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F Halter

Publications and source records attributed to F Halter.

At least 19 recordsLinked to original sources
PubMed1992

Effect of acute and chronic acid suppression on plasma gastrin release in the rat.

The mechanisms by which administration of the H+,K(+)-ATPase inhibitor B 831-78 or intragastric perfusion with NaHCO3 induces plasma gastrin release were studied in the rat. Experiments were performed after a washout of residual intragastric contents in fasted animals provided with chronic gastric fistulae. Acute and chronic administration of B 831-78 elevated plasma gastrin dose-dependently up to 5-6 times above control levels, while the increase was only twofold with intragastric NaHCO3 infusion despite similar neutralization of gastric acidity. The profound hypergastrinaemia induced by the H+,K(+)-ATPase inhibitor, after both acute and chronic treatment, was completely prevented or reversed by intragastric perfusion with physiological amounts of acid (0.15 N HCl, 2.5 ml/h). The hypergastrinaemia was, however, largely resistant to high doses of atropine (4.3 mumol/kg) and of the M1 selective muscarinic antagonist telenzepine (10 mumol/kg). In contrast, the modest increase in plasma gastrin induced by gastric perfusion with NaHCO3 was completely suppressed by the high atropine dose and was attenuated by small doses of atropine or telenzepine (0.01 mumol/kg and 1 mumol/kg). These results demonstrate that, in the rat, blockade of the H+,K(+)-ATPase can potently induce gastrin release in the absence of a meal. Moreover, they suggest that interruption of the negative feedback between acid and gastrin release is the main mechanism through which this class of drugs releases gastrin in the rat. Since a similar degree of gastrin release cannot be achieved by alkalinization of gastric contents, additional hormonal or neural regulatory factors may contribute to the drug-induced hypergastrinaemia.

Adenosine Triphosphatases↗
PubMed1992

pH-feedback controlled infusions of ranitidine are no more effective than fixed-dose infusions in reducing gastric acidity and variability in antisecretory responses.

1. The antisecretory responses to pH-feedback controlled (maximum dose 800 mg 24 h-1) and fixed-dose (0.25 mg kg-1 h-1) continuous infusions of ranitidine were compared in a randomised, placebo-controlled, cross-over study in 10 healthy male volunteers. 2. To assess tolerance during repeated dosing with ranitidine, the same infusion regimens were given before and after 6 days oral dosing with ranitidine 300 mg four times daily. 3. With the pH-feedback controlled infusion of ranitidine the median % time (interquartile range) with pH greater than 4 in the 24 h period was 57% (45-76) before and 23% (17-34) after 6 days oral dosing (P less than 0.001). The respective values with fixed-dose infusion were 51% (38-63) and 26% (15-32) (P less than 0.002). 4. The median 24 h doses (interquartile range) of ranitidine given by feedback-controlled infusion before and after 6 days oral dosing were 675 mg (542-728) and 749 mg (709-760), respectively (P less than 0.01). The dose of ranitidine given by fixed-rate infusion was 423 mg (393-502) on both study days (P less than 0.001 vs feedback infusion). 5. Plasma gastrin concentrations remained slightly elevated after 6 days of oral ranitidine dosing, whereas pancreatic polypeptide plasma levels remained unchanged. 6. The antisecretory efficacy of infusions of ranitidine is significantly decreased by circadian stimuli and tolerance. Individually-adapted infusions of high doses of ranitidine were not superior to fixed-dose infusion of 0.25 mg kg-1 h-1 in overcoming this variability.

Adult↗
PubMed1992

Identification of somatostatin and gastrin receptors on enterochromaffin-like cells from Mastomys gastric tumors.

