Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular pathogenesis of Barrett's esophagus is poorly understood. Evidence suggests that at a phenotypic level, the metaplastic process begins with the transformation of squamous epithelium in the distal esophagus to cardiac mucosa, which subsequently becomes intestinalized. The homeobox gene Cdx-2 has been shown to be an important transcriptional regulator of embryonic differentiation and maintenance of adult intestinal type epithelium. We hypothesized that Cdx-2 gene expression levels increase with the phenotypic transformation of normal squamous mucosa to the intestinalized columnar mucosa of Barrett's esophagus. Endoscopic biopsies were obtained at the gastroesophageal junction in patients with symptoms of gastroesophageal reflux disease and classified according to histology: normal squamous mucosa (n = 62), cardiac mucosa (n = 19), oxynto-cardiac mucosa (n = 14), and intestinal metaplasia (n = 15). Duodenal biopsies (n = 26) served as the columnar control. After laser capture microdissection and RNA isolation, gene expression levels of Cdx-2 were measured in each tissue type by quantitative reverse transcription polymerase chain reaction. Consistent with its known function, Cdx-2 gene expression levels were highest in duodenal mucosa and nearly absent in squamous epithelium. There was a stepwise increase in Cdx-2 gene expression from cardiac to Barrett's epithelium (P < 0.001). Expression levels of Cdx-2 in cardiac and oxynto-cardiac mucosa were 40-70 times higher and Barrett's mucosa 400 times higher than that found in squamous epithelium. Relative expression of the homeobox gene Cdx-2, known to induce differentiation of intestinal type epithelium, increases in a stepwise fashion during the phenotypic transformation of distal esophageal squamous mucosa to cardiac columnar mucosa and to the intestinalized columnar mucosa of Barrett's esophagus. Therefore, Cdx-2 may be a potential biomarker to detect the early transition to Barrett's esophagus.
Dis Esophagus 2006
PMID:Cdx-2 expression in squamous and metaplastic columnar epithelia of the esophagus. 1686 57

Although confounded by some factors such as medications or surgical complications, the relationship between esophageal pathology and pulmonary disorders has been the subject of many studies. The present study sought to investigate the said relationship in patients inflicted by respiratory disorders induced by mustard gas (MG). A case group of patients complaining of respiratory complications and chronic coughs following MG exposure, and a control group of patients with chronic coughs but without a history of MG exposure were studied. All the case and control subjects had symptoms of gastro-esophageal reflux disease. Chest high resolution tomography (HRCT) was performed to evaluate the existence of pulmonary disorders. Endoscopy and histological studies were carried out to determine the severity of esophagitis in both groups presenting with gastroesophageal reflux. Ninety male patients, who had met our criteria, along with 40 male control cases underwent the diagnostic procedures. The frequency of endoscopic esophagitis findings in the chemically exposed group was significantly higher than that in the control group (70.0%vs. 42.5%). A pathological evaluation revealed that the frequency of esophagitis in the cases was more than that in the controls (32.3%vs. 14.2%). Chest HRCT evaluation demonstrated that half the case group had more than 25% air trapping in expiratory films, mostly compatible with bronchiolitis obliterans (BO). In addition, they were suffering from asthma, chronic bronchitis and bronchiectasis. Bronchiolitis obliterans, along with other lung disorders, can be considered as contributors in the pathogenesis of esophagitis in MG exposed patients.
Dis Esophagus 2006
PMID:Distal esophagitis in patients with mustard-gas induced chronic cough. 1686 62

Gastrooesophageal reflux disease (GERD) is highly prevalent in the Western world but its true population prevalence is difficult to estimate without a validated instrument to detect it. The evaluation of health-related quality of life (HRQoL) is an useful tool in this assessment. The aims of this study are to translate and validate a GERD specific HRQoL questionnaire and evaluate HRQoL in a Brazilian population before and after GERD treatment. GERD patients with typical symptoms and Los Angeles Classes A to C esophagitis were included in the study. Two HRQoL questionnaires and upper digestive endoscopy were performed before and after 6 weeks treatment with pantoprazole 40 mg/day followed by 80 mg/day for another 8 weeks if healing did not occur. A generic (SF-36) and one disease-specific questionnaire (GERD score) were used. The latter was translated and validated for Brazilian Portuguese. From January 2002 to December 2003, 100 patients were enrolled. Of these, 78 patients were evaluated in a per protocol analysis (35 men, mean age: 40 years). The translated questionnaire (Brazilian GERD Score, BGERDS) demonstrated adequate psychometric properties (validity, responsiveness and reliability). SF-36 and BGERDS domains significantly improved after treatment (P < 0.01 and P < 0.001 respectively). The BGERDS was shown to be valid and reliable. Patients with esophagitis showed an impaired HRQoL that improved or normalized after treatment with pantoprazole.
Dis Esophagus 2006
PMID:Evaluation of health-related quality of life in gastroesophageal reflux disease patients before and after treatment with pantoprazole. 1686 63

