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Acid Reflux (acid + reflux)
Selected AbstractsThe effects of high-dose esomeprazole on gastric and oesophageal acid exposure and molecular markers in Barrett's oesophagusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010A. Abu-Sneineh Aliment Pharmacol Ther 2010; 32: 1023,1030 Summary Background, Acid reflux is often difficult to control medically. Aim, To assess the effect of 40 mg twice daily esomeprazole (high-dose) on gastric and oesophageal pH and symptoms, and biomarkers relevant to adenocarcinoma, in patients with Barrett's oesophagus (BO). Methods, Eighteen patients, treated with proton pump inhibitors as prescribed by their treating doctor, had their therapy increased to high-dose esomeprazole for 6 months. Results, At entry into the study, 9/18 patients had excessive 24-h oesophageal acid exposure, and gastric pH remained <4 for >16 h in 8/18. With high-dose esomeprazole, excessive acid exposure occurred in 2/18 patients, and gastric pH <4 was decreased from 38% of overall recording time and 53% of the nocturnal period to 15% and 17%, respectively (P < 0.001). There was a reduction in self-assessed symptoms of heartburn (P = 0.0005) and regurgitation (P < 0.0001), and inflammation and proliferation in the Barrett's mucosa. There was no significant change in p53, MGMT or COX-2 expression, or in aberrant DNA methylation. Conclusions, High-dose esomeprazole achieved higher levels of gastric acid suppression and control of oesophageal acid reflux and symptoms, with significant decreases in inflammation and epithelial proliferation. There was no reversal of aberrant DNA methylation. [source] The GABAB receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009H. BEAUMONT Summary Background, Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro-oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required. Aim, To study the effect of AZD9343, a new selective GABAB receptor agonist, in healthy volunteers. Methods, A total of 27 subjects participated in a placebo-controlled, randomized, two-centre phase I study. Subjects underwent oesophageal manometry and pH-metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days. Results, Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short-lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate. Conclusions, Like baclofen, AZD9343 dose-dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABAB agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted. [source] Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic coughALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007K. BLONDEAU Summary Background Symptoms, oesophageal pHmetry and proton pump inhibitor treatment are used for diagnosing gastro-oesophageal reflux-related cough. Weakly acidic reflux is now increasingly associated with reflux symptoms such as regurgitation or chest pain. Aim To study the association between weakly acidic reflux and cough in a selected, large group of patients with unexplained chronic cough. Methods A total of 100 patients with chronic cough (77 ,off' and 23 ,on' a proton pump inhibitor) were studied using impedance-pHmetry for reflux detection and manometry for objective cough monitoring. Symptom Association Probability (SAP) Analysis characterized the reflux,cough association. Results Acid reflux could be a potential mechanism for cough in 45 patients (with either heartburn, high acid exposure or +SAP for acid reflux). Weakly acidic reflux could be a potential mechanism for cough in 24 patients (with either increased oesophageal volume exposure, increased number of weakly acidic reflux or +SAP for weakly acidic reflux). Reflux could not be identified as a potential mechanism for cough in 31 patients. Conclusion A positive association between cough and weakly acidic reflux was found in a significant subgroup of patients with unexplained chronic cough. Impedance-pH-manometry identified patients in whom cough can be related to reflux that would have been disregarded using the standard diagnostic criteria for acid reflux. [source] Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009M. FRAZZONI Summary Background, In short-segment Barrett's oesophagus (SSBO) heartburn may be absent and oesophageal acid exposure time (OAET) assessed with pH-only monitoring may be normal. By detecting reflux episodes independently of their acidity, multichannel intraluminal impedance-pH (MII-pH) monitoring allows a comprehensive characterization of reflux events, either off or on proton pump inhibitor (PPI) therapy. Aim, To assess reflux parameters by MII-pH monitoring in newly diagnosed SSBO, at baseline and as modified with PPI therapy. Methods, Short-segment Barrett's oesophagus was defined by oesophageal intestinal metaplasia up to 3 cm in length. 