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Helicobacter pylori infection contributes to hypergastrinemia and hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and parietal cells normally activated by antral distention. Our aim was to investigate whether a similar blockade of inhibitory responses could be provoked by inducing gastritis with aspirin, thus implicating a common inflammatory component, possibly a proinflammatory cytokine(s).We studied the effects of antral distention on stimulated acid secretion and gastrin release in H. pylori-negative volunteers, before and after 3 days of aspirin therapy (2 g daily). Immediately before the examinations, the severity of gastric mucosal injury was evaluated macroscopically and histologically, and the production of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma was determined by immunohistochemistry.Most subjects had severe gastric injury after aspirin therapy, resulting in a substantially increased production of IL-1beta, IL-6, and IL-8 but not of TNF-alpha and IFN-gamma in the antral mucosa. In these subjects the acid-inhibitory response was abolished or markedly reduced. Conversely, aspirin therapy failed to affect the gastrin release in all subjects studied.The disinhibition of acid secretion in response to antral distention is a joint feature of the gastritis induced by aspirin and H. pylori infection, possibly related to the increased production of IL-1beta, IL-6, and IL-8. The H. pylori-related hypergastrinemia apparently has a different background.

The effect of repeated once daily administration of 20 mg omeprazole orally and 10 mg and 40 mg intravenously on 24-h intragastric acidity was studied in nine healthy subjects. On day 1, 20 mg orally and 10 mg intravenously reduced integrated intragastric acidity by 18% and 15%, respectively (NS). On day 5 the reduction had increased to 60% and 53%, respectively (p0.05). The first dose of 40 mg intravenously produced a reduction of 71% (p0.05) with no further increase during continued administration. An increase in plasma omeprazole concentrations by 56% (p0.05) was seen during repeated dosing with 40 mg intravenously, while no significant change occurred with the two other doses. Thus once daily administration of 10 mg omeprazole intravenously produced an effect on 24-h intragastric acidity comparable to that of once daily administration of 20 mg omeprazole orally. However, for both these dosage regimens it took a few days before their maximal effect was obtained. Parenteral administration of 40 mg omeprazole produced, already on the first day of treatment, an effect similar to that seen after 5 days of oral administration of 20 mg omeprazole or intravenous administration of 10 mg and can therefore overcome this initial delay in drug action. The reduction of 24-h intragastric acidity seen in the present study appeared to be lower than that seen in a similar study in duodenal ulcer patients, a finding not explained by differences in age or pharmacokinetics.

The relationship between interdigestive gastric motility and secretion was studied in eight healthy volunteers. Acid and bicarbonate output rates were measured with a high time resolution, using a perfusion system based on continuous registration of pH and PCO2 of gastric effluent. Antral pressure was measured by manometry. The total duration of the interdigestive motility cycle (time between two phase-III complexes) was 96 +/- 12 min (mean +/- SE). In late migrating motor complex phase II, acid output, bicarbonate output, and bile reflux increased significantly. Acid secretion reached a peak in association with motor phase III. The gastric lumen was then rapidly alkalinized; this phenomenon was due to a simultaneous decrease in acid secretion and a short-lasting (15 +/- 2 min, mean +/- SE) phasic increase in bicarbonate output, which was not associated with bile reflux (bilirubin). After these phase-III-related events both acid and bicarbonate output rates reached a relatively stable level during phase I and early phase II. This period of stability constituted 47 +/- 3% (acid) and 41 +/- 6% (bicarbonate, means +/- SE), respectively, of the cycle. The peak to base line output ratio was 6.6 +/- 1.2 (p0.001) for acid and 2.8 +/- 0.3 (p0.001) for bicarbonate (means +/- SE). The results show a marked variability in acid and bicarbonate output rates during the interdigestive motility cycle. The magnitude of this variability has previously been underestimated owing to poor time resolution of the secretion measurements. If not taken into account, these 'spontaneous' secretory variations may constitute a considerable source of error in gastric secretion studies.

The effects of a 150-ml antral balloon distension on pentagastrin-stimulated gastric acid secretion and bicarbonate secretion were studied in nine healthy subjects and eight duodenal ulcer (DU) patients. The gastric secretions were simultaneously measured, using a luminal perfusion and pH/PCO2 measurements. Two of the healthy subjects and six of the DU patients were positive for Helicobacter pylori. When H. pylori-positive and -negative subjects were compared, basal gastric acid and bicarbonate outputs did not differ significantly. In H. pylori-infected subjects the bicarbonate transport increased by about 70% on pentagastrin stimulation. In the H. pylori-negative group pentagastrin had no effect on the bicarbonate secretion. Antral distension elicited a 30-35% inhibition of pentagastrin-stimulated gastric acid secretion in the group of H. pylori-negative subjects, whereas the acid secretory level remained essentially unchanged in the positive group. Bicarbonate secretion decreased transiently by the distension in the negative subjects, whereas a slight increase was observed in the infected group. We conclude that antral distension inhibits pentagastrin-stimulated gastric acid output in healthy H. pylori-negative subjects. Our results strongly suggest that the underlying mechanism is a direct inhibition of gastric parietal cell function and not an increased gastric bicarbonate secretion. Furthermore, the results indicate that this defective distension-induced acid inhibition may be correlated to H. pylori infection rather than to duodenal ulcer disease.

