[A prospective controlled study of vagotomy in the treatment of duodenal ulcer. Results after 11-15 years]. / Prospektiv kontrolleret undersøgelse of vagotomi ved behandling af duodenalt ulcus. Resultater efter 11-15 år.

A prospective, randomized, controlled trial was conducted to compare truncal vagotomy and drainage (TV), selective vagotomy and drainage (SV) and parietal cell vagotomy (PCV) as elective treatment for duodenal ulcer. Between 11 and 15 years post-operatively, 248 patients were available for study of the recurrent ulceration rate by a life table method and 197 patients could be studied with regard to post-vagotomy symptoms. The recurrent ulcer rates were TV 28.5%, SV 37.4% and PCV 39.3%. These differences were not statistically significant. There was no significant difference in the Visick gradings among the three groups either before or after treatment of the failures. About two-thirds of the patients in each group were finally satisfied with their operation, often after second operations or prolonged medical treatment.

Prospective controlled vagotomy trial for duodenal ulcer. Results after 11-15 years.

A prospective, randomized, controlled trial was conducted to compare truncal vagotomy and drainage (TV), selective vagotomy and drainage (SV) and parietal cell vagotomy (PCV) as elective treatment for duodenal ulcer. Between 11 and 15 years after operation, 248 patients were available for study of the recurrent ulceration rate by a life table method, and 197 patients could be studied with regard to postvagotomy symptoms. The recurrent ulcer rates were 28.5% for TV, 37.4% for SV, and 39.3% for PCV. These differences were not statistically significant. The incidence of severe postvagotomy symptoms was as follows: dyspepsia, 18.4% for TV, 20.5% for SV, 8.6% for PCV; dumping, 5.9% for TV, 19.6% for SV, 2.2% for PCV; diarrhea, 9.8% for TV, 11.8% for SV, 4.4% for PCV. The incidence of severe dumping was significantly less frequent among the PCV patients than the SV group. The differences did not reach statistical significance in any of the other groups. There was no significant difference in the Visick gradings among the three groups either before or after treatment of the failures. About two thirds of the patients in each group were finally satisfied with their operation, often after second operations or prolonged medical treatment. It is concluded that none of the three forms of vagotomy can be recommended as the standard operative treatment of duodenal ulceration.

Inhibition of gastric acid secretion in humans by glucagon during euglycemia, hyperglycemia, and hypoglycemia.

The effect of intravenous infusion of glucagon in a dose of 85 pmol/kg/hr on submaximal pentagastrin-stimulated gastric acid secretion was studied in eight healthy volunteers. The study was repeated four times in each subject. By a glucose-insulin clamp technique blood glucose levels were kept constant during the studies at 5.0 mmol/liter (euglycemic clamp), 2.5 mmol/liter (hypoglycemic clamp), or 7.0 mmol/liter (hyperglycemic clamp) on three different days. Glucose and insulin were not infused during one control day study. During glucagon infusion, plasma glucagon levels increased but the level reached was lower during the hyperglycemic condition when compared to euglycemic and hypoglycemic conditions. Glucagon infusion inhibited gastric acid secretion during hyper- and euglycemic conditions but not during hypoglycemic conditions. Hyperglycemia caused a modest but significant inhibition of acid secretion. Serum gastric concentrations were unaltered during glucagon infusion regardless of the level of blood glucose. The present observations indicate that the inhibitory effect of glucagon is independent of the glucagon-induced hyperglycemia, but the effect is lost when blood glucose is below a certain limit, suggesting that blood glucose may have a modulating effect on gastric acid secretion.

Effect of glucagon on vagally induced gastric acid secretion in humans.

The effect of a physiologically relevant dose of pancreatic glucagon, 85 pmol/kg/hr, or saline on gastric acid secretion induced by modified sham feeding (chew and spit), was studied in 10 healthy volunteers. Gastric pH was held constant (pH 5.5) by intragastric titration. Glucagon infusion inhibited gastric acid secretion significantly, from 19.6 +/- 1.5 mmol H+ per hour during saline, to 10.4 +/- 1.4 mmol H+ per hour. Blood glucose increased during glucagon infusion and remained constant during saline infusion. Serum gastrin concentrations increased significantly by sham feeding, during saline as well as glucagon infusion, and no difference between the gastrin response during saline or glucagon infusion was found. Thus glucagon, in a physiologic dose, reduces vagally mediated acid secretion by a gastrin-independent mechanism.