Histamine-secreting enterochromaffin-like (ECL) cells of the gastric fundus of the Mastomys can develop into solid ECL cell tumors, either spontaneously or after induction by acid inhibition. We used this tumor tissue to perform in vitro receptor autoradiography for somatostatin (SS), gastrin, and substance-P, using, respectively, [125I]Tyr3-octreotide, [125I]gastrin-17, and [125I]Bolton-Hunter-labeled substance-P as radioligands. A high density of SS receptors was found in the nontumor fundic mucosa, where gastrin receptors were only barely detectable. However, in the group of spontaneously developing ECL cell tumors, a high density of SS and gastrin receptors was observed, homogeneously distributed in the tumor tissue. In addition, the loxtidine-induced ECL cell tumors expressed a high density of SS and gastrin receptors. The receptors were specific for the respective peptide and of high affinity, with a dissociation constant (Kd) of 0.90 nM for SS receptor and 0.87 nM for gastrin receptors. No substance-P receptors were detected on the ECL cell tumors, although they were present in the muscle layers of the Mastomys gastric fundus. These results demonstrate that ECL-derived tumors express receptors for both SS and gastrin. This observation is consistent with the proposal that there is substantial regulation of the histamine-producing ECL cell by SS and gastrin. The presence of gastrin receptors is compatible with a role for gastrin as a trophic factor in ECL cell hyperplasia and neoplasia. The expression of SS receptors may be of diagnostic and therapeutic relevance in the regulation of ECL function and neoplastic transformation.

Animals↗
PubMed1992

Interaction of liquid aluminium phosphate and aluminium hydroxide with the gastric acid profile. Influence of food components and timing of meals.

AlPO4 is generally perceived as a particularly weak antacid. Its neutralizing capacity, when evaluated with the classical Fordtran test at the pH 3 standard, is several times smaller than that of Al(OH)3, which is considered a particularly potent antacid. This difference of in vitro reactivity of the two antacids is largely due to the fact that the pKa value is considerably lower for AlPO4 than for Al(OH)3. The object of this study was to evaluate in vivo and in vitro the impact of the pKa value of these antacids on their efficacy at low pH values and the modulation of their neutralizing capacity through proteins. Since both preparations display a much closer antacid activity at pH 2, we felt it appropriate to reevaluate the comparative in vivo neutralizing capacity of the two antacids at doses matched with their in vitro reactivity at pH 2. In vivo antacid effects were measured by ambulant pH-metry in 18 healthy volunteers after randomized ingestion of carbohydrate or protein meals. Antacid or placebo medication was given 1 and 3 h after meals. At pH 3.0, the standard milieu of the Fordtran test, preparation A, composed of Al(OH)3 and a small fraction of Mg(OH)2, displayed in vitro a neutralizing capacity of 4.4 mmol/ml, whereas this was 0.18 mmol/ml for preparation B, composed solely of AlPO4 (p less than 0.001). When tested at pH 1, 1.5, and 2, however, the ratio between A and B was below 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Combined surgical and interventional radiological approach for complex benign biliary tract obstruction.

In patients with complicated high benign biliary strictures surgical technique alone cannot exclude the possibility of recurrent problems, and hepatic atrophy/hypertrophy, portal hypertension and intrahepatic stones may all complicate surgical management. A multidisciplinary approach to these complex cases, which minimizes the need for repeated surgical interventions, has been pursued. Roux-en-Y hepaticojejunostomy was performed and an extended limb of the jejunum brought to the abdominal wall to allow access for later radiological intervention. Over a 30-month period 58 biliary-enteric anastomoses for benign disease were performed. Seventeen of these 58 patients were managed using the combined approach. Ten of these 17 patients had complex postcholecystectomy strictures and seven had strictures resulting from inflammatory disease, hepatic resection or congenital problems. A new classification of results of management of bile duct strictures is proposed. Seven patients were classified as 'excellent', six 'good', two 'fair' and two 'poor'. Results were obtained at a mean follow-up of 16 months and it seems likely that in some patients major surgical reinterventions were avoided.

Adult↗
PubMed1991

Tolerance and rebound to H2-receptor antagonists: intragastric acidity in patients with duodenal ulcer.

