The effect of vagotomy on human gastroesophageal sphincter pressure in the resting state and following increases in intra-abdominal pressure.

The effect of surgical isolation and extrinsic denervation of the distal 5 to 7 cm of the human esophagus on resting gastroesophageal sphincter pressure and its response to graded increases of external abdominal compression was determined in 89 patients with duodenal ulcer. Fasting serum gastrin concentration also was measured. No significant changes in resting sphincter pressure were obtained before and after vagotomy of various types: parietal cell vagotomy, selective gastric vagotomy plus drainage, and selective gastric vagotomy plus precise antrectomy. No correlation between resting sphincter pressure and fasting serum gastrin concentration was found in any of the groups studied. The increase in gastroesophageal sphincter pressure was similar to the increase in intragastric pressure after 10, 20, and 30 mm Hg of external abdominal compression and was unchanged after all types of vagotomies. These results suggest that (1) extrinsic innervation of the lower esophageal sphincter in humans does not regulate the resting tone of the sphincter; (2) extrinsic "mechanical" influence does not play any role in the maintenance of resting pressure; (3) the effect of increased abdominal pressure is a pure mechanical effect, is unchanged after vagotomy, and therefore is not regulated by external neural reflex.

Trisomy 10 survival: a literature review and presentation of seven new cases.

Trisomy 10 as the only chromosome aberration is a rare phenomenon in malignant and premalignant hemopoietic disorders. We describe 7 new cases and have found another 12 in the literature. It appears that, whereas adult patients have myeloid disorders (acute myeloid leukemia, myeloproliferative, or myelodysplastic syndromes), in children the diagnosis is lymphocytic leukemia or lymphoma. The median survival was 122 months in the total material. Age above 60 years proved to be a significant adverse factor (median survival only 5 months; p = 0.003). None of the other clinical, cytogenetic, or hematological variables were of demonstrable prognostic importance. In contrast with the larger trisomy 10 clones, those of limited size were associated with nonleukemic diagnoses, normal or slightly elevated leukocyte counts, and few or no circulating blasts. This may suggest that expansion of the trisomy 10 clone is associated with clinical and hematological progression.

Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24 h methotrexate infusions.

1 Methotrexate (MTX) concentrations were studied in serum, mixed saliva and sweat during and after 24 h continuous MTX infusions (0.5-6 g m-2) in 14 patients with various malignant diseases. 2 The serum-MTX concentrations declined in a biphasic manner, but the MTX elimination in saliva and sweat varied to a much greater extent. 3 Saliva/serum and sweat/serum ratios during the MTX infusion were 2.3% and 0.55% respectively. The ratios had increased significantly 20 and 44 h postinfusion. 4 No correlations were demonstrated between salivary- and serum-MTX concentrations during the MTX infusion or 20 and 44 h later. 5 Markedly delayed renal MTX excretions were demonstrated in two patients. In one of them the salivary MTX elimination was also retarded, whereas this was not seen in the other one. 6 We conclude that measurements of MTX concentrations in mixed saliva cannot substitute for serum-MTX determinations in the monitoring of patients after 24 h MTX infusions.

The effect of insulin on food-stimulated secretion of gastrin after parietal cell vagotomy and selective gastric vagotomy.

Serum gastrin concentration was measured in 11 patients with Parietal Cell Vagotomy and Drainage (PCV + D) and in 11 patients with Selective Gastric Vagotomy and Drainage (SGV + D) in the basal state, after a meal, and after a meal in combination with insulin-hypoglycaemia. Insulin had an early and transitory, but significant, inhibitory effect on the food-induced rise in serum gastrin concentrations. This inhibition was the same whether the patients had a PCV + D or SGV + D, indicating that it has no relation to the vagal innervation of the antrum. In the second hour after the meal the integrated gastrin output was significantly higher when insulin was added to a meal in patients with PCV + D but not in patients with SGV + D. This may indicate a certain, possibility sensitizing, effect of the vagal antral nerves.

The role of adrenaline and of the vagus in gastrin release and acid secretion in dogs.