24-h MII-pH monitoring was performed before and during PPI therapy. Results, Fifty patients were studied prospectively. Normal OAET was found at baseline in 15 patients (30%), 8 and 2 of whom with a higher than normal number of acid and weakly acidic refluxes, respectively. Overall, abnormal reflux parameters were detected by MII-pH monitoring in 90% of patients. Reflux events were prevalent in the upright period. On PPI therapy, acid refluxes decreased and a correspondent increase in weakly acidic refluxes was observed (median from 48.5 to 9 and from 16 to 57.5, respectively) (P < 0.001). Conclusions, Acid refluxes, mainly in the upright period, characterize SSBO. PPI therapy transforms acid refluxes into weakly acidic refluxes. [source] Effect of pantoprazole in patients with chronic laryngitis and pharyngitis related to gastroesophageal reflux disease: clinical, proximal, and distal pH monitoring resultsDISEASES OF THE ESOPHAGUS, Issue 4 2010S. Karoui SUMMARY Few studies had evaluated the results of proton pump inhibitors on distal and proximal pH recording using a dual-channel probe. The aim of this study was to determine the clinical and pH-metric effect of treatment with pantoprazole 80 mg for 8 weeks in patients with ear, nose, and throat (ENT) manifestations of gastroesophageal reflux disease associated with pathological proximal acid exposure. We conducted a prospective open study. Patients included had to have chronic pharyngitis or laryngitis, and a pathological gastroesophagopharyngeal reflux. All patients received treatment with pantoprazole 80 mg daily for 8 weeks. One week after the end treatment, patients had a second ENT examination and a 24-hour pH monitoring using dual-channel probe. We included 33 patients (11 men, 22 women). A pathological distal acid reflux was found in 30 patients (91%). After treatment, the improvement of ENT symptoms was found in 51.5% of patients. Normalization of 24-hour proximal esophageal pH monitoring was observed in 22 patients (66%). After treatment, the overall distal acid exposure, the number of distal reflux events, and the number of reflux during more than 5 minutes were significantly decreased (respectively: 19.4% vs 7.2% [P < 0.0001], 62.7 vs 28.4 [P < 0.0001], and 10.4 vs 3.9 [P < 0.0001] ). Similarly, in proximal level, the same parameters were significantly decreased after treatment (respectively: 6.8% vs 1.6% [P < 0.0001], 32.6 vs 8.1 [P < 0.0001], and 3.4 vs 0.6 [P= 0.005] ). Treatment with pantoprazole reduced the frequency and severity of gastroesophagopharyngeal acid reflux in patients with chronic pharyngitis and laryngitis. [source] Outcome of floppy Nissen fundoplication with intraoperative manometry to treat sliding hiatal herniaDISEASES OF THE ESOPHAGUS, Issue 4 2008Y. Lei SUMMARY., The aim of this study was to evaluate the effectiveness of floppy Nissen fundoplication with intraoperative esophageal manometry. Between February 1992 and July 2004, there were 102 patients with sliding hiatal hernia undergoing transabdominal Nissen fundoplication. They were divided into three groups: 27 patients were in the Nissen group (CNF), 44 in the floppy Nissen group (FNF, including 5 with laparoscopic Nissen fundoplication), and 31 in the intraoperative-esophageal-manometry group (INF, 13 with laparoscopic Nissen fundoplication). There were no operation-related deaths. Operation-related complications occurred in five patients within 1 month after operation: In CNF, two patients suffered from dysphagia and one from regurgitation; in FNF, one patient had slight dysphagia and two had regurgitation; in INF, there was no one who complained about dysphagia or regurgitation, but pneumothorax occurred in one case. After more than 2 years of follow-up, two patients, in CNF, suffered from severe dysphagia, one recurred and two with abnormal 24 h pH monitoring. In FNF, one patient had dysphagia, one recurred and three had abnormal 24 h pH monitoring; in INF, two patients had acid reflux on 24 h pH monitoring. The postoperative lower esophageal sphincter pressure was in the normal range in 30 of 31 patients (96.5%). The normal rate of postoperative tests in CNF, FNF and INF were 81.5%, 86.4% and 93.5%, respectively. Both the Nissen fundoplication and the floppy Nissen fundoplication are effective approaches to treat patients with sliding hiatal hernia. Intraoperative manometry is useful in standardizing the tightness of the wrap in floppy Nissen fundoplication and may contribute to reducing or avoiding the occurence of postoperative complications. [source] In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epitheliumJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2009D. R. De Vries Abstract Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6,12% and SAP , 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P -value < 1E, 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell,cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function. [source] Esophageal motility in patients with sliding hiatal hernia and reflux esophagitisJOURNAL OF DIGESTIVE DISEASES, Issue 2 2002Ping YE OBJECTIVE: To study the radiographic and esophageal motility changes that are characteristic of patients with both sliding hiatus hernia (HH) and reflux esophagitis. METHODS: Thirty patients were diagnosed with HH by using gastroscopy. These patients were divided into two groups according to the severity of their esophagitis: group HH1 (grades A and B, n= 18); group HH2 (grades C and D, n= 12). Sliding HH was confirmed by barium meal examination. Radiographic techniques were used to test for spasms and strictures, the coarseness of the mucosa, and to study the types of reflux and clearance. Esophageal pH (24-h), lower esophageal sphincter pressure and the frequency and amplitude of esophageal peristalsis during reflux were also studied. RESULTS: Radiography revealed that the mucosa was coarse in all cases. Eighty percent of patients had sucking reflux and 36.7% had passive clearance. The percentages of total, supine and upright acid exposure times were greater in patients with HH than those in the controls (P < 0.01), but the difference between the HH1 and HH2 groups was not significant. Lower esophageal sphincter resting pressure was less in the HH group than that in the control group (P < 0.05). However, there were no differences in the length of the sphincter among groups. During episodes of acid reflux, the frequency and amplitude of