Tolerance to the antisecretory effects of H2-receptor antagonists develops consistently in healthy volunteers. The aim of this study was to determine whether tolerance occurs with repeated dosing of H2-receptor antagonists in patients with duodenal ulcer. Continuous intragastric 24-hr pH measurements were performed in 12 patients with duodenal ulcer in symptomatic remission before, on days 1 and 29, and two days after receiving ranitidine 300 mg four times a day for 34 days. The 24-hr median intragastric pH (interquartile range) was 5.4 (4.4-6.1) on day 1 and 4.6 (4.0-5.2) on day 29 of dosing with ranitidine (not significant). Median nighttime pH was 6.8 (6.3-7.0) on day 1 and 6.8 (6.6-7.1) on day 29 (not significant). During the daytime, the median pH decreased marginally from 4.7 (3.8-5.2) on day 1 to 3.8 (3.0-4.6) on day 29 (P less than 0.03). There was no difference in median intragastric pH during 24-hr, day and night periods before and two days after ranitidine dosing. No significant tolerance or rebound to H2-receptor antagonists was observed in patients with duodenal ulcer disease. This contrasts with data gathered in healthy volunteers and may be due to defects in the regulation of acid secretion in duodenal ulcer disease.

Drug Tolerance↗
PubMed1991

Nonsteroidal antiinflammatory drug-induced colonic strictures: a case report.

Adverse effects of nonsteroidal antiinflammatory drugs can occur throughout the whole gastrointestinal tract. Recently, several cases of "diaphragmlike" thin ileal strictures have been reported. These strictures seem to result from nonsteroidal antiinflammatory drug-induced inflammatory changes and apparently represent a newly recognized nosological entity. The case of a 61-year-old man who gradually developed similar inflammatory changes in the ascending colon during prolonged intake of a slow-release form of diclofenac is presented, and the literature on nonsteroidal antiinflammatory drug-induced intestinal strictures is briefly reviewed.

Anemia, Hypochromic↗
PubMed1991

The cephalic and gastric phases of gastric secretion during H2-antagonist treatment.

The antisecretory effects of H2-receptor antagonists are limited by food ingestion. The contributions of the cephalic-vagal and gastrinergic mechanisms to this interaction were examined in two 14-hour randomized, cross-over studies in 24 healthy volunteers. In the first study, either ranitidine or placebo was administered IV by a pH-feedback-controlled infusion pump during fasting, modified sham feeding, or food ingestion. Sham feeding resulted in a well-defined and abrupt interaction with the antisecretory effect of ranitidine (lasting 2-3 hours), after which fasting pH levels were regained. The second study, with the same design, showed that gastrin release occurred during this cephalic-vagal phase but was not attenuated by the additional infusion of the anticholinergic pirenzepine. Following eating, intragastric acidity increased and remained elevated for more than 6 hours. This increase was accompanied by prolonged hypergastrinemia, which was not diminished by pirenzepine. Pirenzepine did, however, enhance the antisecretory effect of ranitidine after both sham feeding and food ingestion. The interaction of food or sham feeding with the antisecretory effect of H2 antagonists is a consistent phenomenon. In both the cephalic-vagal and the gastric phases of secretion, this interaction appears to be partially mediated by a noncholinergic release of gastrin.

Adult↗
PubMed1991

Inflammation, capillary leakage and healing of experimental gastric ulcers in the rat.

Little information is available on the role of inflammation and small vessel alteration in the development and healing of peptic ulcers. We studied the spontaneous healing of experimental ulcers in the rat stomach with a novel radio-isotope technique for the monitoring of capillary damage in ulcer-related inflammation. Following ulcer induction, healing was assessed on days 1, 7 and 15 by macroscopical and histological determinations of ulcer size and lesion area, parietal cell counts in the ulcer margin and nuclear imaging of the lesion area using Nanocoll, a 99mTc-labelled colloid. The ulcers were re-epithelized after 15 days. However, Nonocoll activity was still significantly enhanced in the ulcer area, and regression of the microscopically visible lesion area, which, from day 1 on, occupied a zone considerably larger than the ulcer itself, was delayed and still incomplete at the end of the study. Compared to the intact mucosa, parietal cells were reduced in the scar tissue up to 15 days (24-40%). However, despite macroscopical and histological re-epithelization, small vessel leakage and substantial tissue alteration persisted in the ulcer scar.

