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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.

Six healthy subjects in random order underwent gastric bicarbonate secretion investigations, including stimulation with increasing doses of the cholinergic agonist carbachol, sham feeding, fundic distension and gastric instillation of 16,16-dimethyl prostaglandin E2. Bicarbonate secretion was measured by a computer-based system which continuously recorded pH and PCO2 of the effluent in a high-volume gastric perfusion system. The peak 30 min gastric bicarbonate output in response to carbachol, 150 mg subcutaneously, was 114% (P less than 0.05). Vagal stimulation by sham feeding resulted in a corresponding increase of 112% (P less than 0.05), while fundic distension to a volume of 600 ml gave an increase of 114% (P less than 0.05). In comparison, the response to 80 micrograms 16,16-dimethyl prostaglandin E2 was much greater, the peak bicarbonate output being increased by 245% (P less than 0.05). Both sham feeding and fundic distension appear to be either submaximal stimuli of gastric bicarbonate secretion in man or may possess both stimulatory and inhibitory actions.

Previous studies have shown that pancreatic polypeptide (PP) secretion is regulated by efferent, vagal stimulation. In the present study the afferent part of a vagovagal pathway has been investigated in two different ways: (I) Graded fundic distention: in 8 patients with duodenal ulcer ballon distention with 150 ml of the fundus and the body of the stomach increased PP concentrations in plasma from 19 (17--26) to 41 (35--48) pmol/l, median and interquartile range. Distention by 300 and 600 ml did not further increase PP concentrations. After denervation of the fundus by proximal gastric vagotomy, no increase in PP levels was observed during distention with 50 and 300 ml whereas distention by 600 ml was followed by a small increase. (II) Graded antral distention: balloon distention with 50, 100 and 150 ml of the antrum increased plasma PP concentrations in 7 healthy subjects and 14 duodenal ulcer patients. Maximal PP response was achieved by distention with 100 ml, healthy subjects: from 14 (12--23) to 40 (26--44) pmol/l, and duodenal ulcer patients: from 25 (13--38) to 47 (22--63) pmol/l, median and interquartile range. It is concluded that a gastropancreatic reflex stimulating PP secretion through a long vagovagal pathway is present in man, and that this mechanism probably is involved in the initial PP response during a meal.

Gastric acid responses to graded i.v. infusion of pentagastrin and Histalog were determined in peptic ulcer patients. Single-day multiple-dose tests were performed. The sensitivity to the humoral stimuli as determined by the calculated ED50's was not significantly different for duodenal ulcer patients with moderate (DUmod) or massive (DUmass) observed hypersecretion or for gastric ulcer (GU) patients: median ED50's of pentagastrin were 6.2, 6.6, and 13.1 mug/h in 18 DUmod, 22 DUmass and 7 GU patients respectively, and median ED50's of Histalog were 16.6, 25.3, and 17.1 mg/h in 14 DUmod, 10 DUmass and 6 GU patients respectively. Antrum-bulb resection significantly reduced basal acid secretion and maximal acid responses to the humoral stimuli (about 45% reduction) but did not significantly change the loss of gastric contents to the intestine or the sensitivity to the humoral stimuli (median ED50 of pentagastrin increased from 5.2 to 6.7 mug/h in 14 patients, and median ED50 of Histalog increased from 16.0 to 20.8 mg/h in 12 patients), suggesting that the intact antrum-bulb region of the ulcer patient is controlling the capacity to secrete acid, and indicating that antrum-bulb gastrin is an important trophic factor for the parietal cells in man.

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.

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.

Adipocyte size, lipoprotein lipase (LPL) activity, and the lipolytic response to noradrenaline and isoproterenol were studied in three intraabdominal depots (mesenteric, omental, retroperitoneal), as well as in subcutaneous abdominal adipose tissue, in nonobese groups of middle-aged men and in premenopausal and postmenopausal women. Subcutaneous adipocytes were larger than intraabdominal adipocytes in all groups. The men had large adipocytes in all intraabdominal depots as compared with the women. The premenopausal women seemed to have low LPL activity in intraabdominal depots. Two types of responses to catecholamine-stimulated lipolysis were observed: a similar response from mesenteric and omental (portal) fat depots and from retroperitoneal and subcutaneous abdominal (nonportal) fat depots. Young women had higher lipolysis in nonportal than in portal adipose tissues. In the men the reverse characteristics were found. These dissimilarities seem to be based on differences in beta-adrenergic responsiveness. Postmenopausal women showed no differences between depots. The differences in lipolytic responsiveness between these groups might be caused by sex steroid hormones.