The aim of this study was to examine the association of obesity with esophageal adenocarcinoma, and with the precursor lesions Barrett esophagus and gastroesophageal reflux disease (GERD). This case-control study included cases with GERD (n = 142), Barrett esophagus (n = 130), and esophageal adenocarcinoma (n = 57). Controls comprised 102 asymptomatic individuals. Using logistic regression methods, we compared obesity rates between cases and controls adjusting for differences in age, gender, and lifestyle risk factors. Relative to normal weight, obese individuals were at increased risk for esophageal adenocarcinoma (Odds Ratio [OR] 4.67, 95% Confidence Interval [CI] 1.27-17.9). Diets high in vitamin C were associated with a lower risk for GERD (OR 0.40, 95% CI 0.19-0.87), Barrett esophagus (OR 0.44, 95% CI 0.20-0.98), and esophageal adenocarcinoma (OR 0.21, 95% CI 0.06-0.77). For the more established risk factors, we confirmed that smoking was a significant risk factor for esophageal adenocarcinoma, and that increased liquor consumption was associated with GERD and Barrett esophagus. In light of the current obesity epidemic, esophageal adenocarcinoma incidence rates are expected to continue to increase. Successful promotion of healthy body weight and diets high in vitamin C may substantially reduce the incidence of this disease.
Dis Esophagus 2006
PMID:Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma. 1698 26

Thus far, there has been a paucity of studies that have assessed the value of the different gastroesophageal reflux disease (GERD) symptom characteristics in identifying patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus. To determine if any of the symptom characteristics of GERD correlates with long-segment Barrett's esophagus versus short-segment Barrett's esophagus. Patients seen in our Barrett's clinic were prospectively approached and recruited into the study. All patients underwent an endoscopy, validated GERD symptoms questionnaire and a personal interview. Of the 88 Barrett's esophagus patients enrolled into the study, 47 had short-segment Barrett's esophagus and 41 long-segment Barrett's esophagus. Patients with short-segment Barrett's esophagus reported significantly more daily heartburn symptoms (84.1%) than patients with long-segment Barrett's esophagus (63.2%, P = 0.02). There was a significant difference in reports of severe to very severe dysphagia in patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus (76.9%vs. 38.1%, P = 0.02). Longer duration in years of chest pain was the only symptom characteristic of gastroesophageal reflux disease associated with longer lengths of Barrett's mucosa. Reports of severe or very severe dysphagia were more common in long-segment Barrett's esophagus patients. Only longer duration of chest pain was correlated with longer lengths of Barrett's esophagus.
Dis Esophagus 2006
PMID:Correlation of gastroesophageal reflux disease symptoms characteristics with long-segment Barrett's esophagus. 1698 33

Barrett's esophagus (BE) patients demonstrate a higher distal esophageal acid exposure profile than other gastroesophageal reflux disease patients. Cellular oxidative stress has been proposed to contribute to the development of BE and esophageal adenocarcinoma. However, a relationship between low esophageal pH and oxidative stress has yet to be elucidated. The aim of this study was to determine the duration of low pH exposure in the esophagus of BE patients compared to those with erosive esophagitis (EE) and to test if brief exposure to low pH leads to the induction of reactive oxygen species (ROS). Seventy-three patients with BE or EE were evaluated by 24-hour esophageal pH monitoring and the percentage of time during which there was exposure to pH < or = 4 and pH < or = 2 was recorded. In vitro, Seg-1 and Het-1A cells were evaluated after brief exposure to pH4 or pH2 by flow cytometry and fluorescent microscopy for the production of ROS. BE patients demonstrated a significantly higher exposure to low pH values (pH < or = 2) than EE patients. The mean percent total time, duration and mean number of reflux episodes at pH < or = 2 were 2.8 +/- 0.53%, 28.8 +/- 3.6 seconds and 79 +/- 11.4 episodes in BE patients, whereas in EE patients they were significantly less, 1.16 +/- 0.3%, 15.6 +/- 1.2 seconds and 48.3 +/- 8.8 episodes, respectively (P < 0.05). In vitro experiments indicate that esophageal cells, when exposed to pH 2, produce ROS. In vitro studies using brief pH 2 exposure are biologically relevant to the clinical situation. Our studies indicate that such exposure induces oxidative stress. This stress may cause DNA damage, mutations and progression to cancer.
Dis Esophagus 2006
PMID:Esophageal acid exposure at pH < or = 2 is more common in Barrett's esophagus patients and is associated with oxidative stress. 1698 34