Animals↗
PubMed1991

Aspects of the role of prostaglandins in gastrin histamine regulation of gastric acid secretion.

There is convincing evidence from in vitro studies that prostaglandins interfere with the gastrin histamine regulation of gastric acid secretion in an opposing manner. They can inhibit the action of histamine on the parietal cell when given as single-dose treatment. Conversely, when given at high doses, they liberate endogenous histamine, probably from nonparietal cells. In in vivo experiments prostaglandins are potent inhibitors of acid secretion when studied with single-dose treatment but are capable of stimulating basal acid secretion when chronically applied to rats. Studies performed in whole animal preparations on the effect of cyclooxygenase inhibitors have not fully clarified which of these two histamine-modulating effects of prostaglandins is of prime physiologic significance but favour suppression of histamine activity with subsequent acid inhibition. It appears that somatostatin release is the mechanism through which prostaglandin can simultaneously inhibit acid secretion and release plasma gastrin. At least in the rat, the pattern of plasma gastrin and somatostatin release is, similarly to acid secretion, partly reversed during prolonged prostaglandin treatment.

Animals↗
PubMed1991

Gastrin: friend or foe of peptic ulcer?

Gastrin represents a direct pathogenic factor only in rare subgroups of ulcer patients, such as in the Zollinger-Ellison syndrome, the antral G-cell hyperplasia syndrome, and in patients in whom the gastric antrum was erroneously retained following partial gastrectomy. Gastrin may play a contributory role in the pathogenesis of uncomplicated peptic ulcer disease, as an exaggerated, but reversible gastrin release appears to be associated with Helicobacter pylori colonization. The known trophic effects of gastrin could account for the overall increase in the parietal cell mass of patients suffering from duodenal ulcer disease. Circumstantial evidence suggests that the abnormal gastrin release could also explain the upregulation of the parietal cell to the acid stimulatory effect and the consequent increase in gastrin sensitivity in patients suffering from duodenal ulcer disease. Conversely, the trophic effects of gastrin have also been linked to ulcer healing, especially since potent acid inhibitors induce a substantial hypergastrinemia. The evidence for such an association, however, is only circumstantial and potent and selective gastrin receptor antagonists are necessary to fully clarify the role gastrin exerts in ulcer healing.

Animals↗
PubMed1990

[Is the prognosis of patients with variceal hemorrhage determined by the severity of the underlying disease?].

This retrospective analysis includes all patients in whom endoscopic sclerotherapy was initiated because of bleeding oesophageal varices during the years 1984 to 1986. Of the total of 107 patients (77 men, 30 women, mean age 56 years) a majority of 71 (66.3%) had alcoholic liver disease as the underlying cause of portal hypertension. Varices were injected with ethoxysclerol 1% in weekly sessions if possible until they were completely eradicated. Initially 27 patients (25.2%) were classified as Child's class A, 52 (48.5%) as Child's class B and 27 as Child's class C. At the time of analysis 46 patients (42.9%) had died. 17 patients died of uncontrolled variceal haemorrhage one of them after a completed course of sclerotherapy, 15 died in hepatic coma. The cumulative survival rate after one year was 63.8% overall, 84.7% for patients in Child's class A, 75.4% for patients in Child's class B and 21.3% for patients in Child's class C. The one year survival rate for the 50 patients who failed to complete a course of sclerotherapy was 26.9%. The one year survival rate for alcoholics as a group (63%) was the same as for non-alcoholics (64.2%). 40 patients had non-fatal episodes of bleeding, 15 of whom bled after completion of a course of endoscopic sclerotherapy (median delay 174 days after completion of sclerotherapy). We conclude from our results that the outcome after sclerotherapy for oesophageal varices is determined mainly by the severity of the underlying liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal and Gastric Varices↗
PubMed1990

Risk of acute upper gastrointestinal bleeding in patients with ulcerative disease and treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Results from the Comprehensive Hospital Drug Monitoring Berne (CHDM).

