciences Commons^™

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 …

Loss Of Atrx Does Not Confer Susceptibility To Osteoarthritis, Lauren A. Solomon, Bailey A. Russell, David Makar, Nathalie G. Bérubé, Frank Beier

Paediatrics Publications

The chromatin remodelling protein ATRX is associated with the rare genetic disorder ATR-X syndrome. This syndrome includes developmental delay, cognitive impairment, and a variety of skeletal deformities. ATRX plays a role in several basic chromatin-mediated cellular events including DNA replication, telomere stability, gene transcription, and chromosome congression and cohesion during cell division. We have used a loss-of-function approach to directly investigate the role of Atrx in the adult skeleton in three different models of selective Atrx loss. We specifically targeted deletion of Atrx to the forelimb mesenchyme, to cartilage and to bone-forming osteoblasts. We previously demonstrated that loss of ATRX …

The Ciliary Protein Cystin Forms A Regulatory Complex With Necdin To Modulate Myc Expression, Maoqing Wu, Chaozhe Yang, Binli Tao, Su Bu, Lisa Guay-Woodford

Pediatrics Faculty Publications

Cystin is a novel cilia-associated protein that is disrupted in the cpk mouse, a well-characterized mouse model of autosomal recessive polycystic kidney disease (ARPKD). Interestingly, overexpression of the Myc gene is evident in animal models of ARPKD and is thought to contribute to the renal cystic phenotype. Using a yeast two-hybrid approach, the growth suppressor protein necdin, known to modulate Myc expression, was found as an interacting partner of cystin. Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, …

Self-Reported Juvenile Firesetting: Results From Two National Survey Datasets, Carrie Howell Bowling, Joav Merrick, 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. Results also indicated that attention problems are predictive of self-reported firesetting. The National Survey Dataset (N = 1158) …

Examining The Claim That 80-90% Of Suicide Cases Had Depression, Said Shahtahmasebi

Pediatrics Faculty Publications

No abstract provided.

Diagnosis And Acute Management Of Patients With Concussion At Children's Hospitals., Jeffrey D. Colvin, Cary Thurm, Brian M. Pate, Jason G. Newland, Matt Hall, William P. Meehan Iii

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: To describe the number of hospital admissions for concussion at paediatric hospitals in the USA. To describe the use of imaging and medications for acute concussion paediatric patients.

Design: Cross-sectional study.

Setting: Children's hospitals participating in the Pediatric Health Information System in the USA during a 10-year period.

Patients: All emergency department (ED) visits and inpatient admissions with the primary diagnosis of concussion, defined as International Classification of Diseases, Ninth Revision, Clinical Modification codes for: (1) concussion, (2) postconcussion syndrome or (3) skull fracture without mention of intracranial injury with concussion.

Main outcome measures: The proportion of concussion patients …

Multicenter Study Of Pectus Excavatum, Final Report: Complications, Static/Exercise Pulmonary Function, And Anatomic Outcomes., Robert E. Kelly, Robert B. Mellins, Robert C. Shamberger, Karen K. Mitchell, M Louise Lawson, Keith T. Oldham, Richard G. Azizkhan, Andre V. Hebra, Donald Nuss, Michael J. Goretsky, Ronald J. Sharp, George W. Holcomb, Walton K T Shim, Stephen M. Megison, R Lawrence Moss, Annie H. Fecteau, Paul M. Colombani, Dan Cooper, Traci Bagley, Amy Quinn, Alan B. Moskowitz, James F. Paulson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: A multicenter study of pectus excavatum was described previously. This report presents our final results.

STUDY DESIGN: Patients treated surgically at 11 centers were followed prospectively. Each underwent a preoperative evaluation with CT scan, pulmonary function tests, and body image survey. Data were collected about associated conditions, complications, and perioperative pain. One year after treatment, patients underwent repeat chest CT scan, pulmonary function tests, and body image survey. A subset of 50 underwent exercise pulmonary function testing.

