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Biomedical subjects

C J Fimmel

Publications and source records attributed to C J Fimmel.

At least 37 records · Page 2Linked to original sources
PubMed1987

Prevention of gastric mucosal lesions following aortic cross-clamping.

Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0.03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0.004). A shorter ischaemic period also reduced the number of lesions (P = 0.02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P less than 0.05).

Allopurinol↗
PubMed1987

Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man?

The interaction between smoking and the effect of histamine H2-antagonists on intragastric acidity was examined in a double blind double dummy placebo controlled study. Healthy volunteers, 11 smokers and 10 non-smokers, were given, on four separate days at least one week apart, either placebo or cimetidine 800 mg nocte or ranitidine 2 X 150 mg per day or ranitidine 300 mg nocte. Tablets were taken at 2115 and 0900 h. Smokers smoked a cigarette hourly from 0700 to 2300 h. Breakfast, lunch, and dinner were standardised. Intragastric acidity was measured with a combined intragastric glass electrode and a solid state recorder. The subjects were fully ambulatory. The three histamine H2-receptor antagonist regimens were less effective (p = 0.04) in smokers than in non-smokers, but the difference between acidity of smokers and non-smokers was small. Means of medians of pH during a 24-h period with placebo, cimetidine 800 mg, ranitidine 2 X 150 mg and ranitidine 300 mg were 1.6, 2.3, 3.1, and 2.7 in smokers and 1.5, 2.7, 3.2, and 3.1 in non-smokers, respectively. In a second part of the study seven chronic smokers were reexamined after acutely stopping smoking: inhibition of gastric acidity by histamine H2-receptor antagonists was similar before and after withdrawal. Smoking does not affect intragastric acidity in untreated volunteers and only slightly decreases the effectiveness of histamine H2-receptor antagonists on intragastric acidity. This effect best in part explains the unfavourable effect of smoking on healing of peptic ulcer in patients treated with these drugs.

Adult↗
PubMed1987

Is there a relationship between gastric mucosal blood flow and stress lesions in hemorrhagic shock?

The relationship between gastric mucosal blood flow and stress lesion formation during hemorrhagic shock was studied in anesthetized dogs. Shock was induced by graded arterial bleeding. Blood flow was measured by means of the radioactive microsphere technique. Mapping of blood flow was achieved by measuring the microsphere accumulation in mucosal and muscle segments of 1-2 cm side length of the entire stomach. To produce a varying incidence of lesions the metabolic acidosis of shock was either fully corrected by intravenous sodium bicarbonate (n = 5), partially corrected (n = 4) or left uncorrected (n = 3). Mucosal lesions developed more frequently in dogs without correction than in dogs with partial correction or full correction. In 4 dogs not subjected to shock, no mucosal lesions were observed at the end of the experiments. Mucosal blood flow varied from segment to segment by a factor of up to 20, but individual segments tended to maintain their relative flow values during shock. Correction of metabolic acidosis did not significantly affect blood flow. Likewise, flow was similar in segments with and without lesions. Therefore, low regional blood flow did not predispose to the development of lesions and high flow did not prevent them. We conclude that focal mucosal ischemia alone does not lead to stress lesion formation during hemorrhagic shock.

Animals↗
PubMed1986

Regulation of free cytosolic Ca2+ in the peptic and parietal cells of the rabbit gastric gland.

