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Biomedical subjects

L Olbe

Publications and source records attributed to L Olbe.

At least 91 records · Page 5Linked to original sources

Do enkephalins participate in vagal activation of gastric acid secretion in man?

The effects of the anticholinergic drug benzilonium bromide and the opiate receptor blocker naloxone, given alone or in combination, on the acid secretory response and on plasma gastrin releasing peptide (GRP) response to sham feeding was tested in eight duodenal ulcer (DU) patients. Naloxone alone had no effect on the acid secretion after sham feeding. Benzilonium reduced basal acid secretion and the acid response to sham feeding but did not abolish the response. The combination of benzilonium and naloxone was not more effective than benzilonium alone. Neither drug, nor the combination had any effect on plasma GRP following sham feeding. It is concluded that enkephalins are unlikely to participate in the acid response to sham feeding in patients with DU.

Adult↗

Biliary excretion of intravenous [14C] omeprazole in humans.

We have studied the biliary excretion of [14C] omeprazole in humans. The study was performed in eight healthy subjects and the technique used was based on multiple marker dilution principles with double-lumen tubes placed in both the stomach and intestine. The results obtained show a 16% biliary excretion of [14C] omeprazole. These data suggest a minimal "spillover" of omeprazole from the gastric mucosa into the gastric lumen in humans. The results also agree with previous data of the fecal recovery of radiolabeled omeprazole that suggest that the fecal excretion of intravenous omeprazole in humans is entirely accounted for by biliary excretion.

Adult↗

Origin of gastrin liberated by gastrin releasing peptide in man.

Gastrin release induced by gastrin releasing peptide (GRP) in man has been studied in patients before and after complete resection of the antrum and duodenal bulb, as well as after pancreaticoduodenectomy according to Whipple. Studies in healthy subjects showed that 400 pmol/kg an hour of GRP induced a maximal release of gastrin. Infusion of this dose of GRP after a complete resection of the antrum and duodenal bulb induced a small, but significant increase in gastrin concentrations. After pancreaticoduodenectomy, however, GRP infusion had no effect on serum gastrin concentrations. In patients previously subjected to an incomplete antrectomy, GRP infusion was followed by a gastrin response considerably higher than after a complete antrectomy. Our results would suggest that GRP is capable of releasing gastrin predominantly from the antrum and the duodenal bulb, but also a small amount of gastrin from the remaining part of the duodenum. Gastrin releasing peptide infusion and determination of gastrin release may be of clinical significance in showing remaining significant gastrin pools in patients with recurrent ulceration after previous gastric resections.

Adult↗

Histamine H2-receptor of human and rabbit parietal cells.

The histamine H2-receptor on the human parietal cell has been characterized by using dose-response curves and the negative logarithm of the molar concentration of an antagonist (pA2) analyses of cimetidine antagonism of betazole, histamine, and impromidine stimulation in isolated human and rabbit gastric glands. To evaluate the in vitro results, betazole-stimulated gastric acid secretion with and without cimetidine was also studied in healthy subjects. In the in vivo model, individual dose-response curves were shifted to the right with increasing cimetidine concentrations, but this was counteracted by increasing betazole doses, indicating competitive, reversible antagonism. The pA2 values ranged from 6.1 to 6.3. In isolated human gastric glands, impromidine was shown to be eight times more potent than histamine, indicating higher receptor affinity, but the maximally stimulated aminopyrine accumulation was the same as for histamine, and the pA2 values for cimetidine antagonism did not differ significantly, i.e., 5.7 (histamine) and 6.1 (impromidine). In isolated rabbit gastric glands, cimetidine inhibited the histamine- and impromidine-stimulated response with pA2 values of 6.0 and 7.3, respectively. Impromidine was shown to be approximately 100 times more potent than in human gastric glands, whereas histamine had the same potency. This confirms the role of the histamine H2-receptor and suggests a difference between the species concerning receptor affinity.

Adult↗

Effect of fundic distension on gastric bicarbonate secretion in man.