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.

Eight patients with severe postgastrectomy syndromes for predominantly bile reflux gastritis were examined by quantification of bile acids in the gastric remnant before and after a standardized liquid meal. Gastroscopy with biopsy and determination of gastric acid secretion and gastric emptying were performed. Six of the patients were also studied 3 months after Roux-en-Y transposition. Controls consisted of six completely asymptomatic partially gastrectomized patients studied 4--11 years postoperatively and six healthy students without any history of gastrointestinal disease. The healthy subjects had virtually no reflux of bile acids in the fasting state or after a meal. Both the symptomatic and asymptomatic patients had reflux in the fasting state and postprandially. The reflux of bile acids was, however, significantly greater late in the fasting period and early in the postprandial period in the symptomatic patients than in those without symptoms. The Roux-en-Y transposition eliminated the bile acid reflux and the symptoms of bile reflux gastritis but did not change the gastric emptying pattern. In patients with reflux gastritis the acid disappearance in the gastric remnant was moderate and the maximal acid output was unchanged after Roux-en-Y transposition.

The gastric acid secretion in response to graded antral distension was determined in healthy subjects and in peptic ulcer patients with water perfusion or alkaline buffer perfusion of the stomach, giving an intragastric pH of 1.8-3.0 and 6.2-8.3 respectively. Intragastric neutralization increased the basal acid secretion in healthy subjects and gastric ulcer patients but did not change the basal acid secretion in duodenal ulcer patients. Distension of the antrum produced the same secretory effect with and without intragastric neutralization: no increased acid response in healthy subjects, a slight acid response in patients with a quiescent duodenal ulcer or a gastric ulcer, and a more pronounced acid response in patients with an active ulcer, amounting to about 30% of the peak acid response to pentagastrin. The results show that: a) the peptic ulcer patients - and particularly patients with an active duodenal ulcer - are more sensitive to the acid secretory effect of antral distension than healthy subjects; b) increasing the intragastric pH above 20 does not enhance the acid response to antral distension; c) the acid secretory effect of antral distension is markedly less in man than the effect observed in the dog.

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%.

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.

The variation in basal acid secretion was determined in 10 patients after resection of the esophagus, an operation resulting in a total transection of all vagal nerves to the abdomen. After recording basal acid secretion over a 3-h period, a 15-min modified sham feeding procedure was performed, and the acid output was studied for an additional hour. The mean basal acid output +2 SD was 0.27 mmol/15 min. The difference between the highest and lowest recorded 15-min output--that is, the oscillation of basal acid output--was calculated for each patient. The mean oscillation of basal acid output +2 SD was 0.58 mmol/15 min. Vagal stimulation accomplished by sham feeding produced no significant increase in acid output above this level. The variation in basal acid secretion was also investigated in 20 duodenal ulcer patients after proximal gastric vagotomy. These patients were insulin-negative and remained asymptomatic during a 7- to 10-year follow-up study. Shortly after the vagotomy, measurement of basal acid secretion over 3 h showed a mean basal acid output +2 SD of 0.58 mmol/15 min. The mean oscillation of basal acid output +2 SD was 0.66 mmol/15 min. On the basis of the oscillation in basal acid secretion after complete vagotomy we propose a new criterion for completeness of vagotomy, namely a response to physiologic vagal stimulation which does not exceed the lowest basal level by more than 0.6 mmol/15 min.

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.

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.

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.

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.

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.

Intraduodenal administration of oleic acid has previously been shown to inhibit gastric acid secretion induced by pentagastrin in man. This inhibition was dose-dependent and significantly correlated to a rise in plasma concentration of neurotensin-like immunoractivity (NTLI). Maximal inhibition occurred with a volume of oleic acid of 20 ml. In the present study intraduodenal instillation of 20 ml. of oleic acid inhibited acid secretion evoked by sham feeding in healthy subjects but did not significantly inhibit the near-maximal acid secretion stimulated by the histamine analogue betazole. The inhibition of acid secretion induced by sham feeding was the same (about 45%) as the inhibition of pentagastrin-stimulated secretion. Plasma NTLI rose significantly in both the sham feeding and betazole experiments and peaked at about 145 pM. The results are in agreement with the inhibitory characteristics of neurotensin and support the hypothesis that the inhibition of gastric acid secretion by small amounts of intestinal fat is at least partly mediated by neurotensin.

