[The ortho-nitrophenyl-sulfenyl derivative of pentagastrin: an antagonist of gastrin receptors? A promising line of research].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Kaess.
Explore the source record for details and available documents.
We have previously demonstrated that insulin hypoglycemia releases antral gastrin by a pH sensitive mechanism in duodenal ulcer (DU) patients. The effect of vagotomy per se on the hypoglycemic release of gastrin therefore might be obscured by alterations in antral pH. In the present study on 11 DU patients, the gastric acid response to intravenously administered insulin (0.2 units/kg-1) was determined before and after selective vagotomy with pyloroplasty (SV + PP). In another preoperative and postoperative test on each patient, the serum gastrin test, the serum gastrin response (radioimmunoassay) to insulin was determined during gastric perfusion with citrate-phosphate buffer pH 7.0. By adjusting the perfusion rate, the intragastric pH was maintained at 5.0 or higher. SV + PP abolished the acid response to insulin in four and reduced the response by 80% to 95% in another six patients. Gastric buffer perfusion or SV + PP did not alter the basal serum gastrin level. The increase of serum gastrin level after insulin was significantly (P less than 0.01) reduced by SV + PP. Before operation the integrated serum gastrin response to insulin was significant (P less than 0.01). SV + PP reduced the response to one-third. The effect of SV + PP on the hypoglycemic release of gastrin varied among the patients but no relationship was found to the effect on the acid response, nor to the variations of the volume or pH of the perfusate (pH range, 5.0 to 7.5). It is concluded that insulin hypoglycemia releases antral gastrin by a vagal and probably also by a nonvagal mechanism and that both mechanisms are pH sensitive.
Explore the source record for details and available documents.
The coagulatory effect of the Nd: YAG laser after puncture of the cholestatic liver was compared with the effect of electrocoagulation. In 11 rabbits, the liver was punctured 7 days after ligature of the common bile duct with a Menghini needle 1.2 mm. The site of injury was coagulated by laser light in 5 animals and by unipolar electrocoagulation in 6 animals. Bleeding and bile leakage was stopped in all cases. Histologically there was no crucial difference between the two methods in their effect on the liver tissue. Autopsy 14 days after common bile duct ligature revealed no bile peritonitis in any rabbit.
The significance of antral pH for the basal serum level of immunoreactive gastrin and for the release of gastrin during insulin hypoglycemia has been studied in duodenal ulcer (DU) patients. To permit paired comparisons, 14 DU patients underwent two or three tests with insulin. Venous blood samples were collected at fixed intervals for determination of gastrin (radioimmunoassay). In the first insulin test, the gastric juice was aspirated; in the second test, the stomach was perfused with citrate-phosphate buffer, pH 7.0; and in the third test the stomach was perfused with 0.1M HCl, pH 1.0. The rate of buffer or acid perfusion was adjusted, and the pH of the perfusate was kept above 5.0 and below 1.3, respectively. Gastric perfusion with buffer or acid for 1 hour did not affect the basal serum gastrin level, nor did perfusion with buffer for 3 hours. Insulin hypoglycemia stimulated acid secretion and produced a significant integrated serum gastrin response during gastric aspiration, but the gastrin response was four times greater during buffer perfusion. Acid perfusion abolished the gastrin response. From our previous and present findings, it is concluded that the gastrin in serum during basal conditions is of extra-antral origin and is independent of antral pH. Insulin hypoglycemia releases antral gastrin by a pH-sensitive mechanism in DU patients; the release is suppressed at pH 1.3 or less and also is markedly inhibited when the gastric juice is aspirated.
In 32 subjects, the HCl secretion, the histological state of the antral and fundic mucosa and the gastrin response to a liquid meal extract were studied. Atrophy of the antrum was associated with normal gastrin concentration in the fasting state and after the test meal, in the presence of normal fundic mucosa and HCl secretion. In achlorhydria and atrophic gastritis, fasting gastrinemia was significantly elevated in subjects with a normal antrum, and only moderately increased in subjects with an atrophic antrum. The gastrin response to feeding was correlated to the fasting gastrin concentration in achlorhydric subjects with normal antral mucosa, in contrast to a uniformly reduced output in achlorhydric subjects with atrophic lesions of the antral mucosa.
