Biomedical subjects

P N Maton

Publications and source records attributed to P N Maton.

At least 19 recordsLinked to original sources

PubMed2001

Safety and efficacy of long term esomeprazole therapy in patients with healed erosive oesophagitis.

OBJECTIVE: To evaluate the safety and tolerability of long term treatment with esomeprazole in patients with healed erosive oesophagitis, and to describe its efficacy in the maintenance of healing. DESIGN AND SETTING: US multicentre, noncomparative, nonblind study. PATIENTS AND PARTICIPANTS: 807 patients with endoscopically confirmed healed erosive oesophagitis. METHODS: Patients received esomeprazole 40 mg once daily for up to 12 months. Adverse events and clinical laboratory tests were assessed over the study period. Endoscopy was performed at the final visit of the antecedent healing trials and at months 6 and 12 of the current safety trial; gastric biopsies were obtained at the initial visit of the healing trials and at the end of the safety trial. RESULTS: 80.9% of patients completed 6 months of treatment; 76.6% completed 12 months of treatment. There were no serious drug-related adverse events. Diarrhoea, abdominal pain, flatulence, and headache were the only treatment-related adverse events reported by >3% of patients. Mean changes in laboratory measures were generally small and not clinically meaningful. Plasma gastrin levels increased, as expected, and reached a plateau after 3 months. No changes in gastric histological scores were noted in the majority of patients. Evaluation of gastric biopsies revealed an overall decline in chronic inflammation and atrophy. Intestinal metaplasia findings remained essentially unchanged. Life table estimates of maintenance of healing were 93.7% [95% confidence interval (CI) 92.0 to 95.5%] at 6 months and 89.4% (95% CI 87.0 to 91.7%) at 12 months. CONCLUSIONS: Daily treatment with esomeprazole 40 mg for up to 1 year in patients with healed erosive oesophagitis was generally well tolerated and effective. No safety concerns arose.

Adolescent↗

PubMed2000

Oral and intravenous dosage forms of pantoprazole are equivalent in their ability to suppress gastric acid secretion in patients with gastroesophageal reflux disease.

OBJECTIVE: The aim of this study was to assess the ability of pantoprazole to maintain gastric acid suppression in patients with gastroesophageal reflux disease who are switched from an oral (p.o.) to an intravenous (i.v.) dosage form. METHODS: A total of 65 patients with gastroesophageal reflux disease were administered either 40 or 20 mg of p.o. pantoprazole daily for 10 days, then were switched to either a matching dose of i.v. pantoprazole or to placebo for 7 days. Acid output (basal and maximal) was measured at the end of the p.o. treatment period and on the first and last days of i.v. therapy. In the primary efficacy analysis, the acid output values at the end of the p.o. pantoprazole treatment were compared with those at the end of the i.v. treatment. Safety was monitored by periodic vital sign measurements, clinical laboratory evaluations, ophthalmic examinations, electrocardiograms, and reports of adverse events. The data were tested by an analysis of covariance and by Wilcoxon signed rank and t tests. RESULTS: Maximal acid output (mean +/- SD) in the 40 mg and 20 mg pantoprazole group after p.o. treatment was 6.5 +/- 5.6 mEq/h and 14.5 +/- 15.5 mEq/h, respectively; whereas, at the end of the i.v. treatment period, the values were 6.6 +/- 6.3 mEq/h and 11.1 +/- 10.2 mEq/h, respectively. In patients given i.v. placebo, acid output was significantly (p < 0.05) increased to 29.2 +/- 13.0 mEq/h by day 7. Both p.o. and i.v. pantoprazole dosage forms had similar favorable safety and tolerability profiles. CONCLUSIONS: The p.o. and i.v. formulations of pantoprazole (40 and 20 mg) are equivalent in their ability to suppress gastric acid output. The i.v. form of pantoprazole offers an alternative for gastroesophageal reflux disease patients who are unable to take the p.o. formulation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2000

Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison syndrome: its protective potential.

