Introduction; The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), affect well over 100,000 people in the United Kingdom Health related quality of life (HRQOL) is influenced by many factors in IBD including; the nature and severity of the disease, socio-economic factors, age, psychological well-being as well as· the efficacy and complications of treatment. Pilot Studies; Quality of life was assessed in 140 IBD patients (70 CD/70 UC). Diarrhoea was, not surprisingly, the most commonly reported physical symptom in both CD and UC and impaired faecal continence caused great social disability, with 72% CD patients and 68% UC patients reporting urgency or incontinence. Over a third of all patients reported occupational problems associated with their disease. Anxiety, but not depression, was common in the CD group and a major source of anxiety in many cases was lack of information. Three-quarters of patients felt additional information would have enabled them to cope with their chronic illness. It is a common perception that the provision of psychological support, such as the use of counselling skills, may alleviate many of the psychosocial problems associated with IBD, but this has not yet been proven. Hypothesis: That a nurse led counselling service improves HRQOL in IB D patients. Study Group/Design: Fifty patients with CD (aged 16-64, 33 females), 50 UC patients (aged 17-60, 26 females), 50 healthy volunteers (HV, aged 17- 61, 27 females) and a disease control group comprising 28 psoriatic arthritis (PS) patients (aged 22-66, 16 females) undeiwent structured interviews and completed a range of questionnaires measuring several facets of quality of life and psychological well-being (Hospital Anxiety and Depression Score (HAD), Attitudes and Preferences (AP), Styles and Strategies (SS) and Short-form 36 (SF36)). Patients with IBD were then randomised to receive either a counselling package or routine clinical follow-up. The counselling package consisted of disease specific information and teaching of stress management techniques, based on the "Challenge to change" programme devised by Dr. Derek Roger at the University of York. HRQOL scores were compared on entry at 6 and 12 months. Results; At baseline the scores for all questionnaires were within the nonnal range in the UC, PS, and HV groups. However CD patients recorded significantly higher anxiety scores (p<O.O I) and demonstrated significantly higher maladaptive coping mechanism scores (p<0.05). At six months, the anxiety scores of the CD patients improved significantly (p<0.05) as did their maladaptive coping mechanism scores (P<0.05). There was no significant change in disease activity over this period. These improvements were maintained at twelve months. Summary/Conclusion; Psychological morbidity is common in CD and can be quantified using validated questionnaires. Psychological morbidity improves with basic psychological support and information provision but sophisticated stress management techniques are probably unnecessary.

Antisera to the basement membrane proteins laminin, fibronectin and type IV collagen were prepared, characterized and rendered monospecific by appropriate treatments. Methods were developed to allow the use of these antisera for inmunohistochemical staining of sections of tissue which had been preserved by several methods. In particular, the use of protease digestion {"unmasking") to allow staining of formalin-fixed, paraffin-embedded material was studied. The presence and intensity of staining was found to be highly dependent on the protease and the conditions of digestion, the type of basement membrane, and whether the tissue was normal or neoplastic. The distributions of the three proteins were studied in normal colorectal mucosa and in colorectal adenocarcinoma. A detailed retrospective study was made of the distribution of laminin in 158 cases of rectal carcinoma. Tumours fell into two groups: those which showed linear basement membrane-like laminin staining (laminin positive) and those which did not (laminin negative). Patients with laminin positive tumours had a reduced incidence of distant metastasis and an increased 5 yr survival rate; these correlations were statistically highly significant. Carparison by multivariate analysis with other widely used prognostic markers indicated that laminin status has considerable potential for use as a prognostic marker in the management of such patients. The antisera were also used in a study of the cellular origin and biosynthesis of basement membrane proteins in three systems. In a basement membrane-producing murine tumour, intracellular staining was seen, but it was found that different methods of tissue preparation and unmasking drastically affected the apparent distributions of the three antigens. In the developing rat intestine, no evidence was seen of basement membrane synthesis by the intestinal epithelial cells. However in isolated rat intestinal epithelial cells, some evidence was found for synthesis of laminin and fibronectin, but not type IV collagen.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

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