The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated. © 1999 Cancer Research Campaign

The metabolism of histamine in the human gastric mucosa was studied in the basal state and during pentagastrin stimulation. Studies were made in healthy volunteers and in patients with peptic ulcer disease. Mucosal biopsies were taken from antral and oxyntic gland areas whereupon histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Histamine content of the oxyntic gland mucosa was decreased as a consequence of pentagastrin administration in all groups studied, and this decrease was numerically largest in patients with duodenal ulcer disease. Pentagastrin induced a significant increase in histidine decarboxylase activity of the oxyntic gland mucosa with the most profound increase seen in patients with duodenal ulcer. The highest rates of histamine formation were present in the oxyntic mucosa of patients with Zollinger-Ellison syndrome. The activity of histamine methyltransferase was the same in all groups studied and was not changed by pentagastrin. In conclusion, pentagastrin administration in humans is followed by a significant mobilization of histamine only from the oxyntic gland mucosa, an effect that is more pronounced in patients with duodenal ulcer disease.

Several mechanisms have been proposed for the development of Crohn's disease. Evidence in favour of a unifying 4-component concept to explain the development of Crohn's disease is presented. The four components are a genetic predisposition to an increased intestinal permeability, the key and initial triggering factor being an oral-pharyngeal bacterium that increases the mucosal permeability of the small intestine with only a minimal inflammatory reaction, an adherent-invasive strain of Escherichia coli that penetrates the mucosa and causes an acute inflammatory reaction in the intestinal wall, and finally a secondary invasion of bacteria causing the chronic inflammatory characteristics. Irritable bowel syndrome (IBS) is a functional bowel disorder with intermittent symptoms of varying intensity. Clinically, there is evidence to suggest a link between IBS patients with diarrhoea and patients with Crohn's disease. The common denominator and initial trigger for IBS with diarrhoea and Crohn's disease seems to be an increased small intestinal permeability, probably caused by an oral-pharyngeal bacterial strain. The important missing factor in IBS patients seems to be the adherent-invasive strain of E. coli in the proximal colon, causing the acute inflammatory process in patients with Crohn's disease. IBS with diarrhoea can then be looked upon as an incomplete Crohn's disease.

Helicobacter pylori infection is considered to be an important factor in the development of gastric cancer, while duodenogastroesophageal reflux is claimed to be the main cause of development of esophageal adenocarcinoma. A pronounced activation of PAR-2 receptors may be a common denominator in triggering the development of these cancers, and possibly pancreatic and colonic cancers as well. Evidence supporting such a concept is presented.

Helicobacter pylori infection engaging mainly the gastric antrum causes hypersecretion of gastric acid. The increased duodenal acid load gives rise to islands of gastric mucosa in the proximal duodenum. As these bacteria thrive only on gastric mucosa it presents an opportunity for Helicobacter pylori to colonize the duodenum. A much higher density of virulent Helicobacter pylori has been found in the duodenum of duodenal ulcer patients in comparison to infected subjects without duodenal ulcer. The high density of virulent Helicobacter pylori in the proximal duodenum results in a strong inflammatory reaction with active duodenitis and impaired bicarbonate secretion. These characteristics of duodenal ulcer patients, together with the acid hypersecretion, seem to be the key factors in evoking a duodenal ulcer.

BACKGROUND We wanted to estimate the incidence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the general population, and the detection of colorectal tumor (CRT) and inflammatory bowel disease (IBD) after the diagnosis of IBS and FD. METHODS Patients aged 20-79 years newly diagnosed with IBS (N = 2956) or FD (N = 9900), together with a comparison cohort randomly sampled from the general source population, were followed-up during a mean time of 3 years. RESULTS We found an overall incidence of 10.3 per 1000 person-years for FD and 2.6 per 1000 person-years for IBS. There was a greater prevalence of depression, stress, fatigue, and pain disorders among IBS and FD patients than in the general population. During the 1st year after a diagnosis of IBS the cumulative risk of detecting CRT was close to 1% in IBS patients. After the 1st year the risk of CRT in IBS patients was close to that in the general population. We found a significantly increased risk of detecting IBD among patients initially diagnosed as having IBS (relative risk (RR), 16.3; 95% confidence interval (CI), 6.6-40.7), which was constant during all the follow-up period. No association was found between dyspepsia and CRT, or IBD. CONCLUSION IBS and FD shared some comorbidity features, yet demographics and incidence rates were different. Unlike the detection of colorectal tumor, the excess risk of IBD after an initial diagnosis of IBS was cumulatively increased during all the follow-up period. The continuously increased risk of IBD detection in IBS patients favors a true association between IBS and IBD.