OBJECTIVE: Evidence is accumulating that epidermal growth factor (EGF) is a major molecule contributing to the maintenance of the integrity of the upper alimentary tract mucosa before and after injury by acid and pepsin. Patients with Zollinger-Ellison Syndrome (ZES) typically have hypersecretion of acid and pepsin; however, the concentration and rate of secretion of salivary and gastric EGF that could counteract these potentially aggressive factors are unknown. Accordingly, this study was conducted to determine whether EGF affords mucosal protection in ZES patients. METHODS: The concentration and output of salivary (sEGF) and gastric epidermal growth factor (gEGF) were measured in eight patients with ZES and the results compared to those in 17 patients with nonulcer dyspepsia (NUD), serving as a control group. All patients had normal esophageal and gastric mucosa as determined by endoscopy. Total saliva was collected during 1-h parafilm- and 1-h pentagastrin/parafilm-stimulated conditions, as well as basal and pentagastrin-stimulated gastric juice. The concentration and output of EGF were determined by radioimmunoassay. RESULTS: The concentration of EGF in saliva collected from ZES patients after parafilm chewing was significantly higher compared to that in NUD patients (4.61 +/- 0.59 vs 2.75 +/- 0.50 ng/ml, p < 0.05). The concentration of EGF in saliva collected after pentagastrin stimulation in ZES patients was also significantly higher than in NUD patients (4.37 +/- 0.73 vs 2.22 +/- 0.37 ng/ml, p < 0.05). Salivary EGF output during parafilm chewing in ZES and NUD were similar (68 +/- 6.4 vs 109 +/- 25.2 ng/h). Salivary EGF output after administration of pentagastrin in ZES and NUD was also similar (66 +/- 6.1 vs 132 +/- 45.4 ng/h). Basal EGF output in the gastric juice of patients with ZES was 3-fold higher than in patients with NUD (801 +/- 73 vs 271 +/- 32 ng/h, p < 0.01). Pentagastrin-stimulated EGF output was similar in both groups (705 +/- 92 vs 675 +/- 168 ng/h). CONCLUSIONS: Patients with ZES have a significantly higher EGF concentration in saliva and EGF output in basal gastric juice. This elevated content of salivary and gastric EGF in ZES patients may play a protective role in preventing the development of reflux esophagitis and gastric ulcer under the impact of gastric acid and pepsin hypersecretion.

Adult↗

PubMed1999

Efficacy of omeprazole versus ranitidine for symptomatic treatment of poorly responsive acid reflux disease-a prospective, controlled trial.

BACKGROUND: H2-receptor antagonists are widely used in patients with gastro-oesophageal reflux disease (GERD) and are frequently continued when symptoms persist. AIM: To compare the efficacy of omeprazole 20 mg once daily with that of ranitidine 150 mg twice daily in relieving GERD symptoms, in patients who remained symptomatic following a 6-week course of ranitidine therapy. METHODS: Patients with heartburn on at least 4 days/week but who did not have endoscopy to assess oesophageal mucosa could participate. This two-phase, prospective trial included a 6-week open-label phase (phase I), followed by an 8-week double-blind phase (phase II). Patients still symptomatic following treatment with ranitidine 150 mg twice daily (phase I) were randomized to double-blind treatment (phase II) with either omeprazole 20 mg once daily or ranitidine 150 mg twice daily. The primary efficacy variable was the proportion of patients with heartburn resolution during weeks 4 and 8 of phase II. RESULTS: Of the 533 patients with GERD who received ranitidine in phase I, 348 patients (65%) were still symptomatic. A total of 317 patients (59%) were randomized to double-blind treatment (phase II). At week 8, a significantly (P < 0.0004) greater proportion of omeprazole-treated patients (70%) experienced no more than mild heartburn compared with ranitidine-treated patients (49%). Complete resolution of heartburn also occurred in a significantly (P < 0. 00001) greater proportion of omeprazole-treated patients (46% vs. 16% of the ranitidine group at week 8). CONCLUSIONS: After 6 weeks of ranitidine treatment, the majority of patients with GERD were still experiencing moderate to severe heartburn. Omeprazole was significantly more effective than ranitidine in resolving heartburn in this group of patients.

Adult↗

PubMed1999

Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use.

