Wednesday, April 25, 2012

Autism: Anguished Citizen of America on the Continuing Controversy.


Autism: Anguished Citizen of America on the Continuing Controversy.
- John Smith (In a reply to a Nature Magazine article on the issue.)

(Andrew Wakefield (born 1956 in the United Kingdom) is a Canadian trained surgeon and the lead author of a 1998 research study, published in The Lancet, which reported bowel symptoms in a selected sample of twelve vaccinated children diagnosed with autism spectrum disorders and other disabilities, and suggested more research on the subject)

It is indeed a sad reflection on the medical professionals that have offered any number of varying opinions on this important debate that none have suggested actually investigating and taking care of the so called "Lancet 12" children.

Except the medical professionals that undertook those investigations.

One the senior co-author of the Lancet 12 study John Walker-Smith, a world renowned paediatric gastroenterologist awarded a lifetime achievement award by his peers, had this to say.

"Am I too naive to ask all people of goodwill on both sides of this debate to speedily agree on an independent research agenda that will finally resolve this matter? Such an agenda must involve non-epidemiological research, focusing on the bowels of these children."


What then are we to make of the published observations of the team of paeditric gastroenterologists that stated in 1998 and examined 'actual patients' and their physiology.

(Simon Murch, Mike Thomson and John Walker-Smith.)
First, this mucosal abnormality has been apparent in 47/50 children within the autistic spectrum, whether or not there is any perceived link with immunisation. Thus the lymphoid hyperplasia/ microscopic colitis changes were found in over 90% of the autistic children studied.

"the lymphoid hyperplasia in many cases is remarkable, with germinal centres showing higher numbers of proliferating (Ki67 positive) cells than we have detected in any immunodeficient controls with lymphoid hyperplasia.... The colitis itself is variable, but may feature crypt abscesses, increased macrophage infiltration and unregulated class II major histocompatibility complex expression."

If there was no bowel disease / colitis then how does one sufficiently explain ...
"we have noted important behavioural responses in several of the children when their intestinal pathology is treated"
Which has been emphasised by the Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report

The prevalence of gastrointestinal abnormalities in individuals with ASDs is incompletely understood.
2006 research conducted by Valicenti-McDermott M et al Prospective descriptive reports from autism clinics have described significant gastrointestinal symptoms in at least 70% of patients"

This has also been further evidenced by 2011 research undertaken by University of California Medical, once again notable that it undertook direct information from autistic patients and families.

Parents reported significantly more GI problems in children with ASD (249/589; 42%) compared with their unaffected siblings (20/163; 12%) (p < .001). The 2 most common Gl problems in children with ASD were constipation (116/589; 20%) and chronic diarrhea (111/589; 19%)

The impact on actual families is serious..
"An emerging literature suggests that individuals with ASDs and gastrointestinal symptoms may be at higher risk for problem behaviors than those with ASDs who do not have gastrointestinal symptoms"

"Problem behaviors are the single most important factor in determining quality of life for individuals with ASDs and their caretakers."

The guidance for medical professionals is clear ...

For a person with an ASD who presents for treatment of a problem behavior, the care provider should consider the possibility that a gastrointestinal symptom, particularly pain, is a setting event, that is, a factor that increases the likelihood that serious problem behavior (eg, self-injury, aggression) may be exhibited.

There is a clear and present danger that prejudicial commentary and investigation of autistic children may result in real harm to not only the child themselves through lack of treatment of underlying gastroenterology symptoms but also to carer's and their families.

