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Title: Pathophysiology of post-operative peritoneal adhesions
Author: Sulaiman, H.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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Post-operative peritoneal adhesions are fibrous bands of tissue joining together organs occurring in the majority of patients following laparotomy, leading to complications such as abdominal pain, infertility in women and intestinal obstruction. However the structure and pathogenesis of adhesions is still not clear. It is proposed that persistence of fibrin between damaged tissues due to impaired plasminogen activator activity induces adhesion formation. This thesis aims to: (a) assess the structure of peritoneal adhesions in humans and in an experimental murine model (b) characterise and assess the growth of nerve fibres in adhesions and (c) to elucidate the role of fibrinolysis in adhesion formation in animals. Human peritoneal adhesions were collected from patients undergoing laparotomy, whereas murine adhesions were generated in a standardised murine model. Adhesion samples were processed and nerve fibres were characterized histologically, immunohistochemically, and ultrastructurally. In mice two-weeks post-operatively adhesions contained nerve fibres which were synaptophysin, calcitonin-gene-related- peptide, and substance-P-immunoreactive. At 4-weeks, nerve fibres originated from both the caecum and abdominal wall and by acetylcholinesterase-histochemistry were found traversing the entire adhesion. Nerve fibres were similarly present in all human adhesion specimens assessed. Ultrastructural analysis showed both myelinated and non myelinated nerve fibres were present in human and mouse adhesions. To elucidate the role of fibrinolysis a novel approach was taken using mice deficient in tissue plasminogen activator (t-PA) or urokinase plasminogen activators (u- PA) and inducing adhesion formation either by surgery or following an inflammatory episode. Mice deficient in t-PA were significantly more susceptible to adhesion formation following chronic inflammatory episode compared with u-PA deficient and wild-type mice. This thesis provides the first direct evidence that sensory nerve fibres grow into peritoneal adhesions suggesting that they may be capable of conducting pain sensation. Furthermore the persistence of fibrin due to decreased t-PA activity plays a major role in peritoneal adhesion formation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available