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Biomedical subjects

W Inauen

Publications and source records attributed to W Inauen.

At least 19 recordsLinked to original sources

Effects of ABT-229, a motilin agonist, on acid reflux, oesophageal motility and gastric emptying in patients with gastro-oesophageal reflux disease.

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.

Adult↗

Influence of pantoprazole on oesophageal motility, and bile and acid reflux in patients with oesophagitis.

BACKGROUND: Reflux of duodeno-gastric juice into the oesophagus appears to be involved in the pathogenesis of both reflux oesophagitis and oesophageal adenocarcinoma. Although proton pump inhibitors have been shown to decrease acid reflux and heal oesophagitis, their effect on biliary reflux and motility is less clear. AIM: To investigate whether pantoprazole also reduces bile reflux and whether this is paralleled by a change in oesophageal motility. METHODS: Combined 24-h measurements of intraoesophageal bilirubin concentration, pH and pressure were performed in 18 symptomatic patients with endoscopically proven reflux oesophagitis before and on day 28 of treatment with pantoprazole, 40 mg/day, under standardized conditions. A reflux symptom score was determined initially and every 2 weeks thereafter. After 56 days on medication, a control endoscopy was performed. RESULTS: The symptom score and the acid and bile reflux improved significantly, whereas the motility parameters did not change during the study period. Helicobacter pylori-positive patients had a significantly higher bile reflux time (32.1 +/- 4.3%) than H. pylori-negative patients (16.3 +/- 3.1%) (P=0.009). The endoscopic healing rate was 89%. The cough symptoms disappeared in three of four patients. CONCLUSIONS: The proton pump inhibitor pantoprazole decreases both acid and bile reflux. The decrease of bile reflux cannot be explained by increased oesophageal clearance as oesophageal motility did not improve with therapy. Interestingly, H. pylori infection of the stomach was associated with higher levels of oesophageal bile reflux.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Impact of food intake on the antisecretory effect of low-dose ranitidine and famotidine.

BACKGROUND: Over-the-counter status has recently been approved for low-dose H2-antagonists in several countries. Insufficient information is currently available on the effect of food in low-dose H2-antagonist therapy. AIM: Compare the antisecretory efficacy of low-dose ranitidine and famotidine in fasting and non-fasting volunteers. METHODS: Twenty volunteers were randomized into a double-blind, placebo-controlled, multiple-step crossover study comparing the antisecretory efficacy of 75 mg ranitidine, 10 mg famotidine and placebo over 12 h using intragastric pH-metry. Two standard meals were given after 4 h and 8 h of medication. Fifteen volunteers also participated in a second study comparing the antisecretory effect of both drugs, both with and without meals. RESULTS: In non-fasting subjects, the percentage of time with pH > 4 was similarly elevated for both drugs compared with placebo over the first 8 h: ranitidine 39.3%, famotidine 29.5%, placebo 9.5% (P < 0. 001); but not for the last 4 h after the second meal (P > 0.05). Comparing the first 4-h period with the second, the percentage of pH > 4 was significantly reduced for both drugs in the second period in the subjects given food at the end of the initial 4-h period (ranitidine 56.9% vs. 26.6%, P = 0.005; famotidine 46.6% vs. 13.3%, P < 0.001). It remained more or less constant, however, for the second 4-h period in fasting subjects (ranitidine 41% vs. 28.1%, P = 0.46; famotidine 52.7% vs. 52.2%, P = 0.12). CONCLUSION: In non-fasting volunteers both low-dose H2-antagonists had comparable antisecretory effects and were superior to placebo over the first 8 h of therapy. Both drugs achieved a slightly higher antisecretory effect without food intake compared to with food intake.

Adult↗

Five-year audit of ambulatory 24-hour esophageal pH-manometry in clinical practice.

