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Biomedical subjects

L Olbe

Publications and source records attributed to L Olbe.

At least 109 records · Page 6Linked to original sources
PubMed1985

Vagal stimulation of human gastric bicarbonate secretion.

Gastric bicarbonate secretion in humans was determined in vivo by using a gastric perfusion-aspiration system. A computer calculated the bicarbonate concentration every 30 s throughout the experiment from measurements of the pH and PCO2 in the aspirate. The total bicarbonate concentration was calculated according to the formula of Henderson and Hasselbalch as the sum of free bicarbonate plus the CO2 that was formed during reaction of bicarbonate with hydrogen ions. In 16 subjects basal gastric bicarbonate secretion was 410 +/- 39 mumol/h (mean +/- SEM). After sham feeding using the chew and spit technique to achieve physiologic vagal activation, the gastric bicarbonate secretion rate increased to 692 +/- 67 mumol/h (p less than 0.001). This response of bicarbonate secretion rate to vagal stimulation was independent of the intragastric pH (range 2-7). In 6 subjects the sham-feeding response was almost abolished (88% inhibition) by the anticholinergic drug benzilonium bromide, however, it was unaffected by premedication with indomethacin. The findings demonstrate that the increase in gastric bicarbonate secretion during the cephalic phase of gastric secretion occurs parallel to the increase in acid secretion. It may therefore be regarded as a physiologic response to reinforce the protective mucus-bicarbonate barrier. The response to vagal stimulation seems to be mediated by a muscarinic transmitter and to be independent of intragastric pH and endogenous prostaglandins.

Adult↗
PubMed1985

Continuous computerized determination of gastric bicarbonate secretion in man.

A method for continuous determination of gastric bicarbonate secretion in man has been developed. A computer-based system calculated the total bicarbonate secretion every 30 sec throughout the experiment on the basis of the continuously recorded pH and Pco2 measurements. A high gastric perfusion rate facilitated the identification of duodenogastric reflux, which was observed as rather short-lived spikes on the curves. The contribution of alkaline saliva to the measured gastric bicarbonate secretion was minimized by continuous salivary suction and was corrected for after determining amylase in the gastric aspirate. Validation of the measuring system, by introducing bicarbonate in the range of 50-400 mumol into the stomach, demonstrated a correlation value of 0.91 (p less than 0.001) between added and recovered bicarbonate. Basal gastric bicarbonate output in seven healthy subjects was 379 +/- 105 mumol/h (mean +/- SEM). Intragastric instillation of 16,16-dimethyl prostaglandin E2 in five subjects resulted in a fourfold increase in gastric bicarbonate output.

Bicarbonates↗
PubMed1985

Acid secretion in isolated gastric glands from healthy subjects and ulcer patients.

Isolated human gastric glands provide an in vitro model that can yield significant information about the mechanisms regulating gastric acid secretion at the parietal cell level. Aminopyrine, a weak base that accumulates in acid compartments, has been used as an indirect probe of H+ secretion. By means of a microscale technique it was possible to isolate oxyntic glands from gastroscopic biopsy specimens and thereby enable studies of healthy subjects and non-operated ulcer patients. Histamine (5.4 X 10(-5) M) and db-cAMP (10(-3) M) both induced a pronounced response, whereas the response to carbachol (4.5 X 10(-6) M), although still statistically significant, was less potent. The response to stimuli was twice as high in duodenal ulcer patients as in normal individuals. In contrast, the response in patients with a gastric ulcer located either in the prepyloric region or at the minor curvature on the antrum-corpus border was of the same magnitude as in healthy subjects. Pentagastrin did not induce any response in isolated gastric glands from normal individuals. Gastric acid secretion in vitro, measured as aminopyrine accumulation, did not decrease with increasing age of the individuals.

Adult↗
PubMed1985

Acid inhibitory characteristics of omeprazole in man.

