Showing papers in "Current Opinion in Pediatrics in 2009"
TL;DR: For several exposures, it has been proved that chemicals can alter epigenetic marks, and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues.
Abstract: Purpose of review Epigenetics investigates heritable changes in gene expression occurring without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA expression, can change genome function under exogenous influence. Here, we review current evidence indicating that epigenetic alterations mediate toxicity from environmental chemicals. Recent findings In-vitro, animal, and human investigations have identified several classes of environmental chemicals that modify epigenetic marks, including metals (cadmium, arsenic, nickel, chromium, and methylmercury), peroxisome proliferators (trichloroethylene, dichloroacetic acid, and TCA), air pollutants (particulate matter, black carbon, and benzene), and endocrine-disrupting/reproductive toxicants (diethylstilbestrol, bisphenol A, persistent organic pollutants, and dioxin). Most studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied environmental chemicals in relation to histone modifications and microRNA. Summary For several exposures, it has been proved that chemicals can alter epigenetic marks, and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. Future prospective investigations are needed to determine whether exposed individuals develop epigenetic alterations over time and, in turn, which such alterations increase the risk of disease. Also, further research is needed to determine whether environmental epigenetic changes are transmitted transgenerationally.
836 citations
TL;DR: The subtle adjustments needed to ensure developmental plasticity in IUGR are provided by epigenetic modulation of critical genes, accompanied by changes in the quantity and activity of enzymes responsible for making modifications to chromatin as well as global and gene-specific modifications of chromatin.
Abstract: Purpose of review—Intrauterine growth restriction (IUGR) is associated with an increased propensity to develop adult onset disease and is described by the developmental origins of adult disease hypothesis. Sequelae of fetal growth restriction include metabolic disease as well as nonmetabolic disorders. Although it has become clear that the morbidities associated with IUGR are complex and result from disruptions to multiple pathways and multiple organs, the mechanisms driving the long-term effects are only just beginning to be understood. Recent findings—IUGR affects most organ systems by either interrupting developmental processes such as apoptosis or producing lasting changes to levels of key regulatory factors. Both of these are associated with an often persistent change in gene expression. Epigenetic modulation of transcription is a mechanism that is at least partially responsible for this. IUGR is accompanied by changes in the quantity and activity of enzymes responsible for making modifications to chromatin as well as global and gene-specific modifications of chromatin. Summary—The subtle adjustments needed to ensure developmental plasticity in IUGR are provided by epigenetic modulation of critical genes. Translating the messages of the epigenetic profile and identifying the players that mediate the effects remains one of the major challenges in the field. An understanding of the mechanisms driving the epigenetic changes will facilitate identification of dietary and pharmaceutical approaches that can be applied in the postnatal period.
813 citations
TL;DR: Empirical research into the causal mechanisms underlying youth suicide and suicidal behavior is needed to inform early identification and prevention efforts.
Abstract: PURPOSE OF REVIEW: Suicide is the third leading cause of death among young people in the U.S. and represents a significant public health problem worldwide. This review focuses on recent developments in our understanding of the epidemiology and risk factors for adolescent suicide and suicidal behavior. RECENT FINDINGS: The suicide rate among children and adolescents in the U.S. has increased dramatically in recent years and has been accompanied by substantial changes in the leading methods of youth suicide, especially among young girls. Much work is currently underway to elucidate the relationships between psychopathology, substance use, child abuse, bullying, internet use, and youth suicidal behavior. Recent evidence also suggests sex-specific and moderating roles of sex in influencing risk for suicide and suicidal behavior. SUMMARY: Empirical research into the causal mechanisms underlying youth suicide and suicidal behavior is needed to inform early identification and prevention efforts. Language: en
506 citations
TL;DR: Current management of food allergy focuses on accurate diagnosis, appropriate counseling regarding strict allergen avoidance with review of available educational resources, emergency preparedness, instruction on the use of self-injectable epinephrine, and ongoing surveillance for the possible development of tolerance.
Abstract: Purpose of review The present review serves to address food allergy, which is a common problem encountered by the general pediatrician. Between 4 and 6% of US children have an allergic reaction to at least one food, and the prevalence of some food allergies appears to be increasing. Recent findings A combination of genetic influences, characteristics of food antigen processing, and timing of food introduction may influence the development of food allergy. Avoidance of highly allergenic foods beyond 4-6 months may not be effective at preventing the development of food allergy in most children, and the effect of specific early introduction of allergenic foods is being investigated. Oral immunotherapy is under investigation but may be limited in future use by several factors, including a significant rate of allergic reactions. Summary Current management of food allergy focuses on accurate diagnosis, appropriate counseling regarding strict allergen avoidance with review of available educational resources, emergency preparedness, instruction on the use of self-injectable epinephrine, and ongoing surveillance for the possible development of tolerance.