Explore the source record for details and available documents.
Submucosal lymphangiomas of the gastrointestinal tract are extremely rare entities. A case of a lymphangioma of the duodenum in a 66-year-old woman is reported. Diagnosis was made by endoscopy and tumor excision with a diathermy snare. The patient complained of crampy upper abdominal pain which only partially was referable to an gastric ulcer and stopped after polypectomy. Endoscopically, compressibility of the tumor is a characteristic sign. Roentgenographically, it may be easily overlooked.
The combination of diarrhea with an islet cell tumor (Verner-Morrison Syndrome) is a clinical picture presenting many diagnostic problems. It is probable that larger numbers of cases will be encountered with more widespread knowledge of this disease. The clinical features and the pathologic-anatomical findings of two characteristic cases are reported and discussed.
In four dogs provided with special gastroduodenal fistulas allowing for the complete separation of stomach and duodenum without interrupting the vagal connections between them, the magnitude of the gastric and intestinal phases was compared and their contribution to the total gastric response to a meal was established. A liver extract (LE) meal, confined to the stomach and maintained at pH 5.0 by an intragastric titration technique, produced acid output reaching 66% of the maximal response to histamine (MRH). Perfusion of the LE meal into the duodenum resulted in acid secretion amounting to 57% of MRH. The combination of the gastric and intestinal phases caused the highest acid output, amounting to about 90% of MRH. Gastric and intestinal phases induced separately were accompanied by a significant elevation in serum gastrin concentrations which reached the highest values when both phases were evoked simultaneously. Acidification of the intestinal meal resulted in pH-dependent inhibition of gastric secretion falling to the basal values at pH 1.0. These secretory changes were mimicked by exogenous secretin. Serum gastrin levels remained essentially unaffected by the acidification of the intestinal meal while exogenous secretin significantly lowered them. In conclusion, in the intact stomach with undisturbed nervous connections between the stomach and duodenum, a peptone meal in the intestine is capable of evoking a potent gastric acid and pepsin stimulation by a mechanism involving the release of antral hormone.
The influence of propranolol, 50 mug/kg administered intravenously, on the gastrin concentration during sham feeding and after a test meal was studied in eight normal subjects. beta-Adrenergic blockade had no inhibitory effect on the gastrin response to feeding. Sham feeding did not provoke a significant rise of serum concentration; however, in three subjects a definite gastrin response occurred in the presence of beta-adrenergic blockade.
The effect of atropine on acid secretion and serum gastrin level after feeding was studied in 8 cats with denervated fundic pouches (Heidenhain pouch, HP). Serum gastrin concentration was measured by radioimmunoassay. In the control experiments, the mean peak acid response occurred 45 min after feeding and the mean peak gastrin concentration 15 min after feeding. After the 1st postprandial hr, acid secretion declined but the gastrin level remained elevated. Atropine, 0.1 mg per kg intravenously 5 min before feeding, depressed both acid secretion and the increase in serum gastrin concentration during the 1st postprandial hr. In both the control and atropine experiments, acid secretion and serum gastrin level were correlated significantly during the 1st postprandial hr, but no correlation was found later in the experiments. The reduction by atropine of the acid and serum gastrin responses varied among the cats but were correlated significantly. It is concluded that a cholinergic mechanism is implicated in the release of gastrin by feeding in cats during the 1st postprandial hr. Atropine reduces the HP acid response to feeding at least in part by depressing the release of gastrin.
Gastric acid and serum gastrin (radioimmunoassay) responses to insulin (0.2 U/kg i.v.) and 2-deoxy-D-glucose (2DG) (50 mg/kg i.v.) were determined in 11 male duodenal ulcer patients before and after partial gastrectomy involving complete antral resection. In 8 of the patients the acid response to pentagastrin (6 mug/kg subc.) was also determined. Before operation, 2DG produced higher acid and gastrin responses than insulin. Partial gastrectomy reduced basal acid secretion by 54% but did not alter the basal gastrin level, suggesting that this gastrin is of extra-antral origin. Partial gastrectomy reduced the acid responses to insulin and 2DG by 66% and 78%, respectively; after operation the acid responses to these stimulants were equal. The ratio for the acid response to insulin and pentagastrin was 65% before and 56% after partial gastrectomy; corresponding ratios for 2DG and pentagastrin were 112% and 48%. Partial gastrectomy abolished the peak gastrin response to insulin hypoglycemia and reduced that to 2DG by 64%. The integrated gastrin response to insulin and 2DG was insignificant in the operated patients. Both insulin and 2DG release mainly antral gastrin which appears to be of greater importance for the acid response to 2DG than insulin.
Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0.5 M bicarbonate a significant increase of gastrinaemia from 133 to 158 pg/ml (p less than 0.01) occurred in ten subjects during respiratory acidosis (pCO2 62 torr, pH 7.25). Under the intragastric instillation of 100 ml/h 0.1 N HCl the rise of gastrin concentration in response to CO2 rebreathing (pCO2 68 torr, pH 7.20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 mug/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p less than 0.01) and a total suppression of hypergastrinaemia in response to CO2 rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0.6 to 1.8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p less than 0.01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.
In ten normal subjects the effect of propranolol on serum gastrin concentration and HC1 secretion during insulin hypoglycemia (0.2 U/kg) was studied. Under the influence of propranolol (50 mug/kg intravenously in 3 min) the gastrin response to insulin was abolished. The insulin-induced HC1 secretion was reduced by propranolol from 38 to 18 mEq/2h (p less than 0.01). These results are compatible with the hypothesis of beta-adrenergic stimulation on serum gastrin concentration and HC1 secretion during insulin hypoglycemia.
In 16 dogs, serum gastrin levels were determined after resection of the distal and proximal half of the small intestine. The response to feeding was significantly increased after intestinal resection. Higher postresectional levels were reached after resection of the proximal half of the intestine. This may be evidence that the proximal half of the small intestine, in addition to the liver and kidney, plays an important role in the inactivation of endogenous gastrin.
A new method for the intragastric titration of hydrochloric acid with a pH sensitive telemetric antimone electrode connected via a receiver to an electronic trigger, which regulates a pump for the inflow of 1 M KHCO3 solution, was evaluated in 22 achlorhydric patients by a series of intragastric instillations of 0.1 N HCl. In vitro this procedure presented a high precision (r = 0.99). Under in vivo conditions a significant correlationship (r = 0.84, p = 0.001) between the input of hydrochloric acid and bicarbonate in a range from 1.4 to 16.7 mEq/30 min could be established in non-operated subjects. The average coefficient of variation was 34%. In subjects with partial gastrectomy (Billroth II) overtitration of 100% (y = 2.1 x -1.7, r = 0.78, p = 0.001) was recorded, suggesting an increased loss of bicarbonate related to the accelerated gastric evacuation.
A double-blind study with intra-individual comparisons was carried out to investigate the effects of 15 mg of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH-tropanium bromide(+/-)-tropate (Sch 1000), 15 mg Sch 1000 + 10 mg oxazepam, 10 mg oxazepam and placebo with oral administration in randomized sequence on gastric juice volume, amount of acid, concentration and pH values in 12 healthy volunteers. The secretion parameters were measured during a 1-h basal period and a 2-h stimulation period. The gastric juice was obtained in 15 min portions via stomach tube. Stimulation was effected by 1 mug/kg/h pentagastrin via drip infusion. The Friedman test was used for the comparative statistical evaluation, and individual comparisons were carried out by means of the Wilcoxon test (pair-differences rank). The results show that Sch 1000 and Sch 1000 + oxazepam were equal in effect on basal and stimulated secretion volume. As compared with placebo, it was not possible to establish an effect on secretion volume for oxazepam alone. Sch 1000 and Sch 1000 + oxazepam were found to be equipotent in reducing the amount of basal acid, while oxazepam reduced this quantity only during the first 30 min of basal secretion. None of the three active preparations was capable of inhibiting the stimulated acid, although both Sch 1000 preparations produced a clear trend towards lowered mean values. During the basal secretion period, all three test preparations had an inhibiting action on acid concentration, but none of them had a significant effect during the stimulation period. The pH value was savely increased only by Sch 1000 and Sch 1000 + oxazepam, and this even only during the basal period. The results are discussed.