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The effect of nitric oxide (NO) upon gallbladder motility as examined in a group of volunteers after fatty meal during infusion with NO donors (glyceryltrinitrate and sodium nitroprusside), normal saline and hydralazine as a hypotensive control agent. Postprandial gallbladder emptying was significantly reduced during infusion with the NO donors. This inhibitory effect was independent of hypotension and CCK release. This inhibitory effect of NO donors was also observed on isometric contraction of isolated gallbladder muscle strips. The effect of NO on the SO was examined by infusion of glyceryltrinitrate to the ampulla during SO manometry. Basal tone and phasic activity were both suppressed. This finding may have therapeutic application for stone extraction during endoscopic retrograde cholangiopancreatography. Symptoms were assessed in 100 patients before and six months after laparoscopic cholecystectomy (LC) with standard questionnaire. 13% of patients had persistent biliary symptoms and abdominal bloating, constipation and consumption of antidepressant were fund to be significantly more prevalent in these subjects compared to patients who had successful operations. SO dysfunction is a cause of post-cholecystectomy pain. We hypothesised that LC could destroy cholecysto-sphincteric nerves leading to SO dysfunction. SO manometry was performed in a group of volunteers before and six months after LC. Following LC, the SO was not inhibited by CCK. This could lead to relative post-prandial biliary obstruction and result in post-cholecystectomy pain in susceptible individuals and to dilatation of the common bile duct. Several issues and concepts arose from the work of this thesis. The mechanism underlying the early release of CCK needs further investigation. The clinical relevance of the effects of NO upon biliary tract motility remains to be explored. It is hoped that future research in this area will help to clarify these issues.

No description available.

In this thesis I have investigated the direct contribution of inflammatory bowel disease in specific nutritional problems such as osteopenia. I have also developed clinically applicable objective measures of different aspects of gut inflammation so that the interface between gut inflammation and nutritional abnormalities may be explored. Bone mineral density and biochemical parameters of bone metabolism were measured in patients with newly diagnosed inflammatory bowel disease prior to medical therapy or surgery. I established that, at diagnosis, low bone mineralization is a feature of Crohn's disease but not ulcerative colitis. Disease activity, anatomy of involvement, body mass index, smoking habits, sex, physical activity or biochemical parameters did not account for this difference. Follow-up over a period of one year showed no further bone loss in spite of steroid therapy. Previous studies which had not shown any difference between Crohn's disease and ulcerative colitis had recruited unselected patients with predominantly long-standing disease. When I studied patients with long-standing inactive inflammatory bowel disease, spine and forearm bone mineral density were equally low in both Crohn's disease and ulcerative colitis. Adolescents with long-standing inflammatory bowel disease were identified as a specially vulnerable group for osteopenia. Since bone is only one of the compartments of the body, I next investigated methods to assess body composition in clinical practice. Simple portable, user-friendly bioelectrical impedance analysis machines have recently become available. I evaluated one such machine by comparing it with a standard bioelectrical impedance machine available in medical physics department and with dual energy X-ray absorptiometry, a standard method of measuring lean body mass. The results showed that this machine measured lean body mass as accurately as the more expensive, non-portable machines.

Inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are disorders of the gastro-intestinal system whose aetiology and pathogenesis remain unknown. It has long been known that changes in the diet can be beneficial and elemental diets (ED), devoid of polypeptide antigens, have been successfully used in the management of these conditions. Thus, the aim of this thesis was to study the role of food antigens and the effect of their withdrawal on IBD immune activity by the use of ED. Humoral immunity was studied by measuring total immunoglobulins and antibodies to: ovalbumin, B-lactoglobulin and gliadin in serum, whole gut lavage fluid (WGLF) and parotid saliva. T-cell activity was studied by measuring soluble interleukin-2 receptor in WGLF (LIL2R) and in serum (SIL2R). Macrophage activity was studied by measuring tumour necrosis factor (TNF) in WGLF and a-1 acid glycoprotein (a-1) in serum and WGLF. Comparisons were made between levels of these parameters in active and inactive IBD and healthy controls. Disease activity was quantified by measuring the concentration of immunoglobulin (Ig)G in WGLF. Patients with active IBD were prescribed ED for at least 7 days. During the course of the ED, WGLF and serum were collected prior to and after the 7th day and assayed for the above mentioned factors. There was no difference in serum immunoglobulins and antibodies between IBD patients and controls. Total IgM and IgG in WGLF were higher in active IBD than in controls. Food antibodies were also higher in CD, but not in UC patients compared with controls. However, there was no change in the level of immunoglobulins and food antibodies in serum, WGLF or parotid saliva in patients treated with ED, regardless of the outcome. LIL2R and SIL2R were higher in active IBD compared to controls. Patients with high initial LIL2R responded to ED and showed reduction of LIL2R with improvement of disease. a-1 was raised in all IBD (active and inactive) patients in both serum and WGLF compared to controls. a-1 changes in IBD patients on ED were unrelated to disease response. TNF levels werehigher in active IBD patients than in controls. Patientswith high levels did worse on ED.

The thesis discusses disorders of anorectal and pelvic floor function, i.e. faecal incontinence and intractable constipation. Relevant anatomy, physiology and methodology are first described. Newer forms of apparatus were applied such as a surface anal plug electrode for non-invasive integrated electromyography, a pudendo-anal reflex electrical stimulator for activating the external anal sphincter and a form of EMG biofeedback for relaxation of the pelvic floor musculature. An essential part of the study is anorectal manometry. Various systems for the measurement of pressure are contrasted using both analogue and digital recorders. The digital system was the more sensitive, but the analogue system using a microballoon was free of orientational changes. Over 200 patients with idiopathic faecal incontinence were examined by manometric and somatosensory testing, the majority of whom had pudendal neuropathy. Four subgroups were characterised, two with impairment of either the external or internal anal sphincters, another with both sphincters affected and a fourth with no apparent sphincter deficit but presenting an abnormal rectal compliance. The effect of stimulating the sacral outflow from the spinal cord, via the pudendal nerve to the sphincter mechanism, was therefore assessed and revealed significant improvement in tests of anorectal function.