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Aetiology of Hirschsprung's disease associated enterocolitis

Hardy, Simon Paul; (1993) Aetiology of Hirschsprung's disease associated enterocolitis. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The aetiology of Hirschsprung's disease-associated enterocolitis was investigated. Similar isolation rates and toxigenicity of C.difficile were found in children with Hirschsprung's disease with or without diarrhoea and from children without Hirschsprung's disease. No evidence of cholera toxin-like enterotoxins was found in Esch coli or Bacteroides spp isolated from children with Hirschsprung's disease. Neither was secretory activity demonstrable in culture filtrates tested on piglet colon in Ussing chambers or cultured cell lines. The efficacy of creating colonic aganglionosis using benzalkonium chloride was evaluated in neonatal piglets. Insufficient ablation of ganglia occurred with either BAC or the 14-carbon homologue for the model to be of use in assessing neurally- mediated colonic secretion. The effect of the neural abnormalities in children with Hirschsprung's disease on the response to secretory stimuli was investigated using Ussing chambers. Basal electrogenic ion transport in aganglionic and ganglionic rectosigmoid and transverse colon from children with Hirschsprung's disease and in normally-innervated colon from children with anorectal anomalies were similar. Impaired neurally mediated secretion to Iloprost (prostacyclin PGI2 analogue) and acetylcholine was demonstrated in aganglionic colon. The response to carbachol varied between children but the mean response was not significantly reduced. Ganglionic colon proximal to the aganglionic colon also had a reduced response to acetylcholine despite a normal acetylcholinesterase staining pattern. Direct colonocyte secretion with Esch coli STa enterotoxin was unimpaired and resistant to neural blockade with tetrodotoxin. The responses to theophylline but not IBMX were reduced in aganglionic colon. Hypertrophic acetylcholinesterase-positive nerve fibres are likely to contribute to the reduced secretion to acetylcholine. Conclusions: i) No evidence was found for C difficile, or of other toxigenic bacterial products in the aetiology of idiopathic diarrhoea in children with Hirschsprung's disease. ii) In contrast, human aganglionic colon had an overall reduced net secretory potential, particularly to neurally-mediated secretagogues.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Aetiology of Hirschsprung's disease associated enterocolitis
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10102311
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