Quin 2-loaded isolated rabbit gastric glands and purified peptic cells were used to measure free cytosolic Ca2+ ([Ca2+]i) during hormone stimulation. Rabbit gastric glands are composed of peptic and parietal cells with less than 1% endocrine cells. Although both cell types responded to the same hormones, they may be distinguished in terms of the source of Ca2+ bringing about the change in [Ca2+]i. Experiments were designed to assign changes in [Ca2+]i to either the peptic or parietal cells and to attempt to maintain these distinctions in the mixed cell population of gastric glands. It was shown that the peptide cholecystokinin octapeptide induced a rapid and transient increase in [Ca2+]i of isolated peptic cells. This signal was independent of medium Ca2+ and insensitive to the Ca2+ channel blockers La3+ and nifedipine. In gastric glands, the Ca2+ outdependent increase in (Ca2+)i (the secondary transient) was slower and dose dependently blocked by La3+ and nifedipine. This allowed [Ca2+]i levels in the physiologically more intact rabbit gastric glands to be dissected and correlated with fluorescence changes of quin 2 in either cell type. The transient increase in [Ca2+]i coincided with a burst of pepsin but not acid secretion. A subsequent slower phase of pepsin secretion took place while the cells restored near resting [Ca2+]i. Using a combination of the Ca2+ ionophore A23187 and the protein kinase C activating phorbol ester 12-O-tetra-decanoylphorbol 13-acetate, the hormone response pattern of pepsin secretion could be mimicked. The intracellular Ca2+ stores of the peptic cells in the gastric gland remained depleted of Ca2+ until specific antagonists were added. The reloading of intracellular stores required medium Ca2+ although [Ca2+]i was maintained at resting level during the entire reloading period. Hence, a specialized pathway of Ca2+ reloading is postulated.

Aminopyrine↗
PubMed1986

Relationship of spinal cord blood flow to vascular anatomy during thoracic aortic cross-clamping and shunting.

No satisfactory explanation exists as to why paraplegia occurs despite distal aortic perfusion during thoracic aortic operations. We studied the hemodynamics, paraplegia rate, and spinal cord blood flow with radioactive microspheres in 17 male adult baboons, with particular reference to the arteria radicularis magna. The groups consisted of control animals, subjected to cross-clamping for 60 minutes, and animals with aorto-aortic shunts operational for 60 minutes. There were no significant left ventricular hemodynamic advantages with shunting. Shunting significantly increased lumbar spinal cord blood flow (p = 0.0009), which correlated with the distal aortic mean pressure (r = 0.59, p = 0.008). However, lower thoracic spinal cord blood flow did not increase during shunting (p = 0.2) and did not correlate with the distal aortic pressure (r = 0.11, p = 0.64). This is due to the vascular anatomy of the anterior spinal artery, which was, as in man, smaller above (0.278 mm) than below (0.744 mm) the entry of the arteria radicularis magna. Resistance to flow, as calculated by Poiseuille's equation, was 51.7 times greater up the anterior spinal artery as compared with down this artery. The vascular anatomy explains the absence of paraplegia in one baboon in the cross-clamp group and paraplegia in one baboon in the shunt group. Thus, distal aortic perfusion protects the spinal cord below the arteria radicularis magna but not above it.

Animals↗
PubMed1985

[Continuous intragastric pH-metry].

Ambulatory intragastric pH-metry is a suitable method of assessing gastric acidity under conditions of normal daily life. A detailed profile of intragastric acidity is given which is a reproducible individual characteristic. There is a circadian rhythm of gastric acidity in which pH rises during the night and after meals. pH-metry was used to determine the effects of H2-antagonists and antacids, and the results are the basis for the clinical use of intragastric pH-metry.

Antacids↗
PubMed1985

[Therapy of stomach ulcer with low-dose antacid gel and cimetidine. A multicenter double-blind study].

In a multi-centre double-blind (double-dummy) trial the effectiveness of low-dose antacid gel (6 X 12 ml/d; neutralisation capacity 120 mmol) was compared with that of a standard dose of cimetidine (1 g/d) in the curative treatment of gastric ulcer. Antacid gel was given to 65 patients, cimetidine to 60. Diagnosis was confirmed by endoscopic biopsy, which was also employed in a serial follow-up. After 4 weeks antacid gel and cimetidine produced cures in 43% and 52%, respectively; after 8 weeks 76% and 89%, respectively, the difference between the two methods not being statistically significant. There was also no statistically significant difference with regard to ulcer pain. In one case each in the antacid and cimetidine groups, the treatment had to be stopped because of side effects. Diarrhoea was more common on cimetidine than on antacid gel. It is concluded that both low-dose antacids gels and cimetidine are suitable in the treatment of gastric ulcers.

Adult↗
PubMed1985

Long-term ambulatory gastric pH monitoring: validation of a new method and effect of H2-antagonists.