Inhibition of meal stimulated gastric acid secretion by an octapeptide somatostatin analogue SMS 201-995.

A dose response study of the effect of an octapeptide somatostatin analogue, SMS 201-995, on meal stimulated gastric acid secretion was carried out in 12 healthy volunteers. Infusion of SMS 201-995 in a dose of 50 pmol/kg/h almost completely abolished the acid response to the meal. Pl-gastrin was significantly decreased during infusion of 10 pmol/kg/h of SMS 201-995 and insulin was significantly inhibited during infusion of 50 pmol/kg/h. SMS 201-995 in a dose of 50 pmol/kg/h inhibited basal and submaximal pentagastrin stimulated acid secretion by 77% and 84% respectively (p less than 0.01). On a molar basis SMS 201-995 is substantially more potent than natural somatostatin in inhibiting gastric acid secretion.

Is somatostatin a humoral regulator of the endocrine pancreas and gastric acid secretion in man?

The effect of low dose infusions of somatostatin on meal stimulated gastric acid secretion was studied in eight healthy volunteers by intragastric titration after a peptone test meal with radioimmunoassay control of the plasma concentrations of somatostatin and the pancreatic hormones glucagon and insulin. Infusion of somatostatin in a dose of 100 ng/kg/h, resulting in a plasma concentration of 13.4 +/- 2.1 pmol/l, inhibited acid secretion significantly, and in a dose of 800 ng/kg/h, with corresponding plasma concentration of 66.5 +/- 12.0 pmol/l the acid secretion was virtually abolished. Plasma concentrations of insulin and pancreatic glucagon decreased significantly during infusion of 200 ng/kg/h (24.5 +/- 7.5 pmol/l) and glucose concentrations increased. Serum gastrin was only significantly decreased during the highest dose of somatostatin. The range of plasma somatostatin concentrations obtained with the lower doses correspond to reported physiological variations. The results support the concept that somatostatin participates in the hormonal control of the pancreatic endocrine and the acid secretion.

Content and gel filtration profiles of glucagon-like and somatostatin-like immunoreactivity in human fundic mucosa.

Biopsies from the fundic gastric mucosa of eight human subjects were extracted with acid-ethanol and analyzed for somatostatin- and glucagon-like immunoreactivity using region-specific RIAs. Five extracts were studied by gel filtration. The glucagon content was close to the detection limit in all extracts, and none of the known glucagon components could be identified by gel filtration. The concentration of somatostatin-like immunoreactivity was 17.4 +/- 2.0 pmol/g wet wt, and the immunoreactivity was distributed among four well defined peaks, two of which corresponded to somatostatin 1-14 and 1-28, respectively.

Effect of endogenous pancreatic glucagon on gastric acid secretion in patients with duodenal ulcer before and after parietal cell vagotomy.

The effect of endogenous pancreatic glucagon on submaximal pentagastrin stimulated gastric acid secretion was studied by infusion of 1-arginine in patients with duodenal ulcer before and after parietal cell vagotomy without drainage (PCV). Preoperatively infusion of 1-arginine resulted in a marked inhibition of acid secretion, whereas no effect was found postoperatively. Plasma glucagon concentrations were identical pre- and postoperatively, fasting as well as during arginine infusion. Serum gastrin concentration rose after PCV but not unaffected by arginine infusion both pre- and postoperatively. The study demonstrates that intact vagal innervation of the fundic glands is a condition of inhibition of pentagastrin induced acid secretion by pancreatic glucagon released by infusion of 1-arginine.

The effect of cysteamine on the Brunner gland secretion in the rat.