peristalsis, and the percentage of normal primary esophageal peristalsis were all lower in HH patients than in the controls, and the duration of peristalsis was increased relative to that of the controls (P < 0.05). CONCLUSIONS: Sucking reflux and passive clearance are very important in HH. Esophageal acid exposure time does not correlate with the severity of esophagitis. Lowered lower esophageal sphincter resting pressure, decreased frequency and amplitude, and increased duration of esophageal peristalsis during the episode of reflux may play an important role in the pathogenesis of sliding HH. [source] Epidemiological study of symptomatic gastroesophageal reflux disease in China: Beijing and ShanghaiJOURNAL OF DIGESTIVE DISEASES, Issue 1 2000Pan Guozong OBJECTIVE: To explore the 1-year point prevalences (July,September 1996) of symptomatic gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD) and reflux esophagitis (RE) in the adult population of two Chinese city-regions (Beijing and Shanghai) and to identify the conditions that predispose patients to GERD. METHODS: Phase I: 5000 residents of the two regions aged between 18 and 70 years were studied via a questionnaire. The study was carried out by cluster sampling from city, suburban and rural areas by using simple random sampling. Symptom scores (Sc) of the intensity and frequency of heartburn, acid reflux and regurgitation within 1 year of the time of study were taken as indices of acid reflux (highest score, Sc = 18) and Sc , 6 indicated the presence of symptomatic GER. Phase II: a small number of patients who were identified as having symptomatic GER in the survey were enrolled in a case, control study using gastroscopy and 24-h pH monitoring to obtain correct diagnostic rates of GERD and RE. Estimates of the prevalence of GERD and RE were then adjusted according to the rates of correct diagnosis. RESULTS: A total of 4992 subjects completed the survey, 2.5% had heartburn once daily, 8.97% had symptomatic GER (Sc , 6) and the male to female ratio was 1:1.11. Point prevalences for the year for GERD and RE were 5.77 and 1.92%, respectively. Stratified analysis indicated that the prevalence of symptomatic GER in Beijing (10.19%) was higher than that in Shanghai (7.76%) and there was also a higher prevalence of GER in males, manual laborers, people from rural areas and people older than 40 years of age in Beijing as compared with Shanghai. Stepwise logistic analysis indicated that GER had a close relationship with dental, pharyngolaryngeal disorders and respiratory diseases. The conditions that predispose patients to GERD are (OR, odds ratio): age > 40 (OR = 1.01), eating greasy/oily food (OR = 6.56), overeating (OR = 1.99), tiredness (OR = 2.35), emotional stress (OR = 2.22), pregnancy (OR = 6.80) and constipation (OR = 1.65). CONCLUSIONS: Gastroesophageal reflux disease is a common disease in the adult Chinese population and it is more common in Beijing than in Shanghai. [source] Non-cardiac chest pain: Prevalence of reflux disease and response to acid suppression in an Asian populationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2009Hanizam Mohd Abstract Background:, Gastroesophageal reflux disease is thought to be the commonest cause of ,non-cardiac chest pain'. The use of proton-pump inhibitors resulting in improvement in the chest pain symptom would support this causal association. Objectives:, To determine the prevalence of gastroesophageal reflux disease in non-cardiac chest pain and the response of chest pain to proton-pump inhibitor therapy. Methods:, Patients with recurrent angina-like chest pain and normal coronary angiogram were recruited. The frequency and severity of chest pain were recorded. All patients underwent esophagogastroduodenoscopy and 48-h Bravo ambulatory pH monitoring before receiving rabeprazole 20 mg bd for 2 weeks. Results:, The prevalence of gastroesophageal reflux disease was 66.7% (18/27). The improvement in chest pain score was significantly higher in reflux compared to non-reflux patients (P = 0.006). The proportion of patients with complete or marked/moderate improvement in chest pain symptoms were significantly higher in patients with reflux (15/18, 83.3%) compared to those without (1/9, 11.1%) (P < 0.001). Conclusion:, The prevalence of gastroesophageal reflux disease in patients with ,non-cardiac chest pain' was high. The response to treatment with proton-pump inhibitors in patients with reflux disease, but not in those without, underlined the critical role of acid reflux in a subset of patients with ,non-cardiac chest pain'. [source] The effects of high-dose esomeprazole on gastric and oesophageal acid exposure and molecular markers in Barrett's oesophagusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010A. Abu-Sneineh Aliment Pharmacol Ther 2010; 32: 1023,1030 Summary Background, Acid reflux is often difficult to control medically. Aim, To assess the effect of 40 mg twice daily esomeprazole (high-dose) on gastric and oesophageal pH and symptoms, and biomarkers relevant to adenocarcinoma, in patients with Barrett's oesophagus (BO). Methods, Eighteen patients, treated with proton pump inhibitors as prescribed by their treating doctor, had their therapy increased to high-dose esomeprazole for 6 months. Results, At entry into the study, 9/18 patients had excessive 24-h oesophageal acid exposure, and gastric pH remained <4 for >16 h in 8/18. With high-dose esomeprazole, excessive acid exposure occurred in 2/18 patients, and gastric pH <4 was decreased from 38% of overall recording time and 53% of the nocturnal period to 15% and 17%, respectively (P < 0.001). There was a reduction in self-assessed symptoms of heartburn (P = 0.0005) and regurgitation (P < 0.0001), and inflammation and proliferation in the Barrett's mucosa. There was no significant change in p53, MGMT or COX-2 expression, or in aberrant DNA methylation. Conclusions, High-dose esomeprazole achieved higher levels of gastric acid suppression and control of oesophageal acid reflux and symptoms, with significant decreases in inflammation and epithelial proliferation. There was no reversal of aberrant DNA methylation. [source] Increased oesophageal acid exposure at the beginning of the recumbent period is primarily a recumbent-awake phenomenonALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010L. Allen Summary Background, A significant increase in oesophageal acid exposure during early recumbent period has been demonstrated. Aim, To determine if acid reflux during the early recumbent period occurs in the recumbent-asleep or recumbent-awake period using a novel integrative actigraphy and pH programme. Method, Thirty-nine subjects with heartburn at least three times a week were included. Subjects underwent pH testing concomitantly with actigraphy. Simultaneously recorded actigraphy and pH data were incorporated using a novel integrative technique to determine sleep and awake periods. Characteristics of acid reflux were compared between the recumbent-awake and recumbent-asleep periods. Results, Seventeen (44.7%) subjects had acid reflux events during recumbent-awake period as compared to seven (18.4%) in the corresponding recumbent-asleep period (P = 0.046). The mean number of acid reflux events in recumbent-awake period was significantly higher than in the corresponding recumbent-asleep period (8.1 ± 4.4 vs. 3.2 ± 1.5, P < 0.001). In the recumbent-awake period, 38.4% of acid reflux events were associated with GERD-related symptoms as compared with 3.7% of acid reflux events during the corresponding recumbent-asleep period (P = 0.01). Conclusion, Increased acid reflux in the early recumbent period occurs primarily during the recumbent-awake and not during the recumbent-asleep period. [source] Modulation of salivation and heartburn in response to the site of acid infusion in the human oesophagusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010S. K. Dutta Summary Background, The pathogenesis of gastro-oesophageal reflux disease includes increased acid reflux, reduced salivation and impaired peristalsis. This may depend upon the height of acid wave and magnitude of oesophageal mucosal exposure. Interestingly, the effect of site of acid infusion upon salivary secretion and heartburn has not been examined in any detail. Aim, To examine whether acid infusion in the upper oesophagus may cause increased salivation and heartburn as compared with acid infusion in the lower oesophagus. Methods, Twelve healthy male subjects (mean age 30) received infusions of HCl, citric acid and acetic acid at 10 and 20 cm above the lower oesophageal sphincter (LES) for fixed time periods. Parotid saliva collected periodically and heartburn severity scored using standardized scale. Standard statistical methods (paired t -tests, analysis of variance) were used to determine the significance of results. Results, Acid infusion in the upper oesophagus increased parotid flow rate as compared with that in the lower oesophagus (P < 0.05). Likewise, there was a significantly increased heartburn score at 20 cm as well as 10 cm above LES (P < 0.05) as compared with that in the stomach. Conclusion, These data suggest a significant increase in salivation and heartburn in response to acid infusion in the upper vs. lower part of the oesophagus. [source] Body mass index, chronic atrophic gastritis and heartburn: a population-based study among 8936 older adults from GermanyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010L. Gao Aliment Pharmacol Ther 2010; 32: 296,302 Summary Background, Obesity and overweight have been positively related to gastro-oesophageal reflux disease (GERD). It has been suggested that this relationship is as a consequence of an increased gastric acid reflux, which is caused by an enhanced intra-abdominal pressure. Aim, To assess potential interaction of the association between body mass index (BMI) and GERD by chronic atrophic gastritis, which goes along with decreased acid production. Methods, In the baseline examination of ESTHER, a study conducted in 9953 older adults in Saarland, information on frequency of heartburn, potential risk factors and medical history was obtained by self-administered standardized questionnaire. Serological measurements of pepsinogen I and II were taken for definition of chronic atrophic gastritis. Results, In total, 2565 (28.7%) of the included subjects experienced heartburn within the previous 4 weeks. A pronounced dose-response relationship was observed between BMI and heartburn occurrence (P < 0.001) among people without chronic atrophic gastritis, but not among people with chronic atrophic gastritis (P -value for interaction = 0.018). Obese/overweight people with chronic atrophic gastritis had a much lower risk of heartburn compared with obese/overweight people without chronic atrophic gastritis (OR = 0.31, 95% CI = 0.24,0.40). Conclusion, Our results are consistent with the hypothesis that BMI is related positively to GERD symptoms by its impact on acid reflux. [source] The GABAB receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009H. BEAUMONT Summary Background, Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro-oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required. Aim, To study