A new ambulatory monitoring system was evaluated for long-term measurements of gastric acidity. A close correlation was observed between values indicated by the pH electrode of the system and the pH of simultaneously aspirated gastric juice, suggesting that the electrode signaled the pH of the gastric fluid content. When the pH electrode was passed via an endoscope, and its bulb was placed against the corpus mucosa, a higher acidity was recorded as compared with gastric juice. To test whether the electrodes measured mucosal pH during ordinary test conditions, the readings of pH probes with mechanically shielded bulbs that did not come into direct contact with the mucosa were compared with those of nonshielded probes in identical positions. Similar results were observed, supporting the hypothesis that nonshielded probes measured the pH of gastric contents rather than that of the mucosa. The importance of a standardized electrode position and a fixed meal schedule was demonstrated in simultaneous recordings of antral and fundic pH. Under fasting conditions, acidity was similar in both regions. After ingestion of a meal, gastric contents were more alkaline in the fundus than in the antrum. A wide range of 24-h acidity (19-83 mmol/L) was detected in 25 healthy subjects. The day-to-day reproducibility of the method as revealed in two consecutive 24-h tests was good. The effect of cimetidine and ranitidine on gastric acidity was evaluated in 9 subjects in a double-blind, double-dummy trial. Mean 24-h H+ activity was 37.4 +/- 4.6 mmol/L under placebo medication. It was lower with cimetidine, two doses of 400 mg (23.8 +/- 4.0); cimetidine, four doses of 400 mg (10.2 +/- 3.0); ranitidine, two doses of 150 mg (10.3 +/- 3.6), and two doses of 300 mg (10.0 +/- 3.5), respectively. In conclusion, ambulatory long-term pH monitoring is a suitable method to assess the physiologic pattern of gastric acidity and the effect of antisecretory drugs.

Adolescent↗
PubMed1985

Evaluation of pirenzepine on gastric acidity in healthy volunteers using ambulatory 24 hour intragastric pH-monitoring.

The effect of pirenzepine on 24 hour intragastric acidity was studied in 10 healthy volunteers using ambulatory 24 hour intragastric pH-monitoring in a double blind crossover study. Tests were performed on the seventh day of ingestion of either placebo, 75 mg pirenzepine or 150 mg pirenzepine per day. The drugs were given at two doses at 8.30 am and 8.30 pm. Mean nocturnal hydrogen ion activity during placebo treatment was 68 mmol/l +/- 9 SEM and was reduced by 75 mg (26%, p less than 0.01) and 150 mg of pirenzepine (36%, p less than 0.01), respectively. Mean diurnal hydrogen ion activity was 32 mmol/l +/- 6 SEM and was not significantly reduced (p greater than 0.1) by either dose of pirenzepine (4% and 12% respectively). Thus, the effect of pirenzepine on intragastric acidity is small, even with high doses of the drug, and becomes apparent only during the night.

Adult↗
PubMed1985

Distribution of intraventricular salmon calcitonin and suppression of gastric secretion.

Intracerebroventricularly (ICV) administered [125I] salmon calcitonin (sCT) was rapidly transported to the blood, but the permeability of the blood-brain barrier to sCT was low. ICV injected intact [125I]sCT was predominantly deposited in the periventricular mesencephalon and in the kidneys, and intravenously (IV) injected [125I]sCT in the kidneys, respectively. After both ICV and IV administration [125I]sCT was not retained by the stomach in large amounts. ICV and subcutaneously (SC) injected sCT caused suppression of gastric secretion volume, and of acid and pepsin outputs; the potency ratios between half maximal inhibitory amounts of sCT administered SC and ICV were 161, 252 and 13, respectively. On the other hand, perfusion of isolated whole mouse stomachs with sCT did not affect basal or stimulated acid and pepsin secretion. These findings indicate that sCT inhibits gastric acid secretion via receptors localized in the hypothalamus and in adjacent areas of the brain.

Animals↗
PubMed1984

[Substituted benzimidazoles--a new dimension in ulcer therapy?].