Antacids are commonly used self-prescribed medications. They consist of calcium carbonate and magnesium and aluminum salts in various compounds or combinations. The effect of antacids on the stomach is due to partial neutralisation of gastric hydrochloric acid and inhibition of the proteolytic enzyme, pepsin. Each cation salt has its own pharmacological characteristics that are important for determination of which product can be used for certain indications. Antacids have been used for duodenal and gastric ulcers, stress gastritis, gastro-oesophageal reflux disease, pancreatic insufficiency, non-ulcer dyspepsia, bile acid mediated diarrhoea, biliary reflux, constipation, osteoporosis, urinary alkalinisation and chronic renal failure as a dietary phosphate binder. The development of histamine H2-receptor antagonists and proton pump inhibitors has significantly reduced usage for duodenal and gastric ulcers and gastro-oesophageal reflux disease. However, antacids can still be useful for stress gastritis and non-ulcer dyspepsia. The recent release of proprietary H2 antagonists has likely further reduced antacid use for non-ulcer dyspepsia. Other indications are still valid but represent minor uses. Antacid drug interactions are well noted, but can be avoided by rescheduling medication administration times. This can be inconvenient and discourage compliance with other medications. All antacids can produce drug interactions by changing gastric pH, thus altering drug dissolution of dosage forms, reduction of gastric acid hydrolysis of drugs, or alter drug elimination by changing urinary pH. Most antacids, except sodium bicarbonate, may decrease drug absorption by adsorption or chelation of other drugs. Most adverse effects from antacids are minor with periodic use of small amounts. However, when large doses are taken for long periods of time, significant adverse effects may occur especially patients with underlying diseases such as chronic renal failure. These adverse effects can be reduced by monitoring of electrolyte status and avoiding aluminum-containing antacids to bind dietary phosphate in chronic renal failure. Antacids, although effective for discussed indications of duodenal and gastric ulcer and gastro-oesophageal reflux disease, have been replaced by newer, more effective agents that are more palatable to patients. Antacids are likely to continue to be used for non-ulcer dyspepsia, minor episodes of heartburn (gastro-oesophageal reflux disease) and other clear indications. Although their wide-spread use may decline, these drugs will still be used, and clinicians should be aware of their potential drug interactions and adverse effects.

Antacids↗

PubMed1998

The impact of gastroesophageal reflux disease on health-related quality of life.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects health-related quality of life. METHODS: We enrolled 533 adults with a history of heartburn symptoms for at least 6 months of moderate to severe heartburn in 4 of the 7 days before study entry. Patients were treated with ranitidine 150 mg twice a day for 6 weeks and Gelusil antacid tablets as needed. We measured physician-rated symptoms and the Medical Outcomes Study short-form 36 (SF-36) Health Survey at baseline and after 6 weeks of treatment. Baseline results were compared with normative data for the US population and for patients with selected chronic diseases. Treatment response was defined as no episode of moderate to severe heartburn for 7 days. Statistical significance was set at P <0.001. RESULTS: GERD patients reported significantly worse scores on all 8 SF-36 scales, physical function and well-being, and emotional well-being compared with the general population. Patients with GERD reported worse emotional well-being than patients with diabetes or hypertension. Treatment responders demonstrated significantly less pain and better physical function, social function, vitality, and emotional well-being compared with nonresponders. CONCLUSIONS: Patients with GERD experience decrements in health-related quality of life compared with the general population. The impact of GERD is most striking on measures of pain, mental health, and social function. Successful treatment for GERD results in improvements in health-related quality of life.

Adult↗

PubMed1998

Meal type affects heartburn severity.

This study compared heartburn severity, number of episodes, and changes in esophageal pH induced by three meals. Symptomatic volunteers consumed the following on different occasions: McDonald's Quarter Pounder, french fries, and chocolate shake; McDonald's Sausage Biscuit with Egg, cheese, raw onion, and chocolate milk; and Wendy's Chili and red wine. Increases in reflux episodes over baseline for the hamburger, sausage biscuit, and chili meals were 28.8 +/- 5.7, 36 +/- 5.5 and 43.7 +/- 8.8, respectively. The sausage biscuit and chili increased reflux compared to the hamburger (P < 0.05), but the chili did not differ statistically from the sausage biscuit meal. Onset and peak heartburn for the hamburger, sausage biscuit, and chili meals were 45 and 90, 30 and 120, and 15 and 150 min, respectively. Despite lower fat content, chili and red wine promoted more reflux and heartburn pain than the other meals, demonstrating the importance of meal selection in provocative meal studies.