Single-dose studies in man have shown that omeprazole is a potent inhibitor of acid secretion stimulated by betazole, pentagastrin, modified sham-feeding and peptone. The degree of inhibition is dose-dependent and correlates to the area under the plasma omeprazole concentration-time curve. The duration of action of a single oral dose is 2-3 days and not dependent on a sustained plasma concentration of omeprazole. During repeated once-daily administration the level of acid inhibition increases over the first 5 days, after which it stabilises. With once-daily omeprazole treatment it is possible to almost abolish 24-hour intragastric acidity in the majority of DU patients.

Anti-Ulcer Agents↗
PubMed1985

Early dumping reaction after partial gastrectomy and its relation to preoperative apomorphine testing.

Risk factors for postoperative early dumping symptoms were studied prospectively in 289 consecutive peptic ulcer patients followed up for 5 years after antrectomy and gastroduodenostomy with or without vagotomy. Grade 2 or 3 dumping was present in 14% of the patients and was about four times as frequent in women as in men after antrectomy alone. The incidence of such dumping grades was twice as high after combined antrectomy and vagotomy as after antrectomy alone. Both differences were statistically significant. Milk intolerance, which often appeared as a symptom of dumping, was more common after combined antrectomy and vagotomy. Dumping seemed primarily to be related to the sex of the patient or to milk intolerance, whereas vagotomy additional to antrectomy seemed to enhance the risk of incurring dumping by causing milk intolerance. Grade 2 or 3 dumping was statistically associated with postoperative loss of weight. Pre operative apomorphine test was performed with the aim of detecting predisposition to postoperative dumping reaction. The authors conclude that apomorphine test preoperatively cannot predict postoperative dumping.

Animals↗
PubMed1985

Analytical and clinical evaluation of a radioimmunoassay for gastrin.

Prior to a study of the pathophysiological significance of chronic atrophic gastritis and hypergastrinemia, we evaluated a new radioimmunoassay kit for serum total gastrin (Diagnostic Products Corp.). The mean intra-assay CV ranged from 2 to 5% (2386 patients' samples in 47 assay runs done during four months). Total CVs for two controls ranged from 4 to 10%. Within-assay bias was 5%. Oleate decreased the values, indicating that intravenous heparin, which releases endothelial lipase, causing in vitro lipolysis, should be avoided if indwelling catheters are used for sampling, e.g., during provocation tests for gastrin release. Of three other commercial kits examined, two were affected by oleate. Other anions such as heparin and EDTA also affected the assay. Values for gastrin in heparinized plasma from surgical patients representing a variety of disorders agreed well with results obtained by a reference laboratory. We confirm the usefulness of this assay for discriminating clinical situations and conclude that ligand assays, besides those for thyroid assessment, should be assessed for interference from nonesterified fatty acids. Preliminary data also suggest a marked age dependence of serum gastrin concentration.

Adult↗
PubMed1985

Intestinal intussusception valve for postgastrectomy bile reflux and/or dumping.

The short-term results of a new surgical procedure for prevention of duodenogastric reflux and rapid gastric emptying after partial gastric resection are reported. A jejunal segment provided with an intussusception valve was interposed between the gastric remnant and the duodenum in six patients with severe postgastrectomy symptoms. Duodenogastric reflux, determined with an isotope derivative method, was found to be completely eliminated after the remedial operation. Gastric emptying of a glucose solution showed no significant delay. Previous gastroscopic findings of "gastritis" could not be recognized at postoperative examination. The histologic mucosal changes showed no remission, however. No patient became completely free from gastric symptoms after the remedial operation. The residual symptoms possibly were caused by impaired emptying of the gastric remnant. Gastric mycosis was found occasionally in all the patients during follow-up. The jejunal intussusception valve effectively prevented bile reflux and seemed to have a beneficial effect on dumping symptoms.

Adult↗
PubMed1984

[Acid secretion inhibition with new mechanisms of action: substituted benzimidazole].