BACKGROUND: Esophageal function testing was developed to aid diagnosis in patients with negative endoscopy. Although combined 24-h esophageal pH-manometry is now commercially available, its routine clinical effectiveness has not yet been studied. METHODS: From 1992 to 1996 we evaluated 303 consecutive patients who were first-time referrals to our unit for 24-h esophageal pH-manometry. The referral indications were gastroesophageal reflux disease, 47.2%; dysphagia, 18.5%; non-cardiac chest pain, 14.9%; connective tissue disease, 13.2%; and symptomatic patients after antireflux surgery, 6.3%. RESULTS: Overall, esophageal function testing altered the diagnosis of 44% of the patients, confirmed it in 38%, and specifically changed the management of 66%. The final clinical 'diagnosis' was reflux disease, 54% (32% with non-specific esophageal motility disorder); connective tissue disease, 9.9%; achalasia, 9.6%; other specific esophageal motility disorders, 3.3%; non-specific esophageal motility disorders, 6.9%; and normal, 16.2%. The cost per testing was estimated to be US$305 and per change in management US$465. CONCLUSION: Combined 24-h pH-manometry has been shown to be a useful and cost-effective test for the management of selected patients in whom the primary investigation was insufficient.

Adolescent↗

Effect of repeated injection and continuous infusion of omeprazole and ranitidine on intragastric pH over 72 hours.

OBJECTIVE: In healthy subjects and patients with bleeding peptic ulcers, ranitidine and omeprazole, given parenterally, achieve high intragastric pH values on the first day of therapy. However, data on the antisecretory effect beyond the first 24 h is scanty. In addition, the superiority of either infusion or injection of omeprazole remains unproven. Thus, we have compared the antisecretory effect of high dose omeprazole and ranitidine infusion and injection over the critical first 72 h. METHODS: A total of 34 healthy volunteers were randomized into a double-blind crossover 72 h intragastric pH-metry study (data compared: median pH, percentage of time with pH >4 and pH >6). Omeprazole-infusion: initial bolus of 80 mg + 8 mg/h; omeprazole-injection: initial bolus of 80 mg + 40 mg/6 h; Ranitidine-infusion: initial bolus of 50 mg + 0.25 mg/kg/h; ranitidine-injection: 100 mg/6 h. RESULTS: Omeprazole-infusion versus ranitidine-infusion: on day 1: median pH 6.1 vs 5.1 (p = 0.01) and 95% vs 70% was pH >4 (p < 0.01); on day 2: median pH 6.2 vs 3.2 (p < 0.01); and 100% vs 38% was pH >4 (p < 0.01); on day 3: median pH 6.3 vs 2.7 (p < 0.01); 100% vs 26% was pH >4 (p < 0.01). Injections of both drugs were significantly less effective than the infusions on day 1. Thereafter, omeprazole injection was almost as effective as omeprazole infusion, whereas ranitidine injection and infusion were equally effective. CONCLUSION: Our study shows, for the first time, that omeprazole infusion was significantly superior to all other regimens by having a high median pH >6 on each day. The tolerance effect of ranitidine, however, led to a rapid loss of antisecretory activity on days 2 and 3, rendering it inappropriate for situations in which high intragastric pH-levels appear to be essential.

Adult↗

Self-expanding metal stents in malignant esophageal obstruction: a comparison between two stent types.

OBJECTIVES: Self-expanding metal stents are a promising alternative in the palliation of malignant esophageal obstruction, but the relative value of different stent types is not well established. METHODS: During a 3-year enrollment period in four different centers, 82 consecutive patients with malignant dysphagia without tumor recurrence after surgery or esophagorespiratory fistulas received either an uncovered Wallstent (44 patients) or a knitted nitinol stent (38 patients). RESULTS: Age (median: 79 yr), sex (F:M = 33:67), dysphagia score (median: 3), Karnofsky score (median: 53), body mass index (median: 19), type of pretreatment, tumor stage, stricture length (median: 5.4 cm), and stricture location were comparable in both stent groups. After stent placement, median dysphagia score improved markedly in both groups by two points. Procedure-related mortality (16 vs 0%; p < 0.01), early complication rate (32 vs 8%; p < 0.01), and severe persistent pain after stent placement (23 vs 0%; p < 0.002) were higher in the Wallstent compared with the knitted nitinol stent group. In contrast, stent dysfunction (7 vs 32%; p < 0.005), reintervention rate (9 vs 34%; p < 0.005), and costs were lower in the Wallstent compared with the nitinol stent group. CONCLUSIONS: In malignant esophageal obstruction, both stents markedly improved dysphagia. Uncovered Wallstents seem to cause more early severe complications than knitted nitinol stents. In contrast, stent dysfunction, reintervention rate, and costs appear to be higher in the nitinol stent group.

Adult↗

Effect of Rennie Liquid versus Maalox Liquid on intragastric pH in a double-blind, randomized, placebo-controlled, triple cross-over study in healthy volunteers.

