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)

Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.
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PMID:Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas. 1643 85

A 43-year-old white man presented with an 8-month history of redness and swelling on the back of the neck. He also noted a decrease in range of motion of his upper body. There was no improvement with a 4-week course of topical corticosteroids. Review of systems was negative for polydipsia, polyuria, polyphagia, and bone pain. His medical history included depression, gastroesophageal reflux disease, and microdiscectomy. His medications included sertraline and omeprazole. Physical examination revealed a 20-cm erythematous, indurated plaque on the posterior part of the upper back and neck (Figure 1). A lack of skin wrinkling was noted with lateral pressure. Biopsy revealed a periadnexal and mild interface dermatitis with an increase in connective tissue mucin as demonstrated with colloidal iron (Figures 2A and 2B). Serum protein electrophoresis, hemoglobin A1C, and antinuclear antibody titer were within normal limits. A diagnosis of tumid lupus erythematosus mimicking scleredema was made. Hydroxychloroquine therapy was started at a dose of 200 mg and, at 2 months' follow-up, the patient's symptoms and appearance were improved.
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PMID:Tumid lupus erythematosus: an unusual scleredema-like presentation. 1660 43

the present study was performed to examine the sequential process of the development of Barrett's oesophagus (BE) and oesophageal adenocarcinoma (ADC) induced by duodeno-oesophageal reflux (DER) in rats. Total gastrectomy was performed in male Wistar rats weighing approximately 250 g followed by reconstruction with oesophago-jejunostomy, which causes unavoidable DER without exposure to exogenous carcinogens. Animals were selected at random and sacrificed every 10 weeks after surgery until 50 weeks. Severe squamous oesophagitis with erosion, regenerative thickening (RT), and basal cell hyperplasia (BCH) were observed on the 10th week after surgery. On the 20th week, glandular structures that stained positively with Galactose oxidase-Schiff (foveolar metaplasia) were observed in the basal layer of the oesophageal squamous epithelium. On the 30th week, the glands developed and formed cysts that stained positively with concanavalin A (pyloric glandular metaplasia) and/or high-iron diamine and Alcian blue (intestinal metaplasia). From the 40th week after surgery, ADC cells surrounded by columnar-lined epithelium were found. Persistent stimulation with DER can alter the stem cells in the squamous epithelial basal layer leading to the formation of columnar-lined cells and subsequent ADC. Foveolar metaplasia was observed as part of the sequence of events leading to the development of columnar-lined epithelium (CLE), followed by the appearance of pyloric glandular metaplasia and intestinal metaplasia, completing the histogenesis of BE.
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PMID:Duodenal juice stimulates oesophageal stem cells to induce Barrett's oesophagus and oesophageal adenocarcinoma in rats. 1668 81

Laryngopharyngeal or gastroesophageal reflux is associated with laryngeal airway hyperreactivity (LAH), but neither the cause-effect relationship nor the underlying mechanism has been elucidated. Here we established a rat model with enhanced laryngeal reflex reactivity induced by laryngeal acid-pepsin insult and investigated the neural and hydroxyl radical (*OH) mechanisms involved. The laryngeal segments of 103 anesthetized rats were functionally isolated while animals breathed spontaneously. Ammonia vapor was delivered into the laryngeal segment to measure laryngeal reflex reactivity. We found that the laryngeal pH 5-pepsin treatment doubled the reflex apneic response to ammonia, whereas laryngeal pH 7.4-pepsin, pH 2-pepsin, and pH 5-denatured pepsin treatment had no effect. Histological examination revealed limited laryngeal inflammation and epithelial damage after pH 5-pepsin treatment and more severe damage after pH 2-pepsin treatment. In rats that had received the laryngeal pH 5-pepsin treatment, the apneic response to ammonia was abolished by either denervation or perineural capsaicin treatment (PCT; a procedure that selectively blocks capsaicin-sensitive afferent fibers) of the superior laryngeal nerves, but was unaffected by perineural sham treatment. LAH was prevented by laryngeal application of either dimethylthiourea (DMTU; a *OH scavenger) or deferoxamine (DEF; an antioxidant for *OH), but was unaltered by the DMTU vehicle or iron-saturated DEF (ineffective DEF). LAH reappeared after recovery from PCT, DMTU, or DEF treatment. We conclude that 1) laryngeal insult by pepsin at a weakly acidic pH, but not at acidic pH, can produce LAH; and 2) LAH is probably mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by a *OH mechanism.
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PMID:Neural and hydroxyl radical mechanisms underlying laryngeal airway hyperreactivity induced by laryngeal acid-pepsin insult in anesthetized rats. 1678 36