412 citations
TL;DR: It seems likely that there are multiple causes of human age-related nondisjunction, complicating efforts to understand – and, ultimately, to provide preventive measures for – errors associated with increasing maternal age.
Abstract: Purpose of review
The relationship between increasing maternal age and trisomy has been recognized for over 50 years and is one of the most important etiological factors associated with any human genetic disorder. Specifically, the risk of trisomy in a clinically recognized pregnancy rises from about 2–3% for women in their twenties to an astounding 30% or more for women in their forties. Thus, as women approach the end of their child-bearing years, errors of chromosome segregation represent the most important impediment to a successful pregnancy.
201 citations
TL;DR: An overview of the current treatment options and long-term complications in primary malignant bone tumors for the pediatrician caring for a child with these problems is provided.
Abstract: Purpose of reviewOsteosarcoma and Ewing's sarcoma are the two most common primary malignant bone tumors in children and account for approximately 6% of all childhood malignancies. Treatment methods have seen significant advancements, particularly in regard to chemotherapy and limb-sparing surgery. T
185 citations
TL;DR: Valid, brief and easy-to-administer screening tools can be utilized to detect risk of suicide in children and adolescents, and universal suicide screening in primary care clinics and emergency departments may be the most effective way to recognize and prevent self-harm.
Abstract: PURPOSE OF REVIEW: Every year, suicide claims the lives of tens of thousands of young people worldwide. Despite its high prevalence and known risk factors, suicidality is often undetected. Early identification of suicide risk may be an important method of mitigating this public health crisis. Screening youth for suicide may be a critical step in suicide prevention. This paper reviews suicide screening in three different settings: schools, primary care clinics and emergency departments (EDs). RECENT FINDINGS: Unrecognized and thus untreated suicidality leads to substantial morbidity and mortality. With the onus of detection falling on nonmental health professionals, brief screening tools can be used to initiate more in-depth evaluations. Nonetheless, there are serious complexities and implications of screening all children and adolescents for suicide. Recent studies show that managing positive screens is a monumental challenge, including the problem of false positives and the burden subsequently posed on systems of care. Furthermore, nearly 60% of youth in need of mental health services do not receive the care they need, even after suicide attempt. Schools, primary care clinics and EDs are logical settings where screening that leads to intervention can be initiated. SUMMARY: Valid, brief and easy-to-administer screening tools can be utilized to detect risk of suicide in children and adolescents. Targeted suicide screening in schools, and universal suicide screening in primary care clinics and EDs may be the most effective way to recognize and prevent self-harm. These settings must be equipped to manage youth who screen positive with effective and timely interventions. Most importantly, the impact of suicide screening in various settings needs to be further assessed. Language: en
165 citations
TL;DR: The available probiotics for prevention of atopic disease are disappointing, and the results with prebiotics need further confirmation, and new studies on the relation between gut microbiota and disease should consider asthma and atopic dermatitis separately.
Abstract: Purpose of reviewThe development of the intestinal microbiota occurs primarily during infancy, and a distortion could potentially contribute to a wide range of diseases. This review summarizes the current understanding of the intestinal microbiota in infants. The potential consequences of different
165 citations
TL;DR: Simulation is an effective training tool for pediatric acute care providers and demonstrates increased retention of knowledge and skills after simulation-based training in the areas of resuscitation, trauma, airway management, procedural training, team training, and disaster management.
Abstract: Purpose of reviewSimulation has been widely adopted as a training and assessment tool in medical education. Conventional teaching methods may be inadequate to properly train healthcare providers for rare but potentially lethal events in pediatrics such as trauma and respiratory arrest. Recent studie
143 citations
TL;DR: Caustic ingestions remain a significant cause of pediatric morbidity in the United States and abroad and endoscopy is the primary method of staging injury following a caustic ingestion.