RESULTS: Of 327 patients, 284 underwent Nuss procedure and 43 underwent open procedure without mortality. Of 182 patients with complete follow-up (56%), …

Characterization Of Prophylactic Antiemetic Regimens In Pediatric Patients Receiving Moderately And Highly Emetogenic Chemotherapy, Jessica Degiacomo Pharmd, Kristin M. Held Pharmd, Bcop

Department of Pharmacy

No abstract provided.

Anthracycline-Induced Cardiotoxicity: Prospective Cohort Study From Pakistan, Abdul Sattar Shaikh, Ali Faisal Saleem, Shazia Samad Mohsin, Muhammad Matloob Alam, Mehnaz Atiq Ahmed

Department of Paediatrics and Child Health

Objectives: To identify anthracycline-induced acute (within 1 month) and early-onset chronic progressive (within 1 year) cardiotoxicity in children younger than 16 years of age with childhood malignancies at a tertiary care centre of Pakistan.

Design: Prospective cohort study.

Setting: Aga Khan University, Karachi, Pakistan.

Participants: 110 children (aged 1 month–16 years).

Intervention: Anthracycline (doxorubicin and/or daunorubicin).

Outcome measurements: All children who received anthracycline as chemotherapy and three echocardiographic evaluations (baseline, 1 month and 1 year) between July 2010 and June 2012 were prospectively analysed for cardiac dysfunction. Statistical analysis including systolic and diastolic functions at baseline, 1 month and 1 …

Severe Painful Vaso-Occlusive Crises And Mortality In A Contemporary Adult Sickle Cell Anemia Cohort Study., Deepika S. Darbari, Zhengyuan Wang, Minjung Kwak, Mariana Hildesheim, James Nichols, Darlene Allen, Catherine Seamon, Marlene Peters-Lawrence, Anna Conrey, Mary K. Hall, Gregory J. Kato, James G. Taylor Vi

Pediatrics Faculty Publications

BACKGROUND: Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

METHODS: Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations …

The Centre Of The Brain: Topographical Model Of Motor, Cognitive, Affective, And Somatosensory Functions Of The Basal Ganglia, Marie Arsalidou, Emma G. Duerden, Margot J. Taylor

Paediatrics Publications

The basal ganglia have traditionally been viewed as motor processing nuclei; however, functional neuroimaging evidence has implicated these structures in more complex cognitive and affective processes that are fundamental for a range of human activities. Using quantitative meta-analysis methods we assessed the functional subdivisions of basal ganglia nuclei in relation to motor (body and eye movements), cognitive (working-memory and executive), affective (emotion and reward) and somatosensory functions in healthy participants. We document affective processes in the anterior parts of the caudate head with the most overlap within the left hemisphere. Cognitive processes showed the most widespread response, whereas motor processes …

Techniques For The Isolation Of High-Quality Rna From Cells Encapsulated In Chitosan Hydrogels, Claire Yu, Stuart Young, Valerio Russo, Brian G. Amsden, Lauren E. Flynn

Paediatrics Publications

Extracting high-quality RNA from hydrogels containing polysaccharide components is challenging, as traditional RNA isolation techniques designed for cells and tissues can have limited yields and purity due to physiochemical interactions between the nucleic acids and the biomaterials. In this study, a comparative analysis of several different RNA isolation methods was performed on human adipose-derived stem cells photo-encapsulated within methacrylated glycol chitosan hydrogels. The results demonstrated that RNA isolation methods with cetyl trimethylammonium bromide (CTAB) buffer followed by purification with an RNeasy® mini kit resulted in low yields of RNA, except when the samples were preminced directly within the buffer. In …

A Profile Of Children With Complex Chronic Conditions At End Of Life Among Medicaid Beneficiaries: Implications For Health Care Reform, Lisa C. Lindley, Maureen E. Lyon

Pediatrics Faculty Publications

Background: As the United States braces for full implementation of health care reform, the eyes of the nation are on Medicaid. The large number of newly eligible Medicaid beneficiaries may challenge health care resources and ultimately impact quality of care. This is a special concern among current Medicaid beneficiaries such as children with complex chronic conditions (CCCs) who have significant health care needs, especially at end of life (EOL). Yet, a comprehensive profile of these children is lacking.