Human gastric mucosa secretes small amounts of bicarbonate into the mucus layer to maintain the pH at the cell surface as close to neutrality as possible. We have measured gastric bicarbonate secretion continuously with a computer-based system, using recordings of pH and PCO2. The formula of Henderson and Hasselbalch was used in the calculations. Graded fundic distension of the stomach with a balloon in six healthy subjects increased the gastric bicarbonate output by 46% (p less than 0.05), 28% (NS), and 84% (p less than 0.05) during 1 h of distension to 150 ml, 300 ml, and 600 ml, respectively. Continuous fundic distension during 2 1/2 h with a volume of 300 ml elicited a response that peaked after 45 min and vanished after 90 min. The rather short duration of gastric bicarbonate secretion response to fundic distension may be due to a fading caused by a volume adaptation or, alternatively, to an activation of inhibitory mechanisms. Seven duodenal ulcer patients who had undergone proximal gastric vagotomy showed virtually the same gastric bicarbonate secretion response to graded fundic distension. The anticholinergic drug benzilonium bromide totally inhibited the gastric bicarbonate response to 30 min of fundic distension to 150 ml, whereas indomethacin did not significantly affect the response to distension. These studies indicate that the gastric bicarbonate response to fundic distension is mainly mediated by short intramural neural cholinergic pathways and is independent of mucosal production of prostaglandins.

Adult↗

Effect of proximal gastric vagotomy on basal and vagally stimulated gastric bicarbonate secretion in duodenal ulcer patients.

Basal gastric bicarbonate secretion and the response to vagal stimulation accomplished by sham feeding were investigated in duodenal ulcer patients before and after proximal gastric vagotomy. Gastric bicarbonate secretion was measured with a computer-based system, which continuously recorded the pH and PCO2 of the gastric perfusate. Preoperatively, basal bicarbonate secretion was 414 +/- 57 mumol/h (mean +/- SEM, n = 9), and the secretory response to vagal stimulation 691 +/- 83 mumol/h (p less than 0.01). About 2 months after proximal gastric vagotomy the basal gastric bicarbonate secretion was 539 +/- 74 mumol/h, and the response to vagal stimulation 693 +/- 72 mumol/h (p less than 0.01). The basal bicarbonate secretion thus increased by 30% after vagotomy (p less than 0.01) but about 1 year later was not significantly different from the basal preoperative value. In the early postoperative period anticholinergics significantly reduced the enhanced basal bicarbonate secretion to a preoperative level. When tested 1 year after the operation anticholinergics did not affect basal bicarbonate secretion but abolished the response to sham feeding. The findings of the study suggest the existence of cholinergic vagal nerve fibres stimulating human gastric bicarbonate secretion and indicate that inhibitory nerve fibres may modulate gastric bicarbonate secretion.

Adult↗

Basal and stimulated human gastric bicarbonate secretion.

The mucus-bicarbonate barrier on the gastric mucosa is regarded as a first-line of defence against acid. Both mucus and bicarbonate originate from the mucus cells in the gastric mucosa. Bicarbonate is secreted actively by Cl-/HCO3- exchange at the luminal cell membrane. A computer based system with continuous measurement of pH and PCO2 in a gastric perfusion system was used to determine human gastric bicarbonate secretion. The rate of basal gastric bicarbonate secretion in 24 healthy subjects was 386 +/- 31 mumol/h (mean +/- SEM). The 95% confidence interval for basal bicarbonate output was 103-669 mumol/h. Vagal stimulation by sham feeding increased the bicarbonate output by 63% and instillation of 16,16 dimethyl prostaglandin E2 increased the bicarbonate output by 214%. The response to vagal stimulation was independent of intragastric pH. The sham feeding response was abolished by premedication with anticholinergics. Basal and vagally stimulated bicarbonate secretion was unaffected by prostaglandin biosynthesis blockade.

16,16-Dimethylprostaglandin E2↗

Antibiotic prophylaxis in high-risk gastric surgery. A prospective, randomized clinical comparison of cefuroxime and doxycycline.

