Using immunohistochemistry at the conventional light, confocal and electron microscopic levels, we have demonstrated that rat stomach ECL cells store histamine and pancreastatin in granules and secretory vesicles, while histidine decarboxylase occurs in the cytosol. Furthermore the ECL cells display immunoreactivity for vesicular monoamine transporter type 2 (VMAT-2), synaptophysin, synaptotagmin III, vesicle-associated membrane protein-2, cysteine string protein, synaptosomal-associated protein of 25 kDa, syntaxin and Munc-18. Using electron microscopy in combination with stereological methods, we have evidence to suggest the existence of both an exocytotic and a crinophagic pathway in the ECL cells. The process of exocytosis in the ECL cells seems to involve a class of proteins that promote or participate in the fusion between the granule/vesicle membrane and the plasma membrane. The granules take up histamine by VMAT-2 from the cytosol during transport from the Golgi zone to the more peripheral parts of the cells. As a result, they turn into secretory vesicles. As a consequence of stimulation (e.g., by gastrin), the secretory vesicles fuse with the cell membrane to release their contents by exocytosis. The crinophagic pathway was studied in hypergastrinemic rats. In the ECL cells of such animals, the secretory vesicles were found to fuse not only with the cell membrane but also with each other to form vacuoles. Subsequent lysosomal degradation of the vacuoles and their contents resulted in the development of lipofuscin bodies. (+info)
The role of endogenous gastrin in the development of enterochromaffin-like cell carcinoid tumors in Mastomys natalensis: a study with the specific gastrin receptor antagonist AG-041R.
(50/1291)
We examined the effects of a newly synthesized gastrin receptor antagonist, AG-041R, on the growth of enterochromaffin-like (ECL) carcinoid tumors in Mastomys natalensis both in vitro and in vivo. AG-041R was as potent as the well known gastrin antagonist L365,260 in inhibiting not only the gastrin-induced release of histamine from but also histidine decarboxylase (HDC) gene expression in the ECL carcinoid tumor cells. AG-041R also inhibited gastrin-induced DNA synthesis and c-fos gene expression in the tumor cells. Furthermore, AG-041R significantly inhibited the growth of the transplanted Mastomys ECL carcinoid tumors in vivo. From these data, it is concluded that endogenous gastrin is involved in the growth of ECL carcinoid tumors in Mastomys natalensis. Moreover, AG-041R is shown to have a potential as an anti-neoplastic agent for ECL carcinoid tumor of the stomach. (+info)
Diagnosis and treatment of ECL cell tumors.
(51/1291)
The diagnosis of ECL-omas is easy to perform. In patients with Zollinger-Ellison syndrome (ZES), ECL-omas are almost always observed in the setting of multiple endocrine neoplasia type I. In patients without ZES, the first step is to discard non-gastrin-related sporadic ECL-omas whose prognosis is poor. By contrast, prognosis of ECL-omas in patients with ZES or chronic atrophic gastritis is good. Metastases are rare, and tumor-related deaths are exceptional. In both conditions, ECL-omas measuring less than 1 cm should be treated by endoscopic polypectomy and survey. Treatment modalities (surgery, endoscopic polypectomy) for larger tumors are still discussed. The impact of endoscopic ultrasonography on the therapeutic decision has not yet been evaluated. Considering the good prognosis of these tumors, aggressive surgery could be limited to selected patients. Multicentric studies should be undertaken to determine the best treatment modalities. (+info)
Heartburn treatment in primary care: randomised, double blind study for 8 weeks.
(52/1291)
OBJECTIVE: To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients. DESIGN: Randomised, double blind, placebo controlled study. SETTING: 65 primary care practices in Norway. PARTICIPANTS: 483 untreated patients with complaints of heartburn >/=3 days a week, with at most grade 1 reflux oesophagitis. INTERVENTIONS: Omeprazole 20 mg once daily, cisapride 20 mg twice daily, or placebo for 8 weeks. MAIN OUTCOME MEASURES: Adequate control of heartburn, defined as +info)
The effect of omeprazole on gastro-oesophageal reflux and symptoms during strenuous exercise.
(53/1291)
BACKGROUND: Strenuous exercise exacerbates gastro-oesophageal reflux and symptoms and this may be diminished by antisecretory medication with omeprazole. METHODS: Fourteen well-trained athletes (13 men, one woman), who indicated suffering from either heartburn, regurgitation or chest pain during competition running, performed two experimental trials at 2-week intervals using a randomized, double-blind, placebo-controlled crossover design. During the 6 days preceding the trial and on the trial day itself either 20 mg of omeprazole or a placebo was administered. Two hours after a low-fat breakfast and 1 h after the last study dose, the trial started with five successive 50-min periods: rest, three running periods on a treadmill, and recovery. Reflux (percentage time and number of periods oesophageal pH <4) was measured with an ambulant pH system during these periods. RESULTS: Compared to rest, reflux lasted significantly longer and occurred more frequently during the first running period, irrespective of the intervention, whereas during the second running period this effect was only observed with the placebo. Reflux occurred for longer and more frequently with the placebo than with omeprazole, but this was significant during the first two running periods only. Seven subjects reported heartburn, regurgitation and/or chest pain during exercise, irrespective of the intervention. Only a minority of the symptom periods was actually associated with acid reflux and in all cases this concerned periods with heartburn. CONCLUSIONS: Running-induced acid reflux, but not symptoms, were decreased by omeprazole, probably because most symptoms were not related to acid reflux. (+info)
Safety and efficacy of pantoprazole 40 mg daily as relapse prophylaxis in patients with healed reflux oesophagitis-a 2-year follow-up.
(54/1291)
BACKGROUND: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+, K+-ATPase, necessary for the final step in gastric acid secretion. AIM: To assess safety and efficacy of oral pantoprazole (40 mg o.d.) used as a prophylaxis against relapse in patients with healed reflux oesophagitis during an open-label, 2-year study. METHODS: Outpatients (n=157) with healed stage II or III reflux oesophagitis (Savary-Miller classification) were enrolled into a long-term, multicentre maintenance study. Endoscopy was performed at entry into the study, after 12 and 24 months, or when disease-specific symptoms occurred on more than three consecutive days. Symptoms were assessed at 3-monthly intervals. Endoscopically confirmed relapses (at least stage I) were evaluated as treatment failures. RESULTS: Of the 178 adverse events, experienced by 88 (56%) patients (intention-to-treat population), 12 (7%) were assessed by the investigators as possibly related to the study medication. Median serum gastrin levels increased from a baseline of 46 ng/L to 90 ng/L, reaching a plateau after 9 months. For the intention-to-treat population the endoscopic remission rates after 12 and 24 months were 87% and 76%, respectively (Life-Table survival analysis, Kaplan-Meier). CONCLUSION: Pantoprazole 40 mg proved to be safe and efficacious during a 2-year prophylaxis treatment in patients with healed reflux oesophagitis. (+info)
On demand therapy of reflux oesophagitis--a prospective study of symptoms, patient satisfaction and quality of life.
(55/1291)
BACKGROUND: In patients with low-grade reflux oesophagitis adequate symptom control is the aim of treatment. Effervescent tablets alleviate heartburn more rapidly than ordinary tablets. AIM: To investigate symptom control, patient satisfaction, health-related quality of life and disease progress when ranitidine 150 mg effervescent tablets were offered as on demand treatment. We also wanted to investigate whether any biological or psycho-social factor could predict patient satisfaction. METHOD: Consecutive patients with endoscopically verified reflux oesophagitis grade I-II were followed up for 12 months. 24 h pH-metry, disease history, symptoms and several psycho-social factors were registered at baseline and 12 months follow-up. RESULTS: Eighty-one patients were included. Mean age was 50.7 years (range 21-82), 63% were men. Mean tablet consumption was 1.21 per day (range 7-1016 tablets/year). At the 1-year follow-up discomfort resulting from reflux symptoms was significantly reduced (P<0.001), and the patients' social and vocational life improved. Eighty-four percentage of the patients were satisfied with the treatment. 24 h pH-metry or number of reflux episodes did not change. We did not find any factors able to predict patient satisfaction. CONCLUSIONS: On demand therapy with ranitidine effervescent tablets was well accepted by the majority of patients with reflux oesophagitis grade I. Even though the number of reflux episodes did not change, the patients experienced less discomfort due to reflux symptoms, and their social and vocational life was better. There was no significant progression of the disorder during the 1-year follow-up. No predictive factor for patient satisfaction was found. (+info)
Omeprazole therapy decreases the need for dilatation of peptic oesophageal strictures.
(56/1291)
BACKGROUND: Better control of gastric acid secretion with omeprazole appeared to decrease the need for dilatation of oesophageal strictures complicating gastro-oesophageal reflux disease in our hospital-based endoscopy service. AIM: To investigate whether the perceived decrease in the need for oesophageal dilatation could be documented from endoscopy records, and, if confirmed, whether this could be related to the treatment used. PATIENTS AND METHODS: Retrospective study of the records of 69 patients who had peptic oesophageal strictures dilated, followed by treatment with acid inhibition for at least 6 months. Mean duration of follow-up was 3.9 years during treatment with H2-receptor antagonists and 2.1 years while on omeprazole (258 and 78 patient-years, respectively). Re-dilatation rates were compared between those treated with H2-receptor antagonists or omeprazole. RESULTS: There has been a significant decrease in dilatations performed for gastro-oesophageal reflux induced strictures (P<0.001), while dilatation rates for other indications remained constant. Treatment with omeprazole not only decreased the need for further dilatations, but also prolonged the mean time between any further dilatations to 26.3 months compared to 9.3 months for those on an H2-receptor antagonist (P<0.0001). CONCLUSIONS: Following dilatation of peptic oesophageal strictures, treatment with omeprazole in place of an H2-blocker significantly decreases the need for repeat dilatation. (+info)