Although gastric resection may cause a variety of functional gastrointestinal disorders, malabsorption is rare. When such a disturbance occurs other complicating factors are mostly involved. Two patients who developed a severe malabsorption after partial gastric resection are presented. They both had the prerequisites for intestinal stasis--one had small bowel diverticula and the other a "blind loop" after previous surgery. Their malabsorption was cured by surgical correction of stasis.

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.

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.

Experiments were performed to validate the computerized pH/PCO2 technique for measurement of HCO3 secretion at a physiologic pH in the human stomach. In bench-side experiments the system detected 103 +/- 2% (mean +/- SE, n = 66) of boluses or infusions of NaHCO3. The standard curve was linear in the physiologic concentration range, and in the pH interval from 1.8 to 6.9 the recovery rate of added HCO3 was independent of the pH of the aspirate. In vivo the recovery rate of an exogenous NaHCO3 infusion (240 mumol/15 min) was 95 +/- 5% (n = 9), and there was no significant correlation between basal gastric pH and recovery rate. The results support that our computerized gastric perfusion method can be used for quantification of gastric bicarbonate secretion also at a physiologic acid pH.

Studies both in vivo and in vitro have shown that substituted benzimidazoles inhibit the stimulation of acid secretion produced by dibutyryl cyclic AMP and histamine. Furthermore, the results differ from those produced by H2 antagonists and anticholinergic agents in that the inhibition is not competitive, and the site of action is intracellular and peripheral to that of dibutyryl cyclic AMP. To investigate the biochemical mechanism of action of substituted benzimidazoles, one such compound, H 149/94 (2-([2-(3-methyl)pyridyl-methyl]-sulphinyl)-5-methoxycarbonyl-6-methylbenzimidazol), has been tested either directly on an (H+ + K+)ATPase isolated from pig and human gastric mucosa or on the function of this enzyme in gastric glands isolated from rabbit and human gastric mucosa. (H+ + K+)ATPase, which has only been found at the secretory surface of the parietal cell, catalyses a one-to-one exchange of protons and potassium ions. It is possibly the proton pump within the gastric mucosa, and may thus be the terminal or one of the terminal steps of the acid secretory process. We show here that H 149/94 inhibits (H+ + K+)ATPase, which may explain its inhibitory action on acid secretion in vitro and in vivo. Because of the unique distribution and properties of the (H+ + K+)ATPase, the inhibitory action of H 149/94 on this enzyme may be a highly selective clinical means of suppressing the acid secretory process.

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.

The oxygen consumption of human adipose tissue (AT) was determined in 53 adults, lean and obese, and in nine lean boys. The oxygen consumption was positively related to fat cell weight and negatively to age and degree of obesity. Men and women did not differ with respect to oxygen consumption of AT. The positive relationship between oxygen consumption per cell and fat cell size was also demonstrated in size-separated cells from the same donors. Expressed per cell the oxygen consumption was higher in fat cells from obese than in cells from lean subjects, but expressed per gram of tissue the opposite result was found. The oxygen consumption of the total AT organ was higher in obese than in lean subjects. The energy expenditure of AT constituted approximately 4% of the estimated 24-h energy expenditure in both groups. It is concluded that obese subjects do not maintain their obesity because of a reduced energy expenditure of the total AT (or of the total body). After a partial weight reduction in five subjects, the energy metabolism tended to change in direction toward the conditions seen in lean subjects. However, it is still an open question whether the observed energy metabolic aberrations of obese human AT are only secondary to the obese state or partly primary and thus of etiological importance.

Plasma gastrin concentrations and gastric acid output were measured during graded balloon distention of the gastric fundus and body in 20 patients with duodenal ulcer. Acid output rose stepwise with increasing distention volumes but plasma gastrin remained unchanged. During intragastric neutralization in 5 of these subjects, fundic distention did not elicit a significant rise in plasma gastrin, whereas the acid response was similar to that observed in the control study when the gastric contents were acid. In 8 of the 20 patients, proximal gastric vagotomy profoundly suppressed the acid response to fundic distention. Basal plasma gastrin concentrations were elevated after vagotomy but were unchanged during graded fundic distention. The results suggest that neural reflex activation of the oxyntic glands is the main mechanism by which fundic distention stimulates acid secretion in man. The failure of fundic distention to release gastrin does not, however, completely rule out the existence of an oxyntopyloric distention reflex for gastrin release in man. Fundic distention in man seems to both stimulate acid secretion and induce an inhibitory mechanism acting on acid secretion. This inhibitory mechanism may, purely speculatively, also mask the effect of an oxyntopyloric reflex for gastrin release. The present study and earlier work suggest that in man distention of the stomach is a poor stimulus for release of gastrin, regardless of whether the pyloric or the oxyntic gland area, or both, are distended.