The hospital prevalence rate for upper gastrointestinal ulcerative disease in 28,531 inpatients consecutively admitted in two teaching hospitals in the Comprehensive Hospital Drug Monitoring (CHDM) in Berne, from 1974 to 1985, was 2.2% (1.8% for gastric or duodenal ulcer, and 0.4% for erosive gastritis). This was based on the evaluation of 634 patients after exclusion of the subgroup of patients with hepatic cirrhosis or upper gastrointestinal neoplasia. After exclusion of patients on anticoagulant therapy (n = 73), 561 (= 100%) patients could be further studied. Of them, 33.3% (n = 187) were found to have been exposed to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, within 21 days prior to confirmation of the diagnosis. The observed relative risk (RR) of developing a substantial acute upper gastrointestinal bleeding (Hb less than 10 g/100 ml for men, and less than 9 g/100 ml for women, or a decrease in Hb of more than 25%) was 1.61 when patients exposed to NSAIDs (n = 187) were compared to patients not exposed to those drugs (n = 374). Although there was no significant sex difference overall, the RR for gastrointestinal bleeding differed considerably in the various age-groups; it was elevated in men under 40 years (RR = 2.86) and in women over 60 years of age (RR = 1.89), as compared to the mean RR of 1.61.

Adult↗
PubMed1990

Tolerance to oral H2-receptor antagonists.

The acid-inhibitory action of H2-receptor antagonists was shown to decrease after one to two weeks of dosing in healthy volunteers. This tolerance was evaluated in three randomized, placebo-controlled trials with the H2-receptor antagonists famotidine, 40 mg given after the evening meal for 28 days; ranitidine, 300 mg four times a day for seven days followed by 300 mg at night until day 28; and ranitidine, 300 mg three times a day vs 300 mg at night for 14 days. Continuous 24-hr pH monitoring with glass electrodes was performed under fed conditions. The median 24-hr pH decreased from 3.2 on day 1 with famotidine 40 mg to 1.9 on day 28 (P less than 0.0012). After seven days of dosing with ranitidine 300 mg four times a day the median 24-hr pH dropped from 5.0 on day 1 to 3.0 on day 7 (P less than 0.001) and then to 2.2 with ranitidine 300 mg at night on day 28. With ranitidine 300 mg three times a day the median 24-hr pH fell from 4.3 on day 1 to 2.4 on day 14 (P less than 0.0005). With ranitidine 300 mg at night the respective pH values were 2.5 and 1.8 (P less than 0.003). Tolerance to H2-receptor antagonists given in a single evening dose was only evident during the night, whereas tolerance occurred throughout the day and night with the three- and four-times-a-day regimens. A large increase in the interindividual variability of pH response was seen during the nighttime.

Administration, Oral↗
PubMed1990

Effect of food on H2-receptor blockade in normal subjects and duodenal ulcer patients.

Two separate studies of 24 hour intragastric acidity were carried out in normal volunteers and duodenal ulcer patients to define the interaction of food and the antisecretory effects of H2-receptor blockers. Both investigations were double blind randomised comparisons using ranitidine 300 mg with either different meal times or ad libitum snacks after an evening meal. Meals taken after drug administration nearly abolished measurable antisectory effects. Median 24 hour pH was 1.3 on placebo, 2.6 when ranitidine was administered after the evening meal and 1.9 when administered before the evening meal. Snacks taken after evening dosing with ranitidine also significantly decreased pharmacodynamic efficacy. During placebo, median night-time pH was 1.3 without snacks and 1.4 with snacks. pH rose to 5.9 during ranitidine treatment when snacks were forbidden but was only 3.1 when snacks were allowed. These findings could be of therapeutic importance and should rationalise dietary advise to patients receiving H2 blockers. The timing of drug administration can be adjusted according to individual life styles.

