Fung E.B.,Childrens Hospital and Research Center |
Kwiatkowski J.L.,Children's Hospital of Philadelphia |
Huang J.N.,University of California at San Francisco |
Gildengorin G.,Pediatric Clinical Research Center |
And 2 more authors.
American Journal of Clinical Nutrition | Year: 2013
Background: Patients with thalassemia major (Thal) frequently have low plasma zinc, which has been associated with low bone mass Objective: The objective was to determine the effect of zinc supplementation on bone mass in patients with Thal Design: Forty-two subjects (21 females aged 10-30 y) with Thal and low bone mass were randomly assigned to receive 25 mg Zn/d or placebo. Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed by using dual-energy X-ray absorptiometry, and fasting blood was collected for the measurement of plasma zinc at 0, 12, and 18 mo Results: Thirty-two subjects, 81% of whom were transfusion dependent, completed the study (mean 6 SD: 17.1 6 5.2 y). Plasma zinc was #70 mg/dL in 11 subjects at baseline and increased significantly with zinc supplementation (P = 0.014). Use of intentionto- treat analysis and linear models for longitudinal data, adjusted for baseline and pubertal stage, showed that the zinc group had significantly greater increases in whole-body BMC (adjusted mean 6 SE: 63 6 15 g; P = 0.02), and aBMD (0.023 6 0.006 g/cm2; P = 0.04) than did the placebo group after 18 mo. Furthermore, adjusted spine and hip aBMD z scores each decreased by 0.3 SDs (both P = 0.04) in the placebo compared with the zinc group over the 18-mo study Conclusions: In young patients with Thal, zinc supplementation resulted in greater gains in total-body bone mass than did placebo Zinc was well tolerated and is worthy of investigation in larger trials in Thal patients across a range of ages and disease severity. © 2013 American Society for Nutrition.
Sapru A.,University of California at San Francisco |
Curley M.A.Q.,University of Pennsylvania |
Brady S.,University of California at San Francisco |
Matthay M.A.,University of California at San Francisco |
Flori H.,Childrens Hospital and Research Center
Intensive Care Medicine | Year: 2010
Purpose: Deposition of fibrin in the alveolar space is a hallmark of acute lung injury (ALI). Plasminogen activator inhibitor-1 (PAI-1) is an antifibrinolytic agent that is activated during inflammation. Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI. This relationship has not been examined in children. The objective of this study was to test whether increased plasma PAI-1 levels are associated with worse clinical outcomes in pediatric patients with ALI. Design/methods: We measured plasma PAI-1 levels on the first day of ALI among 94 pediatric patients enrolled in two separate prospective, multicenter investigations and followed them for clinical outcomes. All patients met American European Consensus Conference criteria for ALI. Results: A total of 94 patients were included. The median age was 3.2 years (range 16 days-18 years), the PaO2/FiO2 was 141 ± 72 (mean ± SD), and overall mortality was 14/94 (15%). PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01). The adjusted odds of mortality doubled for every log increase in the level of plasma PAI-1 after adjustment for age and severity of illness. Conclusions: Higher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI. These findings suggest that impaired fibrinolysis may play a role in the pathogenesis of ALI in pediatric patients and suggest that PAI-1 may serve as a useful biomarker of prognosis in patients with ALI. © 2009 The Author(s).
Singer S.T.,Childrens Hospital and Research Center |
Vichinsky E.P.,Childrens Hospital and Research Center |
Gildengorin G.,Childrens Hospital and Research Center |
Van Disseldorp J.,University Utrecht |
And 2 more authors.
Blood | Year: 2011
The pathophysiology of iron-induced compromised fertility in women with thalassemia major (TM) was evaluated in 26 adult TM females. Low gonadotropin secretion resulted in reduced ovarian antral follicle count and ovarian volume, but levels of anti-müllerian hormone (AMH), a sensitive marker for ovarian reserve independent of gonadotropin effect, were mostly normal. AMH correlated with non-transferrin-bound iron (NTBI), suggesting a role of labile iron in the pathogenesis of decreased reproductive capacity, possibly occurring in parallel to cardiac iron toxicity, as cardiac iron was associated with the presence of amenorrhea and with NTBI levels. AMH emerges as an important biomarker for assessment of reproductive capacity in TM, demonstrating that fertility is preserved in the majority of those younger than 30 to 35 years. AMH can be useful in future studies aiming at improved chelation for fertility preservation, whereas NTBI and labile plasma iron may be valuable for monitoring iron effect on the reproductive system. © 2011 by The American Society of Hematology.
