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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progressive systemic sclerosis (PSS) is a systemic disease with a high frequency of gastro-intestinal involvement. The present thesis deals with the occurrence of, the complications to, and the treatment of the esophageal manifestations combined with more experimental studies on small intestine manifestations. The conclusions in this thesis are based on results achieved in 9 original previously published papers. The pattern of esophageal dysmotility is thoroughly evaluated in 156 consecutive PSS patients and is found to be identical to what is found in other large series of PSS patients. In paper no. I dysmotility variables are correlated to the occurrence of gastroesophageal reflux (GER) and it is shown that also in this group of patients with well defined dysmotility problems the only reliable GER test is pH-metry. Esophageal dysmotility furthers esophageal candidosis, which is further facilitated by anti-reflux treatment. This problem is evaluated in paper no. V. Progression of esophageal dysmotility in spite of D-penicillamine treatment is shown in paper no. VII and confirms the non-stable condition of the PSS patient in regard to esophageal manifestations and complications. This point is also outlined in paper no. IX concerning surveillance and continuous treatment of esophageal PSS. Esophageal stricturing is a well-known entity in PSS. The etiologic question of esophageal stricturing being a manifestation of PSS and/or a peptic complication, is approached in paper no. VIII. PSS manifestations of the small intestine are not as frequent as in the esophagus, in the present material only 19% presented with X-ray changes. However, bacterial count of duodenal juice as an indirect measurement of small intestinal dysmotility in paper no. VI indicates a much larger percentage of small intestinal involvement than revealed by X-ray. In paper no. VI the exocrine pancreatic function was assessed in 16 PSS patients. It is shown that the endogenous stimulation capacity is preserved even in spite of demonstrable small intestinal PSS involvement and that exocrine pancreatic function is frequently reduced, but rarely to a degree of clinical significance. Small intestinal enterocyte function is evaluated according to the ability to hydrolyse folatepolyglutamates and to absorb D-penicillamine, and is in both respects found less than normal. In an ultrastructural evaluation (paper II) the enterocytes presented signs of defective fat transport. PSS manifestations of the gastrointestinal tract are frequent and burdensome to the patient. Omeprazole and new prokinetic drugs have rendered new therapeutic potentialities, which, however, more than ever demand constant surveillance and individualized regulation of treatment.
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PMID:Esophageal and small intestinal manifestations of progressive systemic sclerosis. A clinical and experimental study. 781 47

Eleven adult patients with nocturnal asthma, and gastro-oesophageal reflux documented by endoscopy or ambulatory oesophageal pH monitoring completed a double-blind cross-over study (4 week treatment, one week run-in and cross-over periods) comparing the effects of omeprazole 20 mg daily and placebo on asthma control assessed by symptoms, peak expiratory flow rate and bronchodilator usage. Omeprazole treatment did not improve asthma symptoms during the day or night, or peak expiratory flow rate readings. There was no difference in bronchodilator inhaler usage during omeprazole therapy. Treatment of gastro-oesophageal reflux with omeprazole in patients with nocturnal asthma and gastro-oesophageal reflux does not improve asthma symptoms or peak expiratory flow rate. This suggests that gastro-oesophageal reflux does not exacerbate bronchoconstriction in nocturnal asthma.
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PMID:Omeprazole in the treatment of asthmatics with nocturnal symptoms and gastro-oesophageal reflux: a placebo-controlled cross-over study. 801 6

The phases of therapy for gastroesophageal reflux disease (GERD) and the efficacy, safety, and cost of the various drugs used are discussed. The therapeutic goals for patients with GERD are to relieve pain, promote healing, avoid complications, and prevent recurrence. Sustained inhibition of gastric acid secretion is necessary to facilitate healing of eroded esophageal mucosa. Phase 1 treatment involves lifestyle changes to remove factors that may help to precipitate reflux, such as overeating, alcohol, and tobacco. Phase 2 involves pharmacologic manipulation of the secretion, concentration, and transport of gastric acid. The drugs used are antacids, alginic acid, the histamine H2-receptor antagonists, the prokinetic agents, sucralfate, and omeprazole. While all of these agents may provide symptomatic relief, only the H2 antagonists and omeprazole have been convincingly shown to relieve symptoms and promote healing. The H2 antagonists differ in potency, pharmacodynamic effect, pharmacokinetics in certain patient groups, drug interactions, and adverse effects. The H2 antagonists may not be effective at standard dosages in patients who secrete especially large quantities of gastric acid. Because of its mechanism of action, omeprazole provides greater inhibition of gastric acid than any other antisecretory drug. Omeprazole may also be the most cost-effective treatment. The availability of omeprazole may reduce the number of patients for whom clinicians must resort to phase 3 treatment, surgery. Although many drugs provide symptomatic relief in patients with GERD, the healing that is necessary to break the cycle of damage and symptoms is promoted only by the H2 antagonists and omeprazole.
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PMID:Efficacy, safety, and cost issues in managing patients with gastroesophageal reflux disease. 809 63