Conditions causing high iron levels, such as hemochromatosis, are proposed risk factors for esophageal adenocarcinoma. Although this hypothesis is supported by animal models, no human data currently exist. We conducted a case-control study of persons with a new Barrett's esophagus diagnosis (cases), persons with gastroesophageal reflux disease (GERD) (without Barrett's esophagus), and population controls. Subjects completed detailed examinations and assays for hemochromatosis mutations and serum iron stores. We evaluated 317 cases, 306 GERD patients, and 308 population controls. There was no significant association between Barrett's esophagus and any hemochromatosis gene defect (odds ratio [OR] = 1.32, 95% confidence interval [CI]: 0.95-1.84), a moderate or severe mutation (OR = 1.54, 95% CI: 0.94-2.52), or a severe mutation (C282Y homozygote or C282Y/H63D heterozygote; OR = 0.77, 95% CI: 0.24-2.48) compared with the population controls. As expected, gene defects were associated with increased iron stores. We can conclude from our findings that Barrett's esophagus was not associated with hemochromatosis gene defects, although we cannot exclude small effects.
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PMID:Hemochromatosis gene status as a risk factor for Barrett's esophagus. 1847 Jun 14

Proton pump inhibitors (PPIs) have become the mainstay of therapy in acid-related upper gastrointestinal disorders including gastroesophageal reflux disease and peptic ulcer disease. Alltough these medications are generally accepted as safe, the long-term clinical consequences of the inducing hypochlorhydria are not completely clear. Gastric acid production is mainly controlled by the hormone gastrin through a negative feedback in which hypochlorhydria induces an increase in serum gastrin. PPIs have been shown to increase serum gastrin levels. Gastric endocrine cell hyperplasia can occur in 10 to 30% of patients without carcinoid tumors. Recent studies indicate no association between PPI use and the risk of colorectal and gastric cancers. Proton pump inhibitor-associated gastric polyps are totally benign tumors that should not be followed. There is an association between PPIs-induced acid suppression and an increased risk of enteric infection. PPIs do not inhibit intestinal absorption of lipids, iron, phosphorus, magnesium or zinc from food but can affect vitamin B12 status in older patients. Despite the undoubted benefits of PPIs, the practitioner always needs to consider risks and benefits before initiating them.
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PMID:[Risk of long-term treatment with proton pump inhibitors]. 1892 30

Bariatric surgery is the most durable intervention for severe obesity. Appropriate candidates for surgery include those with a body mass index over 40 kg/m(2), or those with a BMI over 35 kg/m(2) who also have weight-related comorbidities. Bariatric procedures are categorized as restrictive, where food intake is limited by a small gastric 'pouch'; malabsorptive, where the length of intestine available for nutrient absorption is decreased; or a combination of both. Although pure malabsorptive procedures, such as the now-historical jejunoileal bypass, achieve greater weight loss than restrictive procedures, they are generally associated with more postoperative metabolic problems. The Roux-en-Y gastric bypass is currently considered the gold standard bariatric procedure for most patients. It results in excellent weight loss with minimal complications, but does require life-long vitamin supplementation. Compliance with vitamins and supplements is also mandatory after malabsorptive procedures. With these procedures, decreased oral intake, as well as altered absorption of nutrients from the GI tract, results in potentially low blood levels of a variety of micronutrients, especially iron, vitamin B12 and folate. Bariatric surgery also improves the comorbid conditions that are associated with obesity, such as diabetes, hypertension, dyslipidemia, obstructive sleep apnea, obesity hypoventilation, gastroesophageal reflux disease, asthma, venous stasis, polycystic ovary syndrome and pseudotumor cerebri. The resolution of diabetes is secondary to weight loss and may also be due to alteration of the enteroinsular axis.
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PMID:Metabolic and nutritional changes after bariatric surgery. 2035 Feb 67