The effect of antral balloon distension on acid secretion and the plasma gastrin concentration was studied in 8 duodenal ulcer patients. Antral distension significantly increased the acid secretion to about 30% of the peak acid response to pentagastrin without any change in the plasma gastrin concentration. Antral distension and concomitant intragastric neutralization, with the intention of facilitating release of antral gastrin, produced about the same acid response and did not evoke any plasma gastrin increment. The results suggest that the acid response to antral distension in duodenal ulcer patients is evoked without contribution of the gastrin mechanism, and that the acid response is probably mediated via a pyloro-oxyntic reflex. In this respect the duodenal ulcer patient seems to differ from the healthy subject, in whom antral distension produces no acid response, and from the dog, in which release of gastrin as well as pyloro-oxyntic reflex participate in the acid response to antral distension.

The effects of intraduodenal administration of oleic acid (5, 10, 20, and 40 ml) on gastric acid secretion stimulated by a submaximal intravenous pentagastrin infusion and on plasma concentrations on neurotensin-like plasma immunoreactivity (NTLI) were studied in 18 healthy subjects. Each volume of oleic acid or saline (controls) was tested in six subjects except the volume of 20 ml, which was given to ten subjects. Gastric acid secretion was studied for a 2-h period at 15-min intervals after intraduodenal infusion. Five milliliters oleic acid evoked a significant inhibition (29%) of gastric acid secretion. Maximal inhibition by oleic acid appeared after 20 ml (43%), which was significantly greater than after 10 ml. In seven duodenal ulcer (DU) patients 20 ml oleic acid evoked an inhibition of 20%, which was significantly lower than in the healthy subjects. Proximal gastric vagotomy (PGV) abolished the fat inhibition in DU patients. Basal and peak NTLI concentrations after 20 ml oleic acid were significantly lower in DU patients than in health subjects. In DU patients there was no significant difference in the integrated response of NTLI before and after PGV. The 2-h integrated NTLI response was dependent on the administered volume of oleic acid in healthy subjects. There was a correlation between acid inhibition and the integrated response ot NTLI in healthy subjects. This suggests that immunoreactive neurotensin may be involved in the oleic-acid-induced inhibition of gastric acid secretion. Neurotensin, or a neurotensin metabolite, apparently exerts its inhibitory effect at a synaptic level, which explains the finding that oleic acid did not inhibit gastric acid secretion after PGV. Neurotensin may have a physiological role as a hormone with enterogastrone functions.

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.

The palliative effect of repeated endoscopic dilatation of malignant strictures of the esophagus and esophagogastric junction was prospectively evaluated in 41 patients. Dilatation was performed with Eder-Puestow technique in brief general anesthesia. Substantial improvement in swallowing ability was experienced after each treatment. The dysphagia recurred, however, and the dilatations were repeated at intervals of about 4 weeks. Most patients required less than or equal to three treatments during their remaining lifespan. There were few complications, the most prominent being perforation (in 5% of 128 sessions). Only short hospital stay was required, and 18 patients remained at home during the periods between dilatations. Endoscopic dilation of the esophagus and esophagogastric junction gives good palliation. The technique is simple, cheap and safe. It is suitable for lesions at any site, not time-consuming, available at almost all endoscopy units, and consequently to be recommended in this clinical setting.

In the present study the influence of duodenal exclusion and vagotomy on basal release of gastrin from extra-antral stores has been investigated in addition to the consequences of these procedures on the gastrin response to gastrin-releasing peptide (GRP) infusion. Basal gastrin concentrations and the response to GRP were measured in seven patients after a Whipple operation, in seven patients after antrectomy combined with selective gastric vagotomy and B I reconstruction, in seven patients operated on with antrectomy, selective gastric vagotomy, and Roux-en-Y reconstruction, and finally in seven patients after antrectomy, truncal vagotomy, and Roux-en-Y reconstruction. Gastrin was measured by a highly specific radioimmunoassay. Very low concentrations were obtained after a Whipple operation, and no increase followed GRP infusion. The basal gastrin concentrations were slightly higher in antrectomized patients, irrespective of whether a selective gastric vagotomy had been added. However, in these patients a significant gastrin response followed GRP infusion. Duodenal exclusion seemed not to influence the response to GRP. On the other hand, extragastric vagotomy was followed by low gastrin concentrations in the basal state and only a marginal response to GRP administration. These results strongly suggest that GRP releases gastrin from the human duodenal mucosa and that duodenal exclusion does not alter the response of the duodenal gastrin cells to GRP stimulation. Vagal denervation of the duodenal mucosa seems to suppress the gastrin response to GRP, indicating an excitatory influence of the vagus nerve.