Cross-Over Studies↗

PubMed1997

Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease.

BACKGROUND: This study examined the dose-response effects of the new proton-pump inhibitor rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease. METHODS: This study had a single-centre, double-blind, randomized, two-way crossover design. Twenty patients were treated for two 7-day periods separated by a 7-10-day washout period. Patients were randomly assigned to receive either 20 mg of rabeprazole once daily during the first treatment period and 40 mg once daily during the second treatment period, or 40 mg during the first treatment period and 20 mg during the second treatment period. The primary efficacy variable was oesophageal acid exposure determined by 24-hour ambulatory pH monitoring. Acid-reflux time was defined as the percentage of time over 24 h that oesophageal pH was < 4. A dosage was considered effective if reflux time was reduced to < 6%, a number which has been our internal laboratory reference. RESULTS: Both rabeprazole 20 mg and 40 mg, given once daily, normalized reflux time, with decreases of 79% and 92% in acid exposure by day 7. Both dosages also decreased the mean total number of reflux episodes and the number of episodes lasting > 5 min, with no significant differences between dosages for any reflux parameter. Mean gastric pH increased with 20 mg from 1.86 at baseline to 3.71 on day 1 and 4.17 on day 7. Rabeprazole 40 mg once daily increased gastric pH from 2.01 to 4.37 on day 1, and to 4.65 on day 7. Safety analyses revealed no significant acute side-effects for either dosage. CONCLUSIONS: Pathological oesophageal acid exposure was normalized with both 20 mg and 40 mg dosages of rabeprazole, and the effects of these two doses did not differ. Rabeprazole was well-tolerated in this short-term study.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Zollinger-Ellison syndrome. Recognition and management of acid hypersecretion.

Zollinger-Ellison syndrome (ZES) should be suspected if a patient has severe peptic ulceration, ulcers and kidney stones, a family history of ulcers or endocrine diseases, watery diarrhoea or malabsorption with or without ulcers, or if hypergastrinaemia is found. Any patient in whom ZES is suspected, and certainly if diagnosed, should be given large doses of antisecretory medication immediately. This should never be stopped except under controlled conditions or unless acid outputs have been reduced surgically. Patients cannot be managed safely without measuring acid outputs. These should be lowered to < 10 mmol/h, or < 5 mmol/h in patients with a previous gastric resection or severe oesophageal disease. Acid secretion can be controlled acutely in 70% of patients with an infusion of ranitidine 1 mg/kg/h, while 4 mg/kg/h will control acid in all. The initial oral dosage of omeprazole or lansoprazole should be 60 mg/day. Doses should then be adjusted daily on the basis of acid outputs. Proton pump inhibitors in a dosage of 60 mg/day will control acid output in most patients and 60 mg every 12 hours will control acid output in all. Doses can then often be slowly and progressively reduced. A parietal cell vagotomy reduces acid secretion and reduces, but does not abolish, the need for antisecretory medication. In patients with multiple endocrine neoplasia type 1 and hyperparathyroidism, a parathyroidectomy that results in normocalcaemia will reduce acid secretion and drug requirements. A total gastrectomy is rarely if ever needed nowadays. Given the high degree of safety of gastric antisecretory medications versus the risks of acid hypersecretion in patients with ZES, the mistakes in management of acid hypersecretion that must be avoided are those of giving insufficient medication and not measuring acid secretory rates.

Animals↗

PubMed1996

Irritable bowel syndrome: a study to investigate the mechanism(s) of visceral hypersensitivity.