There is evidence in the literature that psychosocial aspects affect the symptoms and results of surgery for gastroesophageal reflux. The purpose of this study was to estimate the prevalence of psychopathological disorders measured using the General Health Questionnaire (GHQ-28) in a sample of patients with gastroesophageal reflux, and to assess the influence of such disorders on their quality of life. A prospective study was conducted in 74 consecutive patients before gastroesophageal reflux surgery; patients answered the GHQ-28, the health questionnaire SF-36, and the Gastrointestinal Quality of Life Index (GIQLI). The convergent validity of the GHQ-28 questionnaire as compared to the other two questionnaires and preoperative quality of life was tested. A pathological result of the GHQ-28 questionnaire was found in 38.3% of patients. A correlation was seen between the results of the GHQ-28 questionnaire and all categories of the SF-36 and GIQLI questionnaires. Patients with pathological results in the GHQ-28 questionnaire had poorer results in all dimensions of the SF-36 and GIQLI quality of life questionnaires as compared to patients with a normal result in the GHQ-28 questionnaire. In conclusion, 38.3% of patients with gastroesophageal reflux showed psychopathological disorders when administered the GHQ-28 questionnaire. These patients also had poorer results in quality of life studies.
Dis Esophagus 2006
PMID:Gastroesophageal reflux: prevalence of psychopathological disorders and quality of life implications. 1698 35

Laryngopharyngeal reflux (LPR) has been extensively studied in patients with laryngeal signs and symptoms, gastroesophageal reflux being identified in approximately 50%. Few studies have investigated the incidence and significance of LPR in GERD patients. Two-hundred and seventy-six consecutive patients referred with symptoms of gastroesophageal reflux had dual probe 24 h pH, esophageal manometry, GERD and ENT questionnaires. LPR was defined as at least three pharyngeal reflux events less than pH 5.0 with corresponding esophageal reflux, but excluding meal periods. Fourty-two percent of patients were positive for LPR on 24 h pH monitoring and 91.3% corresponded with an abnormal esophageal acid score. Distal esophageal acid exposure was significantly greater (P < 0.001) in patients with LPR but symptoms of GERD and regurgitation scores showed no significant differences between patients with positive and negative LPR on 24 h pH. There was no significant difference between the incidence of LPR in patients with or without laryngeal symptoms. There is a high incidence of LPR in patients with GERD but its significance for laryngeal symptoms is tenuous. Fixed distance dual probe pH monitoring allows documentation of conventional esophageal reflux and LPR.
Dis Esophagus 2006
PMID:Laryngopharyngeal reflux in patients with symptoms of gastroesophageal reflux disease. 1698 36

In this article we present our experience in the management of achalasia. From May 1988 through August 2005, 71 patients with achalasia underwent transabdominal esophagocardiomyotomy and partial posterior fundoplication. Barium swallow, manometry, and 24-h pH studies were performed in all patients preoperatively. Manometry and 24-h pH monitoring were only carried out in 58 patients at the third post-operative week and in 43 patients during follow-up, even though 52 patients were included in the follow-up. There were no operative deaths or complications. All the 71 patients were able to eat semifluid or solid food without dysphagia and heartburn at discharge. Esophageal barium studies showed that the maximum esophageal diameter decreased 2.2 cm and the minimum gastroesophageal junction diameter increased 8.4 mm after operation. Manometry examination in 58 patients revealed that the lower esophageal sphincter resting pressure decreased 15.0 mmHg in the wake of the procedure. Twenty-four hour pH monitoring demonstrated that reflux events were within the normal post-operative range. Fifty-five of the 58 patients had normal DeMeester scores. Among the patients with a mean 90-month follow-up, 49 patients had normal intake of food without reflux, the remaining three had mild dysphagia without requiring treatment. All the patients resumed their preoperative work and social activities. The manometry and 24-h pH studies in the 43 patients showed there were no significant changes between the third post-operative week and during follow-up. Transabdominal esophagocardiomyotomy and posterior partial fundoplication are able to relieve the functional outflow obstruction of the lower esophageal sphincter, obviate the rehealing of the myotomy edge and prevent gastroesophageal reflux in patients who have undergone myotomy alone.
Dis Esophagus 2006
PMID:Management of achalasia with transabdominal esophagocardiomyotomy and partial posterior fundoplication. 1698 38

Oesophageal adenocarcinoma (OA) remains one of the more deadly forms of gastro-intestinal cancer with a mortality rate exceeding 90%. The incidence of OA remains unabated and has a reported fivefold increase since 1970 [Pera M, Cameron AJ, Trastek VF, Carpenter HA & Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993; 104(2): 510-513]. Gastro-oesophageal reflux disease and its sequelae, Barrett's oesophagus, is one of the principle risk factors in the development of OA, with a 30-fold increased risk in Barrett's patients compared with the general population [Tytgat GNJ. Does endoscopic surveillance in esophageal columnar metaplasia (Barrett's-Esophagus) have any real value. Endoscopy 1995; 27(1): 19-26]. OA is thought to be a microcosm of evolution, developing sequentially along the metaplasia-dysplasia-adenocarcinoma sequence. Progression is attributed to a series of genetic and epigenetic events that ultimately allow for clonal selection of Barrett's cells via subversion of intrinsic control mechanisms regulating cellular proliferation and/or apoptosis. This review will describe the current suppositions of the mechanisms behind the selection and subsequent expansion of Barrett's clones, and focus on some of the principle hallmarks associated with this transition.
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PMID:Molecular biology of Barrett's cancer. 1699 63


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