Serum gastrin, gastric acid secretion and plasma adrenaline in response to intravenous injection of 2-deoxy-D-glucose and to insulin were measured in six dogs with gastric fistulae before and after denervation of the antrum and the intestine (antral-intestinal vagotomy). Serum gastrin and gastric acid secretion were also measured in the same dogs during intravenous infusion of adrenaline in doses which produced an elevation of plasma adrenaline to levels occurring during hypoglycaemia and after the injection of 2-deoxy-D-glucose. Antral-intestinal vagotomy reduced basal gastrin concentration slightly and basal gastric acid secretion considerably. The rise in serum gastrin in response to 2-deoxy-D-glucose and hypoglycaemia was abolished while the increase in gastric acid secretion was reduced after antral-intestinal vagotomy. Beef meal-stimulated gastrin secretion was the same before and after vagotomy. Intravenous infusion of adrenaline had no effect on either serum gastrin or gastric acid secretion. It is concluded that in the dog, in contradistinction to man, gastrin release after insulin is dependent on an intact vagus. Release of gastrin by adrenaline in the dog does not appear to be physiological since it is not achieved by the amount of adrenaline released in response to hypoglycaemia.

The role of the beta-adrnergic receptor in the secretion of gastrin: studies in normal subjects and in patients with duodenal ulcers.

Intravenous infusion of isoproterenol, a beta-adrenergic receptor stimulatory agent, increased serum gastrin concentration significantly more in patients with a duodenal ulcer than in healthy subjects. The rise in pulse rate, blood glucose concentration and in serum insulin was the same in both groups of subjects. Gastrin secretion was also increased significantly more in the patients than in the control subjects after a beef-meal. Basal serum gastrin concentrations were higher in the patients than in the control subjects and correlated to the rise in serum gastrin during both tests in the patients with a duodenal ulcer. Isoproterenol and meal stimulated gastrin secretion, expressed as percent of the basal value, were twice as higher in the patients as in the control subjects. The combined administration of isoproterenol and the meal had an additive effect on the rise in serum gastrin. Isoproterenol stimulated gastrin secretion was completely suppressed by propranolol, a beta-adrenergic receptor blocking agent, which had no effect on meal stimulated gastrin secretion. It is concluded that the mechanism of the hypersecretion of gastrin in patients with a duodenal ulcer did not involve a specific abnormality of the beta-adrenergic receptor or the receptor which recognized proteins and their digested products. There is no established role of beta-adrenergic receptor activity in the hypersecretion of gastrin in patients with duodenal ulcers. It is suggested that the beta-adrenergic receptor may have some yet unknown function unrelated to the acute secretory response of gastrin.

Plasma adrenaline and serum gastrin: studies in insulin-induced hypoglycemia and after adrenaline infusions.

Serum gastrin, plasma adrenaline, and blood glucose concentration were measured in 12 patients during insulin-induced hypoglycemia. Six patients had a duodenal ulcer, and 6 patients, 2 to 3 months earlier, had undergone a selective gastric vagotomy due to a duodenal ulcer. The lowest blood glucose concentration was obtained 30 min after the injection of insulin. The rise in plasma adrenaline showed a significant correlation with the degree of hypoglycemia attained. Serum gastrin was approximately doubled in both groups of subjects during the test. There was a strong correlation between rise in serum gastrin expressed in percentage of the basal value and the plasma adrenaline during hypoglycemia. In other experiments, adrenaline was infused intravenously in normal subjects in amounts (6 mug per min for 20 min) resulting in plasma concentrations comparable to those seen during the infusion. It is concluded that adrenaline is a hitherto little recognized factor influencing the gastrin response to hypoglycemia.

The influence of cimetidine on basal gastro-oesophageal sphincter pressure, intargastric pH, and serum gastrin concentration in normal subjects.

A pressure and pH-sensitive probe has been constructed for simultaneous measurement of gastro-oesophageal sphincter pressure and intragastric pH. The coefficient of variation for measurements of the gastro-oesophageal sphincter was 0.24, and for the intragastric pH, 0.09. After peroral ingestion of 400 mg of cimetidine or placebo, simultaneous measurements of gastro-oesophageal sphincter pressure and intragastric pH were made at fixed time intervals, and at the same time blood samples were taken for determination of serum gastrin and serum cimetidine concentrations. No demonstrable difference was found in the time-course of the gastro-oesophageal sphincter pressure after ingestion of cimetidine or placebo. After ingestion of cimetidine a significant rise in intragastric pH (p less than 0.05) occurred after 40 min, and this increased pH was maintained for the remainder of the experimental period, corresponding to a serum cimetidine concentration of over 1.00 mg/l. Similarly, there was a significant rise (p less than 0.05) in serum gastrin concentration after 150 min. There was a significant direct correlation between corresponding measurements of intragastric pH and serum gastrin (p less than 0.001), between intragastric pH and serum cimetidine (p less than 0.001), and between serum gastrin and serum cimetidine (p less than 0.05). Ingestion of cimetidine results in an increase in the serum gastrin concentration in healthy subjects, presumably as a result of reduced secretion of acid in the stomach. Neither the endogenous increase in serum gastrin concentration nor the increase in intragastric pH causes alteration in the gastro-oesophageal sphincter pressure.

