Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children
TL;DR: In this paper, the authors investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder, and identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
About: This article is published in The Lancet.The article was published on 1998-02-28. It has received 2505 citations till now. The article focuses on the topics: Pervasive developmental disorder & Lymphoid hyperplasia.
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TL;DR: The approach of GRADE to rating quality of evidence specifies four categories-high, moderate, low, and very low-that are applied to a body of evidence, not to individual studies.
5,228 citations
TL;DR: This report addresses background information, including definition, history, epidemiology, diagnostic criteria, early signs, neuropathologic aspects, and etiologic possibilities in autism spectrum disorders, and provides an algorithm to help the pediatrician develop a strategy for early identification of children with autism Spectrum disorders.
Abstract: Autism spectrum disorders are not rare; many primary care pediatricians care for several children with autism spectrum disorders. Pediatricians play an important role in early recognition of autism spectrum disorders, because they usually are the first point of contact for parents. Parents are now much more aware of the early signs of autism spectrum disorders because of frequent coverage in the media; if their child demonstrates any of the published signs, they will most likely raise their concerns to their child's pediatrician. It is important that pediatricians be able to recognize the signs and symptoms of autism spectrum disorders and have a strategy for assessing them systematically. Pediatricians also must be aware of local resources that can assist in making a definitive diagnosis of, and in managing, autism spectrum disorders. The pediatrician must be familiar with developmental, educational, and community resources as well as medical subspecialty clinics. This clinical report is 1 of 2 documents that replace the original American Academy of Pediatrics policy statement and technical report published in 2001. This report addresses background information, including definition, history, epidemiology, diagnostic criteria, early signs, neuropathologic aspects, and etiologic possibilities in autism spectrum disorders. In addition, this report provides an algorithm to help the pediatrician develop a strategy for early identification of children with autism spectrum disorders. The accompanying clinical report addresses the management of children with autism spectrum disorders and follows this report on page 1162 [available at www.pediatrics.org/cgi/content/full/120/5/1162]. Both clinical reports are complemented by the toolkit titled "Autism: Caring for Children With Autism Spectrum Disorders: A Resource Toolkit for Clinicians," which contains screening and surveillance tools, practical forms, tables, and parent handouts to assist the pediatrician in the identification, evaluation, and management of autism spectrum disorders in children.
1,731 citations
1,125 citations
TL;DR: Significant evidence is found for multiple interacting genetic factors as the main causative determinants of autism and for interactions between multiple genes cause "idiopathic" autism but that epigenetic factors and exposure to environmental modifiers may contribute to variable expression of autism-related traits.
Abstract: Autism is a complex, behaviorally defined, static disorder of the immature brain that is of great concern to the practicing pediatrician because of an astonishing 556% reported increase in pediatric prevalence between 1991 and 1997, to a prevalence higher than that of spina bifida, cancer, or Down syndrome. This jump is probably attributable to heightened awareness and changing diagnostic criteria rather than to new environmental influences. Autism is not a disease but a syndrome with multiple nongenetic and genetic causes. By autism (the autistic spectrum disorders [ASDs]), we mean the wide spectrum of developmental disorders characterized by impairments in 3 behavioral domains: 1) social interaction; 2) language, communication, and imaginative play; and 3) range of interests and activities. Autism corresponds in this article to pervasive developmental disorder (PDD) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and International Classification of Diseases, Tenth Revision. Except for Rett syndrome--attributable in most affected individuals to mutations of the methyl-CpG-binding protein 2 (MeCP2) gene--the other PDD subtypes (autistic disorder, Asperger disorder, disintegrative disorder, and PDD Not Otherwise Specified [PDD-NOS]) are not linked to any particular genetic or nongenetic cause. Review of 2 major textbooks on autism and of papers published between 1961 and 2003 yields convincing evidence for multiple interacting genetic factors as the main causative determinants of autism. Epidemiologic studies indicate that environmental factors such as toxic exposures, teratogens, perinatal insults, and prenatal infections such as rubella and cytomegalovirus account for few cases. These studies fail to confirm that immunizations with the measles-mumps-rubella vaccine are responsible for the surge in autism. Epilepsy, the medical condition most highly associated with autism, has equally complex genetic/nongenetic (but mostly unknown) causes. Autism is frequent in tuberous sclerosis complex and fragile X syndrome, but these 2 disorders account for but a small minority of cases. Currently, diagnosable medical conditions, cytogenetic abnormalities, and single-gene defects (eg, tuberous sclerosis complex, fragile X syndrome, and other rare diseases) together account for 1 affected family member; 2) cytogenetic studies that may guide molecular studies by pointing to relevant inherited or de novo chromosomal abnormalities in affected individuals and their families; and 3) evaluation of candidate genes known to affect brain development in these significantly linked regions or, alternatively, linkage of candidate genes selected a priori because of their presumptive contribution to the pathogenesis of autism. Data from whole-genome screens in multiplex families suggest interactions of at least 10 genes in the causation of autism. Thus far, a putative speech and language region at 7q31-q33 seems most strongly linked to autism, with linkages to multiple other loci under investigation. Cytogenetic abnormalities at the 15q11-q13 locus are fairly frequent in people with autism, and a "chromosome 15 phenotype" was described in individuals with chromosome 15 duplications. Among other candidate genes are the FOXP2, RAY1/ST7, IMMP2L, and RELN genes at 7q22-q33 and the GABA(A) receptor subunit and UBE3A genes on chromosome 15q11-q13. Variant alleles of the serotonin transporter gene (5-HTT) on 17q11-q12 are more frequent in individuals with autism than in nonautistic populations. In addition, animal models and linkage data from genome screens implicate the oxytocin receptor at 3p25-p26. Most pediatricians will have 1 or more children with this disorder in their practices. They must diagnose ASD expeditiously because early intervention increases its effectiveness. Children with dysmorphic features, congenital anomalies, mental retardation, or family members with developmental disorders are those most likely to benefit from extensive medical testing and genetic consultation. The yield of testing is much less in high-functioning children with a normal appearance and IQ and moderate social and language impairments. Genetic counseling justifies testing, but until autism genes are identified and their functions are understood, prenatal diagnosis will exist only for the rare cases ascribable to single-gene defects or overt chromosomal abnormalities. Parents who wish to have more children must be told of their increased statistical risk. It is crucial for pediatricians to try to involve families with multiple affected members in formal research projects, as family studies are key to unraveling the causes and pathogenesis of autism. Parents need to understand that they and their affected children are the only available sources for identifying and studying the elusive genes responsible for autism. Future clinically useful insights and potential medications depend on identifying these genes and elucidating the influences of their products on brain development and physiology.