Key pharmacokinetic and pharmacodynamic aspects of gastric acid-suppressive agents in patients with gastroesophageal reflux disease (GERD) are discussed. The acid-suppressive potencies of the histamine H2-receptor antagonists vary widely because of differences in clearance and other factors. The durations of action of cimetidine, ranitidine, and famotidine are similar to the dosage intervals usually chosen (6, 8, and 12 hours, respectively). Single bedtime doses of these drugs will effectively treat duodenal ulcer disease, but GERD requires a different approach since its symptoms are not well controlled by partial (less than 24-hour) suppression of gastric acid. One way to achieve greater efficacy in treating GERD is to administer higher doses more frequently. Another approach is to adjust the dosage upward until symptoms disappear. The improved acid-suppression characteristic of the proton-pump inhibitors was quickly applied to GERD therapy. Unlike the H2 antagonists, omeprazole completely suppresses circadian peaks in acid secretion, and omeprazole performs better than ranitidine in clinical trials. The use of omeprazole is limited, however, by concerns over secondary elevation of serum gastrin and the association between achlorhydria and gastric carcinoma in rats. Omeprazole may offer cost advantages over other agents. Because the effective dosages of all these agents vary, individualized dosage-adjustment strategies are necessary. Pharmacists can help to optimize treatment by monitoring pharmacodynamic markers. With a flexible approach to drug and dosage selection, it should be possible to manage GERD in most patients in a cost-effective manner.
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PMID:Pharmacokinetics and pharmacodynamics of acid-suppressive agents in patients with gastroesophageal reflux disease. 809 64

Omeprazole, a potent inhibitor of acid secretion, is effective in adults with severe gastroesophageal reflux, but no such data are available on children. We studied 15 children in whom treatment with histamine (type 2) blockers and prokinetic agents had failed; 4 had also had one or more fundoplications. Their ages were 0.8 to 17 years (mean, 8.1 years) and weights were 7.5 to 30.7 kg (mean, 18.6 kg). Of the 15 children, 8 were neurologically handicapped. All patients had endoscopic and histologic evidence of esophagitis; most had esophagitis grade 3 to 4. Patients were initially given omeprazole at 10 to 20 mg; the dose was titrated upward until results of a subsequent 24-hour intraesophageal pH study was normal. Symptoms and signs abated and evidence of esophagitis diminished in all patients. Omeprazole was given for periods of 5.5 to 26 months (mean, 12.2 months). The effective total dose was 20 to 40 mg (0.7 to 3.3 mg/kg) in 11 patients, 10 mg (0.7 mg/kg) in 1 patient, and 60 mg (1.9 to 2.4 mg/kg) in 3 patients. The dosage range was 0.7 to 3.3 to mg/kg per day (mean, 1.9 mg/kg). Mildly elevated transaminase values in 7 patients and elevated fasting gastrin levels in 11 patients were present; in 6 of the 11, gastrin levels were 3 to 5.5 times the upper limit of normal. We found omeprazole to be highly effective in this group of patients with severe esophagitis refractory to other measures. We recommend a starting dose of 0.7 mg/kg as a single morning dose; the adequacy of reflux control is then determined by follow-up 24-hour intraesophageal pH studies. Omeprazole appears to be safe for short-term use, but further studies are needed to assess long-term safety because the significance of chronically elevated gastrin levels in children is unknown.
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PMID:Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. 830 51

Omeprazole is a member of a new class of substituted benzimidazoles. These agents inhibit the proton pump in the gastric parietal cell, blocking the final step in the gastric acid secretory pathway. Omeprazole has been investigated for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux, and various hypersecretory states. The prolonged inhibition of gastric acid secretion allows for once-daily dosing in patients with peptic ulcer disease and gastroesophageal reflux, and once- or twice-daily dosing in patients with Zollinger-Ellison syndrome. Compared with currently available therapies, omeprazole is well tolerated and demonstrates a more rapid ulcer healing rate. It is superior to conventional therapies in the treatment of Zollinger-Ellison syndrome. Side effects are infrequent when the drug is used for the short-term management of ulcers.
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PMID:Omeprazole: a comprehensive review. 843 67