Substituted benzimidazoles represent a new class of gastric secretory inhibitors, which suppress acid secretion via direct inhibition of the parietal cell H+/K+-ATPase. The most potent derivative so far is omeprazole, which inhibits basal acid secretion and prevents the stimulatory effect of all classical acid secretory stimulants. In man, a single dose of 80 mg leads to almost complete achlorhydria over 24 hours. The results of the first duodenal ulcer trial with omeprazole are encouraging. No definite side effects have been attributed to the drug so far. Omeprazole may possibly initiate a new era in the medical treatment of peptic ulcer disease.

Benzimidazoles↗
PubMed1984

Dissociated response of acid and pepsin secretion to omeprazole in an in vitro perfused mouse stomach.

The effect of omeprazole, an inhibitor of the parietal cell H+-K+-ATPase, on pepsin and acid secretion was studied in an in vitro perfused whole mouse stomach model. Omeprazole inhibited basal and dibutyryl cAMP (DBcAMP)- and histamine-stimulated acid secretion in a dose-dependent fashion with a maximally effective dose of 10(-4) M. At the same time, omeprazole induced a dose-dependent increase of unstimulated pepsin release. This increase was not affected by pretreatment with 10(-3) M atropine or 10(-4) M cimetidine. It was, however, inhibited by preincubation with 10(-4) M carbonyl cyanide m-chlorophenylhydrazone (CCCP). Pepsin secretion after maximally effective doses of histamine or DBcAMP was not affected by 10(-4) M omeprazole. In a concentration of 10(-5) M, the effect of omeprazole was additive to the effect of submaximal concentrations of carbachol and histamine. NaSCN and imidazole mimicked the effect of omeprazole on acid secretion, but pepsin release was only stimulated with 10(-2) M imidazole. Another weak base, benzylamine, stimulated acid and pepsin in parallel. Luminal perfusion with solutions of high K+ concentration did not enhance basal pepsin release. The dissociated response of acid and pepsin secretion indicates that omeprazole does not act selectively on the parietal cell. The stimulation of pepsin secretion might be related to the weak base properties of the compound.

Animals↗
PubMed1984

Pepsin secretion: neurohumoral regulation and drug effects.

The regulation of pepsin secretion was studied in the in vitro perfused mouse stomach. In contrast to acid secretion, basal pepsin release was not inhibited by 10(-4) M carbonyl cyanide m-chlorophenylhydrazine (CCCP) and by N2-induced hypoxia. Both secretions were not affected by 10(-3) M cimetidine, 10(-3) M atropine or cycloheximide (2 mg i.p. + 10(-5) M). Secretory responses to classical stimulants were similar to those obtained under in vivo conditions: carbamylcholine (CCH) and histamine stimulated acid and pepsin secretion in parallel, with a maximal pepsin/acid ration of 34 +/- 4 (mean +/- SEM) and 40 +/- 5, respectively. CCH-induced pepsin secretion was inhibited by atropine and pirenzepine. Dibutyrylic cyclic AMP(db-cAMP) strongly stimulated pepsin release. This stimulation was partially inhibited by trifluoperazine. Pentagastrin was a weak stimulant of pepsin secretion (pepsin/acid ratio: 10 +/- 3), whereas 10(-4) M bombesin and 10(-6) M salmon calcitonin had no effect. Omeprazole (H168/68) strongly inhibited basal acid secretion and stimulated pepsin release in a dose-and energy-dependent fashion. In contrast to acid, basal pepsin release probably represents an 'overflow secretion'. Although pepsin and acid are usually stimulated in parallel, dissociated responses are obtained under in vitro conditions, indicating that separate regulatory pathways exist.

Animals↗
PubMed1984

Bile salt-induced, acute gastric mucosal damage in man: time course and effect of misoprostol, a PGE1-analogue.

