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)

Esophageal acid exposure is common in normal subjects. The aim of this study was to investigate proximal and distal esophageal acid exposure in asymptomatic volunteers using dual-channel esophageal pH-metry with probe positioning by pH step-up. A total of 21 healthy subjects (9 male; mean age, 51 years) underwent 24-hour ambulatory esophageal pH recording with the pH step-up method using a two-channel pH probe, a portable digital data recorder, and computerized data analysis. All reflux episodes, episodes longer than 5 minutes, longest reflux episode, duration of acidity (pH <4), and percentage of time with acidity were analyzed. The 95th percentile for reflux parameters assessed in the distal/proximal esophagus were: total reflux episodes, 100/34; episodes greater than 5 minutes, 2.9/0; longest reflux episode, 16.6/2.95 minutes; duration of acidity, 87.95/15.5 minutes; and percentage of time with acidity, 7.0%/1.3%. Proximal and distal acid exposure were well correlated. Results showed that neither gender nor age influenced reflux parameters and that asymptomatic volunteers might experience some gastroesophageal reflux.
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PMID:Esophageal acid exposure in healthy adults in Taiwan: experience with pH step-up method by dual-channel pH-metry. 1608 6

Combining GERD tests allows strengths and weaknesses of each method to be identified in detecting and characterizing reflux (RE). Aim of this study was to compare two methods that measure bolus volume of a refluxant (impedance monitoring (Imp) and manometry (common cavity)) to pH monitoring which measures changes in acid concentration of a refluxant. Nineteen symptomatic GERD patients and 10 normal volunteers were studied before and after a meal. All had 2-hr simultaneous manometry, pH, and Imp (six sites: 3, 5, 7, 9, 15, 17 cm above LES). Reflux by pH was a fall in pH from above to below 4. There were 973 RE's in all subjects, but only 19% were detected simultaneously by all three methods. Imp detected more RE's (96%) than manometry (76%) or pH probe (28%). Imp was the only method to detect 15% (144/973) of RE's, while detection only by pH probe (2%) or manometry (2%) was rare. Most RE's detected by Imp were detected simultaneously by manometry (75%,720/937). Those not detected by manometry were usually in blind spots either in the vulnerable period 2-3 sec after a swallow, during a posture change, or during a Valsalva. Most RE's detected by Imp were not detected by the pH probe. Though most liquid RE's fasting were detected by pH, most liquid postprandial RE's were not, due primarily to weakly acidic rather than superimposed acid RE's. Bolus clearing time by Imp and manometry was nearly identical, while acid clearing was threefold longer than bolus clearing by Imp or manometry. In conclusion, impedance monitoring is better than manometry and pH monitoring in RE detection before and after a meal, and manometry in determining RE composition as liquid or gas. The pH probe measures RE acidity and acid clearing. Simultaneous impedance and pH combines the two methods strengths, and is a powerful tool for reflux detection and characterization.
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PMID:Direct comparison of impedance, manometry, and pH Probe in detecting reflux before and after a meal. 1683 16

Immediate-release omeprazole (Zegerid, Santarus) is the first immediate-release oral proton pump inhibitor to reach the market. As a powder formulation for oral suspension, it is indicated for the treatment of gastroesophageal reflux disease, erosive oesophagitis, duodenal ulcer and gastric ulcer, and is the only proton pump inhibitor approved for the reduction of risk of upper gastrointestinal bleeding in critically ill patients. Administration of immediate-release omeprazole at bedtime results in a rapid and sustained elevation of gastric pH, and seems to provide better night time control of gastric acidity than that observed with conventional morning dosing of delayed-release proton pump inhibitors. The immediate-release formulation may provide a good treatment option for patients who require flexible dosing, quick onset of action and nocturnal gastric acid control.
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PMID:Review of immediate-release omeprazole for the treatment of gastric acid-related disorders. 1625 81

Nocturnal gastro-oesphageal reflux is an under-appreciated clinical challenge. This condition may cause symptoms such as nocturnal heartburn, or it may be asymptomatic. In addition, patients may experience sleep disturbances that can potentially lead to complications such as erosive oesophagitis and Barrett's oesophagus, and may be a risk factor for development of oesophageal adenocarcinoma. Delayed-release proton-pump inhibitors (PPIs) have traditionally been effective in treating both daytime and night-time reflux symptoms, but are limited in control of nocturnal acidity by their pharmacodynamic characteristics. This narrative review addresses the prevalence, impact and pharmacologic approaches used to control nocturnal acidity. Methods to optimize nocturnal acid control include careful attention to dosing schedule, using higher doses of PPIs, adding an histamine H2-receptor antagonist at bedtime to once or twice daily delayed-release PPI, or using immediate-release omeprazole (Zegerid powder for oral suspension; Santarus, Inc., San Diego, CA, USA). This new formulation appears to provide sustained control of intragastric pH at steady state, and when dosed at bedtime, and may be effective in improving control of nocturnal pH and treating night-time GERD.
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PMID:Review article: putting immediate-release proton-pump inhibitors into clinical practice--improving nocturnal acid control and avoiding the possible complications of excessive acid exposure. 1630 35