Abstract: PURPOSE OF REVIEW: The purpose of this review is to outline the current epidemiology, mechanism of injury, clinical manifestations, management and long-term complications of caustic ingestions in pediatric patients. RECENT FINDINGS: Recent data suggest that more than 200,000 exposures to household or industrial cleaning products occur annually in the United States. It is difficult to determine what fraction of these exposures represents caustic ingestions. Caustic ingestions occur most commonly in children less than age 6 years. Because of the accidental nature of the ingestions, the case fatality rate for pediatric patients is significantly less than that of adolescents and adults. Despite laws to limit the concentration of household cleaning products, farm and industrial products and products stored in nonoriginal containers represent a significant source of caustic agents. Endoscopy remains the preferred method of staging injury. In children the absence of symptoms does not predict lack of relevant injury. However, the presence of three or more symptoms is associated with a high likelihood of significant injury. Long-term complications in pediatric patients may be severe and include esophageal cancer. SUMMARY: Caustic ingestions remain a significant cause of pediatric morbidity in the United States and abroad. Endoscopy is the primary method of staging injury following a caustic ingestion. Extent of injury at initial evaluation remains the best predictor of morbidity and mortality in pediatric patients following an accidental caustic ingestion. Language: en
127 citations
TL;DR: The current literature on the various musculoskeletal effects associated with obesity in children and adolescents suggests that obesity affects the child's locomotor system both functionally and structurally.
Abstract: Purpose of reviewThe problem of obesity has become a global concern, with increased prevalence reported in the literature. Numerous comorbid conditions are known to be associated with obesity; its relationship with the development and function of the musculoskeletal system in the growing child is po
TL;DR: Current levels of air pollution are consistently associated with asthma development and morbidity among children, suggesting that current regulatory policies may be insufficient and further research is needed to identify additional host factors that confer increased susceptibility to air pollution exposure.
Abstract: Purpose of review
Current levels of air pollution are consistently associated with asthma development and morbidity among children, suggesting that current regulatory policies may be insufficient. This review will describe recent studies that have examined specific emission sources or components of pollutants that may be associated with pediatric asthma and identify subpopulations that may be particularly susceptible to the effects of air pollution exposure.
TL;DR: In most resource-limited countries the birth of an HIV-infected child in a resource-rich country is now a sentinel health event, and comprehensive PMTCT, including antiretroviral treatment for HIV- infected women and children, should be paramount in resource- limited countries.
Abstract: PURPOSE OF REVIEW: There is an unprecedented global commitment to reverse the pediatric HIV epidemic by making prevention of mother-to-child transmission (PMTCT) services accessible in all countries. This review outlines the successes made and the challenges that remain. RECENT FINDINGS: In resource-rich countries mother-to-child transmission rates of HIV as low as 1% have been achieved. The efficacy of short-course antiretrovirals for PMTCT in Africa is estimated at 50%. Coinfections with herpes simplex virus type 2 other sexually transmitted infections resulting in genital ulcers and endemic infectious diseases (e.g. malaria) may increase the risk of mother-to-child transmission of HIV. Vertical transmission of drug-resistant viruses has been reported; the prevalence and effect of transmitted resistant virus on treatment outcomes are under investigation. Obstacles facing PMTCT in resource-limited countries include the lack of healthcare infrastructure limited manpower and competing public health priorities with the limited healthcare budget. SUMMARY: Although the birth of an HIV-infected child in a resource-rich country is now a sentinel health event in most resource-limited countries the birth of an HIV-infected child continues to be the status quo. Comprehensive PMTCT including antiretroviral treatment for HIV-infected women and children should be paramount in resource-limited countries.
TL;DR: Doctors and other healthcare providers must be aware of these health implications, as well as federal policies, common law, and their individual state's laws pertaining to this important topic.
Abstract: Purpose of reviewThis study reviews the healthcare-related rationale for providing confidential care to adolescents, as well as the legal framework for the provision of such care.Recent findingsPhysician assurances of confidentiality increase adolescents' willingness to disclose sensitive health inf
TL;DR: In this article, the authors highlight the importance of early diagnosis and treatment of SCFE in early stages, not only in childhood but also as a cause of osteoarthritis in adulthood.
Abstract: Purpose of reviewSlipped capital femoral epiphysis (SCFE) is the most common adolescent hip condition. Its importance lies in its high morbidity if not diagnosed and treated in its early stages, not only in childhood but also as a cause of osteoarthritis in adulthood. This article highlights key dia
TL;DR: Genetics in food allergy is a promising research area but is still in its infancy, and future studies need to integrate environment, genomics, and epigenomics in order to better understand the multifaceted etiology and biological mechanisms of food allergy.
Abstract: Purpose of reviewFood allergy, a growing clinical and public health problem in the United States and worldwide, is likely determined by multiple environmental and genetic factors. The purpose of this review is to summarize recent advances in food allergy genetic research.Recent findingsThere is comp
TL;DR: Presenting symptoms may vary widely based on location; however, independent of primary location, definitive therapy for teratomas is complete surgical resection, which is critical in the long-term favorable outcome.