A model is presented that allows the assessment of acute mucosal damage in man. Damage is revealed by changes of gastric mucosal potential difference (PD), urea net fluxes and DNA shedding. Sodium taurocholate (TC) damages the mucosa in a dose-dependent fashion: 1 mM TC leads to a transient drop of PD with a subsequent rise of DNA-, but not of urea net fluxes. With 5 mM TC, the drop of PD drop lasts for more than 15 min, urea net fluxes are increased, and the rise in DNA is more pronounced. We examined in this model, whether misoprostol (SC 29333), a prostaglandin E1 derivative, could prevent the TC-induced damage. Misoprostol in an antisecretory dose lead to an overall increase of PD even in presence of TC, but did neither prevent the TC-induced drop of PD, nor the changes in urea and DNA net fluxes. Similar results were obtained, when a non-antisecretory ('cytoprotective') dose of misoprostol was given prior to TC. Misoprostol has gastrin antisecretory properties, but no cytoprotective effects against acute, taurocholate-induced mucosal damage in man.

DNA↗
PubMed1983

Novel approach to quantify duodenogastric reflux in healthy volunteers and in patients with type I gastric ulcer.

A new method is described which allows simultaneous measurement of gastric emptying and duodenogastric reflux and avoids transpyloric intubation. After intragastric instillation of a liquid lipid meal in six healthy volunteers the fractional gastric emptying rate was 2.9 +/- 0.3 in the upright and 2.5 +/- 0.6 SEM X 10(-2)/min in the supine position, respectively (p greater than 0.5). The duodenogastric reflux rate (expressed as fraction of the intraduodenal amount of duodenal marker) was 0.30 (range 0.03-0.81) and 0.22 (0.01-0.55) X 10(-2)/min, respectively (p greater than 0.2). Atropine (40 micrograms/kg) decreased the supine gastric emptying rate to 1.1 +/- 0.2 (p less than 0.05) and increased the supine duodenogastric reflux rate to 2.74 (0.04-9.80) X 10(-2)/min (p less than 0.05). Fasting duodenogastric reflux rate was similar in the supine and upright position, 0.49 (0.04-0.89) and 0.42 (0.06-0.97) X 10(-2)/min, respectively (p greater than 0.5). Fractional gastric emptying rate was similar in 10 volunteers and 17 patients with type I gastric ulcer (2.1 +/- 0.4 vs 1.7 +/- 0.2 SEM X 10(-2)/min, p greater than 0.2). Their duodenogastric reflux rates were also similar, 0.65 (0.01-5.24) vs 1.10 (0.01-10.83) X 10(-2)/min (p greater than 0.5). We conclude therefore that (1) gastric emptying and both fasting and postprandial duodenogastric reflux are independent of the posture; (2) fasting and postprandial reflux are of similar magnitude; (3) atropine shows gastric emptying and increases duodenogastric reflux; and (4) patients with type I gastric ulcer have neither slowed gastric emptying nor increased duodenogastric reflux.

Adult↗
PubMed1983

Failure of 16,16-dimethyl-PGE2 to protect the human stomach from taurocholate induced damage.

This study examined the question as to whether 16,16-dimethyl prostaglandin E2 prevents bile-induced gastric mucosal damage in man. Damage was induced by intragastric instillation of a 10 millimolar taurocholate solution. DNA-shedding, gastric transmucosal electrical potential difference, and the outputs of potassium and urea in gastric washings were measured as indices of mucosal damage. DNA-shedding during gastric washings with saline was 0.24 mg/15 min +/- 0.05 SEM and rose to 0.46 +/- 0.08 (p less than 0.025) during washings with taurocholate. Potential difference dropped from -35.6 mV +/- 1.6 to -21.9 +/- 2.3 (p less than 0.005). Potassium output was increased from 0.21 mmol/15 min +/- 0.01 to 0.50 +/- 0.03 (p less than 0.005), and urea output was increased from 0.45 mmol/15 min +/- 0.09 to 1.33 +/- 0.21 (p less than 0.05). These changes could be prevented neither by 20 micrograms/100 ml of 16,16-dimethyl PGE2 instilled intragastrically 45 minutes prior to the start of taurocholate administration, nor by 10 micrograms/100 ml of 16,16-dimethyl PGE2 instilled prior to taurocholate plus 0.7 micrograms/100 ml given together with taurocholate. It is concluded that "cytoprotection" appears to depend on the nature of the damaging agent, and may not occur under some conditions which play an important role in the pathophysiology of gastric mucosal diseases.

16,16-Dimethylprostaglandin E2↗