Trachtenberg E.A.,Childrens Hospital and Research Center |
Holcomb C.L.,Hoffmann-La Roche
Methods in Molecular Biology | Year: 2013
Next-generation sequencing (NGS) of HLA class I and II loci (HLA-A, HLA-B, HLA-C, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPB1) is described here in detail using the 454 Life Sciences GS FLX System and Titanium chemistry. An overview of the protocol with our experience on sequence performance efficiencies, read depth and ambiguity analyses using the GS FLX System are also presented. A total of 14 HLA primer pairs with multiplex identifiers (MIDs) are used in clonal, amplicon-based pyrosequencing of up to 44 samples per plate using the GS FLX. Genotype assignment and ambiguity reduction analysis is performed using Conexio Assign ATF 454 software. Clonal NGS gives a significant reduction in genotyping ambiguity during analysis of the highly complex HLA system. © Springer Science+Business Media, LLC 2013.
Franz D.N.,Cincinnati Childrens Hospital Medical Center |
Belousova E.,Moscow Research Institute of Paediatry and Paediatric Surgery |
Sparagana S.,Texas Scottish Rite Hospital for Children |
Bebin E.M.,University of Alabama at Birmingham |
And 16 more authors.
The Lancet | Year: 2013
Background Tuberous sclerosis complex is a genetic disorder leading to constitutive activation of mammalian target of rapamycin (mTOR) and growth of benign tumours in several organs. In the brain, growth of subependymal giant cell astrocytomas can cause life-threatening symptoms-eg, hydrocephalus, requiring surgery. In an open-label, phase 1/2 study, the mTOR inhibitor everolimus substantially and significantly reduced the volume of subependymal giant cell astrocytomas. We assessed the efficacy and safety of everolimus in patients with subependymal giant cell astrocytomas associated with tuberous sclerosis complex. Methods In this double-blind, placebo-controlled, phase 3 trial, patients (aged 0-65 years) in 24 centres in Australia, Belgium, Canada, Germany, the UK, Italy, the Netherlands, Poland, Russian Federation, and the USA were randomly assigned, with an interactive internet-response system, in a 2:1 ratio to oral everolimus 4·5 mg/m2 per day (titrated to achieve blood trough concentrations of 5-15 ng/mL) or placebo. Eligible patients had a definite diagnosis of tuberous sclerosis complex and at least one lesion with a diameter of 1 cm or greater, and either serial growth of a subependymal giant cell astrocytoma, a new lesion of 1 cm or greater, or new or worsening hydrocephalus. The primary endpoint was the proportion of patients with confirmed response-ie, reduction in target volume of 50% or greater relative to baseline in subependymal giant cell astrocytomas. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00789828. Findings 117 patients were randomly assigned to everolimus (n=78) or placebo (n=39). 27 (35%) patients in the everolimus group had at least 50% reduction in the volume of subependymal giant cell astrocytomas versus none in the placebo group (difference 35%, 95% CI 15-52; one-sided exact Cochran-Mantel-Haenszel test, p<0·0001). Adverse events were mostly grade 1 or 2; no patients discontinued treatment because of adverse events. The most common adverse events were mouth ulceration (25 [32%] in the everolimus group vs two [5%] in the placebo group), stomatitis (24 [31%] vs eight [21%]), convulsion (18 [23%] vs ten [26%]), and pyrexia (17 [22%] vs six [15%]). Interpretation These results support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis. Additionally, everolimus might represent a disease-modifying treatment for other aspects of tuberous sclerosis.
Wooldridge T.,Childrens Hospital and Research Center |
Lytle P.P.,Argosy University
Eating Disorders | Year: 2012
This article presents an integrative overview of existing research on anorexia nervosa (AN) in adolescent males. AN is commonly thought of as a female disorder. Even though as much as 25% of the clinical population is male, research on AN in males is limited. Additionally, most conceptualizations of male AN emphasize a single etiological factor and, therefore, produce treatments that fail to address it as a global phenomenon. In contrast, an integrative understanding that incorporates research on the familial, biological, cultural, and psychodynamic elements involved in male AN encourages treatment that comprehensively addresses the disorder. © 2012 Copyright Taylor and Francis Group, LLC.
