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Journal ArticleDOI

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children

28 Feb 1998-The Lancet (Elsevier)-Vol. 351, Iss: 9103, pp 637-641

Abstract: Summary Background We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. Methods 12 children (mean age 6 years [range 3–10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. Findings Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with agematched controls (p=0·003), low haemoglobin in four children, and a low serum IgA in four children. Interpretation We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
Citations
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Journal ArticleDOI
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.
Abstract: This article introduces the approach of GRADE to rating quality of evidence GRADE specifies four categories-high, moderate, low, and very low-that are applied to a body of evidence, not to individual studies In the context of a systematic review, quality reflects our confidence that the estimates of the effect are correct In the context of recommendations, quality reflects our confidence that the effect estimates are adequate to support a particular recommendation Randomized trials begin as high-quality evidence, observational studies as low quality "Quality" as used in GRADE means more than risk of bias and so may also be compromised by imprecision, inconsistency, indirectness of study results, and publication bias In addition, several factors can increase our confidence in an estimate of effect GRADE provides a systematic approach for considering and reporting each of these factors GRADE separates the process of assessing quality of evidence from the process of making recommendations Judgments about the strength of a recommendation depend on more than just the quality of evidence

3,986 citations


Journal ArticleDOI
01 Nov 2007-Pediatrics
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.

1,600 citations



Journal ArticleDOI
01 May 2004-Pediatrics
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.

1,049 citations


Book ChapterDOI
Colin Mathers1Institutions (1)
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.

983 citations


References
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Reference EntryDOI
11 Jun 2013-

113,026 citations


Journal ArticleDOI
John A. Walker-Smith1, Judith Andrews1Institutions (1)
21 Oct 1972-The Lancet

553 citations


Book
10 May 2001-
TL;DR: A simple system of subgrouping based solely on a description of the type of social impairment will be used, which avoids the confusion inherent in trying to identify the named syndromes.
Abstract: simple practical skills and social adaptation from early childhood and that abnormalities were recognisable from the second year of life. Many clinicians diagnose on their interpretation of Asperger’s clinical descriptions, rather than insisting on normal development before 3 years in the areas mentioned. In this article, a simple system of subgrouping based solely on a description of the type of social impairment will be used, which avoids the confusion inherent in trying to identify the named syndromes. This simple subgrouping has proved helpful in clinical practice even though the groups are no more sharply differentiated and permanent than in any other existing method of classification in the specialty.

514 citations


"Ileal-lymphoid-nodular hyperplasia,..." refers background or methods in this paper

  • ...[ 15 ] Rubella virus is associated with autism and the...

    [...]

  • ...[ 15 ] In the context of susceptibility to infection, a genetic...

    [...]


Journal ArticleDOI
Patrizia D'Eufemia1, Mauro Celli1, R. Finocchiaro1, Lucia Pacifico1  +4 moreInstitutions (1)
01 Sep 1996-Acta Paediatrica
TL;DR: It is speculated that an altered intestinal permeability could represent a possible mechanism for the increased passage through the gut mucosa of peptides derived from foods with subsequent behavioural abnormalities.
Abstract: We determined the occurrence of gut mucosal damage using the intestinal permeability test in 21 autistic children who had no clinical and laboratory findings consistent with known intestinal disorders. An altered intestinal permeability was found in 9 of the 21 (43%) autistic patients, but in none of the 40 controls. Compared to the controls, these nine patients showed a similar mean mannitol recovery, but a significantly higher mean lactulose recovery (1.64% +/- 1.43 vs 0.38% +/- 0.14; P < 0.001). We speculate that an altered intestinal permeability could represent a possible mechanism for the increased passage through the gut mucosa of peptides derived from foods with subsequent behavioural abnormalities.

362 citations


"Ileal-lymphoid-nodular hyperplasia,..." refers background in this paper

  • ...Walker-Smith and colleagues [5] detected low concentrations of alpha-1 antitrypsin in children with typical autism, and D'Eufemia and colleagues [ 6 ] identified abnormal intestinal permeability,...

    [...]


Journal ArticleDOI
Abstract: The appreciation of the existence of a brain disorder as encapsulated in early childhood autism has only come to the fore in recent years. Possibly for this reason, there is no apparent agreement as to which of the symptoms of the disorder, namely emotional disturbances or cognitive defects, are primary, and which are secondary. Nor is there yet either a generally accepted medical treatment or a coherent neurochemical theory of autism. In this article, Jaak Panksepp puts forward the idea that autism is an emotional disturbance arising from an upset in the opiate systems in the brain, and hence proposes, as a possibility, opiate antagonist therapy for the autistic syndrome.

297 citations


"Ileal-lymphoid-nodular hyperplasia,..." refers background in this paper

  • ...The "opioid excess" theory of autism, put forward first by Panksepp and colleagues [ 7 ] and later by Reichelt and colleagues [8] and Shattock and colleagues [9] proposes that autistic...

    [...]


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