A new theory was tested that swallowing the wrong way is the cause of the strong correlation between bronchial symptoms and gastroesophageal reflux disease (GERD). One hundred and nineteen patients who were operated on for hiatal hernia and GERD were compared with 89 patients treated with the proton pump inhibitor omeprazole concerning bronchial symptoms before and after treatment. Both groups had a frequency of cough of 34% before treatment. Omeprazole did not give any significant relief of cough, whereas patients who were operated on with fundoplication and crural repair showed a highly significant reduction of cough and bronchitis. It is believed that the distal anchoring of the longitudinal esophageal muscle by surgery improves esophageal transit and restores the delicate coordination in the swallowing centre between deglutition, the opening of the upper esophageal sphincter, and the epiglottic closure of the laryngeal entrance. It is concluded that the main reason for chronic bronchitis in patients with GERD is intermittent aspiration due to partial mis-swallowing.
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PMID:Wrong-way swallowing as a possible cause of bronchitis in patients with gastroesophageal reflux disease. 851 46

We investigated whether duodenogastric reflux (DGR) together with gastroesophageal reflux causes growth stimulation of the foregut mucosa and if additional gastric acid suppression enhances the effect of DGR. DGR was induced in rats using a split gastroenterostomy. A cardiomyotomy was performed across the gastroeophageal junction in order to enhance reflux into the esophagus. DGR rats were divided into six subgroups: DGR, DGR + truncal vagotomy, DGR + omeprazole, DGR + gastrin receptor blockade, DGR + omeprazole + gastrin receptor blockade, and DGR + gastrin. Two sham groups, one with and one without omeprazole treatment, served as controls. DGR significantly increased the weight and DNA content of the esophageal and gastric mucosa, which was further enhanced by vagotomy or omeprazole. Histology revealed foveolar hyperplasia in the stomach and esophageal mucosal hyperplasia in these groups. In addition, severe esophagitis was found in the DGR group receiving omeprazole. Omeprazole without DGR had no growth-stimulating effect on the foregut mucosa. DGR-induced growth stimulation was accompanied by hypergastrinemia. Increased growth in the stomach but not the esophagus was inhibited by gastrin receptor blockade. Gastrin administration did not result in enhancement of DGR-induced growth stimulation of the foregut mucosa. It is concluded that DGR, often present in severe reflux esophagitis, causes mucosal growth of the foregut of rats. This trophic response may explain why severe reflux esophagitis is associated with an increased risk of esophageal adenocarcinoma. DGR-induced growth stimulation of the foregut is potentiated by gastric acid suppression, suggesting that chronic antisecretory medication in gastroesophageal reflux may not always be advisable. Omeprazole + DGR caused severe esophageal damage, which may explain why antisecretory medication may fail to heal severe reflux esophagitis.
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PMID:Duodenogastric reflux causes growth stimulation of foregut mucosa potentiated by gastric acid blockade. 894 68

Columnar epithelial metaplasia of the distal esophagus (i.e. barrett's esophagus) is an acquired condition showing a prevalence of 4%. It is probably due to abnormal reparative processes of the esophageal squamous epithelium after gastroesophageal reflux damage. "Mixed" (both acid and biliary) reflux seems more relevant for the pathogenesis of Barrett's esophagus than acid reflux alone, as shown by recent studies with Bilitec 2000. Its diagnosis is not easy for the "cardiac", "fundic" or "indeterminate" types of columnar metaplasia and needs a close cooperation between the endoscopist and the pathologist. On the contrary, it is less difficult for the "distinctive" type of metaplasia. Barrett's esophagus surveillance represents a major challenge in the perspective of its malignant degeneration (adenocarcinoma risk 350 times greater than in the general population). Therapy of Barrett's esophagus includes drugs and surgical treatment. Among the drugs proton pump inhibitors such as Omeprazole seem, at the moment, the most effective for reflux control, as well as the Nissen-Rossetti operation seems the most widely accepted among the anti-reflux surgical procedures. The novelty concerning Barrett's esophagus therapy is represented by laser photoablation associated with proton pump inhibiting therapy. But the experience with this treatment is still at a preliminary stage. For Barrett's esophagus with severe dysplasia and/or adenocarcinoma and/or squamous cell carcinoma esophagectomy is needed with a different extent and approach, according to the extent of Barrett's esophagus and to the stage and site of the neoplastic changes.
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PMID:[Barrett esophagus. Diagnosis and treatment]. 894

Gastro-oesophageal reflux disease (GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are move variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, buy may affect absorption of H2 receptor antagonists like cimetidine and ranitidine. Aluminium-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of GORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H2 receptor antagonists is still the most frequently use therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decrease likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H2 receptor antagonists are recommended. The most effective medical therapy for any severity of GORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), are prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H(+)-K+ ATPase molecules, allows once daily administration in most patients. Interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may e be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in GORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in terms of longer plasma t1/2 and less toxicity. Amongst H2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control througho
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PMID:Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease. 911 86


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