Rainbow Babies and Childrens Hospital
Rainbow Babies and Childrens Hospital
Costa A.C.S.,Rainbow Babies and Childrens Hospital
CNS and Neurological Disorders - Drug Targets | Year: 2014
Down syndrome (DS) is the most common genetically defined cause of intellectual disability and accounts for over 50% of the cases of Alzheimer-type dementia in persons younger than 50 years of age. At present, no pharmacotherapy aimed at counteracting either the neurodevelopmental or the neurodegenerative component of this genetic disorder has been approved. Recent preclinical and clinical work on the N-methyl-D-aspartate (NMDA) receptor antagonist memantine give us some reason for optimism, at least in relation to the potential for a partial pharmacological improvement of hippocampus dependent memory deficits associated with DS. Here, we will review briefly the roles of NMDA receptors in health and disease, including the glutamatergic hypothesis for Alzheimer disease. Then, we will describe the basis for a glutamatergic hypothesis for DS, by reviewing the available preclinical evidence and assessing potential molecular mechanisms for NMDA receptor dysfunction in DS. A short description of the first two clinical trials of memantine in young and older adults with DS will follow. We will conclude by reviewing three caregiver reports from our recent clinical study and some lessons we have learned designing and conducting the first translational study in the field of DS to arise directly from experimental results in animal models. © 2014 Bentham Science Publishers.
Thompson G.H.,Case Western Reserve University |
Thompson G.H.,Rainbow Babies and Childrens Hospital
Journal of Pediatric Orthopaedics | Year: 2011
Background: Femoral head containment in Legg-Calvé-Perthes disease (LCPD) can be either surgical or nonsurgical. The Salter or innominate osteotomy is a common method of surgical containment. This is a review of the technique and results of this osteotomy in LCPD. Methods: The operative technique is relatively simple but requires considerable experience to perform correctly. It can be used alone or in combination with a proximal femoral varus osteotomy. The indications for a Salter osteotomy are essentially the same as in any form of containment treatment in LCPD. This includes: age at clinical onset of 6 to 10 years (perhaps, 5 y in female), more than one-half capital femoral epiphyseal involvement (Catterall groups III or IV, Salter-Thompson group B, and lateral pillar groups B, B/C, and C), and a good range of hip motion before surgery. The osteotomy alone is usually indicated for younger children with recent clinical onset and no femoral head deformity or subluxation. The combined procedure is better suited for older children and those with subluxation or a deformed femoral head. Results: Currently, the results of treatment are best determined at skeletal maturity using the Stulberg et al classification. When used alone, approximately 90% to 95% of the involved hips will have achieved a Stulberg et al class I, II, or III result. When combined with a proximal femoral varus osteotomy, the results are somewhat less because of the older age at onset and/or the presence of a deformed hip. Conclusions: The Salter osteotomy in LCPD is an effective method of surgical treatment that can alter the natural history of the disease process. The main advantage of this osteotomy is its effect on femoral head remodeling during remaining growth. Copyright © 2011 by Lippincott Williams & Wilkins.
Cousino M.K.,Case Western Reserve University |
Hazen R.A.,Case Western Reserve University |
Hazen R.A.,Rainbow Babies and Childrens Hospital
Journal of Pediatric Psychology | Year: 2013
Objective To critically review, analyze, and synthesize the literature on parenting stress among caregivers of children with asthma, cancer, cystic fibrosis, diabetes, epilepsy, juvenile rheumatoid arthritis, and/or sickle cell disease. Method PsychInfo, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature were searched according to inclusion criteria. Meta-analysis of 13 studies and qualitative analysis of 96 studies was conducted. Results Caregivers of children with chronic illness reported significantly greater general parenting stress than caregivers of healthy children (d =. 40; p = ≤.0001). Qualitative analysis revealed that greater general parenting stress was associated with greater parental responsibility for treatment management and was unrelated to illness duration and severity across illness populations. Greater parenting stress was associated with poorer psychological adjustment in caregivers and children with chronic illness. Conclusion Parenting stress is an important target for future intervention. General and illness-specific measures of parenting stress should be used in future studies. © 2013 The Author email@example.com.
Sammons J.S.,Children's Hospital of Philadelphia |
Toltzis P.,Rainbow Babies and Childrens Hospital
Current Opinion in Pediatrics | Year: 2013
PURPOSE OF REVIEW: Clostridium difficile is the most common cause of healthcare-associated diarrhea among adults in Western countries, and is increasingly recognized as an important pathogen in children. This review provides an update on the changing epidemiology of C. difficile infection (CDI) for pediatric providers and summarizes current knowledge regarding available therapies. RECENT FINDINGS: The incidence of CDI has more than doubled among adults over the past decade, with a particular rise in incidence among patients presenting from the community. CDI has also increased among children in both inpatient and outpatient settings and there is growing evidence that specific populations of children may be at highest risk. Antibiotic-based therapies remain the mainstay of treatment for CDI, but new therapies have been developed with potential future applications in children. Use of nonantibiotic-based therapies is limited in children, but their use has been studied among adults with intractable or recurrent disease. SUMMARY: The rise in incidence of CDI over the past decade warrants increased recognition by pediatric providers. Knowledge of the pediatric populations at highest risk for infection as well as the options for therapy will improve understanding of this changing disease. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.