The role of serum gastrin in the secretion of calcitonin: studies in patients with pernicious anaemia and in healthy subjects.

Basal concentrations of serum gastrin and serum calcitonin were measured in 38 patients with pernicious anaemia and in 32 healthy control subjects. The fasting level of serum gastrin was greatly elevated in 32 patients and was within normal range in 6 patients, the difference between pernicious anaemia patients and controls being highly significant (P less than 0.001). No significant difference between fasting serum calcitonin concentrations in patients and healthy subjects was found. Furthermore, these hormones were studied before and after a beef meal in eight of the patients with hypergastrinaemia and in six healthy control subjects. After the meal serum gastrin concentrations increased significantly from basal values in both patients and controls, the peak values being reached 60 and 30 min after the meal, respectively. No significant changes in serum calcitonin concentrations were observed after the meal in either group. In five patients a transient rise in serum calcitonin occurred 5-10 min after ingestion, beginning, however, before any rise in serum gastrin was observed. Our results indicate that serum gastrin is without influence on calcitonin release, either in hypergastrinaemic patients with pernicious anaemia or in healthy subjects.

Abnormal duodenal loop demonstrated by X-ray. Relation to gastric emptying time.

Gastric emptying time of a solid meal was estimated on X-ray in 7 patients with a normal duodenal loop, 7 patients with a proximal duodenal anomaly, and 12 patients with a distal duodenal anomaly. A determination coefficient between gastric emptying time and duration of serum gastrin increase was calculated. The food-stimulated serum gastrin secretory pattern was studied in 9 patients with a normal duodenal loop, 6 with a proximal duodenal anomaly, and 13 with a distal duodenal anomaly. The various groups presented significantly different gastric emptying times; thus patients with normal duodenal loop had a mean gastric emptying time of 6 h, patients with proximal duodenal anomalies ahd a mean gastric emptying time of 4.5 h, and patients with distal duodenal anomalies had a mean gastric emptying time of 9 h. Gastric emptying time and duration of increased serum gastrin secretion was positively correlated (R2 = 0.89). The food-stimulated serum gastric secretory pattern was equal in patients with proximal duodenal anomalies and those with distal duodenal anomalies and furthermore, reached significantly higher serum gastrin concentrations than in patients with a normal duodenal loop.

Increased sensitivity of gastrin release to adrenaline in duodenal ulcer.

Serum gastrin concentrations were measured in patients with duodenal ulcer and controls before, during, and after one-hour intravenous infusion of various doses of adrenaline (0.12 microgram to 6 microgram/min). Gastrin concentrations in the basal state were significantly increased in duodenal ulcer patients compared to controls. The maximal rise in serum gastrin concentrations was obtained at a dose of 4 microgram/min adrenaline in both groups of subjects, and the increase was significantly higher in duodenal ulcer patients than in controls. Adrenaline increased predominantly the gastrin III component (gastrin-17 like) in both duodenal ulcer patients and controls. The threshold level of adrenaline-induced gastrin release was significantly lower in duodenal ulcer patients: intravenous infusion of adrenaline in a dose of 0.12 microgram and 0.25 microgram/min increased serum gastrin concentrations 23 and 43%, respectively, but had no effect in controls. Rises in plasma adrenaline concentrations were similar in both groups of subjects in response to the various doses of adrenaline employed. Only the smallest dose of adrenaline (0.12 microgram/min) resulted in clearly physiological variations in plasma adrenaline concentrations. The results indicate that endogenous adrenaline may stimulate the secretion of gastrin during physiological conditions in patients with duodenal ulcer.

Antral vagotomy in parietal cell vagotomized dogs with a Heineke-Mikulicz pyloroplasty. Effect upon gastric emptying and motility, serum gastrin concentration, and Heidenhain pouch acid secretion.