the effect of AZD9343, a new selective GABAB receptor agonist, in healthy volunteers. Methods, A total of 27 subjects participated in a placebo-controlled, randomized, two-centre phase I study. Subjects underwent oesophageal manometry and pH-metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days. Results, Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short-lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate. Conclusions, Like baclofen, AZD9343 dose-dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABAB agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted. [source] Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis , a randomized controlled, cross-over trialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2007P. JANIAK Summary Background, Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function. Aim, To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high-dose omeprazole. Methods, Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross-over, placebo controlled study. At the end of each period a 24 h pH-study with intragastric and oesophageal pH measurement was performed. Results, Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH-studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH-studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life. Conclusion, Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high-dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population. [source] Review article: acidity and volume of the refluxate in the genesis of gastro-oesophageal reflux disease symptomsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2007D. SIFRIM Summary Background A number of mechanisms, other than acid reflux, may be responsible for the symptoms of gastro-oesophageal reflux disease. Aim To assess the importance of non-acid reflux mechanisms. Methods This review is based on presentations and discussion at a workshop, where specialists in the field analysed data relating to these mechanisms. Results Weakly acidic reflux, pH (4,7), detected with impedance,pHmetry is associated with regurgitation and atypical gastro-oesophageal reflux disease symptoms. It is not clear whether pepsin and trypsin can elicit symptoms, but bile can elicit heartburn. The magnitude of reflux-induced oesophageal distension can be determined by high frequency ultrasonography and is not reduced by proton pump inhibition, suggesting that persisting symptoms ,on' a proton pump inhibitor may still be due to oesophageal distension by non-acidic reflux. Exaggerated longitudinal muscle contraction can induce non-acid-related heartburn. Preliminary studies showed a positive effect of baclofen, surgery or endoscopic procedures to reduce weakly acidic reflux. Conclusion Mechanisms other than acid reflux are involved in some of the symptoms of gastro-oesophageal reflux disease. Controlled outcome studies are needed to clarify their roles and the indications for antireflux procedures in patients with persistent symptoms whilst ,on' a proton pump inhibitor. [source] Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic coughALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007K. BLONDEAU Summary Background Symptoms, oesophageal pHmetry and proton pump inhibitor treatment are used for diagnosing gastro-oesophageal reflux-related cough. Weakly acidic reflux is now increasingly associated with reflux symptoms such as regurgitation or chest pain. Aim To study the association between weakly acidic reflux and cough in a selected, large group of patients with unexplained chronic cough. Methods A total of 100 patients with chronic cough (77 ,off' and 23 ,on' a proton pump inhibitor) were studied using impedance-pHmetry for reflux detection and manometry for objective cough monitoring. Symptom Association Probability (SAP) Analysis characterized the reflux,cough association. Results Acid reflux could be a potential mechanism for cough in 45 patients (with either heartburn, high acid exposure or +SAP for acid reflux). Weakly acidic reflux could be a potential mechanism for cough in 24 patients (with either increased oesophageal volume exposure, increased number of weakly acidic reflux or +SAP for weakly acidic reflux). Reflux could not be identified as a potential mechanism for cough in 31 patients. Conclusion A positive association between cough and weakly acidic reflux was found in a significant subgroup of patients with unexplained chronic cough. Impedance-pH-manometry identified patients in whom cough can be related to reflux that would have been disregarded using the standard diagnostic criteria for acid reflux. [source] Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2006S. EMERENZIANI Summary Background Proximal acid reflux is common in gastro-oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton-pump inhibitors. Aim To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux. Methods Thirty seven consecutive gastro-oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24-h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis. Results At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non-hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: , + 2.5 min (95% confidence interval: 0.4,4.5); P < 0.02]. Conclusions The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro-oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease. [source] The effect of acid suppression on sleep patterns and sleep-related gastro-oesophageal refluxALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2005W. C. Orr Summary Background :,Several studies have demonstrated that night-time gastro-oesophageal reflux affects sleep