References for this  post:


Autism, inflammatory bowel disease, and MMR vaccine
Original Text
Simon Murch a, Mike Thomson a, John Walker-Smith a
Authors’ reply The Lancet, Volume 351, Issue 9106, Page 908, 21 March 1998 doi:10.1016/S0140-6736(05)70323-8


Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report – Timothy Buie et al Pediatrics Vol. 125 No. Supplement 1 January 1, 2010
pp. S1 -S18 (doi: 10.1542/peds.2009-1878C)

Valicenti-McDermott M, McVicar K, Rapin I, Wershil BK, Cohen H, Shinnar S. Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease. J Dev Behav Pediatr.2006;27 (2 suppl):S128– S136


J Dev Behav Pediatr. 2011 Jun;32(5):351-60. doi: 10.1097/DBP.0b013e31821bd06a.
The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members.
Wang LW,

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More studies find the same conclusion:
Furlano R, Anthony A, Day R, Brown A, Mc Garvey L, Thomson M, et al. “Colonic CD8 and T cell filtration with epithelial damage in children with autism.“ J Pediatr 2001;138:366-72.

Sabra S, Bellanti JA, Colon AR. “Ileal lymphoid hyperplasia, non-specific colitis and pervasive developmental disorder in children”. The Lancet 1998;352:234-5.

Torrente F., Machado N., Perez-Machado M., Furlano R., Thomson M., Davies S., Walker-Smith JA, Murch SH. “Enteropathy with T cell infiltration and epithelial IgG deposition in autism.” Molecular Psychiatry. 2002;7:375-382

Ashwood P, Anthony A, Pellicer AA, Torrente F. “Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology.” Journal of Clinical Immunology, 2003;23:504-517.

Gonzalez, L. et al., “Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms“. Arch Venez Pueric Pediatr, 2005;69:19-25.

Balzola, F., et al., “Panenteric IBD-like disease in a patient with regressive autism shown for the first time by wireless capsule enteroscopy: Another piece in the jig-saw of the gut-brain syndrome?” American Journal of Gastroenterology, 2005. 100(4): p. 979- 981.

S. Walker, K. Hepner, J. Segal, A. Krigsman “Persistent Ileal Measles Virus in a Large Cohort of Regressive Autistic Children with Ileocolitis and Lymphonodular Hyperplasia: Revisitation of an Earlier Study” 

Balzola F et al . “Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients.” Gastroenterology 2005;128(Suppl. 2);A-303.
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Age of Autism: 
It is now well accepted in mainstream published medical scientific papers and there is now a medical scientific consensus that:

 ”Gastrointestinal disorders and associated symptoms are commonly reported in individuals with ASDs” [4]

“Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. ” [5]

“People with autism are also known to suffer from gastrointestinal disorders and they have a different makeup of bacteria in their guts from non-autistic people.” [6]

[1] Amar P Dhillon, Pathologist, Department of Cellular Pathology, UCL Medical School,”Re: Pathology reports solve “new bowel disease” riddle BMJ Rapid Responses Thu, 2011-11-17 09:10

[2]  (Jenkins D et al. “Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic inflammatory bowel disease. The British Society of Gastroenterology Initiative“. J Clin Pathol 50,93-105;1997). British Society of Gastroenterology Guidelines in Gastroenterology July 1997

[3] Day 113 Friday 16 January 2008 Pages 43/44

[4] Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: PEDIATRICS Volume 125, Supplement 1, January 2010 [Added 22 May 2010].

[5] Williams BL, Hornig M, Buie T, Bauman ML, Cho Paik M, et al. (2011) Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances. PLoS ONE 6(9): e24585. doi:10.1371/journal.pone.0024585