Objective: To understand the demographic and health characteristics, health care utilization, and expenditures among Medicaid children with CCCs at EOL.

Methods: Our …

Multicenter Study Comparing Shunt Type In The Norwood Procedure For Single-Ventricle Lesions: Three-Dimensional Echocardiographic Analysis., Gerald R. Marx, Girish S. Shirali, Jami C. Levine, Lin T. Guey, James F. Cnota, Jeanne M. Baffa, William L. Border, Steve Colan, Gregory Ensing, Mark K. Friedberg, David J. Goldberg, Salim F. Idriss, J Blaine John, Wyman W. Lai, Minmin Lu, Shaji C. Menon, Richard G. Ohye, David Saudek, Pierre C. Wong, Gail D. Pearson, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network's Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography.

METHODS AND RESULTS: Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, …

Predictors Of Disease Progression In Pediatric Dilated Cardiomyopathy., Kimberly M. Molina, Peter Shrader, Steven D. Colan, Seema Mital, Renee Margossian, Lynn A. Sleeper, Girish S. Shirali, Piers Barker, Charles E. Canter, Karen Altmann, Elizabeth Radojewski, Elif Seda Selamet Tierney, Jack Rychik, Lloyd Y. Tani, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Background: Despite medical advances, children with dilated cardiomyopathy (DCM) remain at high risk of death or need for cardiac transplantation. We sought to identify predictors of disease progression in pediatric DCM.

Methods and results: The Pediatric Heart Network evaluated chronic DCM patients with prospective echocardiographic and clinical data collection during an 18-month follow-up. Inclusion criteria were age <22 years and DCM disease duration >2 months. Patients requiring intravenous inotropic/mechanical support or listed status 1A/1B for transplant were excluded. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, intravenous inotropes, mechanical support, or death. Predictors of disease progression were identified using …

Childhood Acute Iymphoblastic Leukaemia: Experience From A Single Tertiary Care Facility Of Pakistan, Naureen Mushtaq, Zehra Fadoo, Ahmed Naqvi

Department of Paediatrics and Child Health

Objective: To evaluate the demographic features, outcome and prognostic factors seen in children with acute lymphoplastic leukaemia at a tertiary care hospital.
Methods: The retrospective descriptive study was conducted at Aga Khan University Hospital, Karachi, comprising data related to children below 15 years of age and treated between January 1997 and December 2006. Kaplan Meir survival curves were used to describe overall and event-free survival rates. Cox Proportional Hazards model was used to describe factors associated with death and relapse. SPSS 16 was the main statistical tool.
Results: Of the total 121 children diagnosed with the condition, 79 (65.3%) were …

Community-Based Management And Outcome Of Omphalitis In Newborns In Karachi, Pakistan, Farah Naz Qamar, Shiyam Sundar Tikmani, Fatima Mir, Anita Kazmi Mehdi Zaidi

Department of Paediatrics and Child Health

Objectives: To describe the clinical profile and outcome in newborns with omphalitis managed with home or clinic-based therapy.
Methods: The descriptive study was conducted from September 2004 to August 2007 in three low-income communities in Karachi, Pakistan. Newborns with omphalitis detected by community health workers through active surveillance were referred to local clinics. Those with physician-confirmed omphalitis were treated for 7 days with topical gentian violet or oral cephalexin (as monotherapy) or topical gentian violet and oral cephalexin (combination therapy) at physician discretion, or injectable therapy (procaine penicillin and gentamicin) if clinical signs of sepsis were also present and family …

Prenatal Development: Annotated Bibliography, Victoria J. Molfese, Amanda Prokasky, Kathleen Moritz Rudasill, Ibrahim H. Acar, Xiaoqing Tu, Kate Sirota, Brian Keiser