OBJECTIVES: Despite years of successful use of calcium-containing antacids in acid-related disease, allegations of gastric rebound following their intake has brought these agents into disrepute. By assessing intragastric acidity over the 24-h period, we evaluated whether antacids induce a clinically relevant acid rebound. METHODS: Twelve healthy volunteers were assigned to a double-blind, placebo-controlled, triple cross-over comparison of placebo, Maalox Liquid, and a calcium-containing antacid, Rennie Liquid. The two antacids had identical neutralizing capacity. Each drug was administered at standard doses q.i.d 1 h after the main meals (at 1000, 1400, and 1900 h) and at bedtime (2300 h). Intragastric acidity was monitored by continuous ambulatory 24-h pH-metry on 3 separate days with a wash-out period of 1 wk. Special attention was given to the acidity of pre-determined postantacid time intervals during the day and night. RESULTS: Both antacids led to a significant increase of the median 24-h pH and the median pH of the first postantacid hour, compared with placebo. Neither Rennie Liquid nor Maalox Liquid led to a drop of intragastric pH during the putative acid rebound time (2nd and 3rd postantacid hr and at night). A marginal increase in serum calcium and gastrin concentration with Rennie Liquid, and magnesium concentration with Maalox Liquid, were observed. CONCLUSIONS: No gastric acid rebound was detected with the calcium carbonate-containing antacid, Rennie Liquid, or with Maalox Liquid at standard doses. An identical increase of intragastric pH was achieved with Rennie Liquid and Maalox Liquid during the first postantacid hour and the entire 24-h period.

Adult↗

[Acute pancreatitis: conservative therapy)].

Conservative treatment of acute pancreatitis is symptomatic and depends on the severity of the disease. For treatment of mild pancreatitis, fasting and intravenous application of fluids and analgetics is usually sufficient. Patients with severe pancreatitis should be monitored in an Intensive Care Unit and may require antibiotics. For treatment of acute pancreatitis, a large number of interventions has been suggested. They include nasogastric tubes, drugs which reduce pancreatic and gastric secretion, and treatments which inhibit activated proteases. Controlled studies have shown that most of these measures are ineffective. The value of early ERCP in acute pancreatitis is still under debate. ERCP appears to be helpful in biliary pancreatitis, especially if choledocholithiasis is present. Surgery should be reserved to those patients who do not respond to conservative treatment.

Acute Disease↗

[Gluten-sensitive enteropathy with intestinal T-cell lymphoma: an unusual cause of in disabling osteomalacia].

We describe a 64-year-old woman with a malignant intestinal T-cell lymphoma who presented four years later with disabling osteomalacia and secondary hyperparathyroidism due to malabsorption. Only two years later, when the patient had developed fatty stools, flatulence and weight loss, diagnosis of gluten-sensitive enteropathy (GSE) was confirmed by small-intestine biopsy. This case report illustrates that in adults GSE can be oligosymptomatic for long periods. In cases of osteomalacia or rare intestinal T-cell lymphoma a detailed history of bowel movements, inspection of stools, quantification of fat excretion in stools and laboratory tests for malabsorption are recommended. Positive antibodies against gliadin, endomysium and reticulin may support the diagnosis of GSE. However, intestinal biopsy is necessary to verify the presence of GSE. In view of the unspecific histological changes, a follow-up biopsy is recommended in oligosymptomatic cases. Serial measurements of antibodies allow supervision of compliance for a diet strictly free of gluten. In addition, lactose containing milk products need to be restricted initially because of secondary lactase deficiency.

Celiac Disease↗

[Gastroduodenal ulcer disease: therapeutic possibilities].

With the modern antisecretory drugs, healing of gastroduodenal ulcers can be achieved in almost every patient. If helicobacter pylori (H. pylori) infection is treated successfully, relapse rates are reduced by up to 90%. Research on the ideal regimen for H. pylori eradication, i.e. short treatment with only few drugs, is still in progress. The combination of a proton pump inhibitor and a single antibiotic appears most promising. Proton pump inhibitors can successfully heal gastroduodenal ulcers associated with the intake of nonsteroidal anti-inflammatory drugs (NSAIDs), even if drug intake is continued. Ulcer prophylaxis in all patients taking NSAIDs is too expensive and should be restricted to patients with an increased risk for ulcer development.

