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)

Gastro-oesophageal reflux disease is a condition in which the reflux of gastric contents into the oesophagus provokes symptoms or complications and impairs quality of life. Typical symptoms of gastro-oesophageal reflux disease are heartburn and regurgitation but gastro-oesophageal reflux disease has also been related to extra-oesophageal manifestations, such as asthma, chronic cough and laryngitis. The pathogenesis of gastro-oesophageal reflux disease is multifactorial, involving transient lower oesophageal sphincter relaxations and other lower oesophageal sphincter pressure abnormalities. As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury. Other factors contributing to the pathophysiology of gastro-oesophageal reflux disease include hiatal hernia, impaired oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Hiatal hernia contributes to gastro-oesophageal reflux disease by promoting lower oesophageal sphincter dysfunction. Impaired oesophageal clearance is responsible for prolonged acid exposure of the mucosa. Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of transient lower oesophageal sphincter relaxations, contributing to postprandial gastro-oesophageal reflux disease. The mucosal defensive factors play an important role against development of gastro-oesophageal reflux disease, by neutralizing the backdiffusion of hydrogen ion into the oesophageal tissue. While the pathogenesis of oesophageal symptoms is now well known, the mechanisms underlying extra-oesophageal airway manifestations are still poorly understood. Two hypotheses have been proposed: direct contact of gastric acid with the upper airway and a vago-vagal reflex elicited by acidification of the distal oesophagus, leading to bronchospasm. In conclusion, gastro-oesophageal reflux disease can be considered as the result of a complex interplay of factors, all promoting the contact of gastric acidic contents with the oesophageal mucosa, leading to different degrees of oesophageal damage.
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PMID:Pathophysiology of gastro-oesophageal reflux disease. 1734 25

Proton-pump inhibitors remain the most effective treatment for relieving symptoms, healing lesions and preventing recurrences of gastroesophageal reflux (GER). Drugs inhibiting transient relaxation of the lower esophageal sphincter have an unfavorable benefit/risk ratio. Endoscopic methods developed in recent years have not been shown effective in trials versus sham procedures. Surgical treatment is effective in GER but causes frequent uncomfortable side effects that are difficult to treat.
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PMID:[Therapeutic innovations in gastroesophageal reflux]. 1753 31

Proton-pump inhibitor (PPI) failure in gastro-oesophageal reflux disease (GORD) patients has become the main reason for referral of these patients to gastroenterology specialists. It is estimated that 30% of GORD patients requiring a PPI once daily will experience treatment failure. Patients with non-erosive reflux disease are the most common GORD-related group in which once-daily PPI therapy fails. Various mechanisms have been suggested to underlie PPI failure in GORD patients. The most pertinent include weakly acidic reflux, duodenogastro-oesophageal reflux, visceral hyperalgesia, delayed gastric emptying, psychological co-morbidity and concomitant functional bowel disorders, as well as others. Because of the importance of PPI failure as a target for future drug development, further understanding of the most relevant underlying mechanisms is needed.
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PMID:Proton-pump inhibitor therapy in patients with gastro-oesophageal reflux disease: putative mechanisms of failure. 1766 25

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists.
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PMID:Molecular mechanisms in therapy of acid-related diseases. 1792 53

Proton Pump Inhibitors (PPIs) are widely used in the treatment of acid-peptic diseases. Their mechanism of action involves inhibition of the H-K-adenosine triphosphatase enzyme present in the parietal cells of the gastric mucosa. Because PPIs are the most potent inhibitors of gastric acid secretion available, they effectively alleviate acid-peptic symptoms and facilitate healing of inflamed or ulcerated mucosa. Although the use of PPIs is nowadays short term in patients with Helicobacter pylori-related peptic ulcer disease, these drugs are increasingly used long term, frequently for a lifetime, in patients with typical or atypical symptoms of gastro-oesophageal reflux disease, and in NSAID or aspirin users at risk for gastrotoxicity and related complications, such as bleeding, perforation and gastric outlet obstruction. This review outlines the essentials of PPI pharmacology, the safety and adverse profiles of the various available agents, and balances them against their clinical short- and long-term benefits. PPI use, prophylactically or with a therapeutic intent may also be combined with other strategies, such as endoscopic therapy, surgery or antibacterial use. Various clinical endpoints, such as symptom relief, mucosal healing, prevention of disease recurrence or complications, and cancer chemoprevention, are discussed and unmet needs are highlighted.
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PMID:Guide to the use of proton pump inhibitors in adult patients. 1845 60

The prevalence of Gastroesophageal Reflux Disease (GERD) is rapidly rising in Asia. We describe here a case of 51 years old man who had surgery for esophageal leiomyoma and received long-term therapy with Proton Pump Inhibitors (PPIs) for persisting reflux symptoms. On Esophago-Gastroduodenoscopy (EGD) several sessile polyps were seen in the gastric corpus. Earlier EGD done 15 years back had not demonstrated those polyps. Sections revealed polypoid fragments of glandular epithelium with dilated glands and negative histology for H. pylori. Polymerase chain reaction for 16S ribosomal RNA gene (16S rRNA PCR) of H. pylori was also negative. This is the first report originating from an Asian country describing Fundal Gland Polyps (FGPs) in the corpus of stomach rather than fundus in a patient on long-term PPI therapy.
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PMID:Gastric corpus polyps associated with Proton Pump Inhibitors therapy. 1846 Feb 47