Proton pump inhibitors (PPI) are one of the most widely used classes of drugs. PPIs have a very favorable safety profile, and it is unusual for a patient to stop them because of side effects. However, with increasing numbers of patients chronically taking PPIs for gastroesophageal reflux disease and other common, persistent conditions, the long-term potential adverse effects are receiving increasing attention. An insufficiently studied area receiving much attention is the long-term effect of chronic acid suppression on the absorption of vitamins and nutrients. This increased attention results from the reported potential adverse effect of chronic PPI treatment leading to an increased occurrence of bone fractures. Interest in this area has led to examination of the effects of PPIs on calcium absorption/metabolism and numerous cohort, case-control, and prospective studies of their ability to affect bone density and cause bone fractures. In this article, these studies are systematically examined, as are studies of the effects of chronic PPI use on absorption of VB(12), iron, and magnesium. Studies in each area have led to differing conclusions, but when examined systematically, consistent results of several studies support the conclusion that long-term adverse effects on these processes can have important clinical implications.
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PMID:Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. 2088 39

Complications associated with gastroesophageal reflux disease (GERD) can include esophageal stricture, Barrett's esophagus, gastrointestinal hemorrhage, and extraesophageal symptoms. The impact of GERD-associated complications on health-care utilization deserves further evaluation. We identified commercial enrollees 18-75 years old with claims for GERD (International Classification of Diseases, Ninth Revision, Clinical Modification Codes: 530.81 or 530.11) and subsequent usage of proton pump inhibitors from 01/01/05 to 06/30/09. The initial GERD diagnosis date was designated as the index date, and patients were studied for 6 months preindex and postindex. Eligible patients were subsequently stratified based on medical claims for GERD-associated complications as follows: stage A (GERD diagnosis, no other symptoms), stage B (GERD + extraesophageal symptoms), stage C (GERD + Barrett's esophagus), stage D (GERD + esophageal stricture), and stage E (GERD + iron-deficiency anemia or acute upper gastrointestinal hemorrhage). Patient characteristics, health-care utilization, and costs were compared between stage A and each stage with complicated GERD (B-D). Of the 174,597 patients who were eligible for analysis, 74% were classified as stage A, 20% stage B, 1% stage C, 2% stage D, and 3% stage E. Relative to stage A, patients in stages C, D, and E were significantly more likely to visit a gastroenterologist (13% vs. 68%, 71%, and 38%, respectively) and had higher rates of esophageal ulcers (0.3% vs. 8%, 5%, and 3%, respectively) and Nissen fundoplication (0.05% vs. 0.6%, 0.3%, and 0.2%, respectively). Six-month GERD-related costs ranged from $615/patient (stage A) to $1714/patient (stage D); all-cause costs ranged from $4195/patient (stage A) to $11,340/patient (stage E). Compared with stage A, all other cohorts had significantly higher all-cause and GERD-related costs (P < 0.0001 for all comparisons). While patients with more severe GERD represented a relatively small portion of the GERD cohort, they demonstrated significantly greater health-care costs and overall utilization than patients with uncomplicated GERD.
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PMID:Variation of health-care resource utilization according to GERD-associated complications. 2229 44

Extrinsic staining of teeth due to excessive iron intake has been reported previously in the literature. We describe a 7-month-old infant who presented with extrinsic teeth staining due to inadvertent over consumption of dietary iron. The infant was fed iron-fortified formula and rice cereal. Rice cereal, fortified with iron, was being used as part of a normal infant diet and as a thickening agent when added to the formula for treatment of gastroesophageal reflux. After several months of administration, "blackening" of the infant's teeth was noted by the mother. The stain was removed by the pediatric dentist who simply scraped the affected teeth. No further staining occurred after the amount of dietary iron was reduced.
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PMID:Extrinsic iron staining in infant teeth from iron-fortified formula and rice cereal. 2305 77


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