McDowell K.M.,Cincinnati Childrens Hospital |
Craven D.I.,Rainbow Babies and Childrens Hospital
Journal of Pediatrics | Year: 2011
The pulmonary problems often seen in children with DS include recurrent and more severe respiratory tract infections, airway abnormalities, pulmonary vascular disease, cystic lung disease, and sleep apnea. Common conditions associated with DS such as hypotonia, dysphagia, and immune abnormalities may all contribute to recurrent respiratory issues, thus evalutation for these problems needs to be considered in the assessment and treatment of children with DS with frequent or persistent respiratory difficulties. CHD, gastrointestinal disease, or need for surgery further increases the risk of morbidity and mortality from respiratory illness for patients with DS. Structural airway anomalies may be complex and require surgical intervention from centers with specialized expertise. Even issues well known to be associated with DS, such as OSA, are more difficult to treat than in those without DS. In summary, children with DS are predisposed to a wide variety of respiratory problems that may originate at any level of the respiratory tract, may be the result of abnormalities in multiple organ systems, and require heightened surveillance throughout childhood to prevent increased morbidity. Copyright © 2011 Mosby Inc. All rights reserved.
Trembath A.,Rainbow Babies and Childrens Hospital |
Laughon M.M.,University of North Carolina at Chapel Hill
Clinics in Perinatology | Year: 2012
Although significant advances in respiratory care have been made in neonatal medicine, bronchopulmonary dysplasia (BPD) remains the most common serious pulmonary morbidity in premature infants. The development of BPD is the result of the complex interactions between multiple perinatal and postnatal factors. Early identification of infants at the most risk of developing BPD through the use of estimators and models may allow a targeted approach at reducing BPD in the future. © 2012 Elsevier Inc.
Manjila S.,Rainbow Babies and Childrens Hospital
Neurosurgical focus | Year: 2010
The history and evolution of surgical strategies for the treatment of Kleeblattschädel deformity are not well described in the medical literature. Kleeblattschädel anomaly is one of the most formidable of the craniosynostoses, requiring a multidisciplinary team for surgical treatment. The initial descriptions of this cloverleaf deformity and the evolution of surgical treatment are detailed in the present report. Two illustrative cases of Kleeblattschädel deformity, syndromic and nonsyndromic craniosynostoses treated by the senior authors, are also described along with insights into operative strategies.
Manjila S.,Rainbow Babies and Childrens Hospital
Neurosurgical focus | Year: 2011
Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently identified variant of primitive neuroectodermal tumor, with fewer than 50 cases reported in the literature to date. Histologically, this tumor has features of ependymoblastoma and neuroblastoma, demonstrating areas of fine fibrillary neuropil intermingled with ependymoblastic rosettes and zones of undifferentiated neuroepithelial cells. However, ETANTR is distinguished pathologically from other embryonal tumors by the striking abundance of neuropil. Clinically, ETANTRs have shown high malignant potential and poor clinical outcome despite aggressive treatment. The authors describe 2 illustrative surgical cases of ETANTR, one involving the longest reported survival in the literature to date. The other had a poor outcome despite high-dose adjuvant chemotherapy with sequential autologous hematopoietic stem cell rescue. The authors review the natural history and treatment strategies available for this unusual malignant pediatric brain tumor.
Norris R.E.,Rainbow Babies and Childrens Hospital |
Adamson P.C.,Rainbow Babies and Childrens Hospital
Nature Reviews Cancer | Year: 2012
Advances made in the treatment of childhood malignancies over the past four decades have resulted in overall 5-year survival rates of approximately 80%. However, despite these advances, several childhood cancers still have unacceptably low cure rates, and, even when treatment is successful, the acute and long-term morbidity of current therapy can be substantial. The development of molecularly targeted anticancer drugs offers the prospect of more effective therapy with fewer side effects, but will require increasing partnership between governments, and the academic and private sectors. © 2012 Macmillan Publishers Limited. All rights reserved.
Gubitosi-Klug R.A.,Rainbow Babies and Childrens Hospital
Diabetes Care | Year: 2014
Objective The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study continues to address knowledge gaps in our understanding of type 1 diabetes and the effects of intensive therapy on its long-term complications. Research Design And Methods During the DCCT (1982-1993), a controlled clinical trial of 1,441 subjects with type 1 diabetes, and the EDIC (1994-present), an observational study of the DCCT cohort, core data collection has included medical history questionnaires, surveillance health exams, and frequent laboratory and other evaluations for microvascular and macrovascular disease. Numerous collaborations have expanded the outcome data with more detailed investigations of cardiovascular disease, cognitive function, neuropathy, genetics, and potential biological pathways involved in the development of complications. Results The longitudinal follow-up of the DCCT/EDIC cohort provides the opportunity to continue monitoring the durability of intensive treatment as well as to address lingering questions in type 1 diabetes research. Future planned analyses will address the onset and progression of microvascular triopathy, evidence-based screening for retinopathy and nephropathy, effects of glycemic variability and nonglycemic risk factors on outcomes, long-term impact of intensive therapy on cognitive decline, and health economics. Three new proposed investigations include an examination of residual C-peptide secretion and its impact, prevalence of hearing impairment, and evaluation of gastrointestinal dysfunction. Conclusions With the comprehensive data collection and the remarkable participant retention over 30 years, the DCCT/EDIC continues as an irreplaceable resource for understanding type 1 diabetes and its long-term complications. © 2014 by the American Diabetes Association.