Irritable bowel syndrome (IBS), is characterized by gastrointestinal hyperalgesia. In this study we investigated mucosal application of dyclonine on urge to defecate and pain threshold in volunteers and IBS patients (n = 10). Either saline or dyclonine (40 ml enema) was administered 10 minutes prior to rectosigmoid distension or cutaneous cold water pressor test. In IBS patients and volunteers no differences in cutaneous pain thresholds were noted. However, IBS patients had a lower pain threshold in the rectosigmoid than volunteers. In volunteers there was a significant difference between the threshold for urge to defecate and the threshold for rectosigmoid pain that was not apparent in IBS patients. Dyclonine administered directly into the rectosigmoid did not alter urge to defecate or pain threshold induced by distension in volunteers or IBS patients. These data suggest that the origin of pain perception is localized in deeper structures within the wall of the rectosigmoid colon.

Adult↗

PubMed1995

Pathophysiological effects of long-term acid suppression in man.

A critical evaluation has been made of the available evidence in man of the effects of prolonged low acid states on the structure and function of the stomach. Various human models have been examined. 1. Ageing does not affect acid output from the normal male stomach, and there may be an increase in women. With progressive atrophy of the corpus mucosa, which is more frequent and rapid in patients with gastric ulcer, there is an associated loss of secretory function. Chronic gastritis and atrophy are the most important age-related changes, which in many cultures are hypothesized to develop via a prior Helicobacter pylori-related gastritis. However, H. pylori colonization of the mucosa decreases with increasing grades of gastric atrophy probably because intestinal metaplasia provides a hostile environment. Atrophy and intestinal metaplasia are associated with precancerous lesions and gastric cancer. Apparent hyperplasia of the gastric argyrophil endocrine cells is a common and spontaneous phenomenon in patients with atrophic gastritis, which in part may be related to the preferential loss of nonendocrine cells. 2. Pernicious anemia is associated with a complete lack of acid production, marked hypergastrinemia, and endocrine cell hyperplasia in the majority of patients. ECL-cell carcinoids and gastric cancer occur with a prevalence of 3-7%, and endoscopic surveillance in routine clinical practice is not warranted. 3. Gastric ECL-cell carcinoids are rare events that have been described in association with two diseases in man, pernicious anemia and Zollinger-Ellison syndrome as part of multiple endocrine neoplasia syndrome type I, and usually relate to marked hypergastrinemia and the presence of chronic atrophic gastritis with gastric antibodies or a genetic defect rather than the presence or absence of acid. Regression or disappearance of ECL-cell carcinoids, either spontaneously or after removal of the gastrin drive, has been recorded. Lymph node, and rarely hepatic, metastases are documented but death in these cases has been anecdotal. 4. Therapy with H2 antagonists may result in up to a twofold rise in serum gastrin levels but in man no endocrine cell hyperplasia has been recorded. However, the data for H2 antagonists on these aspects are very limited. There is no drug-related risk of gastric or esophageal cancer, although the incidence of the latter may be raised. Long-term treatment with omeprazole is associated with a two- to fourfold increase in gastrin levels over baseline values in one third of patients and apparent endocrine cell hyperplasia in 7% of cases overall.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1995

Somatostatin receptor subtype 3 mediates the inhibitory action of somatostatin on gastric smooth muscle cells.

Previous functional studies show that somatostatin (SS) interacts with specific receptors to inhibit relaxation in gastric smooth muscle cells. There are no ligand binding studies, and it is unknown which of the five subtypes of SS receptors mediates the action. Dispersed gastric smooth muscle cells from guinea pig bound both 125I-labeled SS-14 and 125I-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (where Nal indicates N-naphthylalanine) (cyclo-SS-8), a synthetic peptidase-resistant octapeptide SS analogue. SS-28 and SS-14, cyclo-SS-8, and SS analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol [SMS-(201-995) (octreotide)] inhibited 125I-cyclo-SS-8 binding with relative potencies of SS-28 = cyclo-SS-8 = SMS-(201-995) (octreotide), and the binding was not affected by the addition of protease inhibitors. SS-14 caused inhibition only in the presence of protease inhibitors. Ligand analysis demonstrated a two-binding-site model. Analysis of the relationship between biological function and binding suggested the high-affinity sites mediated the relaxant action of SS. 5'-Guanylylimidodiphosphate [Gpp-(NH)p] inhibited binding by reducing the affinity of the high-affinity site. Six SS-8 analogues that distinguish SS subtypes showed that 125I-SS-14 bound to somatostatin receptor subtype 3 (SSTR3). The results demonstrated that gastric smooth muscle cells possess distinct receptors for SS of the SSTR3 subtype. Occupation of these sites inhibits relaxation in gastric smooth muscle cells. Modulation between the high- and low- affinity binding states of SSTR3 is at least partially mediated by activation of guanine nucleotide regulatory proteins.