quality, and thereby impairs daytime functioning. Aim :,To determine whether treatment with a proton-pump inhibitor (rabeprazole) would improve both objective and subjective measures of sleep. Methods :,Individuals with complaints of significant gastro-oesophageal reflux disease were studied by polysomnography and 24-h pH monitoring on two separate nights. On one occasion, participants received 20 mg rabeprazole b.d., and on another they received placebo. Both study conditions were preceded by a week of treatment with either rabeprazole or placebo. The order of treatments was randomized. Results :,Rabeprazole significantly reduced overall acid reflux, but it did not significantly reduce night-time acid contact. Rabeprazole treatment significantly improved subjective indices of sleep quality. There were no significant differences on objective measures of sleep between placebo and rabeprazole treatment. Conclusions :,Consistent with other studies of pharmacological treatments for gastro-oesophageal reflux, subjective measures of sleep improved with heartburn medication but objective measures were not affected. [source] The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2002M. A. Van Herwaarden SUMMARY Background :,Baclofen decreases gastro-oesophageal reflux episodes in healthy subjects by reducing the incidence of transient lower oesophageal sphincter relaxations. Aim :,To investigate the effect of baclofen on reflux symptoms, oesophageal pH and lower oesophageal sphincter manometry in patients with gastro-oesophageal reflux disease. Methods :,A double-blind, placebo-controlled, two-way crossover design was used to study the effect of baclofen on heartburn and regurgitation 3 h after a provocation test meal in 37 patients with gastro-oesophageal reflux disease. Additionally, in 20 of these patients, the effect of baclofen on oesophageal pH, transient lower oesophageal sphincter relaxations and basal lower oesophageal sphincter pressure was studied. Results :,Baclofen significantly decreased the acid reflux time and the incidence of gastro-oesophageal reflux episodes (8.3 ± 8.8% vs. 12.4 ± 12.0%, P = 0.03 and 10.9 ± 7.3 per 3 h vs. 18.7 ± 12.4 per 3 h). The incidence of transient lower oesophageal sphincter relaxations was significantly lower with baclofen than with placebo (15.1 ± 6.4 per 3 h vs. 22.8 ± 5.4 per 3 h, P < 0.0001). Lower oesophageal sphincter pressure and the percentage of transient lower oesophageal sphincter relaxations associated with reflux were not affected by baclofen. No significant effect on symptom scores was observed. Conclusions :,Baclofen decreases post-prandial acid reflux in patients with gastro-oesophageal reflux disease by reducing the incidence of transient lower oesophageal sphincter relaxations. No effect of a single dose of baclofen on reflux symptoms could be demonstrated in this 3-h post-prandial study. [source] Effects of ABT-229, a motilin agonist, on acid reflux, oesophageal motility and gastric emptying in patients with gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2002P. Netzer Summary Aim : The effect of ABT-229, a new macrolide with no antibacterial activity, on gastro-oesophageal reflux, oesophageal motility and gastric emptying in patients with gastro-oesophageal reflux disease was investigated. Methods : Twenty-one patients were treated with a placebo and ABT-229 (2.5, 5 or 10 mg b.d.) in a randomized, incomplete crossover study design. Ambulatory 24-h pH manometry was performed and gastric emptying was assessed by the 13C-octanoic acid breath test on the seventh day of treatment. Results : A significant decrease was found in the mean (± s.e.) percentage of reflux time (intra-oesophageal pH < 4) for ABT-229 5 mg b.d. and 10 mg b.d., but not for 2.5 mg b.d., compared with placebo. For ABT-229 5 mg, it was 8.5 ± 0.5% vs. 10.7 ± 0.7% (P < 0.038) and, for ABT-229 10 mg, it was 6.6 ± 0.5% vs. 8.4 ± 0.5% (P < 0.019). There were no significant differences in any of the analysed manometric parameters. In addition, the gastric half-emptying time for all doses of ABT-229 did not differ significantly from that after placebo. Conclusions : ABT-229 is able to reduce slightly, but significantly, acid reflux in patients with gastro-oesophageal reflux disease. This effect does not appear to be due to a measurable improvement in oesophageal motility or gastric emptying. [source] Lower oesophageal sphincter relaxation evoked by stimulation of the dorsal motor nucleus of the vagus in ferretsNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2002T. P. Abrahams Abstract, An understanding of the neural control of lower oesophageal sphincter (LOS) relaxation is clinically relevant because transient LOS relaxations (TLOSRs) are a mechanism of acid reflux into the oesophagus. Preganglionic motor neurones innervating the LOS are localized in the dorsal motor nucleus of the vagus (DMV). Based on a single study in cats, it is now widely accepted that these neurones are functionally organized into two separate populations, such that stimulation of the caudal and rostral DMV evokes LOS relaxation and contraction, respectively. Our goal was to map the functional LOS responses to chemical stimulation in the DMV and nucleus tractus solitarius (NTS) of ferrets, an animal model commonly used for conscious studies on TLOSRs, and to test whether DMV-evoked LOS relaxation is mediated through hexamethonium-sensitive vagal-inhibitory pathways to the LOS. We used miniaturized manometry with Dentsleeve to monitor LOS and oesophageal pressures in decerebrate unanaesthetized ferrets. LOS relaxation was evoked readily in response to gastric