Abstract: Purpose of reviewTeratomas are rare neoplasms composed of tissue elements derived from the germinal layers of the embryo. Although they may originate anywhere along the midline, teratomas are most commonly found in sacrococcygeal, gonadal, mediastinal, retroperitoneal, cervicofacial and intracranial
TL;DR: The implications of current trends in molecular infectious diseases are moving towards high-throughput, simple, array-type technologies that will provide a wealth of data regarding types of organisms present in a sample and the virulence factors/resistance determinants that influence the severity of disease.
Abstract: Purpose of reviewThe purpose of this article is to review the molecular methods commonly used in medical microbiology as well as to update the clinician as to newer molecular technologies that show promise in the identification of microorganisms as well as evaluation of the presence of virulence fac
TL;DR: Identification of biologically distinctive subsets of ALL through cytogenetic, molecular, and gene expression studies, as well as investigations of minimal residual disease and host pharmacogenomics, offer promising avenues of research.
Abstract: Purpose of reviewWith current treatment regimens, event-free survival rates for childhood acute lymphoblastic leukemia (ALL) approach or exceed 80%. This success was achieved, in part, through the implementation of risk-stratified therapy. However, for the 15–20% of children with newly diagnosed ALL
TL;DR: Powerful molecular tools have been developed that have shed light on the nature of the susceptibility genes for and the pathophysiology of AITD and these have already led to improved diagnostic tools and, hopefully, will permit the development of more specific immune therapy in the future.
Abstract: Purpose of review The autoimmune thyroid diseases (AITD), Graves' disease and chronic lymphocytic thyroiditis (CLT) are amongst the most common endocrine diseases in childhood and adolescence. The application of molecular biology has permitted an unparalleled insight into susceptibility genes that predispose to their development and has allowed enhanced understanding of their complex immune pathophysiology. Recent findings The susceptibility genes that predispose to AITD can be subdivided into those that affect the immune response in general and thyroid-specific antigens. Both known and new susceptibility genes have been the focus of recent attention. Although there is no known human leukocyte antigen (HLA) association in CLT, recent work has demonstrated an association with a specific amino acid pocket signature irrespective of the HLA-DR class. In Graves' disease a specific combination of polymorphisms for thyroglobulin and HLA-DR markedly increases the odds ratio for developing disease. The availability of recombinant antigen [particularly thyroid peroxidase and thyrotropin (TSH) receptor] and of high affinity monoclonal antibodies has provided insight into the specific epitopes recognized by antibodies in AITD and has confirmed the increased affinity of stimulating TSH receptor antibodies for the shed A subunit rather than the holoreceptor. Summary Powerful molecular tools have been developed that have shed light on the nature of the susceptibility genes for and the pathophysiology of AITD. These have already led to improved diagnostic tools and, hopefully, will permit the development of more specific immune therapy in the future.
TL;DR: Red cell transfusion is currently the most studied and accepted therapy for most acute and many chronic complications of SCD and Physicians caring for patients with sickle cell disease should be aware of the unique complications and transfusion requirements in this population.
Abstract: Purpose of review Although blood transfusion has been felt to be a beneficial therapy for sickle cell disease (SCD) since the 1950s, associated complications initially limited this therapy for these patients. With advances now reducing the side effects of transfusion and several landmark studies over the last decade clearly defining the efficacy for decreasing sickle cell morbidity, the indications for transfusion have increased. This review will discuss the indications, methods and goals of transfusion as well as complications and recent changes in transfusion therapy for SCD. Recent findings Recently studies have established the efficacy of transfusion for prevention of stroke, treatment of acute chest syndrome and perioperative transfusion management of SCD. Pulmonary hypertension is increasingly recognized as a significant source of morbidity and mortality and is an evolving indication for transfusion therapy. Phenotypically matching transfused blood has been shown to decrease alloimmunization, and genotyping for antigen matching may help match donors to patients in the future. Summary The increased use of transfusions may ultimately be balanced by hydroxyurea and other newer therapies developed as the complex pathophysiology of SCD is better understood; however, red cell transfusion is currently the most studied and accepted therapy for most acute and many chronic complications of SCD. Physicians caring for patients with sickle cell disease should be aware of the unique complications and transfusion requirements in this population.
TL;DR: The close association between NAFLD and the MetS supports screening for other comorbidities associated with themetS, and its close association with MetS argues for a focus on strategies designed to improve insulin resistance and components of the metS.