The efficacy of two antibiotics as prophylaxis in high-risk gastric surgery was evaluated in a prospective, randomized trial: 400 mg doxycycline in a single dose (98 patients) was compared with 1.5 g cefuroxime given twice with an 8-hour interval (101 patients). The two groups were comparable in regard to all relevant factors of importance for susceptibility to infection. The incidence of postoperative abdominal infection was 8.2% in the doxycycline group and 7.9% in the cefuroxime group. The most common extraabdominal infectious complications were in the lungs (20% of the patients in both groups). No subgroup of patients was identifiable in which one antibiotic was superior to the other. The efficacy of the two investigated prophylaxis regimens was apparently identical.

Cefuroxime↗

Measurement of pouch volume and stoma diameter after gastroplasty.

A balloon technique has been developed for measurement of the pouch volume and stoma diameter after gastroplasty. Twenty-seven patients prospectively included in a randomized study of two types of gastroplasty operation have been investigated 6 months postoperatively. During the operation the proximal pouch was calibrated to be about 40 ml and the stoma diameter to 11 min. Six months after the operation the patients had on average reduced weight by 29 kg. Using the balloon technique, the stoma diameter was 12 +/- 1.6 (s.e.m.) mm and the pouch volume 80 +/- 11.0 ml. There was a significant correlation between the stoma diameter and weight reduction during the first 6 months postoperatively (P less than 0.01). The relationship between the stoma diameter and weight reduction followed best an exponential equation. No correlation was found between the pouch volume and weight reduction. The presented technique for measurement of pouch volume and stoma diameter after gastroplasty may be an important tool to evaluate the influence of various factors on the long-term results of surgical treatment for morbid obesity.

Body Weight↗

Zinc status and dark adaptation in patients subjected to total gastrectomy: effect of zinc supplementation.

Totally gastrectomized patients could be regarded at risk for development of nutritional deficiencies including trace elements. Sensitive indices for early detection of these deficiencies are lacking. In order to evaluate the nutritional status of trace elements in patients previously subjected to a total gastrectomy we studied the zinc status in 10 patients by determining serum zinc, urinary zinc excretion and also, by a simplified dark adaptation test, the effect on these parameters of 4 weeks of zinc supplementation. The serum zinc level but not the 24-h urinary zinc excretion was lower in gastrectomized patients compared to age-matched controls. A slower dark adaptation was observed in the former patients when measured in the non-fasting state but not when fasted. Dark adaptation was slower in the patients as well as the age-matched controls compared to younger healthy subjects. Zinc supplementation increased the serum zinc levels and the urinary zinc excretion in the gastrectomized patients but had no effect on dark adaptation.

Aged↗

Stereological investigations on human gastric mucosa: I. Normal oxyntic mucosa.

Quantitative morphological data on normal human oxyntic mucosa were obtained from endoscopic biopsies in ten healthy male volunteers. Corpus mucosa was biopsied in the resting state and during maximal acid secretion and then processed for light and electron microscopy. Stereological analyses were carried out on sections comprising the entire thickness of the epithelial layer. About one-third of the mucosal volume was taken up by lamina propria and 15% by parietal cells. Counts of cells that displayed their nucleus in the sections revealed that in average of 12% of the epithelial cells were parietal cells, 43% were mucous cells, 40% were zymogen cells, and 4% were endocrine cells. Parietal cells displaying two nuclei were twice as large as those with only one nucleus. Six percent of the parietal cell volume was taken up by the nucleus, and 33% of the cytoplasmic volume was occupied by mitochondria. Stimulation of acid secretion resulted in a 76% increase in the secretory surface density; simultaneously there was a slight decrease in the mean size of the parietal cells and an increase in the relative volume of the nucleus. During maximal stimulation of acid the parietal cells from the superficial mucosal layers displayed a 40% larger secretory surface than those from the deeper parts of the mucosa. The data, which will serve as a basis for studies of pathological mucosae, are compared with those obtained in other species.

Adult↗

Intravenous omeprazole: effect on 24-hour intragastric pH in duodenal ulcer patients.