Omeprazole and other substituted benzimidazoles produce a marked inhibition of gastric acid secretion with a long duration of action. Any kind of stimulated acid secretion is inhibited by the substituted benzimidazoles. The inhibitory mechanism of action is very selective. The substituted benzimidazoles inhibit the parietal cell H+, K+-ATPase, an enzyme which is the proton pump in the secretory membrane of the parietal cell. An oral daily dose of 15 mg omeprazole in humans produced about 80% acid inhibition just after dosage and about 40% 24 hours later. Preliminary results in duodenal ulcer patients show that a daily dose of 20-60 mg omeprazole produces fast ulcer healing in almost all patients.

Animals↗
PubMed1984

Omeprazole in Zollinger-Ellison syndrome. Effects of a single dose and of long-term treatment in patients resistant to histamine H2-receptor antagonists.

We studied the effect of omeprazole, a benzimidazole inhibitor of gastric acid secretion, in patients with Zollinger-Ellison syndrome. In five patients ingestion of 80 mg of omeprazole inhibited gastric acid secretion by 26 to 100 per cent after 6 hours and by 76 to 100 per cent after 24 hours. Seven patients were continuously treated with omeprazole once or twice daily for 8 to 19 months (average, 14). Six of these seven had symptoms that were resistant to high doses of histamine H2-receptor antagonists, and the seventh could not take high doses of cimetidine because of a possible drug-related increase in the serum creatinine concentration. Symptoms resolved in all patients within two weeks, and peptic lesions were healed at endoscopy after four weeks. All patients remained free of symptoms, and gastric acid secretion continued to be markedly inhibited by omeprazole therapy. We conclude that omeprazole is a potent and long-acting antisecretory drug in patients with Zollinger-Ellison syndrome and that it is effective in patients whose peptic-ulcer disease is relatively resistant to treatment with histamine H2-receptor antagonists. Its safety and effectiveness in long-term therapy remain to be assessed.

Adult↗
PubMed1984

Effects of proximal gastric vagotomy and antrectomy on parietal cell function in humans.

Both proximal gastric vagotomy and antrectomy reduce maximal gastric acid secretion in vivo by about 60%. The combination of vagotomy and antrectomy reduces the maximal acid secretion by about 80%. This additive effect indicates that these surgical procedures differ in their mode of action. The function of isolated human oxyntic glands was studied before and after vagotomy and antrectomy, respectively, using radioactively labeled aminopyrine as a marker of parietal cell response. The basal accumulation increased after vagotomy, suggesting a vagally controlled inhibitory component. The carbachol response disappeared and the maximal response induced by histamine or dibutyryl-cyclic adenosine monophosphate was reduced by 60% (p less than 0.01) after vagotomy. This reduction could not be overcome by increasing the dose of dibutyryl-cyclic adenosine monophosphate. This indicates an intracellular effect of vagotomy peripheral to dibutyryl-cyclic adenosine monophosphate point of action. Antrectomy did not induce any statistically significant change at the glandular level, indicating that the reduced gastric acid secretion in vivo may be caused by a reduction in the number of oxyntic glands due to a removal of a trophic effect of antral gastrin.

Adult↗
PubMed1983

Pitfalls in postoperative testing of the completeness of vagotomy.

The gastric acid response to insulin hypoglycemia represents an effect of several stimulatory and inhibitory mechanisms. In the intact stomach the direct vagal excitation of the acid secreting glands is the predominant mechanism. After vagotomy, however, the balance between the stimulatory and inhibitory mechanisms is unpredictable. Some stimulatory and inhibitory mechanisms are non-vagal, and may after vagotomy result in a false conception of remaining vagal fibers and complete vagotomy, respectively. Sham feeding may be a safer and more reliable test of completeness of vagotomy. A study of the spontaneous variation of basal acid secretion over several hours after vagotomy in 22 patients showed in 15-min samples a maximal range of 0.49 and 0.65 mmol with a P value of 0.05 and 0.01, respectively. A higher range may thus indicate a true acid response to a given stimulus. In 3 patients with an acid response to sham feeding but no acid response to insulin in a dose of 0.2 IU/kg after vagotomy, a repeated test with a lower dose of insulin resulted in an unequivocal acid response. In 4 patients with no acid response to sham feeding and a substantial acid response to insulin after vagotomy, the acid response to insulin was abolished after pretreatment with an adrenergic blocker. The insulin test may thus give false negative and positive information about the completeness of vagotomy.