Cysteamine in a single subcutaneous administration induces release of gastrin, acid hypersecretion, and duodenal ulcer in rats. Pentagastrin-induced acid hypersecretion has no ulcerogenic effect. The Brunner glands in the proximal duodenum have previously been shown to be an important factor in the natural defence of the duodenal mucosa, and this study has been performed to determine the effect of cysteamine and pentagastrin on the Brunner glands in the rat. The proximal duodenum was isolated in situ and drained by a polyethylene tube. The secretion was studied for two 5-h periods after administration of cysteamine or pentagastrin, and then the Brunner glands were studied histologically. Pentagastrin did not affect spontaneous Brunner gland secretion, whereas cysteamine inhibited the output approximately 50%. After cysteamine the secretory cells were low and depleted of mucus, suggesting that cysteamine interferes with the synthesis of the secretory product. The depression of the Brunner gland secretion may be an important factor in the pathogenesis of cysteamine-induced duodenal ulceration.

Effect of arginine infusion on endogenous pancreatic glucagon and gastric acid secretion in duodenal ulcer patients and normal subjects.

The effect of intravenous infusion of L-arginine on pentagastrin-stimulated gastric acid secretion was studied in 15 duodenal ulcer patients and 12 healthy subjects. In both groups L-arginine enhanced plasma concentrations of pancreatic glucagon equally and to levels similar to those seen after a protein-rich meal and inhibited the acid response in duodenal ulcer patients and in normal subjects. The study supports previous findings suggesting that pancreatic glucagon is a physiological inhibitor of gastric acid secretion but does not support the hypothesis of a defect in this inhibitory system in duodenal ulcer patients.

Zinc depletion in alcoholic liver diseases.

Liver and serum zinc concentrations were investigated in 24 patients with alcoholic liver diseases, 22 patients with non-alcoholic liver diseases, and in 36 control subjects. The liver samples were obtained by percutaneous liver biopsies, and the ratio of hepatocytes to fibrous connective tissue was estimated. The liver zinc concentration was expressed in relation to the amount of hepatocytes, and the serum zinc concentration was calculated in relation to total, albumin-, and alpha 2-macroglobulin-bound serum zinc. The results show that the liver zinc concentration was decreased in patients with alcoholic liver diseases (P < 0.01), in contrast to in patients with non-alcoholic liver diseases. Albumin-bound serum zinc was decreased in both groups (P < 0.001). The results indicate that alcoholic liver damage is associated with zinc deficiency.

Cysteamine-induced duodenal ulcer and acid secretion in the rat.

Duodenal ulcers can be produced in rats within 24 h by a single subcutaneous administration of cysteamine. To determine the role of gastric acid secretion in the pathogenesis of these ulcers, secretory and pathoanatomic studies were performed in chronic fistula rats ater an ulcerogenic dose of cysteamine. A prolonged increase of acid secretion was seen after cysteamine, reaching fourfold the basal level after 5 h. The acid response lasted for 10 to 11 h. After vagotomy cysteamine-induced acid secretion was markedly reduced. Ulcer formation was prevented by vagotomy and by drainage of the gastric juice before it entered the duodenum. When a gastric acid output equivalent to that produced by the ulcerogenic dose of cysteamine was induced by repeated injections of pentagastrin, no mucosal changes were seen in the duodenum. These results indicate that, although some acid in the duodenum is required for ulcer formation, the hypersecretion of acid induced by cysteamine is not the only factor responsible for the development of duodenal ulcer.

Inhibition of meal-stimulated gastric acid secretion in man by exogenous and endogenous pancreatic glucagon.

The effect of intravenous infusion of glucagon (300 ng x kg(-1) x h(-1)), 1-arginine (0.6 g x kg(-1) x h(-1)) and of saline on meal-stimulated gastric acid secretion was studied in six healthy volunteers. Infusion of glucagon and 1-arginine enhanced plasma concentrations of pancreatic glucagon to 65--85 pmol/l, a level similar to that seen after a normal protein-rich meal. Both infusions significantly inhibited the acid response to the meal, most pronounced after 1-arginine. The difference in acid inhibition could not be ascribed either to differences in plasma glucagon concentrations or to differences in serum gastrin concentrations. The study supports the concept that pancreatic glucagon is a physiological inhibitor of gastric acid secretion.