Thoua, NM; (2013) A study of gastrointestinal disease in systemic sclerosis and the effect on anorectal function and nutrition. Doctoral thesis , University of London.

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Abstract

This thesis investigates the prevalence and pathophysiology of gastrointestinal involvement in systemic sclerosis (SSc). The primary pathologies within the gastrointestinal tract affect the mucosa, vasculature, smooth muscle and enteric nervous system. The aim of this thesis was to conduct experiments to assess these pathologies within a well-characterised SSc patient cohort. Introduction: A review of the current understanding of the pathophysiology of gastrointestinal disease in systemic sclerosis. Prevalence of GI symptoms: A prospective questionnaire study of 400 patients in order to assess gut disease burden and review of patient disease characteristics. Anorectal involvement: Extensive anorectal physiological assessment of symptomatic and asymptomatic systemic sclerosis patients compared with incontinent controls in order to assess aspects of neuropathy and myopathy. Nutritional effect as an assessment of mucosal involvement: Nutritional assessment of patients with and without gastrointestinal symptoms through anthropometric assessment, indirect calorimetry and bioelectrical impedance. The pathophysiology of gastrointestinal involvement in systemic sclerosis was further investigated in an established mouse model of scleroderma. This transgenic mouse model expresses a kinase deficient type II TGFβ receptor (TβRIIΔk) in fibroblasts and the mice develop skin fibrosis as well as pulmonary fibrosis and a structural vasculopathy. Gastrointestinal tissue from these mice was examined histologically and the contractile activity of gut tissue was examined in vitro.

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