Animals↗
PubMed1983

Effect of omeprazole--a gastric proton pump inhibitor--on pentagastrin stimulated acid secretion in man.

The effect of oral omeprazole on pentagastrin stimulated gastric acid secretion was studied in 11 healthy subjects. Doses of 20-80 mg produced dose dependent inhibition of acid secretion, with total suppression at the highest dose. Omeprazole was absorbed and eliminated from plasma rapidly and the inhibitory effect was related to the area under the plasma concentration time curve. The duration of action was long and single doses of 20 and 40 mg reduced acid secretion significantly for one and three days, respectively. Omeprazole in a dose of 15 mg given once daily for five days, suppressed acid secretion continuously, the inhibitory effect stabilising after three days at a predose inhibition of about 30% and a postdose inhibition of about 80%.

Adult↗
PubMed1983

Inhibition of gastric acid secretion by omeprazole in the dog and rat.

The gastric antisecretory properties of omeprazole, a new potent substituted benzimidazole, have been evaluated in dogs and rats. Omeprazole was compared with another benzimidazole, picoprazole (H 149/94), and with the histamine H2-receptor antagonist cimetidine. The intravenous or intraduodenal administration of omeprazole in the gastric fistula dog inhibited histamine- and pentagastrin-stimulated acid secretion. The intravenous and intraduodenal, ED50 values for inhibition of histamine-stimulated secretion were 0.35 and 0.26 mumol/kg, respectively. Omeprazole was found to be approximately 5-10 times more potent than both picoprazole and cimetidine. After oral omeprazole administration in the Heidenhain pouch dog, the ED50 on histamine-stimulated acid secretion was found to be 1.2 mumol/kg, which corresponded to a potency 2 and 3.5 times greater than that of cimetidine and picoprazole, respectively. Measurement of the plasma concentration of unchanged omeprazole revealed an intraduodenal bioavailability of approximately 70% whereas the oral bioavailability was only approximately 15%. This variation is probably a result of partial degradation of omeprazole in the acid gastric juice. Single intraduodenal doses of omeprazole had a long-lasting inhibitory effect on histamine-stimulated acid secretion in the dog. After a dose of omeprazole, which produced total inhibition initially, the antisecretory effect was detectable for 3-4 days. Omeprazole inhibited basal and stimulated acid secretion in the rat. The intravenous ED50 was calculated to be 1.5 mumol/kg, whereas the oral potency was about 10 times lower. The effect in the rat was also of long duration. After a dose giving maximal inhibition, control acid secretion was restored after approximately 13 h.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1982

Gastric mycosis following gastric resection and vagotomy.

In a prospective five-year follow-up study of 289 consecutive patients subjected to antrectomy and gastroduodenostomy with or without vagotomy, 130 patients underwent gastroscopy. Gastric mycosis was present almost exclusively in patients subjected to combined antrectomy and vagotomy (36%). Gastric acidity seemed to be of only minor or no importance in the development of the mycosis. The residual volume in the gastric remnant was significantly higher in patients with gastric mycosis. The impaired emptying of the gastric remnant is most likely a vagotomy effect and may be the main reason for the development of gastric mycosis. A simple but effective method was developed to evacuate gastric yeast cell aggregates. Gastric mycosis seems to give rise to only slight symptoms, mainly nausea and foul-smelling belching, whereas the reflux of duodenal contents that often occurred in combination with gastric mycosis was more likely to cause gastritis and substantial discomfort.

Bile Reflux↗