insufflation, which shows that the vago,vagal reflex was intact in this preparation. Microinjections of l -glutamate (12.5 nmol L,1in 25 nL) were made into the DMV from approximately ,,1.5 to +,2.0 mm relative to the obex. Microinjections into the caudal (, 1.5 to +,0.0 mm behind obex) and intermediate (+ 0.1 to +,1.0 mm rostral to obex) DMV both significantly decreased LOS pressure, and complete LOS relaxation was noted in 28/32 and 11/18 cases, respectively. LOS relaxation responses to DMV microinjection were highly reproducible and abolished by bilateral vagotomy or hexamethonium (15 mg kg,1intravenously). A nitric oxide synthase inhibitor (l -NAME 100 mg kg,1intramuscularly) significantly increased the time taken to reach the maximal response. Increases in LOS pressure (24 ± 4 mmHg; n = 3) were obtained only when stimulation sites were located equal to greater than 1.5 mm rostral to the obex. LOS relaxation (, 78 ± 10%; n = 6) was evoked by stimulation of the NTS but not immediately outside of the NTS (11 ± 27%; n = 5). We conclude that there is a very extensive population of ,inhibitory' motor neurones in the DMV that may account for the predominant vagal-inhibitory tone in ferrets. As NTS stimulation evokes LOS relaxation and the predominant response to DMV stimulation is also LOS relaxation, this vago,vagal reflex may involve an excitatory interneurone between the NTS and DMV vagal inhibitory output. [source] Correlation of pH Probe,Measured Laryngopharyngeal Reflux With Symptoms and Signs of Reflux Laryngitis,THE LARYNGOSCOPE, Issue 12 2002J. Pieter Noordzij MD Abstract Objectives/Hypothesis Laryngitis secondary to gastric acid reflux is a prevalent, yet incompletely understood, otolaryngological disorder. Further characterization of the relationship between symptoms and signs and reflux severity is needed. Study Design Prospective clinical trial. Methods Forty-two consecutive, nonsmoking patients with one or more reflux laryngitis symptoms were recruited to complete a symptom questionnaire, videostrobolaryngoscopy, and 24-hour, dual-sensor pH probe testing. Twenty-nine patients had more than four episodes of laryngopharyngeal reflux, and the remaining 13 served as control subjects. Symptom scores were produced by multiplying the severity by the frequency for the following: hoarseness, throat pain, "lump-in-throat" sensation, throat clearing, cough, excessive phlegm, dysphagia, odynophagia, and heartburn. Endoscopic laryngeal signs included erythema and edema of the vocal folds and arytenoids, and interarytenoid irregularity. Results Symptom scores varied significantly, with throat clearing being greater than the rest. None of the symptoms, except heartburn, correlated with reflux (laryngopharyngeal and esophageal) severity. Patients with worse laryngopharyngeal reflux were found to have worse esophageal reflux. Endoscopic laryngeal signs were rated as mild, on average, and did not correlate with laryngopharyngeal reflux severity. The number of laryngopharyngeal reflux episodes (per 24 h) ranged from 0 to 40 (mean number, 10.6 episodes). Conclusions Throat clearing was the most intense symptom in the present group of patients with proven reflux laryngitis. Dual-sensor pH probe testing could not predict the severity of patient's reflux laryngitis symptoms or signs. Only the heartburn symptom correlated with laryngopharyngeal and esophageal reflux. [source] Characterization of reflux events after fundoplication using combined impedance,pH recording,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2007S. Roman Background: Laparoscopic fundoplication effectively controls symptoms of gastro-oesophageal reflux disease (GORD) and decreases acid reflux, but its impact on non-acid reflux is not known. The aim of the study was to characterize reflux events after fundoplication using oesophageal combined multichannel intraluminal impedance (MII),pH monitoring, to demonstrate its efficacy on acid as well as non-acid reflux events. Methods: Thirty-six patients in whom ambulatory MII,pH recording was performed after laparoscopic fundoplication were reviewed retrospectively. There were 23 symptomatic and 13 asymptomatic patients, whose results were compared with those of 72 healthy volunteers. Results: Oesophageal acid exposure was low in all but one operated patient, and there was no difference between those with and without symptoms. The median number of reflux events over 24 h was lower after fundoplication (11 in operated patients compared with 44 in healthy volunteers; P < 0·001). Almost all reflux events were non-acid after surgery whereas acid reflux episodes were predominant in healthy volunteers. Proximal reflux events were less common in operated patients. Non-acid reflux events were significantly associated with symptoms after surgery in some patients. Conclusion: Fundoplication restores a competent barrier for all types of reflux. Reflux events are mostly non-acid after surgery, and such events may be positively correlated with symptoms. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Ineffective oesophageal motility does not affect the clinical outcome of open Nissen fundoplicationBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2004V. Munitiz Background: Nissen fundoplication is considered the ,gold standard' in antireflux surgery but some surgeons employ a different surgical strategy when gastro-oesophageal reflux disease (GORD) is associated with motor disorders of the oesophageal body. Methods: Ninety-three patients undergoing surgery for GORD were divided into two groups: 52 patients (group 1) had normal oesophageal body motility and 41 (group 2) had ineffective oesophageal motility (IOM). All patients had a short Nissen fundoplication via a laparotomy. The median follow-up was 5 years in group 1 and 6·5 years in group 2. Results: The clinical outcome was satisfactory in more than 90 per cent of the patients in both groups. Only one of ten patients with IOM and dysphagia before operation still had dysphagia after surgery. One patient in each group developed postoperative dysphagia. Six of 52 patients with normal motility and eight of 41 with IOM had persistent pathological acid reflux after surgery. Significant increases in contractile wave pressure and a decrease in the percentage of non-propagated waves were found in group 2 after fundoplication. Conclusion: Patients with IOM did not have an increased rate of dysphagia after total fundoplication compared with those with normal motility, but they did have a higher rate of recurrence of endoscopic and pH-proven reflux. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Assessment of respiratory symptoms with dual pH monitoring in patients with gastro-oesophageal reflux diseaseBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2004W. K. H. Kauer Background: Gastro-oesophageal reflux disease (GORD) is a commonly underestimated aetiological factor in patients with respiratory symptoms. In this study, acid reflux in healthy volunteers and patients with GORD with and without respiratory symptoms was investigated by dual pH monitoring. Methods: Thirty healthy volunteers and 43 patients with GORD underwent oesophageal manometry and dual pH monitoring with one probe in the proximal and one in the distal oesophagus. Nineteen of the 43 patients complained of respiratory symptoms. Results: There were no differences in proximal probe measurements between volunteers and patients without respiratory symptoms. Patients with GORD and respiratory symptoms had a higher prevalence of abnormally high exposure to gastric juice and more reflux episodes in the proximal oesophagus compared with patients with GORD and no respiratory symptoms. Some 17 of 19 patients with GORD and respiratory symptoms showed deteriorated oesophageal body motility. Conclusion: Dual pH monitoring is feasible and well tolerated, and provides an objective means of evaluating patients with GORD and respiratory symptoms. Prolonged exposure of the proximal oesophagus to gastric juice and disorders of oesophageal body motility seem to be responsible for the development of respiratory symptoms. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Domperidone versus cisapride in the treatment of infant regurgitation and increased acid gastro-oesophageal reflux: a pilot studyACTA PAEDIATRICA, Issue 4 2009Badriul Hegar Abstract Aim: Although domperidone is used frequently to treat infant regurgitation, efficacy data are scarce. Cisapride was previously used in the same indication. Methods: Domperidone and cisapride were compared in an investigator-blinded, prospective comparative trial by evaluating (a) the frequency of regurgitation, (b) acid reflux and (c) cardiac side effects in infants regurgitating >4 times/day since >2 weeks and with reflux-associated symptoms of discomfort, after conservative treatment failure. Results: Within the first treatment week, the frequency of regurgitation decreased in both groups, more rapidly in the cisapride group: the median regurgitation decreased from 6.22 to 3.50 in the cisapride group versus from 4.80 to 3.70 in the domperidone group. The decrease in regurgitation was still significant after 1 month: cisapride from 6.22 to 1.55 versus domperidone from 4.80 to 1.25. However, the natural decrease in the incidence of regurgitation induced by age should also be considered. The median reflux index decreased after 1 month in the cisapride group from 3.60 to 1.75 versus from 2.70 to 2.45 in the domperidone group. One child treated with cisapride developed a significant QT prolongation. Conclusion: The decrease in regurgitation was comparable in both groups, although acid reflux decreased more in the cisapride group. Cisapride induced QT prolongation in one infant. [source] Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009M. FRAZZONI Summary Background, In short-segment Barrett's oesophagus (SSBO) heartburn may be absent and oesophageal acid exposure time (OAET) assessed with pH-only monitoring may be normal. By detecting reflux episodes independently of their acidity, multichannel intraluminal impedance-pH (MII-pH) monitoring allows a comprehensive characterization of reflux events, either off or on proton pump inhibitor (PPI) therapy. Aim, To assess reflux parameters by MII-pH monitoring in newly diagnosed SSBO, at baseline and as modified with PPI therapy. Methods, Short-segment Barrett's oesophagus was defined by oesophageal intestinal metaplasia up to 3 cm in length. 24-h MII-pH monitoring was performed before and during PPI therapy. Results, Fifty patients were studied prospectively. Normal OAET was found at baseline in 15 patients (30%), 8 and 2 of whom with a higher than normal number of acid and weakly acidic refluxes, respectively. Overall, abnormal reflux parameters were detected by MII-pH monitoring in 90% of patients. Reflux events were prevalent in the upright period. On PPI therapy, acid refluxes decreased and a correspondent increase in weakly acidic refluxes was observed (median from 48.5 to 9 and from 16 to 57.5, respectively) (P < 0.001). Conclusions, Acid refluxes, mainly in the upright period, characterize SSBO. PPI therapy transforms acid refluxes into weakly acidic refluxes. [source] | |||||||||||||||||||||||||