Adult↗
PubMed1990

Effect of 16.16 dimethyl prostaglandin E2, N-acetyl-cysteine and the proton pump inhibitor BY 831-78 on hydrogen peroxide-induced mucosal damage in the rat stomach.

Reactive oxygen species are noxious to gastrointestinal mucosa and contribute to a variety of gastrointestinal diseases. We examined whether 16.16 dimethyl prostaglandin E2 (PG) is protective against the oxidizing action of 6% H2O2 causing gross hemorrhagic lesions in rat gastric mucosa. Male Wistar rats were treated with PG, 0.005-5 micrograms/kg, either intragastrically (i.g.) or subcutaneously, 30 min prior to i.g. administration of 6% H2O2, 0.5 ml/100 g. Further animals received 25 mg of the mucus dissolvent N-acetyl-cystein (NAC) following oral PG treatment or 30 mumol/kg of the H+K(+)-ATPase inhibitor BY 831-78 (BY), 4 h before onset of the experiments. Volume, pH and beta-N-acetyl-glucosaminidase and lactate dehydrogenase as parameters of cell damage were determined in the gastric juice. i.g. PG treatment achieved 60 and 55% reduction of the mucosal lesions in doses between 5 and 0.05 micrograms/kg, respectively. i.p. PG administration was effective in all doses tested. Gastric juice volume was only slightly and enzymes were not significantly affected by PG treatment. NAC did not diminish PG efficacy or aggravate mucosal lesions. Gastric acid suppression did not increase PG-induced protection but was strongly protective by itself, reducing damage by 75%. Low-dose PG treatment achieves an effective protection against oxidative damage in gastric mucosa, which is not the result of dilution or enhanced mucus production.

16,16-Dimethylprostaglandin E2↗
PubMed1990

Different motor actions of dynorphins and nonpeptide kappa opioid receptor agonists in the isolated rat colon.

Dynorphin 1-17 has been suggested to be the endogenous ligand for kappa opioid receptors. In this study motor effects of dynorphin 1-17, its N-terminal fragments d-Pen2,d-Pen5-enkephalin (DPDPE) and d-Ser2-[Leu5]enkephalin-Thr (DSLET) without or with pretreatment with naloxone, (-)-2-(furylmethyl)-noretacocine (Mr 2266) or tetrodotoxin (TTX) on the isolated rat colon were compared with those of nonpeptide kappa opioid receptor agonists. Intraluminal pressure changes were measured by perfusion manometry in preparations maintained in a standard organ bath. Dynorphin 1-17, 1-9, 1-8, 1-6, [Leu5]enkephalin, DPDPE and DSLET dose dependently stimulated the tone in the proximal, middle and distal colon with the maximum response at 10(-6) to 10(-5) M. The stimulation produced by Tyr-Gly-Gly-Phe and Tyr-Gly-Gly was 60 and 600 times less potent, respectively. Concentrations of 10(-10) to 10(-6) M des-Tyr1-[Leu5]enkephalin, dynorphin 3-13, 6-17, 1-methyl-2-(3-thienylcarbonyl)-amino-ethyl-5-(2-fluorophenyl)-H-2,3 dihydro-1,4-benzodiazepine, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl) cyclohexyl)-benzene- acetamide-methane sulfonate and (5a,7a,8B)-(-)-N-methyl-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)-dec-8- yl) benzeneacet-amide produced no changes in motor activity of the rat colon. Only doses exceeding 10(-6) M of the latter three substances stimulated colonic tone. This action was inhibited neither by naloxone nor by Mr 2266. In contrast, the stimulation by dynorphin 1-17 and 1-6 was inhibited to a greater extent by naloxone than by Mr 2266.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