Class of 2006 Abstract / Objectives: Gastroesophageal reflux disease (GERD) afflicts close to 20 million adults in the United States. Pharmacy schools should ensure that appropriate teaching measures are implemented to optimize students learning of managing GERD. The purpose of this study was to evaluate the curriculum pertaining to GERD at the University of Arizona College of Pharmacy. Methods: We used a repeated measures design to longitudinally evaluate the curriculum on the subject of GERD. Sixty-six subjects from the class of 2007 were initially enrolled in the study, 31 completed the study. Students were tested using a case-based assessment. Descriptive statistics (mean + SD) were used for baseline demographics and a student’s t-test was used to analyze the results. Results: Student’s mean scores improved significantly over the course of the test administrations from 15.03 + 6.7 to 23.25 + 7.6 (p<0.0001). No significant difference was noted in either administration of the assessment between those who had experienced heartburn and those who had not. Mean scores significantly increased in patients who had work experience (p<0.05). Conclusions: Although student’s scores significantly improved during the study, no student achieved the minimally competent score of 70% and there was a high attrition rate, >50%. This high attrition rate possibly contributed to the poor results of the study. There may be a need for further evaluation and revision of the curriculum in this area at the University of Arizona College of Pharmacy.

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.

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

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

Abstract not available. / Thesis (M.Med.Sc.-Pharm.)-University of KwaZulu-Natal, 2006.

Thesis (M.S.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed Aug. 29, 2007). Includes bibliographical references.

Orientador: Elizete Aparecida Lomazi da Costa Pinto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-09T12:58:44Z (GMT). No. of bitstreams: 1 Vicente_AlessandraMariaBorges_M.pdf: 1347949 bytes, checksum: 33220d2f782629ad1ffff9ceeb2a979a (MD5) Previous issue date: 2007 / Resumo: Doença do refluxo gastroesofágico, em crianças, pode causar prejuízos nutricionais, doença respiratória, alterações neurocomportamentais e inflamação esofágica. O tratamento desta doença requer medidas posturais, orientação alimentar e terapia medicamentosa. O tratamento cirúrgico está indicado para pacientes com doença do refluxo gastroesofágico crônica, associada ou não a complicações. A fundoplicatura é indicada, em substituição ao uso contínuo dos inibidores de bomba de prótons, para pacientes que não respondem ou respondem apenas parcialmente ao tratamento medicamentoso e quando há recorrência dos sintomas com a descontinuação das medicações. No pós-operatório pode ocorrer desmanche da válvula e recorrência da doença de refluxo, sugerindo a necessidade de monitorização da condição cirúrgica. A avaliação do funcionamento da válvula, baseada apenas nos sintomas dos pacientes, tem se mostrado insuficiente para essa monitorização. O objetivo desse estudo foi identificar a freqüência de anormalidades na válvula anti-refluxo e a freqüência de complicações pépticas do esôfago no pós-operatório tardio de fundoplicatura em crianças. Em estudo transversal e descritivo, foram selecionados 45 pacientes que realizaram fundoplicatura de Nissen num período de 12 a 30 meses prévios à avaliação. O estudo foi conduzido de maio de 2004 a fevereiro de 2007, no Hospital de Clínicas da Universidade Estadual de Campinas, onde todas as cirurgias foram realizadas. A faixa etária dos pacientes avaliados variou de 16 meses a 16,9 anos. Endoscopia digestiva alta foi o instrumento utilizado para verificar o aspecto da fundoplicatura e o do esôfago, além de permitir a coleta de amostra para estudo histológico. Dos 45 pacientes avaliados, 26 (57,8%) eram encefalopatas crônicos. Válvula anti-refluxo bem posicionada e configurada foi encontrada em 41 (91,1%) pacientes. A fundoplicatura foi efetiva no tratamento do processo inflamatório esofágico, mesmo quando havia subestenose ou estenose de esôfago associadas no pré-operatório. Contudo, complicações foram identificadas: esofagite péptica em 6 dos 45 pacientes e necessidade de nova fundoplicatura em dois pacientes. Esofagite péptica associou-se, com significância estatística, à presença de anormalidades na válvula anti-refluxo (p=0,005, teste exato de Fisher). Durante o estudo foram diagnosticados dois pacientes com diagnóstico de esôfago de Barrett. Os resultados permitem concluir que a endoscopia digestiva alta realizada no período pós-operatório tardio de fundoplicatura para doença do refluxo gastroesofágico em crianças permite avaliar a condição da válvula anti-refluxo e diagnosticar a presença de complicações / Abstract: Gastroesophageal reflux disease in childhood may cause nutritional impairment, esophagus inflammation, respiratory disorders and neurobehavioral alterations. In most cases, treatment includes postural, dietary and medical therapy. Anti-reflux surgery is recommended to patients who do not present improvement with proton pump inhibitors treatment, or present recurrence of symptoms when medical therapy is discontinued. Fundoplication surgery failed has been detected and it has been showed that wrap condition needs monitoring and that clinical symptoms are not sensitive enough to indicate fundoplication efficacy. The objective of this study was to identify the frequency of defective wrap in the late postoperative period and evaluate esophageal complications related with gastroesophageal reflux recurrence in children. The study was cross sectional and descriptive, by selecting 45 patients who had undergone Nissen fundoplication, 12 to 30 months before. All procedures were done at the Hospital de Clínicas da Universidade Estadual de Campinas, in the period from May 2004 to February 2007. The age range at post-surgery examination varied from 16 months up to 16.9 years. Upper gastrointestinal endoscopy was used to determine esophageal endoscopic and histopathologic appearance and fundoplication condition. In the evaluated sample, 26 patients (57.8%) were neurologically disabled. Intact wrap was identified in 41 patients (91.1%). The fundoplication was effective for treating esophagitis, even in patients with esophagus stenosis. However, some complications were identified: peptic esophagitis in 6 of 45 patients and a second fundoplication was necessary in 2 patients. Peptic esophagitis in the endoscopic evaluation was associated with defective wrap (p=0.005, Fisher¿s exact test). Two patients with Barrett esophagus were identified, during study. We conclude that endoscopic follow up may be useful for patients who underwent anti-reflux surgery. Endoscopy allows the diagnosis of possible complications / Mestrado / Pediatria / Mestre em Saude da Criança e do Adolescente

No description available.

published_or_final_version / abstract / toc / Medicine / Doctoral / Doctor of Philosophy