Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 4 uppsatser.

Introduction: Gastro-oesophageal disease (GORD) is a common disease affecting 20% of adults in the Western world (Dexter 2004) and occurs when the anti-reflux barrier is compromised. Anti-reflux surgery can be recommended to patients with GORD as an alternate to long-term medical therapy. Aim: Laparoscopic anterior fundoplication (LAF) is the preferred type of anti-reflux surgery in our institution. This study aimed to determine the long-term effectiveness of LAF by means of quality of life (QOL) and acid reflux level assessment. Methods: After applying exclusion criteria, patients were sent an invitation for the study along with a QOL questionnaire (QOLRAD) to complete. Selected patients were also invited to undergo 24-hour pH studies. These patients were also asked to complete another QOL questionnaire (Reflux questionnaire (RQ)). Results: QOLRAD questionnaires were analysed (n = 126) and mean scores were calculated for each dimension in addition to an overall QOL score. Over 75% of patients in both the medium-term (2-4 years) and long-term groups (5-14 years) had a good QOL (score 5-7). The median QOL score for the long-term group was 5.89 (±1.36). In addition, Reflux Questionnaire QOL scores (n = 20) (RQLS) indicated that patients were well with a median score of 87.7 out of 100 at long-term. By comparing our post-operative results to published baseline result, our patients QOL had improved since surgery. Most dimensions (QOLRAD) and all symptoms scores (RQ) suggested improvement from baseline. Post-operative 24-hour pH testing (n = 22 0) showed that 55% of patients had a normal TFT pH<4 and that a further 18% had better TFT pH <4 than pre-operatively at long-term follow-up Conclusion: This study suggests that LAF is effective in the long-term by maintaining a good QOL and controlling acid reflux levels. However, larger numbers of participants and pre-operative data are required to confirm these findings.

Over the last three decades, there has been a sharp rise in the incidence of oesophageal adenocracinoma (OA) in the UK. The cause of this rising trend remains unknown. Chronic symptomatic Gastro-Oesophageal Reflux Disease (GORD) has been associated with Barrett's oesophagus (BO), a premalignant stage of OA. The process how acid exposure drives the metaplasia-dysplasia-neoplasia sequence is not known. Oxidative stress plays vital role in carcinogenesis. Selenium is a trace metal element in our diet essential for anti-oxidant selenoproteins synthesis, such as glutathione peroxidases (GPxs). GPxs play a vital role in humans to fight oxidative stress. Epidemiological studies showed that high serum selenium levels are associated with a lower incidence of oesophageal and gastric cardia cancer. This thesis hypothesised that chronic GORD is an initiator of OA pathogenesis by exposing the lower oesophagus to chronic pulse acid, which results in radical oxygen species (ROS) production and oxidative stress damage. GORD patients with suboptimal selenium status are more susceptible to pulse-acid induced oxidative damage because of poor anti-oxidative defence system. The combination of pulse acid exposure and low selenium status potentially drives the OA pathogenesis. The study aims to investigate the effect of pulse-acid exposure, selenium status and its supplementation on cellular proliferation and apoptosis, key processes in carcinogenesis. The study also further investigated the potential pathways through which the pulse acid and low selenium could trigger the carcinogenesis. Ex vivo study was also conducted to examine the selenium status among BO and OA patients, including analysis of single nucleotide polymorphism (SNP) of GPx4 among these patients. The results showed that pulse-acid exposure increased cellular survival and suppressed apoptosis. This result was consistent with previous studies conducted by other researchers. Selenium supplementation at supra-optimal level (100 nM) was shown to potentially mitigate the proliferative effect induced by pulse-acid exposure. Pulse acid exposure was shown to induce ROS production in vitro. This could be mitigated by selenium supplementation. The mitigating effect was likely to be mediated by GPx1, and GPx4, selenoenzymes that are capable of reducing ROS. The study also revealed that apoptosis suppression by selenium supplementation was probably mediated by p53 tumour suppressor gene, but not via Bcl-2 protein. Ex vivo study results showed that OA patients have a 54% significant lower GPx4 mRNA expressions compared to the normal subjects, while the Barrett's subjects were in between OA and Normal. This is in line with the hypothesis that the severity of the disease is closely linked with the levels of anti-oxidant enzymes expression. Expectantly, patients with BO have higher, although not statistically significant, serum selenium compared to the control group. Single nucleotide polymorphism (SNP) of GPx4 could be an explanation for the reason OA and BO patients were unable to synthesise GPx despite an adequate serum selenium level, this rendered them more susceptible to ROS induced oxidative damage. These findings might have potential therapeutic implications for BO and OA. Targeted selenium supplementation could be a cost effective way of OA cancer prevention. Target screening to identify subjects with certain Genotype or SNP, could ensure early intervention to prevent cancer development. A long term, well designed, randomised, placebo controlled selenium supplementation trial to examine the clinical efficacy of selenium supplementation in OA prevention is warrant.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

No description available.

No description available.

Leung Yee Fong. / "August 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 262-287). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Bibliography: leaves 253-299. / 299 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the nature of disordered oesophageal motor function that may be of importance in the pathogenesis of gastro-oesophageal reflux disease. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1995

El motivo de la realización de esta tesis se debe, en primer lugar, a la peculiaridad del reflujo vesicoureteral (RVU), que es una enfermedad importante que afecta a los niños y que puede dañar el riñón llegando en algunos casos a la neuropatía por reflujo.En segundo lugar, encontrar un método sencillo, poco invasivo, para tratar el RVU intentando evitar técnicas tan agresivas como la cirugía, la cual tiene una mayor morbilidad y larga estancia hospitalaria.