Animals↗

PubMed1994

Expanding uses of octreotide.

This chapter reviews the therapeutic use of octreotide in a variety of pancreatic disorders, including acute pancreatitis, in the prevention of postoperative and post-ERCP pancreatitis, in the control of postoperative pancreatic fistulae, and in chronic pancreatitis for the control of pain and of pseudocysts and ascites. The review also discusses the use of octreotide in intestinal disorders of motility, gastrointestinal bleeding, intestinal fistulae and refractory diarrhoea, including the diarrhoeas of AIDS, diabetes, short gut, chemotherapy, ileostomy and gastric surgery. The use of octreotide in neuroendocrine tumours, both for therapy and diagnostic imaging, is reviewed briefly. The paucity of adequately controlled studies in many of these situations is indicated and the potential usefulness of octreotide estimated.

Humans↗

PubMed1994

Management of Zollinger-Ellison syndrome.

Once the diagnosis of Zollinger-Ellison syndrome has been considered, it is important to ensure the safety of the patient by administering adequate antisecretory medication. There then ceases to be any urgency about the diagnostic work-up. It is essential to establish definitively that the patient has fasting hypergastrinemia and acid hypersecretion to establish the diagnosis of Zollinger-Ellison syndrome. The type of disease (i.e., sporadic or occurring as part of multiple endocrine neoplasia type I) should then be determined by assessment of endocrine function and anatomy because this will influence both the approach to control of acid secretion and the management of the tumor. Assessment of tumor extent and decisions about the management of the tumor can be delayed because these tumors are slow-growing. Because of the rarity of this syndrome, surgical aspects of the management of the disease are best undertaken in centers with particular expertise in this area.

Gastric Acid↗

PubMed1993

Prospective study of efficacy and safety of lansoprazole in Zollinger-Ellison syndrome.

Lansoprazole, a new substituted benzimidazole H+,K(+)-ATPase inhibitor, profoundly inhibits gastric acid secretion and has potential use in the management of diseases such as Zollinger-Ellison syndrome (ZES). In the present study we evaluated the efficacy and safety of lansoprazole in controlling acid hypersecretion in 20 patients with ZES. The starting dose was 60 mg once daily. Control of acid hypersecretion was defined as the dose required to reduce acid secretion to < 10 meq/hr in the last hour before the next dose. Doses were adjusted upwards until effective control was achieved. Patients not controlled with 120 mg once daily were placed on twice daily lansoprazole. Most patients (90%) required lansoprazole once daily. During long-term follow-up (mean 18.5 months), 25% of patients required upward dose adjustments and 25% of patients required twice daily lansoprazole. Following cessation of therapy, the mean time for gastric acid output to reach half basal acid output was 39.1 hr. Lansoprazole was well-tolerated without side effects. Clinical chemistry and hematological studies were unchanged, and no gastric carcinoids developed. These results demonstrate that lansoprazole is a safe and effective inhibitor of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Because it has a long duration of action, lansoprazole can be used to control gastric acid hypersecretion in most patients with Zollinger-Ellison syndrome using a once daily dosing schedule.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1993

Omeprazole is superior to ranitidine plus metoclopramide in the short-term treatment of erosive oesophagitis.