Abstract: Purpose of review
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent in pediatric age individuals, in parallel with increasing obesity, and can lead to liver inflammation, fibrosis and even cirrhosis. NAFLD appears tightly linked with features of the metabolic syndrome (MetS). This review aims to review the clinical presentation, laboratory and pathologic assessment, and treatment of NAFLD, with a focus on its relationship with the MetS.
TL;DR: The treatment approaches that have led to this doubling in survival over the last 25 years are reviewed and a complete list of diagnostic tests and imaging required to identify rhabdomyosarcoma in any body site is provided.
Abstract: Purpose of reviewRhabdomyosarcoma is a rare childhood cancer that affects only approximately 300 children per year in the United States. The purpose of this review is to provide the reader a greater understanding of the complex diagnosis, assessment and treatment of rhabdomyosarcoma in children.Rece
TL;DR: Cord blood transplantation is now an established field with enormous potential, and UCB increases access to transplantation therapy for many patients unable to identify a fully matched adult donor.
Abstract: Purpose of review2008 marks the 20th anniversary of the first use of umbilical cord blood (UCB) as a source of donor cells for hematopoietic stem cell transplantation. In those early days, there was great doubt and skepticism about the utility of UCB as a source of hematopoietic stem cells. Doubts a
TL;DR: Although culture of the urine remains the gold standard for diagnosing and treating urinary tract infections, technical considerations including method of collection of the pee as well as the time necessary for culture results remain problematic.
Abstract: Purpose of reviewUrinary tract infections remain a significant cause of serious bacterial infections in children and can result in chronic kidney disease. Thus, prompt diagnosis and initiation of treatment of urinary tract infections are paramount objectives.Recent findingsA number of advances in te
TL;DR: The specific reasons why social determinants should be considered mainstream in children's environmental health research are outlined, with particular focus on interactive effects between social and physical hazards.
Abstract: Purpose of Review—While traditional disciplinary research theory and methods have focused separately on how social and physical environmental factors affect children’s health, evolving research underscores important integrated effects. Recent findings—This review outlines the specific reasons why social determinants should be considered mainstream in children’s environmental health research with particular focus on interactive effects between social and physical hazards. These include (a) sensitivity of overlapping physiological systems, via epigenesis, programming, and plasticity to social and physical environmental moderation that may impact health across the life span; (b) ways in which social environmental vulnerabilities moderate the effects of physical environmental factors providing specific examples related to respiratory health and neurodevelopment; (c) overlapping exposure distribution profiles; and (d) relevance to pediatric health disparities. Summary—Because of the covariance across exposures and evidence that social stress and other environmental toxins (e.g., pollutants, tobacco smoke) may influence common physiological pathways (e.g., oxidative stress, pro-inflammatory immune pathways, autonomic disruption), understanding the potential synergistic effects promises to more completely inform children’s environmental health risk. While this discussion focuses around the respiratory and neurological systems, these concepts extend more broadly to children’s psychological and physical development.
TL;DR: This review summarizes the recent progress made using genome-wide association studies on the identification of common genetic variants that contribute to adult height variation in the general population.
Abstract: Purpose of reviewBoth environmental (e.g., nutrition) and genetic factors contribute to adult height variation in the general population. However, heritability studies have shown that most of the variation in height is genetically controlled. Although height, a classic polygenic trait, has been stud
TL;DR: The authors summarizes current research and understanding of the pathogenesis of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and provides an update on the treatment of these conditions in children.
Abstract: Purpose of reviewThis study summarizes current research and understanding of the pathogenesis of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and provides an update on the treatment of these conditions in children.Recent findingsThe association of specific human leukocyte anti
TL;DR: This report will update the medical and orthopedic approaches to care for children with osteogenesis imperfecta and suggests that DNA analysis is a better test for diagnosis as compared with dermal biopsy.
Abstract: Purpose of reviewConsiderable attention has recently been focused on the pathogenesis, diagnosis and treatment of osteogenesis imperfecta. Two new genes have been defined in patients with recessive severe or lethal osteogenesis imperfecta types. Diagnostic concerns involve testing procedures, either
TL;DR: The recent literature on chronic constipation has provided some new knowledge providing a more evidence-based approach to treating these patients, and newer pharmacological approaches provide optimism for treatment for this common problem.
Abstract: Purpose of reviewChronic constipation remains one of the most frequent complaints in primary and subspecialty pediatric clinics. It is associated with significant emotional and economic burden for both the children and the caregivers. Recently, advances have expanded our understanding of the pathoph