Proefschrift--Utrecht. / Bibliography: p. 101-104.

Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

No description available.

The purpose of this study was to examine the effect that the patient's level of consciousness and the degree of nasogastric tube flexibility would have on the ease of insertion of the tube in patients with an endotracheal tube in place. The statistical hypotheses tested were: 1. The Degree of nasogastric tube flexibility will not influence the ease with which the tube is inserted. 2. The level of consciousness of the patient will not influence the ease with which the nasogastric tube is inserted. 3. There will be no interaction between the degree of flexibility of the nasogastric tube to be inserted and the level of consciousness of the patient in whom the tube is placed. The sample from whom data was collected for the study consisted of 121 patients admitted to the respiratory intensive care unit of a large teaching hospital who required endotrachea intubation and subsequent placement of a nasogastric tube. The number of attempts per patient for successful placement of each tube were recorded over a four month period and the data analysed using a 2 X 3 factorial design. The two independent variables were degree of nasogastric tube flexibility with two levels: flexible and rigid, and level of consciousness with three levels: conscious, obtunded and unconscious. The data collected from the study indicate that the degree of nasogastric tube flexibility significantly affects the ease with which a tube can be inserted in an intubated patient (α=.05) the rigid tube requiring a statistically fewer number of attempts than the flexible tube. The difference among levels of patient consciousness were not found to be statistically significant in this investigation but the interaction between the degree of tube flexibility and level of patient consciousness revealed statistical significance. / Applied Science, Faculty of / Nursing, School of / Graduate

No description available.

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.

Introduction: Gastrointestinal stromal tumours (GIST) are the commonest tumour of mesenchymal origin; favour the stomach, and account for a very small percentage of gastrointestinal tract tumours. Methods: In this retrospective audit of GISTs presenting to the Groote Schuur Hospital surgical and oncological multidisciplinary team (MDT) between 2004 – 2019, gastric GISTs were evaluated as regards presentation, gastric anatomical position, histological subtype with risk stratification, management and outcomes. Results: Of 126 GIST tumours presenting to this MDT, 82 originated in the stomach. Complete histopathological records could be obtained for 64. With an average of 59 years (50 male: 32 female), 18 (28%) presented with a herald bleed. Other common presentations included anaemia, epigastric mass and pain. The tumours were predominantly found in the body and fundus (64%), with a spindle cell subtype predominance (41%). The association between cancer cell subtype and gastric position was not significantly different (p=0.728). Cystic degeneration was found on 11 (17%) analyzed and cell necrosis on 12 (18%). These findings were not related to larger tumor size or prognosis. Five required downstaging with Imatinib prior to surgery. Thirty-seven patients underwent a surgical procedure: 24 wedge resections and 12 anatomical resections. Risk stratification was performed with the modified National Institutes of Health (NIH/Fletcher) score. Twenty-eight cases had inaccurate mitotic counts and couldn't be scored, 17 scored high risk, 9 intermediate risk, 9 low risk and 1 very low risk. Ten patients died of metastatic disease, 34 were discharged with no disease progression after 3 years, 1 patient with disease progression currently remains on Imatinib, and 19 were lost to follow up. Conclusion: Gastric GISTs appear to have a predilection for the proximal stomach; it is unsure whether this is purely due the greater surface area. The spindle cell subtype dominated in the proximal gastric GISTs. Cystic degeneration and cell necrosis did not seem to be related to larger tumours or outcomes.

Cathelicidin, a pleiotropic host defense peptide, has been shown to promote cutaneous wound repair and reaches high levels in the gastric mucosa during acute Helicobacter pylori-associated inflammation. The expression of cathelicidin, nevertheless, has also been found to be down-regulated in gastric hyperplastic polyps, tubular adenomas, and adenocarcinomas. We therefore hypothesized that cathelicidin might contribute to gastric ulcer healing and suppress gastric cancer growth. In this study, the role of this peptide in gastric tissue repair and carcinogenesis was investigated. / Collectively, this study demonstrates for the first time that cathelicidin can promote tissue repair and suppress cancer growth in stomachs by eliciting differential cellular signaling and responses in normal and cancerous gastric epithelial cells. These unique biological activities may open up a novel therapeutic avenue for the treatment of these diseases. / Concerning gastric carcinogenesis, the human cathelicidin LL-37 lowered gastric cancer cell proliferation and delayed G1-S transition in vitro and inhibited the growth of gastric cancer xenograft in vivo. Knockdown or induction of endogenous LL-37 by RNA interference or 1alpha,25-dihydroxylvitamin D3, respectively, increased or suppressed cell proliferation. In this connection, LL-37 increased bone morphogenetic protein (BMP) signaling, manifested as increases in BMP4 expression and the subsequent Smad1/5 phosphorylation and the induction of Smad6 and Smad7. Moreover, LL-37 increased the expression of p21Waf1/Cip1, whose induction was abolished by the knockdown of BMP receptor II. Knockdown of BMP receptor II or p21Waf1/Cip1 also abrogated the anti-mitogenic action of LL-37. The activation of BMP signaling by LL-37 was accompanied with the inhibition of chymotrypsin-like and caspase-like activity of proteasome. In this regard, proteasome inhibitor MG-132 mimicked the effect of LL-37 by increasing BMP4 mRNA expression and Smad1/5 phosphorylation. In addition, cyclin E 2 was down-regulated by LL-37 via a BMP-independent mechanism. Further analysis of clinical samples revealed that LL-37 and p21Waf1/Cip1 mRNA expression were both down-regulated in gastric cancer tissues and their expression were positively correlated. These findings indicate that LL-37 inhibits gastric cancer cell proliferation through activation of BMP signaling via a proteasome-dependent mechanism. / In relation to gastric ulcer healing, results revealed that ulcer induction in rats increased the expression of rat cathelicidin rCRAMP in the gastric mucosa. Further increase in expression of rCRAMP by local injection of rCRAMP-encoding plasmid promoted ulcer healing by enhancing cell proliferation and angiogenesis. rCRAMP directly stimulated proliferation of cultured rat gastric epithelial cells (RGM-1), which was abolished by inhibitors of matrix metalloproteinase (MMP), epidermal growth factor receptors (EGFR) tyrosine kinase, or mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase. rCRAMP also increased EGFR and ERK1/2 phosphorylation via an MMP-dependent mechanism. Knockdown of transforming growth factor alpha (TGFalpha), which is a ligand of EGFR, by small interfering RNA completely nullified the mitogenic signals evoked by rCRAMP in RGM-1 cells. These findings suggest that rCRAMP exhibits pro-healing activity in stomachs through TGFalpha-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells. / Wu, Ka Kei. / Adviser: Joseph J. Y. Sung. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0252. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 153-178). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Call number: LD2668 .T4 1965 S812 / Master of Science

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy