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Biomedical subjects

S E Miederer

Publications and source records attributed to S E Miederer.

At least 37 records · Page 2Linked to original sources
PubMed1985

Effects of hormones (calcitonin, GIP) and pharmacological antagonists (ranitidine and famotidine) on isolated rat parietal cells.

The rationale for the present study was to compare calcitonin and gastric inhibitory polypeptide (GIP) versus two histamine H2 receptor antagonists with respect to their potency of inhibiting parietal cell functions. Adenylate cyclase activity and acid production ([14C]aminopyrine uptake) of isolated rat parietal cells were stimulated by histamine. At 10(-7) and 10(-6) mol/l, calcitonin and GIP reduced the response to histamine by 10-20% following noncompetitive kinetics. Ranitidine and famotidine (MK 208) inhibited the response to histamine by about 50% at 10(-7)-10(-6) mol/l, and at 10(-5) mol/l abolished the histamine effect. On a molar basis famotidine turned out to be 6 times more potent than ranitidine. Both antagonists revealed competitive kinetics. Our data suggest direct inhibition of the parietal cells by the tested compounds which were shown to interfere at the adenylate cyclase cAMP system or at the histamine H2 receptor. However, compared to the histamine H2 receptor antagonists, hormonal inhibition is less pronounced and mediated by a different mechanism.

Adenylyl Cyclases↗
PubMed1985

H+ production by isolated cells from human gastric mucosa.

Gastric mucosal cells were isolated from human mucosa obtained at surgery. H+ production was indirectly estimated by 14C aminopyrine (AP) uptake. The maximal response to histamine occurred after 30 min of incubation whereas intrinsic factor (IF) secretion was maximal after only 7.5 to 15 min. According to the concentration response curve 10(-4) mol/1 histamine proved to be the most effective concentration, the response to which was completely inhibited by ranitidine. Carbachol, dibutyryl cAMP and IMX also enhanced AP uptake, IMX being even more powerful than histamine. Carbachol and IMX failed to potentiate the response to histamine. Parietal cell fractions enriched by a Percoll density gradient revealed a pronounced background stimulation so that additional stimulation by test agents was less effective than in non-fractionized cells.

Adult↗
PubMed1985

Famotidine versus ranitidine for the short-term treatment of duodenal ulcer.

One-hundred and eight-three patients with endoscopically proven duodenal ulcers, enrolled in this prospective, double-blind study, were randomly allocated to receive famotidine 40 mg once at night, 20 mg twice daily, 40 mg twice daily, or ranitidine 150 mg twice daily for 2-8 weeks. Pretreatment characteristics between the four groups were similar. After 4 weeks of treatment, among the famotidine-treated patients, 38 of 42 (90.5%) healed with the 40 mg once nightly regimen, 35 of 42 (83.3%) with 20 mg twice daily, and 37 of 41 (90.2%) with 40 mg twice daily. In the ranitidine group 40 of 43 patients (93.0%) healed. After 8 weeks of treatment, the respective data were: 97.6, 95.2, 100 and 93.0%. Different results between the famotidine groups and the ranitidine group were not statistically significant. All treatments were well tolerated and severe adverse events were rare. Famotidine 40 mg given once at night appears to be as safe and effective as conventional therapy with ranitidine, indicating the importance of overnight gastric acidity in the pathogenesis of duodenal ulcer disease.

Adolescent↗
PubMed1985

[Famotidine versus ranitidine in the acute treatment of duodenal ulcer. A multicenter comparative study in Germany].

185 patients with endoscopically proven duodenal ulcers were randomly allocated to treatment with either famotidine 40 mg nocte, 20 mg bid, 40 mg bid or ranitidine 150 mg bid for 2-8 weeks in a prospective double-blind study. The four groups were similar with regard to age, sex, duration of ulcer disease, smoking habits etc. After 2 weeks treatment 28/42 patients (66.7%) healed on famotidine 40 mg nocte, 24/42 patients (57.1%) on famotidine 20 mg bid, 26/41 patients (63.4%) on famotidine 40 mg bid and 28/43 patients (65,1%) on ranitidine 150 mg bid. The corresponding healing rates after 4 weeks were 90.5%, 83.3%, 90.2% and 93%, respectively. After 8 weeks more than 93% of the patients had healed ulcers. At each time there was no statistical difference between the different famotidine regimens and the ranitidine group. All treatments were well tolerated and severe adverse events were rare. Famotidine 40 mg at night, therefore, appears to be as good as conventional ranitidine.

Adolescent↗
PubMed1984

Intrinsic factor secretion from isolated human gastric mucosal cells.

Human gastric mucosal cells were isolated from the resected fundic mucosa of peptic ulcer patients. The intracellular content and secretion of intrinsic factor were estimated by binding to cyano[57Co]cobalamin. The content was maximal in the enriched parietal cell fraction which also displayed the highest H+ production as measured by amino[14C] pyrine uptake. Secretagogues evoked full response after 15 min of incubation: pentagastrin (181% of basal secretion), carbachol (208%), histamine (250%) and dibutyryl cyclic adenosine monophosphate (304%). The phosphodiesterase inhibitor isobutylmethylxanthine was slightly more effective even than dibutyryl cAMP. The response to histamine was abolished by ranitidine, indicating activation of adenylate cyclase via histamine H2 receptors, but remained unaffected by atropine, which in turn blocked the carbachol effect, whereas ranitidine was ineffective. The mean formation rate was 8.4 fmol intrinsic factor/10(6) cells per h under basal conditions and 14.3 fmol in response to histamine.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Intrinsic factor secretion from isolated gastric mucosal cells of rat and man--two different patterns of secretagogue control.

Intrinsic Factor (IF) secretion was studied using isolated gastric mucosal cells from rat and man. In the rat, IF was localized to the chief cells and its secretion responded most efficaciously to carbachol. DbcAMP and hexoprenaline were less powerful, whereas histamine and pentagastrin lacked any effect. In man, IF secretion derived from the parietal cells and was increasingly enhanced by hexoprenaline, pentagastrin, carbachol, histamine and dbcAMP. In both species, IF secretion differs with respect to its cellular origin and the pattern of secretagogue control: IF release from rat chief cells is due to muscarinic receptor excitation, whereas IF release from human parietal cells responds predominantly to histamine-H2-receptor activation and seems to be mediated by the cAMP system.

Adenylyl Cyclases↗
PubMed1983

Cellular origin and release of intrinsic factor from isolated rat gastric mucosal cells.

The cellular content and secretion of intrinsic factor was measured by [57Co]cyanocobalamin binding using isolated rat gastric mucosal cells. The intrinsic factor/R-protein ratio was above 9:1 as evaluated by specific anti-intrinsic factor antibodies. In unfractionized cells with 23 +/- 1.3% parietal cells the intrinsic factor content of 148 +/- 47 fmol/10(6) cells remained almost unchanged over 3 h, whereas basal secretion rose up to 57 +/- 10. In fractionized cells (Percoll) with 3-85% parietal cells most intrinsic factor was found in the parietal cell-depleted fraction (content: 441 +/- 30, secretion/3 h: 139 +/- 16, mean formation/h: 50 +/- 12 fmol/10(6) cells). The intrinsic factor content of the different cell fractions correlated with that of pepsin. [14C]Aminopyrine uptake, an indirect measure of parietal cell H+ production, was inversely related. Carbachol (1 X 10(-6)-10(-3) mol/l) stimulated intrinsic factor secretion, 1 X 10(-3) mol/l being maximally effective (90 +/- 8% above basal). This response was inhibited by atropine and pirenzepine, but not by prostaglandin E2 (PGE2) and somatostatin. Dibutyryl cyclic adenosine monophosphate (dibutyryl cAMP, 43 +/- 7%) and hexoprenaline (24 +/- 5%) enhanced intrinsic factor secretion less effectively and pentagastrin like histamine lacked any stimulatory effect. We conclude that in the rat intrinsic factor is produced and released from chief cells mainly under cholinergic control.

Aminopyrine↗
PubMed1983

Adenylate cyclase in gastric mucosal biopsies from patients with achlorhydria. Stimulation by PGE2, histamine and gastrointestinal hormones.

Activation of adenylate cyclase (AC) by PGE2, histamine and gastrointestinal hormones was studied in parietal cell-free gastric biopsy specimens from the corpus of patients with proven high gastrin achlorhydria. PGE2, somatostatin, VIP, pentagastrin and secretin activated AC in a concentration-dependent manner both in normal and in atrophic mucosa. Histamine activated AC only in normal gastric mucosa, being entirely ineffective in mucosa devoid of parietal cells. The results indicate that histamine-sensitive AC disappears in patients with achlorhydria, probably due to their loss of parietal cells. Enzyme activity in response to somatostatin, VIP, pentagastrin, secretin and PGE2 remains unchanged in these patients indicating AC localization in nonparietal cells, e.g. chief or mucous cells.

Achlorhydria↗
PubMed1980

[Endoscopic retrograde cholangio-pancreatography in children (author's transl)].

Fifteen endoscopic retrograde cholangio-pancreatographies (ERCP) were performed between 1977 and 1979 in 13 children aged 2 months to 13.9 years (mean 8.9 years). All studies were done without intubation anaesthesia. Main indications were 1. acute (recurrent) biliary stasis, 2. persistent biliary stasis, 3. chronic pancreatitis, and 4. congenital malformation of the biliary system or the pancreas. Thirteen of the 15 investigations were successfully concluded. In nine cases both ductal systems were demonstrated, in two cases each either only the pancreatic or only the biliary ducts. The most frequent abnormal findings were seen in acute biliary stasis (four of five children), persistent biliary stasis (all four children) and congenital malformations (two of three children). There were no serious side effects. Except in young infants, for whom there are no properly sized instruments, ERCP in children provides no greater technical difficulties than in adults.

Adolescent↗
PubMed1980

No influence of age and gastric acid secretion on serum vitamin B12 concentration.

Serum vitamin B12 concentration, parietal cell antibodies (PCA), peak acid output vitamin B12 resorption capacity were determined in 76 patients (age 23 to 82 years). Gastroscopy was performed on all of these patients; guided biopsy was taken from 70 of them. No influence of the inflammatory changes in the gastric mucosa, sex or the presence of PCA on the serum vitamin B12 concentration were demonstrable in our patients, who all revealed a vitamin B12 resorption in the normal range. In particular we were unable to confirm the observation of Döscherholmen et al. (5) of a fall in serum vitamin B12 concentration with increasing age or decreasing PAO. Hence the estimation of the serum vitamin B12 concentration cannot be used as a screening test for selecting those patients suffering from chronic atrophic gastritis and achlorhydria, who should be monitored by gastroscopy and biopsy because of an increased risk of gastric cancer.

Achlorhydria↗
PubMed1979

[Effective out-patient treatment of gastric ulcer with proglumide: preliminary results (author's transl)].

In a double-blind trial 16 persons with gastric ulcer and 35 with duodenal ulcer were treated as out-patients with 1200 mg proglumide daily or 1320 mg magnesium tricilicate daily (as an "active placebo") for four weeks. The ulcers were assessed by endoscopy before and after treatment. The gastric ulcers disappeared in 75% of patients receiving proglumide (six of eight subjects) but in only 25% of those on the placebo (two of eight). There was no significant effect of proglumide on duodenal ulcers (17 in the proglumide and 18 in the placebo groups). Proglumide failed to affect either basal or maximally stimulated acid secretion, nor was there any change in the serum gastrin level. There were no side effects during proglumide administration. This underlines its therapeutic value in the treatment of gastric ulcer, in comparison with cimetidine or carbenoxolone.

Adult↗
PubMed1979

Efficient treatment of gastric ulcer with proglumide (Milid) in outpatients (double blind trial).

Eleven male and five female gastric ulcer outpatients as well as twenty eight male and seven female duodenal ulcer outpatients received Proglumide (1200 mg/day) or magnesiumtrisilicate (1320 mg/day) in a prospective double blind study. The sizes of the ulcers were assessed by endoscopy before and after 4 weeks therapy. A complete healing of gastric ulcers was observed in 75% (n = 8) of the patients receiving Proglumide and 25% (n = 8) of the antacid treated controls (p less than 0.05; x2 test). The healed area was significantly (p less than 0.05) larger in the Proglumide 91 mm2) than in the anticida group (23 mm2). In addition, the half time of the ulcer-healing was significantly (p less than 0.05) shorter in the Proglumide treated patients (18 days and 26 days respectively). There was no significant effect of the drug on the duodenal ulcers. The spontaneous healing rate was 61% in the antacid (n = 18) and 59% in the Proglumide treated (n = 17) patients. The drug does not effect the basal and pentagastrin stimulated gastric secretion nor the serum gastrin concentration. No side effects on blood pressure, blood cell count, transaminases or blood glucose concentrations could be observed.

Clinical Trials as Topic↗