Zwintscher N.P.,U.S. Army |
Steele S.R.,U.S. Army |
Martin M.J.,U.S. Army |
Newton C.R.,Childrens Hospital and Research Center
American Journal of Surgery | Year: 2014
Background: We sought to examine the impact of race on the management and outcomes of appendicitis in children aged 20 years or younger. Methods: We studied 96,865 inpatient admissions for children undergoing an appendectomy for acute appendicitis in 2009 using the Kids' Inpatient Database. Results: Perforation at presentation was more common among African-Americans and Hispanics than Caucasians (27.5% and 32.5%, respectively, vs 23.9%, P <.001). African-Americans were less likely to have a laparoscopic procedure (odds ratio [OR]:.839, P <.001) and more likely to experience a complication (OR: 1.753, P <.001). Hispanics were also more likely to have a complication (OR: 1.123, P =.001). African-Americans and Hispanics remained in the hospital for.73 more days than Caucasians (3.07 vs 2.34 days, P <.001). Conclusions: African-American and Hispanic children present more often with perforation. Adjusting for perforation, they were more likely to have a complication and longer hospital stays. Access to care and delayed presentations may be potential explanations. © 2014 Elsevier Inc. All rights reserved.
Tolar J.,University of Minnesota |
Mehta P.A.,Cincinnati Childrens Hospital Medical Center |
Walters M.C.,Childrens Hospital and Research Center
Biology of Blood and Marrow Transplantation | Year: 2012
Hereditary disorders that trace their origin to the hematopoietic stem cell have been targeted for allogeneic therapy and were among the first human diseases cured by successful hematopoietic cell transplantation (HCT). More recently, the possibility of treating nonhematopoietic hereditary disorders in which engraftment of hematopoietic cells might ameliorate tissue damage in target organs has also been investigated with encouraging results. As in the malignant hematological disorders, transplantation results have improved over the past 3 decades as a consequence of more refined donor selection and patient risk stratification with modifications to the conditioning regimen. The application of these principles is described in this update about HCT for hereditary marrow failure syndromes and hemoglobin disorders. In addition, a novel indication of HCT for epidermolysis bullosa is presented. Together, these representative disorders illustrate the potential for an expanding role of HCT for nonmalignant disorders. © 2012.
Doniger S.J.,Childrens Hospital and Research Center
Journal of Emergencies, Trauma and Shock | Year: 2010
Bedside emergency ultrasound has rapidly developed over the past several years and has now become part of the standard of care for several applications. While it has only recently been applied to critically ill pediatric patients, several of the well-established adult indications may be applied to pediatric patients. One of the most important and life-saving applications is bedside echocardiography. While bedside emergency ultrasonography does not serve to replace formal comprehensive studies, it serves as an extension of the physical examination. It is especially useful as a rapid and effective tool in the diagnosis of pericardial effusions, tamponade and in distinguishing potentially reversible causes of pulseless electrical activity from asystole. Most recently, left ventricular function and inferior vena cava measurements have proven helpful in the assessment of undifferentiated hypotension and shock in adults and children. Future research remains to be carried out in determining the efficacy of bedside ultrasonography in pediatric-specific pathology such as congenital heart disease. This article serves as a comprehensive review of the adult literature and a review of the recent applications in the pediatric emergency department. It also highlights the techniques of bedside ultrasonography with examples of normal and pathologic images.
Kanathezhath B.,Childrens Hospital and Research Center |
Walters M.C.,Childrens Hospital and Research Center
Hematology/Oncology Clinics of North America | Year: 2010
Hematopoietic cell transplantation is curative therapy for thalassemia major. Although the clinical application of hematopoietic cell transplantation has relied on marrow collected from related and unrelated donors as the primary source of donor hematopoietic cells, umbilical cord blood (UCB) is an alternative source of hematopoietic cells and represents a suitable allogeneic donor pool in the event that a marrow donor is not available. Progress in developing UCB transplantation for thalassemia is reviewed and the most likely areas of future clinical investigation are discussed. © 2010 Elsevier Inc.