1,115 citations
01 Jan 2008
TL;DR: This article is reproduced from the previous edition, volume 3, pp. 59–71, of Elsevier Inc.
Abstract: Reliable, comparable information about the main causes of disease and injury in populations, and how these are changing, is a critical input for debates about priorities in the health sector. Traditional sources of information about the descriptive epidemiology of diseases, injuries, and risk factors are generally incomplete, fragmented, and of uncertain reliability and comparability. The Global Burden of Disease (GBD) Study has provided a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability, the disability-adjusted life year (DALY). This article describes key features of the Global Burden of Disease analytic approach, the evolution of the GBD starting from the first study for the year 1990, and summarizes the methodological improvements incorporated into GBD revisions carried out by the World Health Organization. It also reviews controversies and criticisms, and examines priorities and issues for future GBD updates.
1,011 citations
References
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66 citations
TL;DR: A positive relationship was observed between elevated serotonin levels and the MHC types previously associated with autism.
Abstract: Two of the most consistently observed biological findings in autism are increased serotonin levels in the blood and immunological abnormalities (including autoreactivity with tissues of the central nervous system). The purpose of this investigation was to determine if any relationship exists between these two sets of observations. Our laboratory has found and confirmed associations of the major histocompatibility complex (MHC) with autism. Since the MHC is known to regulate the immune system and is also associated with autoimmune disorders, we studied serum serotonin levels in 20 autistic subjects with or without MHC types previously found to be associated with autism. A positive relationship was observed between elevated serotonin levels and the MHC types previously associated with autism.
55 citations
TL;DR: The role of measles virus infection and/or a viral antigen (possibly the M protein) as a causative agent in Crohn's disease poses a challenging avenue for further research.
Abstract: Using immunofluorescence (IF), we investigated reactive antigens present in Crohn's disease patients with monoclonal antibodies derived from cells infected with measles virus, but not with the subacute sclerosing panencephalitis virus. During immunoblotting, one monoclonal antibody (mAb 86) reacted with a polypeptide with a molecular weight of 36 000 dalton (M; matrix protein) in measles virus-infected cells. This monoclonal antibody displayed a positive reaction only with tissues from patients with Crohn's disease by the IF test. It did not react with samples from patients with other chronic inflammatory bowel diseases, such as ulcerative colitis. Other monoclonal antibodies to the measles virus protein, and monoclonal antibodies toHerpes simplex virus type 1 did not react with the same tissue samples. The role of measles virus infection and/or a viral antigen (possibly the M protein) as a causative agent in Crohn's disease poses a challenging avenue for further research.
40 citations
TL;DR: Oral route of administration of transfer factor is efficacious and should be used when possible, and recipients of a specific transfer factor responded to the antigen for which the factor was specific by secreting gamma-IFN, but no other cytokines.
Abstract: This report summarizes three components of our transfer factor research program. Several clinical studies have used oral administration of transfer factor containing materials. Sceptics have rejected these findings by assuming that the acidic and enzymatic environment of the gastrointestinal tract would destroy the factors. To further examine this issue, we have conducted dose-response studies of the delayed-type hypersensitivity reaction in mice that were given transfer factor either by gavage or subcutaneously. There were no difference in the responses that were related to the route of administration. We conclude that oral route of administration is efficacious and should be used when possible. We have also studied the effects of transfer factors on immune responses by recipients. The details of this research are presented in the paper by Dr. Alvarez-Thull. Briefly, the study showed that recipients of a specific transfer factor responded to the antigen for which the factor was specific by secreting gamma-IFN, but no other cytokines. The structures of transfer factor molecules are unknown. We have developed a process for isolating transfer factors in pure form and we have obtained preliminary data concerning amino acid sequences. Our goal is to obtain the complete primary structure of several transfer factor molecules.
39 citations
TL;DR: After cessation of TF therapy, 5 in the autistic group and 3 of the pseudo-autistic group regressed, but they did not drop as low as baseline levels.
Abstract: 40 infantile autistic patients were studied. They ranged from 6 years to 15 years of age at entry. 22 were cases of classical infantile autism; whereas 18 lacked one or more clinical defects associated with infantile autism (“pseudoautism”). Of the 22 with classic autism, 21 responded to transfer factor (TF) treatment by gaining at least 2 points in symptoms severity score average (SSSA); and 10 became normal in that they were main-streamed in school and clinical characteristics were fully normalized. Of the 18 remaining, 4 responded to TF, some to other therapies. After cessation of TF therapy, 5 in the autistic group and 3 of the pseudo-autistic group regressed, but they did not drop as low as baseline levels.
35 citations
"Ileal-lymphoid-nodular hyperplasia,..." refers background in this paper
...Fudenberg [ 16 ] noted that for 15 of 20 autistic children, the first symptoms...
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