published_or_final_version / Medicine / Master / Doctor of Medicine

published_or_final_version / abstract / toc / Surgery / Master / Master of Surgery

This study was designed to examine two premises: that the morphological "severity" of duodenal ulcers (DU) may influence the incidence of drug mediated healing and the morphological "quality" of healing after curative therapy may influence t he duration of remission. Biopsies taken at endoscopy from five healthy volunteers and from 84 patients suffering from DU were examined by light and electron microscopy. The endoscopic and morphological appearance of the mucosa within 8mm of the DU or scar, before and up to 1 year after therapy with either sucralfate, cimetidine, pirenzipine or misoprostol are described. Irrespective of the mode of therapy or whether the biopsies were from normal, juxta-DU or scar mucosa, specimens could be divided into 2 primary morphological classes: gastric metaplastic and non-metaplastic. Based on the degree of metaplastic differentiation and nonmetaplastic degeneration, these classes were further divided into 4 sub-classes. When correlated with the incidence of healing and duration of remission, metaplasia was generally found to be a positive and degenerative nonmetaplasia a negative prognostic criterion. Scores were awarded to primary morphological criteria and weighted to give high total s to favourable (metaplastic) and low totals to non-favourable (degenerative non-metaplastic) prognostic features. The sum of scores expressed as a percentage was termed the morphological index. This proved useful as a means of correlating mucosal morphology with DU healing and duration of remission. It also facilitated comparison of morphology within and between groups of patients before and after each drug regimen. The results showed that the morphological appearance of the ulcerative mucosa influenced healing and remission outcome. Discriminant analysis was applied to the numeric data that described the juxta-DU (group 1) and scar (group 2) morphology of patients treated with cimetidine in 2 studies. Separation between healed and not healed DU was achieved in 92% of group 1 and 100% (remission - more or less than 6 months) of group 2. When applied to the juxta-DU data from patients treated with cimetidine in a third study, the formulae predicted correctly in 88% of cases. In addition to predicting outcome, the formulae were used as standards to accommodate for natural variations in the prognosis of individual DU of patients enrolled for comparative drug studies. These data show that morphological analysis may be usefully employed in duodenal ulcer therapy. / Thesis (Ph.D.)-University of Natal, Durban, 1994.

The pathogenesis of duodenal ulcer is believed to centre around the presence of gastric acid, yet the exact role that acid plays is poorly understood. Previous investigations of the duodenal pH have been restricted by methodological and technical difficulties, and have, for the most part, only monitored the pH in the short-term. A new reliable system for long-term (twenty-four hour), ambulatory, simultaneous measurement of intra-luminal antral and duodenal bulb pH has been developed. The system comprises two glass pH electrodes, a small portable recording unit and a computer-based system for data storage and analyses. Validation of this pH monitoring system was first performed, and the 24-hour ambulatory profiles of antral and duodenal pH of normal healthy subjects were subsequently recorded. Periods of cephalic stimulation and ingestion of a solid meal were included during the study period. Having established the normal profiles, the investigation was repeated in patients with active duodenal ulcer, off-treatment. The gastric pH profile was similar of both study groups. There were no significant differences between the fasting duodenal bulb pH and the total 24-hour duodenal acid exposure of the ulcer patients and healthy subjects. Acid peak analysis demonstrated that the duodenal ulcer patients exhibited a defect in the propulsive duodenal bulb motility. Gastric stimulation caused a similar pattern of duodenal acidification in the two groups. These results suggest that gastric acid is not of primary pathophysiological importance in duodenal ulcer disease. The effects of cephalic stimulation and a meal on plasma gastrin, secretin and somatostatin and duodenal pH were examined in healthy subjects and duodenal ulcer patients. The results showed: vagally-released gastrin is not a significant contributor to stimulation of gastric acid secretion in either health or duodenal ulcer disease; duodenal ulcer patients have excessive basal and post-stimulation plasma gastrin levels but a subset of ulcer patients exists, the "Hypergastrinaemic" patients, who exhibit exaggerated gastrin responses, vagal hyperactivity, a defective somatostatin-induced inhibition of gastrin release and a defect in the "switch-off" mechanism of gastric acid secretion. In addition, the physiological role of secretin in inhibiting gastrin release in Man is questionable. This study reveals new aspects in the physiology and pathophysiology of the duodenal bulb pH.

Some ill. mounted / Bibliography: leaves 179-232 / x, 232, [53] leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1984

published_or_final_version / Medicine / Master / Doctor of Medicine

Includes bibliographical references. / 59 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Various articles published by John Robin Warren on the discovery and pathology of Helicobacter pylori. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 2000

A study was undertaken of the stressful life situations of 87 duodenal ulcer patients (50 Indian and 37 Black males) and a control group of 75 non-ulcer patients (43 Indian and 32 Black males). The majority of the control group were orthopaedic patients selected on the grounds that they were not hospitalised for a psychosomatic complaint. The group emerged, however, as highly stressed in relation to possible work and income loss, because of their injuries. The duodenal ulcer and non-ulcer groups were similar in many demographic details and in several stressful life situations. There was a significantly higher reporting of stress in family life, in the work situation and as a result of the illness itself, by duodenal ulcer patients compared with the controls. The initial hypothesis that there would be more areas perceived of as stressful in the case of duodenal ulcer patients than controls was confirmed in the study. A minor hypothesis that there would be cross-cultural differences in the perception of stress was also confirmed. The follow-up study of Indian duodenal ulcer patients demonstrated the development of an "illness career" consisting of a periodic response to stress with onset or recurrence of duodenal ulcer symptoms accompanied by changes in the individual's family system. Minuchin's (1978) concept of enmeshment or disengagement in family systems was found to be applicable to the duodenal ulcer patient. The symptom served to maintain family homeostasis by transforming family conflict into care and concern, or by legitamising the under-functioning of the sick person. The role of social work intervention in relation to duodenal ulcer disease was explored through the establishment of a medical social work programme at the Gastro-Intestinal Unit, King Edward VIII Hospital, Durban. It was shown that the psychosocial aspects of duodenal ulcer disease must receive attention, together with medical treatment, if comprehensive patient care is to be achieved. Intervention should emphasise self management of stress through behaviour modification and cognitive restructuring. Family therapy is essential in cases where the symptom has a function in the family system. Many systems are involved in the aetiology and treatment of duodenal ulcer disease. A general systems approach is therefore useful in promoting a holistic view of the person and the illness. / Thesis (Ph.D.)-University of Durban-Westville, 1983.