Anti-Bacterial Agents↗

[Esophageal thoracic pain: what can be done?].

At present, an esophageal origin can be identified in as many as 50% of patients with non cardiac chest pain. In about 1/3 of these patients, gastroesophageal reflux can be documented. In the remaining 2/3 of patients, various disorders of esophageal motility have been described. Abnormal esophageal motility may be classified as nutcracker esophagus, diffuse esophageal spasm, achalasia, hypertensive lower esophageal sphincter, and nonspecific esophageal motility disorders. Simultaneous recording of intraesophageal pH, pressure, and symptoms (combined 24-h pH-metry and manometry) makes it possible to test the temporal association between pain, reflux, or abnormal motility. This review describes the diagnostic evaluation and therapeutic options in patients with non cardiac chest pain. Identification of the esophageal origin of chest pain should improve the therapeutic results.

Chest Pain↗

Comparison of acid inhibition by either oral high-dose ranitidine or omeprazole.

BACKGROUND: High-dose once daily oral omeprazole dosing can inhibit acid secretion almost completely but several days elapse before maximum efficacy is established. The acid inhibitory effect obtained with high doses of a histamine H2-receptor antagonist is built up rapidly but has the tendency to fade--the term 'tolerance' has been applied to characterize this phenomenon. METHODS: To obtain more information on the dynamics of acid inhibition during prolonged dosing, we compared the acid suppressory effects of oral high-dose omeprazole with high-dose ranitidine. Twenty-eight healthy volunteers were randomly assigned to a 2-week dosing with omeprazole or ranitidine in a double-blind, double-dummy, parallel-group study design. Omeprazole was given as 1 capsule of 40 mg mane and ranitidine as 2 tabs of 150 mg q.d.s. The median 24-h pH, daytime pH and night-time pH were measured by ambulatory continuous 24-h pH metry on days -8, -6, 1, 2, 7 and 14. RESULTS: High reproducibility was observed for the two baseline acidity measurements. Ranitidine exerted its peak acid suppressant effect on day 1 of dosing; the degree of acid inhibition faded from day 2 to 7, with no significant change thereafter. The decline in antisecretory activity was more pronounced during the day than the night. In contrast, acid inhibition by omeprazole increased throughout the first week, and antisecretory activity was stable thereafter. Despite the considerable differences in median intragastric pH values at the end of the 14-day study, plasma gastrin levels were elevated to a similar degree with both medications. CONCLUSIONS: This study confirms the 'tolerance' phenomenon previously observed with high-dose histamine H2-receptor antagonist dosing. The dynamics with which it occurs exclude a typical exaggerated first-dose response. Prolonged high-dose histamine H2-receptor dosing compromises the feedback mechanism regulating gastrin release, whilst this is maintained during dosing with omeprazole.

Administration, Oral↗

Effects of ranitidine and cisapride on acid reflux and oesophageal motility in patients with reflux oesophagitis: a 24 hour ambulatory combined pH and manometry study.

The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH < 4.0, p < 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p < 0.01), upright reflux (p < 0.05), supine reflux (p < 0.001), and postprandial reflux (p < 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p < 0.01), supine reflux (p < 0.05), and postprandial reflux (p < 0.05). Cisapride also reduced both the number (p<0.01) and duration (p<0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.

Adult↗

[Motility disorders and assessment methods of the esophagus].

Esophageal diseases frequently cause symptoms such as heartburn, epigastric pain and dysphagia. This article discusses the indications, techniques and limitations of currently available diagnostic procedures. Investigation of symptoms should proceed in a logical stepwise manner, beginning with endoscopy to exclude esophagitis or neoplasia. Symptoms due to acid reflux can be identified by 24h esophageal pH-metry to document a temporal association between symptoms and episodes of esophageal acidification. Stationary or ambulatory manometric recording of esophageal pressures can be used to diagnose esophageal motor disorders such as achalasia, nutcracker esophagus, diffuse esophageal spasm, or dysfunction of the upper or lower esophageal sphincter. Combined 24 h pH-manometry should be used to test the temporal association between pain, reflux, or abnormal motility in patients with non-cardiac chest pain. Video-fluoroscopy is the most appropriate technique to diagnose swallowing disorders. Pulmonary aspiration of gastro-esophageal reflux can be documented with scintigraphy.

Deglutition Disorders↗