Gastroesophageal reflux disease (GERD) is a chronic disease affecting up to 40% of people in the Western world. Risk factors associated with GERD include age and lifestyle habits, although the clinically relevant contribution of many of these factors is unclear. In GERD, refluxed gastric acid damages the oesophageal mucosa, generally when the pH falls below 4. GERD patients present a variety of symptoms, most commonly heartburn and regurgitation. Oesophageal complications associated with GERD include erosions, ulcers, peptic strictures, and Barrett's oesophagus which is implicated in the development of oesophageal adenocarcinoma. Diagnosis of GERD is problematic due to the range of symptoms which may be presented to the physician and symptom severity is frequently unrelated to disease severity. While endoscopic monitoring may be used to assess the presence and severity of GERD, a lack of visible damage does not necessarily indicate an absence of GERD. Techniques used to diagnose GERD include addition of an acid solution into the oesophagus in order to replicate symptoms (Bernstein test) or 24-hour intra-oesophageal pH monitoring. Proton pump inhibitors are effective in the treatment of GERD, acting to reduce the acidity of the gastric juice and hence reduce oesophageal damage and symptoms associated with GERD. Symptoms most indicative of GERD are those associated with erosive oesophagitis, including heartburn and acid regurgitation. Less common GERD-associated symptoms include chest pain, a range of ear, nose and throat conditions, and asthma. In contrast to perceptions of the disease as 'merely' heartburn, the impact on patients' quality of life can be profound. Increasing awareness of GERD by health care professionals has led to improved diagnosis and a greater appreciation of the need for maintenance therapy.
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PMID:Gastroesophageal reflux disease: clinical features. 1634 49

Proton pump inhibitors (PPIs) are used widely in the management of acid-related disorders and, for the majority of patients, oral therapy is highly effective. Not all patients with acid-related disorders respond completely to standard, once-daily PPI therapy, but most nonresponders will generally respond to an increase in the dose or frequency of PPI therapy. At equivalent doses, oral and intravenous (IV) PPIs produce comparable acid suppression; thus there are very few clinical indications for IV PPI therapy. IV PPIs are an appropriate substitute for oral PPIs, at an equivalent dose, for patients with, for example, gastroesophageal reflux disease, peptic ulceration, or Zollinger-Ellison syndrome, who cannot take oral medication. For patients with nonvariceal, upper gastrointestinal hemorrhage, profound acid suppression (gastric pH . 6.0) optimizes clot stability and reduces the risk of rebleeding; this is achieved most effectively with an initial IV PPI bolus followed by a continuous infusion. High-dose, IV PPI therapy is beneficial and cost-effective in patients who have a high-risk lesion at endoscopy and it should be preceded by effective endoscopic hemostasis if possible. IV PPIs, preoperatively and in the intensive care setting, effectively reduce gastric acidity, but there are no convincing data that this confers any significant clinical benefit compared with other therapeutic strategies.
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PMID:Intravenous proton pump inhibitor therapy: a rationale for use. 1636 24

The objective of the open, randomised, four-period crossover study was to compare the time of onset of effect of sodium alginate (SA), omeprazole, ranitidine and control, based on oesophageal and intragastric pH and to determine any correlation between reflux symptoms and episodes in volunteers suffering from occasional gastro-oesophageal reflux. SA showed extensive prevention of acid exposure in the oesophagus compared with other treatments during the first hour. Overall, SA was more effective than control or omeprazole and comparable with ranitidine. There was little evidence of association between 'oesophageal' symptoms and reflux episodes, but associations between 'gastric' symptoms and acidity in the oesophagus, fundus and corpus were apparent. For an immediate reduction in gastro-oesophageal reflux into the oesophagus and gastric acidity during the first hour, SA was significantly superior to control, ranitidine and omeprazole. Ranitidine showed a superior effect from 2 h, consistent with its pharmacological mode of action.
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PMID:Rapid onset of effect of sodium alginate on gastro-oesophageal reflux compared with ranitidine and omeprazole, and relationship between symptoms and reflux episodes. 1649 41

No evidence supports one method over another in managing uncomplicated gastroesophageal reflux disease (GERD) for patients aged >65 years. For those with endoscopically documented esophagitis, proton pump inhibitors (PPIs) relieve symptoms faster than histamine H2 receptor antagonists (H2RAs) (strength of recommendation [SOR]: B, extrapolation from randomized controlled trials [RCTs]). Treating elderly patients with pantoprazole (Protonix) after resolution of acute esophagitis results in fewer relapses than with placebo (SOR: B, double-blind RCT). Limited evidence suggests that such maintenance therapy for prior esophagitis with either H2RAs or PPIs, at half- and full-dose strength, decreases the frequency of relapse (SOR: B, extrapolation from uncontrolled clinical trial). Laparoscopic antireflux surgery for treating symptomatic GERD among elderly patients without paraesophageal hernia reduces esophageal acidity, with no apparent increase in postoperative morbidity or mortality compared with younger patients (SOR: C, nonequivalent before-after study). Upper endoscopy is recommended for elderly patients with alarm symptoms, new-onset GERD, or longstanding disease (SOR: C, expert consensus). Elderly patients are at risk for more severe complications from GERD, and their relative discomfort from the disease process is often less than from comparable pathology for younger patients (SOR: C, expert consensus). Based on safety profiles and success in the general patient population, PPIs as a class are considered first-line treatment for GERD and esophagitis for the elderly (SOR: C, expert consensus).
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PMID:What is the best way to manage GERD symptoms in the elderly? 1651 61