This study was aimed to identify an intravenous dosage regime of omeprazole which would sufficiently suppress acid secretion to maintain intragastric pH greater than 4 continuously. Thirteen duodenal ulcer patients in remission received omeprazole in daily intravenous doses ranging from 40 to 200 mg. Doses were successively increased as dictated by patient response. The intragastric pH data indicated that omeprazole given in twice or thrice daily regimes in total intravenous amounts of 200, 160 and 160 mg over a consecutive 3-day period markedly inhibited acid secretion and maintained intragastric pH greater than 4 with few and short-term exceptions.

Adult↗

Inhibition of basal and betazole- and sham-feeding-induced acid secretion by omeprazole in man.

The effect of omeprazole, given as a buffered solution, on basal acid secretion and that induced by betazole and sham feeding in healthy subjects were studied. The three series of experiments showed a dose-dependent acid reduction during the 2nd to 4th h after administration of omeprazole in doses of 10-60 mg, with almost complete inhibition by the highest dose. The ED50 values were of the same magnitude for basal and stimulated acid secretion. This indicates that omeprazole is an equally potent inhibitor of both kinds of acid secretion irrespective of the manner in which the acid is activated.

Adult↗

Inhibitory action of omeprazole on acid formation in gastric glands and on H+,K+-ATPase isolated from human gastric mucosa.

The inhibitory effect of omeprazole on acid formation has been studied in vitro in gastric glands and partly purified H+,K+-ATPase, prepared from mucosa obtained either from healthy subjects by gastroscopic biopsy or from gastric ulcer patients during antrectomy. The effect of omeprazole was compared with the inhibitory pattern of the H2-antagonist cimetidine. Acid production in the glands was determined by measuring the accumulation of 14C-aminopyrine. In glands isolated from patients, omeprazole inhibited acid production maximally stimulated by histamine, db-cAMP, and potassium in a dose-dependent manner, with an IC50 value of about 50 nM irrespective of the agonist used. In contrast, cimetidine inhibited only histamine-induced aminopyrine accumulation, with an IC50 of about 30 micron. The inhibitory effect of omeprazole in db-cAMP-stimulated glands from healthy volunteers was of the same magnitude as seen in glands from gastric ulcer patients. Basal aminopyrine accumulation in glands from both patients and healthy volunteers was almost totally inhibited by omeprazole, whereas cimetidine was without effect. Omeprazole also concentration-dependently inhibited the H+,K+-ATPase activity in isolated gastric membrane vesicles. The estimated IC50 value was 4 micron.

Adenosine Triphosphatases↗

Effect of omeprazole on gastric acid secretion in man.

Omeprazole in doses of 20, 40 or 60 mg dose-dependently inhibits basal acid secretion in young healthy subjects, with almost complete inhibition by 60 mg. Omeprazole has also been shown to dose-dependently inhibit vagally stimulated and meal stimulated acid secretion. Pentagastrin stimulated acid secretion is strongly inhibited by omeprazole for 4-5 hours, with moderate inhibition remaining 24 hours after a single dose. The plasma half-life of omeprazole, however, is about 50 minutes. The inhibitory effect accumulates over the first few days of repeated administration, and the effect continues for at least 24 hours after the last dose. A relatively high dose of intravenous omeprazole is required to keep the gastric pH above 4 over the 24-hour period. Both basal and postprandial serum gastrin concentrations have been observed to increase during omeprazole treatment. These changes, however, are probably secondary to a pronounced reduction of intragastric acidity which relieves acid inhibition of gastrin release from the antrum.

Anti-Ulcer Agents↗

Pancreatic resection additional to gastrectomy for gastric cancer. Effect on postoperative morbidity.

In a 7-year period, 127 patients were treated for gastric carcinoma. Of those younger than 70 years and subjected to gastric resection, 30 (55%) also had pancreatic resection. In older patients the corresponding figure was 11 (28%). The patients with simultaneous pancreatic resection had significantly increased incidence of postoperative intraabdominal complications, the most frequent of which were of septic nature. The number of reoperations was higher and the hospital stay longer in the patients with simultaneous gastrectomy and pancreatic resection.

Aged↗