From experiments on the dog evidence has accumulated of vagal release of a candidate hormone inhibiting gastric acid secretion--vagogastrone. The nature and origin of vagogastrone are uncertain. The inhibitory effect of vagogastrone is characteristically exerted against gastrin-stimulated acid secretion from the vagally denervated parietal cell area. In the present study vagal activation by sham feeding significantly inhibited the submaximal acid response to continuous i.v. infusion of pentagastrin in seven duodenal ulcer patients previously subjected to proximal gastric vagotomy. The inhibitory effect was slight--16% reduction--and of short duration. Sham feeding had no effect on the pentagastrin-stimulated acid secretion in six subjects with an intact stomach. The results favour the existence of a vagogastrone mechanism in man, but the inhibitory effect seems to be of quantitatively minor importance, at least in the duodenal ulcer patient.

Graded antrum distension by 50-, 100-, and 150-ml balloon volumes significantly stimulated gastric acid secretion in 6 duodenal ulcer patients, but had no stimulatory effect in 6 healthy subjects. Antrum distension by 150-ml balloon volume had no effect on the acid response to submaximal stimulation by a continuous intravenous infusion of pentagastrin in the duodenal ulcer patients, but significantly inhibited this response in the healthy subjects. The inhibition by antrum distension in the healthy subjects amounted to 20%. The results suggest that antrum distension elicits stimulatory as well as inhibitory mechanisms in man with inhibition of acid secretion predominating in healthy subjects and stimulation of acid secretion predominating in duodenal ulcer patients. The mechanism of inhibition is unknown.

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.

A patient with atrophic gastritis and excessively raised serum gastrin concentrations (4000 to 5000 pg/ml) was found to have multiple polypous tumors of the gastric corpus mucosa. Following gastrectomy, serum gastrin concentrations decreased to undetectable levels. The tumors consisted of a mixed population of endocrine cells. The majority of tumor cells were of the ECL type, but, in addition, enterochromaffin cells of various subtypes as well as agranular cells were found. The tumors were locally invasive and invaded the walls of submucosal blood vessels. The surrounding mucosa showed a severe atrophic gastritis with intestinalization and contained numerous goblet cells, enterochromaffin cells, and cholecystokinin cells. Cholecystokinin cells do not occur in the normal oxyntic mucosa. Hence, the observation of this cell type in intestinalized gastric epithelium suggests that "intestinalization also is associated with changes in endocrine cell populations. Gastrin has been shown to affect the function of the ECL cells. Indications for a trophic action of gastrin on these cells have been obtained. It is discussed whether greatly raised serum gastrin levels in patients with atrophic gastritis may be associated with increased risks for the development of certain types of gastric tumors.

Heterotopic gastric mucosa was found in the duodenum of a female patient with duodenitis and acid hyposecretion. The heterotopic isolated fundic glands were shown to accumulate 14C-aminopyrine in basal state and on stimulation with histamine suggesting that the heterotopic mucosa secreted acid. The ectopic acid secretion in the duodenal bulb suppressed gastric acid secretion, and might have caused the duodenitis and at least partly the clinical symptoms. The heterotopic gastric mucosa could be removed surgically by local excision. This procedure, combined with a Nissen fundoplication for suspected reflux oesophagitis, was followed by total symptomatic relief and normalization of gastric acid 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.

The inhibitory effect of intraduodenally administered oleic acid in volumes of 5--40 ml on pentagastrin-stimulated gastric acid secretion was determined in healthy volunteers. In the control experiments, corresponding volumes of saline were given. Five and 10 ml oleic acid brought about a significant inhibition of gastric acid secretion of 29% and 32%, respectively. After 20 ml of oleic acid the inhibition was 46%, a significantly stronger inhibition than after 5 or 10 ml. Forty milliliters of oleic acid did not further increase the inhibition. Maximal inhibition appeared 30--60 min after the administration of oleic acid. In seven duodenal ulcer patients 20 ml oleic acid evoked an inhibition of gastric acid secretion of 20%, which was significantly less than the inhibition produced in healthy subjects after the same volume of oleic acid. The results suggest that the intraduodenal administration of relatively small volumes of oleic acid elicits a dose-dependent inhibition of pentagastrin-stimulated gastric acid secretion in man and that maximal inhibition is obtained by 20 ml of oleic acid. The results also indicate that duodenal ulcer patients may have a defective fat inhibitory mechanism.