The dramatic success of pharmacological acid suppression in healing peptic ulcers and managing patients with gastroesophageal reflux disease (GERD) has been reflected in the virtual abolition of elective surgery for ulcer disease, a reduction in nonsteroidal anti-inflammatory drug (NSAID)-associated gastropathy and the decision by most patients with reflux symptoms to continue medical therapy rather than undergo surgical intervention. However, a number of challenges remain in the management of acid-related disorders. These include management of patients with gastroesophageal symptoms who do not respond adequately to proton pump inhibitor (PPI) therapy, treatment of patients with nonvariceal upper gastrointestinal bleeding, prevention of stress-related mucosal bleeding, optimal treatment and prevention of NSAID-related gastrointestinal injury, and optimal combination of antisecretory and antibiotic therapy for the eradication of Helicobacter pylori infection. A number of new drugs are currently being investigated to provide a significant advance on current treatments. Some of them (namely potassium-competitive acid blockers (P-CABs) and CCK2-receptor antagonists) have already reached clinical testing while some others (like the antigastrin vaccine, H3-receptor ligands or gastrin-releasing peptide receptor antagonists) are still in preclinical development and need the proof of concept in human beings. Of the current approaches to reduce acid secretion, P-CABs and CCK2-receptor antagonists hold the greatest promise, with several compounds already in clinical trials. Although the quick onset of action of P-CABs (i.e. a full effect from the first dose) is appealing, the results of phase II studies with one such agent (namely AZD0865) did not show any advantages over esomeprazole. Thanks to their limited efficacy and the development of tolerance it is unlikely that CCK2 antagonists will be used alone as antisecretory compounds but, rather, their combination with PPIs will be attempted with the aim of reducing the long-term consequences of hypergastrinemia. While H2-receptor antagonists (especially soluble or over-the-counter formulations) will become the 'antacids of the third millennium' and will be particularly useful for on-demand symptom relief, clinicians will continue to rely on PPIs to control acid secretion in GERD and other acid-related diseases. In this connection, several new PPI formulations have been developed and two novel drugs (namely ilaprazole and tenatoprazole) are being studied in humans. The recently introduced immediate-release (IR) omeprazole formulation (currently available only in the USA) quickly increases intragastric pH and, given at bedtime, seems to achieve a better control of nocturnal acidity. IR formulations of other PPIs (including the investigational ones) will probably be available in the future and will enlarge our therapeutic armamentarium. Amongst the novel PPIs, tenatoprazole appears to be a true advance in the acid suppression therapy. Its long half-life (the longest among the available compounds) and longer duration of antisecretory action, with no difference between day and night, will allow the drug to go beyond the intrinsic limitations of currently available PPIs. Thanks to its favorable pharmacokinetics, the sodium salt of S-tenatoprazole is being developed and the preliminary results indicate that this drug has the potential to address unmet clinical needs. Although some decades have elapsed since the introduction of effective and safe antisecretory drugs in clinical practice and their use has stood the test of time, the ongoing research will further provide the clinician with more effective means of controlling acid secretion.
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PMID:Acid suppression therapy: where do we go from here? 1669 62

Acid suppression therapy with proton pump inhibitors is associated with well-established benefits in the management of gastro-oesophageal reflux (GERD) and other acid-related disorders. However, a number of issues still remain unsettled. Despite their clinical efficacy, when given once daily, currently available proton pump inhibitors may not adequately control intragastric acidity during the night in a significant proportion of both healthy subjects and GERD patients, in whom symptom relief remains suboptimal. Although some novel proton pump inhibitors have been synthesized, only few reached clinical testing. Amongst them, tenatoprazole represents a true advance displaying a long half-life (five to seven times longer than that of currently available drugs) and extended acid suppression covering both day and night. All the available clinical studies suggest both pharmacokinetic and pharmacodynamic advantages of tenatoprazole over esomeprazole. As this last compound provides - amongst the members of the class - the most effective control of intragastric pH whatever the parameter considered, it is conceivable that tenatoprazole could similarly be better than the other existing proton pump inhibitors. Tenatoprazole appears to be a promising proton pump inhibitor for the treatment of acid-related diseases, where it has the potential to address unmet clinical needs.
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PMID:Review article: the opportunities and benefits of extended acid suppression. 1670 Sep


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