In 6 Heidenhain pouch (HP) dogs who previously had undergone parietal cell vagotomy (PCV) with a Heineke-Mikulicz pyloroplasty (Ppl), the antral nerves were cut. No significant changes in HP acid secretion or serum gastrin concentration occurred. In a similar previous study using HP dogs with a PCV and a gastroduodenostomy (GD), a significant rise in HP acid secretion without concomitant changes in serum gastrin concentration were observed after antral denervation. These findings indicate that the antral vagal nerves have no direct influence on HP acid secretion, but the rised HP acid secretion in the GD dogs after antral denervation may be related to the changed gastroduodenal emptying pattern which partly excludes the food acid stream from the acid inhibitory mechanism in the duodenal bulb.

Gastroesophageal sphincter pressure and serum gastrin: reaction to food stimulation in normal subjects and in patients with gastric or duodenal ulcer.

Gastroesophageal sphincter pressure and serum gastrin concentration were determined in the fasting state and after the intake of a protein food in 6 normal subjects, 6 patients with gastric ulcer, and in 6 patients with duodenal ulcer. No significant differences in the fasting state were found. After the food intake, gastroesophageal sphincter pressure increased significantly over basal values in normals and in patients with duodenal ulcer, but in patients with gastric ulcer a decrease in pressure was noted. Serum gastrin rose in all subjects studied after the food stimulation, but it was significant only in the gastric and duodenal ulcer group. In two normals and two patients with duodenal ulcer the ingestion of a potato meal of similar weight to that of the protein meal showed no change either in serum gastrin or in sphincter pressure. In one additional normal subject and one duodenal ulcer patient the constant intravenous infusion of Aminosol for 2 h produced no change in serum gastrin or sphincter pressure. These results indicate that the effect of protein food on sphincter pressure is different for gastric or duodenal ulcers, and, furthermore, that this effect is mediated by proteins in the gastrointestinal tract.

Gastroesophageal sphincter pressure and serum gastrin studies following food intake before and after vagotomy for duodenal ulcer.

Gastroesophageal sphincter pressure (GESP) and serum gastrin concentration (SGC) were determined in the basal state and after a protein meal in six patients with duodenal ulcer (DU), six patients after parietal cell vagotomy (PCV), six patients after selective gastric vagotomy plus drainage (SGV + D), and six patients after selective gastric vagotomy plus precise antrectomy (SGV + A). No correlation in the resting state between GESP and SGC was observed. After food ingestion, DU patients showed a sustained rise in GESP which lasted up to the end of the experiment. The vagotomized patients, however, showed no rise in sphincter pressure after food intake--rather a tendency to a decrease in pressure occurred. On the contrary, SGC rose significantly after food ingestion in patients with SGV + D or PCV, while in DU patients this rise was less significant. Patients with vagotomy and antrectomy showed no rise in SGC. These results do not suggest that SGC and extrinsic vagal innervation in the resting state play a significant role in the maintenance of the tone of GES. After food ingestion an interaction may occur between intact vagal innervation and rise in SGC in order to obtain an adequate rise in GESP.

The influence of an abnormal duodenal loop on basal and food-stimulated serum gastrin concentrations.

Postprandial serum gastrin secretion was studied in 26 patients with X-ray-negative dyspepsia. Seven patients had a normal duodenum while 19 had duodenal anomalies. In patients with an abnormal duodenal loop, the mean postprandial serum gastrin secretion was significantly higher after 45, 60 and 120 min than that of the control group. No significant difference was demonstrated in the basal state. A delay in gastric emptying rate might be the cause of increased postprandial serum gastrin secretion in patients with an abnormal duodenal loop.

Gastroesophageal sphincter pressure and serum gastrin studies following food intake before and after vagotomy for duodenal ulcer.

Gastroesophageal sphincter pressure (GESP) and serum gastrin concentration (SGC) were determined in the basal state and after a protein meal in 6 patients with duodenal ulcer (DU) 6 patients after parietal cell vagotomy (PCV) 6 patients after selective gastric vagotomy plus drainage (SGV + D), and 6 patients after selective gastric vagotomy plus precise antrectomy (SGV + A). No correlation in the resting state between GESP and SGC was observed. After food ingestion, DU patients showed a sustained rise in GESP which lasted up to the end of the experiment. The vagotomized patients, however, showed no rise in sphincter pressure after food intake--rather a tendency to decrease in pressure occurred. On the contrary, SGC rose significantly after food ingestion in patients with SGV + D or PCV, while in DU patient this rise was less significant. Patients with vagotomy and antrectomy showed no rise in SGC. These results do not suggest that SGC and extrinsic vagal innervation in the resting state play a significant role in the maintenance of the tone of GES. After food ingestion an interaction may occur between intact vagal innervation and rise in SGC in order to obtain an adequate rise in GESP.