Department of Child, Youth, and Family Studies: Faculty Publications

For decades, researchers have investigated how events in the prenatal period impact women and their infants. These studies, particularly by researchers in the medical, neuroscience, and behavioral science fields, led to discoveries of important information regarding the prenatal events that were strongly associated with mortality (or death) and morbidity (or incidences of injury, pathology and abnormalities/anomalies, and neurobehavioral sequelae) in the neonatal and infancy periods. Among the many common findings from early research studies, two are particularly noteworthy. First, maternal and fetal risk conditions arising in the prenatal period do not do so in isolation. Sameroff and Chandler characterized this …

Phenotypic Parameters Predict Time To Normalization In Infants With Hypogammaglobulinemia., Robert C. Van Winkle, Walter W. Hauck, Stephen J. Mcgeady

Department of Pediatrics Faculty Papers

PURPOSE: Infants with recurrent infection may be found to have hypogammaglobulinemia without impaired specific antibody responses. Many will be diagnosed with transient hypogammaglobulinemia of infancy.

METHODS: This study used a parametric survival analysis of 100 infants with hypogammaglobulinemia to predict time to normalization.

RESULTS: Aggregate initial immunoglobulins (IgG + IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution: median time to resolution for the infants in the lowest quartile of aggregate levels (≤81 % of age-adjusted lower limits) was greater than 5 years, with 34 % resolving in 3 years. For infants in the highest quartile …

Diagnosis, Treatment And Follow-Up In Four Children With Biotinidase Deficiency From Pakistan, Bushra Afroze, Mohammad Wasay

Department of Medicine

Biotinidase deficiency is an inherited disorder in which the vitamin biotin is not recycled. If untreated, affected individuals develop neurological and cutaneous symptoms. Untreated individuals with biotinidase deficiency either succumb to disease or are left with significant morbidity. We describe clinical course and follow-up of 4 children from Pakistan. All 4 presented with classical symptoms of biotinidase deficiency and responded dramatically to oral biotin within days to weeks. Biotinidase deficiency is reported in Pakistani children from different part of world, however; there is no such report from Pakistan. This highlights lack of awareness of biotinidase deficiency among physicians in Pakistan

A Rare Aetiology Of Respiratory Failure In A 10-Year-Old Boy: Inflammatory Myofibroblastic Tumour., Ali Khawaja, Prem Kumar Maheshwar, Anwarul Haque, Ali Bin Sarwar Zubairi

Department of Medicine

Primary neoplasms of the respiratory tract are rarely encountered in the paediatric population. Inflammatory myofibroblastic tumour (IMT) is a rare soft tissue mesenchymal tumour but a distinct disease entity accounting for less than 1% of all primary lung tumours. We report a case of a 10-year-old boy who presented with respiratory failure and left lung collapse. On flexible fiberoptic bronchoscopy, a pedunculated mass in the lower part of the trachea originating from the left main stem bronchus was identified. The patient subsequently underwent a left-sided pneumonectomy with complete resection of the mass. The histopathological analysis was consistent with IMT. Two …

The Predictive Value Of Renal Ultrasound Of Vesicoureteral Reflux After First Urinary Tract Infection In Neonates And Infants 0-24 Months, Richard J. Mazzaccaro Md, Michael J. Weiss Mph

Department of Pediatrics

No abstract provided.

Prolonged Febrile Seizures Cause Reversible Reductions In White Matter Integrity☆, M. Yoong, K. Seunarine, M. Martinos, R. F. Chin, C. A. Clark, R. C. Scott

Dartmouth Scholarship

Prolonged febrile seizures (PFS) are the commonest cause of childhood status epilepticus and are believed to carry a risk of neuronal damage, in particular to the mesial temporal lobe. This study was designed to determine: i) the effect of prolonged febrile seizures on white matter and ii) the temporal evolution of any changes seen.

