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Title: Slow transit constipation : clinical and aetiological studies
Author: Knowles, Charles H.
ISNI:       0000 0001 2425 9023
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2000
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Constipation is the second most commonly self-reported gastrointestinal symptom. On the basis of anorectal physiological investigations and colonic transit studies, a subgroup of patients with several intractable symptoms, but without organic disease will be found to have slow transit constipation (STC). STC is a condition of gut dysmotility which predominantly affects young women, and may result in surgical intervention with variable, often unsatisfactory results. The aetiology remains elusive. New aetiological hypotheses for STC were examined following full clinical and pathophysiological characterisation of a large cohort of 130 patients referred to our institution over the last 10 years. Aspects of nerve and muscle dysfunction were studied. A new scoring system demonstrated some ability of multiple symptoms to discriminate STC from other forms of constipation. Detailed clinical and gastrointestinal physiological studies confirmed the heterogeneity of STC patients. Some significant physiological differences were detectable between clinically defined sub-groups of patients and refuted previous assumptions based on smaller numbers. Detailed neurophysiological studies, including quantitative peripheral sensory and autonomic testing, provided evidence of a small fibre neuropathy in a proportion of patients with STC. Mutational screening of some early-onset cases for a possible congenital pathogenetic mechanism, based on the observation that some STC patients had relatives with Hirschsprung's disease demonstrated that mutation of 2 important genes now implicated in this disorder were not a frequent cause of STC. Serum immunoprecipitation assays showed that anti-neuronal ion channel autoantibodies may have an as yet unrecognised role in the development of STC in a small proportion of acquired cases. An inclusion body myopathy was identifiable in colonic tissue of patients with STC, and this appeared to arise secondary to denervation. Further knowledge of the single or multiple pathogenetic mechanisms leading to this clinical condition may allow more rational or directed therapies aimed at the correction of the disease process or processes themselves.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine Medicine