[6] Children with autism have a different chemical fingerprint in their urine than non-autistic children, Imperial College News Release Thursday 3 June 2010, “Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls,”Journal of Proteome Research, published in print 4 June 2010.
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Here's another one:
http://www.ncbi.nlm.nih.gov/pubmed/11950955
Mol Pathol. 2002 Apr;55(2):84-90.
Potential viral pathogenic mechanism for new variant inflammatory bowel disease.
Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, Killalea A, Murch SB, Walker-Smith J, Thomson M, Wakefield AJ, O'Leary JJ.
Source
Department of Pathology, Coombe Women's Hospital, Dublin 8, Ireland.
Abstract
AIMS:
A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) has been described in a cohort of children with developmental disorder. This study investigates the presence of persistent measles virus in the intestinal tissue of these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis.
METHODS:
Formalin fixed, paraffin wax embedded and fresh frozen biopsies from the terminal ileum were examined from affected children and histological normal controls. The measles virus Fusion (F) and Haemagglutinin (H) genes were detected by TaqMan reverse transcription polymerase chain reaction (RT-PCR) and the Nucleocapsid (N) gene by RT in situ PCR. Localisation of the mRNA signal was performed using a specific follicular dendritic cell antibody.
RESULTS:
Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng total RNA.
CONCLUSIONS:
The data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder.
Comment in
  • Mol Pathol. 2002 Apr;55(2):83.
  • Mol Pathol. 2003 Aug;56(4):248.
PMID:
 11950955 [PubMed - indexed for MEDLINE] 
PMCID: PMC1187154
 Free PMC Article
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MMR Vaccine, with 17 scientific refernces to the harm of the MMR vaccine!
http://www.babyjabs.co.uk/mmr.htm#11
1 Jefferson T, Price D, et al. Unintended events following immunization with the MMR: a systematic review. Vaccine 2003; 21: 3954-3960.
2 Wakefield AJ, Montgomery SM. Measles, mumps, rubella vaccine: through a glass darkly. Adverse Drug Reactions and Toxicological Reviews 2000; 19: 265-83.
3 Hilleman MR et al. Live attenuated mumps-virus vaccine. 4. Protective Efficacy as Measured in a Field Evaluation. New England Journal of Medicine 1967; 252-7.
4 Lewis JE et al. Epidemic of mumps in a partially immune population. Canadian Medical Association Journal 1979; 121: 751-4.
5 Wakefield AJ et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet 1998; 351:637-41.
6 Pearce A, Law C, Elliman D, Cole TJ, Bedford H, the Millennium Cohort Study Child Health Group. Factors associated with uptake of measles, mumps and rubella vaccine (MMR) and use of single antigen vaccines in a contemporary UK cohort: prospective cohort study. BMJ 2008; 336: 754-757.
7 Madsen KM et al. A population-based study of measles, mumps and rubella vaccination and autism. The New England Journal of Medicine 2002; 347: 1477-1482.
8 Kaye JA et al. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. British Medical Journal 2001; 322: 460-463.
9 Davis RL et al. Measles-Mumps-Rubella and Other Measles-Containing Vaccines do not increase the risk for Inflammatory Bowel Disease. A Case-control Study from the Vaccine Safety Datalink Project. Archives of Pediatric and Adolescent Medicine 2001; 155: 354-359.
10 Smeeth L. Cook C. Fombonne E. Heavey L. Rodrigues LC. Smith PG. Hall AJ. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet 2004; 364(9438): 963-9.
11 Uhlmann V, Martin CM et al. Potential viral pathogenic mechanism for a new variant inflammatory bowel disease. Molecular Pathology 2002; 55: 84-90.
12 Bradstreet JJ et al. Detection of Measles Virus Genome RNA in Cerebrospinal Fluid of Children with Regressive Autism: a Report of Three Cases. Journal of American Physicians and Surgeons 2004; 9: 38-45.
13 LeBaron CW, Bi D, Sullivan BJ, Beck C, Gargiullo P. Evaluation of Potentially Common Adverse Events Associated With the First and Second Doses of Measles-Mumps-Rubella Vaccine. Pediatrics 2006; 118 (4): 1422-1430.
14 Vestergaard M et al. MMR Vaccination and Febrile Seizures. Evaluation of Susceptible Subgroups and Long-term Prognosis. Journal of the American Medical Association 2004; 292: 351-357.
15 Jonville-Bera AP et al. Thrombocytopenic purpura after measles, mumps and rubella vaccination: a retrospective survey by the French regional pharmacovigilance centres and pasteur-merieux serums et vaccines. Pediatric Infectious Disease Journal 1996; 15: 44-8.
16 Allerdist H. Neurological complications following measles vaccination. Developments in Biological Standardization 1979; 43: 259-64.
17 Miller C et al. Surveillance of symptoms following MMR vaccine in children. Practitioner 1989; 233: 69-74.


Dr Andrew Wakefield

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