[Gastric secretory, ultrastructural and pH changes during prolonged treatment with omeprazole in a severe form of Zollinger-Ellison syndrome].
Omeprazole, a powerful and long-lasting gastric anti-secretory benziimidazole derivative has been used to treat a particularly severe case of Zollinger-Ellison syndrome with familial type I multiple endocrine involvement. Before treatment with omeprazole, the patient's basal acid secretion, ranging from 50 to 100 mmol/h, had been poorly controlled by cimetidine (doses of up to 2,400 mg/d), ranitidine (doses of up to 1,200 mg/d) and even by ranitidine (1,200 mg/d) combined with pirenzepine (150 mg/d). Upon oral administration of four 20-mg capsules of omeprazole twice daily, rapid healing of the diffuse mucosal ulcerations of the upper GI tract as well as control of diarrhea were achieved. Clinical benefit accompagnied dramatic and sustained reductions in gastric acid secretion as demonstrated by repeated basal output measurements and 24-hour intragastric pH recording. The biodisponibility of omeprazole improved as gastric intraluminal acidity was reduced. The effects of omeprazole on pepsin output appeared to be mainly related to the reduction of gastric secretory volume. After more than one year of treatment, neither clinical nor biological side-effects were noted. However, repeated ultrastructural studies of fundic gastric mucosa revealed two types of alterations: a) a pattern of hyper-stimulated parietal cells with turgescent intra-cellular micro-canalicus invested by numerous microvilli; b) in about a fourth of the parietal cells, cytoplasmic modifications resembling auto-phagosomia and mitochondrial reduction in number and morphological transformation. Poorly understood to date, these alterations call for regular histological control of the gastric mucosa in patients with Zollinger-Ellison syndrome submitted to long-term administration of large doses of omeprazole.
D000328:Adult; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism*; D005748:Gastric Fundus / Q000648:ultrastructure; D005750:Gastric Juice / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000648:ultrastructure*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole; D013997:Time Factors; D015043:Zollinger-Ellison Syndrome / Q000188:drug therapy*
D001562:Benzimidazoles; D009853:Omeprazole
Modifications sécrétoires, pHmétriques, et ultrastructurales gastriques au cours d'un traitement prolongé par l'oméprazole dans une forme sévère de syndrome de Zollinger-Ellison.