33 children were recruited 1 month following PFS and underwent diffusion tensor imaging (DTI) with repeat imaging at 6 and 12 months after the original episode of PFS. 18 age-matched healthy control subjects underwent similar investigations at a single time point. Tract-based spatial statistics (TBSS) was …

Autonomic Nervous System Function Following Prenatal Opiate Exposure, Matthew Todd Hambleton, Eric W. Reynolds, Thitinart Sithisarn, Stuart J. Traxel, Abhijit R. Patwardhan, Timothy N. Crawford, Marta S. Mendiondo, Henrietta S. Bada

Pediatrics Faculty Publications

In utero exposure to opiates may affect autonomic functioning of the fetus and newborn. We investigated heart rate variability (HRV) as a measure of autonomic stability in prenatal opiate-exposed neonates (n = 14) and in control term infants (n = 10). Electrocardiographic data during both non-nutritive and nutritive sucking were evaluated for RR intervals, heart rate (HR), standard deviation of the consecutive RR intervals (SDRR), standard deviation of the differences of consecutive RR intervals (SDDRR), and the power spectral densities in low and high frequency bands. In controls, mean HR increased significantly, 143-161 per min (p = …

Vaccination Practice For Pediatric Inflammatory Disease Patients Receiving Immuno-Suppressive Therapy, Naser Tolaymat Md, Clare M. Lenhart Phd, Mph

Department of Pediatrics

No abstract provided.

Marijuana: Current Concepts, Donald E. Greydanus, Elizabeth K. Hawver, Megan M. Greydanus, Joav Merrick

Pediatrics Faculty Publications

Marijuana (cannabis) remains a controversial drug in the twenty-first century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis (pot) use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mainly based on psychological therapy; current research on pharmacologic management of problems related to cannabis consumption is also considered. The potential role of specific cannabinoids for medical benefit will be revealed …

Firesetting In Childhood And Adolescence, Joav Merrick, Carrie Howell Bowling, Hatim A. Omar

Pediatrics Faculty Publications

Fire is the rapid oxidation of a material in the exothermic chemical process of combustion, releasing heat, light, and various reaction products. Fire is intriguing and therefore something that will attract a curious child from an early age.

In 2010, the United States fire department responded to 44,900 fires started by someone, usually a child, playing with fire. These fires caused 90 civilian deaths, 890 civilian injuries, and $210 million in direct property damage. Preschoolers and kindergartners are most likely to start these fires, while playing with matches or lighters and most likely to die in these fires. Most fire-play …

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

Pediatrics Faculty Publications

No abstract provided.

An Assessment Of Hepatitis E Virus (Hev) In Us Blood Donors And Recipients: No Detectable Hev Rna In 1939 Donors Tested And No Evidence For Hev Transmission To 362 Prospectively Followed Recipients., Chenyu Xu, Richard Y. Wang, Cathy A. Schechterly, Shengxiang Ge, James W. Shih, Ning-Shao Xia, Naomi L. Luban, Harvey J. Alter

Pediatrics Faculty Publications

BACKGROUND:

Hepatitis E virus (HEV) infection has become relevant to blood transfusion practice because isolated cases of blood transmission have been reported and because HEV has been found to cause chronic infection and severe liver disease in immunocompromised patients.

STUDY DESIGN AND METHODS:

We tested for immunoglobulin (Ig)G and IgM antibodies to the HEV and for HEV RNA in 1939 unselected volunteer US blood donors. Subsequently, we tested the same variables in pre- and serial posttransfusion samples from 362 prospectively followed blood recipients to assess transfusion risk.

RESULTS:

IgG anti-HEV seroprevalence in the total 1939 donations was 18.8%: 916 of …

Gsk-3Β Function In Bone Regulates Skeletal Development, Whole-Body Metabolism, And Male Life Span, J. R. Gillespie, J. R. Bush, G. I. Bell, L. A. Aubrey, H. Dupuis, F. Ferron, B. Kream, G. Dimattia, S. Patel, J. R. Woodgett, G. Karsenty, D. A. Hess, F. Beier

Paediatrics Publications

Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or “brake” on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of …