Pugh, Stirling; (1990) Endogenous Prostaglandin E2 in Human and Experimental Duodenal Ulceration. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The aetiology of human peptic ulcer disease is multifactorial. Its association with anti-prostaglandin drugs has lead to the suggestion that mucosal deficiency of prostaglandins, which are known to be protective to the gastrointestinal tract, may be an aetiological factor. The thesis documents a short history of duodenal ulceration and previous work into its pathogenesis and epidemiology. The history of prostaglandins in the gastrointestinal tract, the phenomena of mucoprotection and the evidence for the protective role of these substances are explored. A method for using endoscopic biopsies to assess the endogenous ability to synthesise prostaglandin E2 (PGE2) is described and validated. Synthesis of iPGE2 (immunoreactive PGE2) in the upper gastrointestinal tract in control subjects is detailed and the effect of demographic factors explored. Synthesis of iPGE2 in patients with duodenal ulceration is estimated and related to all stages of the disease and to histological and histochemical analyses. The human work suggested a deficiency in iPGE2 in patients with duodenal ulceration, and the timing of this deficiency in relation to ulcer formation is explored in the cysteamine rat model of duodenal ulceration.

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