Histamine H2-receptor antagonists are moderately effective in symptomatic treatment and healing of erosive oesophagitis, but they are not as effective as the proton pump inhibitor omeprazole. In some studies prokinetic agents seem to increase the effectiveness of H2-antagonists, but no study comparing the efficacy of omeprazole to H2-antagonists plus prokinetic agents has been performed. The purpose of this study was to compare the efficacy and tolerability of 20 mg omeprazole daily with 150 mg ranitidine b.d.s. plus the prokinetic agent 10 mg metoclopramide q.d.s. in patients with erosive oesophagitis. After both 4 and 8 weeks of treatment, omeprazole healed the mucosa in significantly more patients than did ranitidine plus metoclopramide. Omeprazole also provided significantly greater relief from daytime heartburn, nighttime heartburn, and acid regurgitation, and was associated with decreased concomitant antacid use. Although the overall incidence of adverse events was similar in the two treatment groups, a significantly higher number of treatment-related adverse events and more treatment-related withdrawals from the study occurred in the ranitidine plus metoclopramide treatment group. Omeprazole is more effective and better tolerated than the combination of standard dose ranitidine plus metoclopramide for patients with erosive oesophagitis.

Adult↗

PubMed1993

Review article: the management of Zollinger-Ellison syndrome.

Awareness of the sometimes subtle features of Zollinger-Ellison syndrome is important in order not to miss the diagnosis. Immediately after initial diagnostic tests, the patient should be given antisecretory medication, while tests for the type of Zollinger-Ellison syndrome and tumour extent can be delayed. Acid output should be decreased to < 10 mmol/h to control symptoms and prevent complications. Histamine H2-antagonists remain the best available intravenous therapy but omeprazole is the most effective long-term oral therapy and has proved to be safe in nearly 10 years of continuous use. The management of the gastrinoma has changed in recent years since the discovery that the majority of gastrinomas arise outside the pancreas. Exploratory surgery with tumour resection is the treatment of choice in sporadic Zollinger-Ellison syndrome but there are few indications for surgery in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type-1. None of the available therapies for metastatic gastrinoma is very effective.

Diagnosis, Differential↗

PubMed1993

Neutral endopeptidase (EC 3.4.24.11) modulates the contractile effects of neuropeptides on muscle cells from the guinea-pig stomach.

The objectives of this investigation were to characterize neuropeptide-degrading enzymes on the surface of gastric muscle cells and to determine their physiological function. Neutral endopeptidase (NEP, EC 3.4.24.11) activity was measured using the fluorogenic substrate glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine. The NEP inhibitors phosphoramidon and DL-thiorphan (1 microM) inhibited degradation of the substrate by gastric muscle membranes by 100% and by freshly dispersed gastric muscle cells by 55-60%. The phosphoramidon or DL-thiorphan-inhibitable activity, attributed to NEP, of membranes was 112 +/- 4.0 pmol h-1 (micrograms protein)-1 and of cells was 4.2 +/- 0.8 nmol h-1 (10(6) cells)-1. This activity was associated with membranes prepared from cells and was not detected in the cytoplasm or in the cell incubation solution. Gastric muscle membranes were fractionated by electrophoresis and analysed by Western blotting using two NEP antisera. Both antisera recognized a protein in membranes with an electrophoretic mobility identical to that of recombinant human NEP and an apparent molecular mass of approximately 95 kDa. Neuropeptides were degraded by membranes with specific activities in the order of [Leu5]enkephalin > [Met5]enkephalin > gastrin-releasing peptide-10 (GRP-10) > [D-Ala2][Leu5]enkephalin > somatostatin-14. Phosphoramidon and DL-thiorphan similarly inhibited the degradation of GRP-10 (mean of 35% inhibition), somatostatin-14 (57%) and the aminopeptidase-resistant analogue, [D-Ala2][Leu5]enkephalin (75%). When aminopeptidases were inhibited with amastatin (10 microM) phosphoramidon inhibited degradation of [Leu5]enkephalin (54%) and [Met5]enkephalin (100%). Phosphoramidon increased the potency of the contractile effects of neuropeptides on muscle cells by > 280-fold for somatostatin-14, 17-fold for GRP-10, 18-fold for [Met5]enkephalin and 14-fold for [Leu5]enkephalin. The results show that an NEP-like enzyme on the surface of gastric muscle cells degrades and inactivates enkephalins, GRP-10 and somatostatin-14 and acts in a manner analogous to that of acetylcholinesterase in the neuromuscular junction of skeletal muscle.

2-Naphthylamine↗