Proton-pump inhibitors (PPIs) are the drugs of choice for the treatment of gastroesophageal reflux disease (GERD). Esomeprazole is the latest PPI and was developed as the S-isomer of omeprazole as an attempt to improve its pharmacokinetic properties. Esomeprazole has been reported to have a somewhat higher potency in acid inhibition than other PPIs. Despite some controversy, data from clinical trials and meta-analyses indicate that esomeprazole 40 mg od for up to 8 weeks provided higher rates of healing of erosive GERD and a greater proportion of patients with sustained resolution of heartburn, than omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg od. Esomeprazole 20 mg od has also been shown to be more effective in maintaining healing of erosive GERD compared with lansoprazole 15 mg od or pantoprazole 20 mg od. However, it is not clear whether these statistically significant differences are of major clinical importance. Esomeprazole 20 mg od is superior to placebo for treatment of non-erosive reflux disease (NERD) but clinical trials have not shown any significant differences in efficacy between esomeprazole 20 mg and omeprazole 20 mg or pantoprazole 20 mg od. Lastly, although esomeprazole treatment in GERD has been reported to result in improvement of health-related quality of life (QoL) indices, no clinical trials have evaluated the possible differential effects of different PPIs on QoL in GERD.
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PMID:A review of esomeprazole in the treatment of gastroesophageal reflux disease (GERD). 1847 88

Gastroesophageal reflux disease complicated by Barrett's esophagus (BE) is a major risk factor for esophageal adenocarcinoma (EA). However, the mechanisms of the progression from BE to EA are not fully understood. Besides acid reflux, bile acid reflux may also play an important role in the progression from BE to EA. In this study, we examined the role of phosphatidylinositol-specific phospholipase C (PI-PLC) and a novel NADPH oxidase NOX5-S in bile acid-induced increase in cell proliferation. We found that taurodeoxycholic acid (TDCA) significantly increased NOX5-S expression, hydrogen peroxide (H(2)O(2)) production, and cell proliferation in EA cells. The TDCA-induced increase in cell proliferation was significantly reduced by U73122, an inhibitor of PI-PLC. PI-PLCbeta1, PI-PLCbeta3, PI-PLCbeta4, PI-PLCgamma1, and PI-PLCgamma2, but not PI-PLCbeta2 and PI-PLCdelta1, were detectable in FLO cells by Western blot analysis. Knockdown of PI-PLCgamma2 or extracellular signal-regulated kinase (ERK) 2 mitogen-activated protein (MAP) kinase with small interfering RNAs (siRNA) significantly decreased TDCA-induced NOX5-S expression, H(2)O(2) production, and cell proliferation. In contrast, knockdown of PI-PLCbeta1, PI-PLCbeta3, PI-PLCbeta4, PI-PLCgamma1, or ERK1 MAP kinase had no significant effect. TDCA significantly increased ERK2 phosphorylation, an increase that was reduced by U73122 or PI-PLCgamma2 siRNA. We conclude that TDCA-induced increase in NOX5-S expression and cell proliferation may depend on sequential activation of PI-PLCgamma2 and ERK2 MAP kinase in EA cells. It is possible that bile acid reflux present in patients with BE may increase reactive oxygen species production and cell proliferation via activation of PI-PLCgamma2, ERK2 MAP kinase, and NADPH oxidase NOX5-S, thereby contributing to the development of EA.
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PMID:Bile acid reflux contributes to development of esophageal adenocarcinoma via activation of phosphatidylinositol-specific phospholipase Cgamma2 and NADPH oxidase NOX5-S. 2008 78

Gastro-oesophageal reflux disease (GERD) is a common disorder in Western countries, and its relationship to airways disorders (e.g. asthma) has been well established. Lung diseases other than asthma have also been associated with GERD, but the nature and scope of this relationship has not been fully defined. Diseases that have been associated with GERD include bronchiolitis syndromes, idiopathic pulmonary fibrosis, scleroderma and nontubercular mycobacterial infection. Diagnostic evaluation centres upon proving both reflux and pulmonary aspiration, which may be accomplished in some cases by lung biopsy. However, in many cases a compatible clinical and radiographic picture coupled with proof of proximal reflux by combined oesophageal probe testing may suffice for a provisional diagnosis and allow institution of anti-reflux measures. Proton-pump inhibitors are the medications of choice for GERD; other interventions shown to reduce reflux are weight loss, elevation of the head of the bed and avoidance of recumbency after meals. However, acid suppression therapy does not address non-acid reflux that may be important in disease pathogenesis in select patients, and lifestyle modifications often fail. Laparoscopic fundoplication is the procedure of choice for medically refractory GERD with excellent short-term results with respect to respiratory symptoms associated with GERD; however, long-term studies document a significant percentage of patients requiring ongoing acid suppression therapy.
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PMID:Gastro-oesophageal reflux disease and non-asthma lung disease. 2095 48

Gastroesophageal reflux (GER) is defined as the passage of gastric contents into the esophagus. It occurs in healthy infants and can be considered physiological process. Uncomplicated GER can present with recurrent vomiting or regurgitation without any other symptoms and is usually managed by educating, reassuring, and guiding the parent without other intervention. GER disease (GERD) refers to the appearance of troublesome symptoms or complications (erosive esophagitis, ulceration, Barrett's esophagus) and may warrant acid suppression. Proton Pump Inhibitors (PPIs) are the most effective pharmacologic agents available for the treatment of children with GERD. In the pediatric practice only omeprazole, lansoprazole and esomeprazole are available over the first year of life. The empiric use in infants with nonspecific symptoms (excessive crying, regurgitation, feeding refusal, chronic cough) is frequent without randomized controlled study. Our paper will focus on the correct indications, dosages, duration of treatment and safety of PPI use in pediatric population.
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PMID:Proton pump inhibitors in pediatrics: evaluation of efficacy in GERD therapy. 2123 62


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