This chapter aims to give a short update on Helicobacter pylori-induced effects on gastric acid and duodenal bicarbonate secretions, and how these disturbances may participate in the development of duodenal ulcer disease. It is not intended to be a full review, but rather a subjectively selected update with some personal speculations.

To assess the effect of vertical banded gastroplasty and gastric banding on the development of gastro-oesophageal reflux using both subjective and objective methods.Prospective, randomised study.Teaching hospital, Sweden.50 consecutive, morbidly obese patients (mean (SD) body mass index (BMI) 42.5 (5), 27 women and 23 men; mean age 48 years, range 38-57 years).Vertical banded gastroplasty (n = 24) or gastric banding (n = 26).Results of evaluation by standardised questionnaire, 24-hour ambulatory pH-metry, and endoscopy.After six months the mean (SD) BMI had decreased to 34.4 (5.7), with no differences between the groups. Mild dysphagia was somewhat more common (13 compared with 1) but the incidence of heartburn (8 compared with 17), and acid regurgitation (12 compared with 14) were less after the operation; 3 patients developed erosive oesophagitis, two in the vertical banded group and one in the banding group. Ambulatory pH-metry readings did not change significantly from preoperatively and there were no differences between the two operations. One patient developed pathological reflux, and in three the values returned to the normal range.Gastric restriction operations including those with a narrow stoma that causes outflow obstruction do not seem to increase the incidence of reflux in patients with functioning antireflux barriers.

BACKGROUND & AIMS: Recently, we postulated a new concept of duodenal ulcer pathogenesis suggesting that antral Helicobacter pylori infection blocks inhibitory pathways to the gastrin and parietal cells, resulting in an increased and prolonged postprandial acid secretion. the aim of this study was to examine duodenal acid load and duodenal bulb pH after a meal before and after eradication of H. pylori. METHODS: Using a marker-dilution method and a pH electrode in the duodenal bulb, gastric emptying, acid secretion, gastrin release, duodenal acid load, and duodenal bulb pH were studied during 2 hours after peptone meals of pH 7.0 and 2.0 in 8 H. pylori-negative controls and 8 H. pylori-infected subjects before and 6 months after eradication. RESULTS: The H. pylori- infected subjects had an increased gastric emptying, gastrin release, and acid secretion, higher duodenal acid load, and lower duodenal bulb pH after the meals. These responses were normalized after eradication. CONCLUSIONS: H. pylori-infected subjects have an increased and prolonged postprandial acid secretion, partly caused by an impaired low pH inhibition of acid secretion, gastrin release, and gastric emptying, resulting in an increased duodenal acid load and a prolongation of low pH in the duodenal bulb, as a general prerequisite for the development of duodenal ulcer disease. (Gastroenterology 1996 Aug;111(2):391-400)

From October 1993 through May 1994, 38 consecutive morbidly obese patients underwent a laparoscopic vertical banded gastroplasty (VBG). During the operation a gastric window was made by a 25-mm circular stapler; and the vertical staple line, establishing the gastric pouch, was constructed by using a 60-mm, four-row linear stapler. The outflow stoma was reinforced by a Gore-Tex band and calibrated to have an internal diameter of 9 mm. Three patients had to be converted to open surgery during the initial laparoscopic procedure because of insufficient operative access. Another three patients had to be reoperated during subsequent postoperative courses, one laparoscopically to reinforce a vertical staple line defect caused by a transected nasogastric tube, another because of an open reoperation during the first postoperative day for a rupture in the vertical staple line, and, finally, a patient was reexplored because of the present of postoperative fever with a left-sided pleuropneumonia and subphrenic accumulation of fluid. However, during the operation no leakage or any other local complications were detected. The subsequent postoperative courses were uneventful in all these patients. Compared with the reference group comprising the latest consecutive 17 obese patients operated with open VBG before the introduction of the laparoscopic technique, the laparoscopy group had less postoperative pain and had mobilization sooner. In the latter group, we recorded an improved respiratory status during the early postoperative period, as reflected by increased oxygen saturation and peak exspiratory flow rates as well as a lower body temperature. In conclusion, laparoscopic VBG is technically feasible and can be safely performed. Our early postoperative experiences suggest that these patients have a shorter and less cumbersome postoperative recovery period compared with conventionally operated obese patients. The long-term follow-up of these patients will determine whether these initial advantages of the laparoscopic approach are corroborated by comparable effects on weight control.

To determine the effects of testosterone (T) on lipid assimilation in different adipose tissue depots, T (250 mg, im) was given to 17 middle-aged men 5 days before abdominal surgery. Twenty-four hours before surgery, 10 microCi labeled oleic acid in 80 g milk fat were administered orally. Lipid radioactivity was measured in adipose tissue biopsies from abdominal ac, omental, and retroperitoneal adipose tissues. Subcutaneous, visceral (omental plus mesenteric), and retroperitoneal adipose tissue masses were determined using computerized tomography scans at 22 levels. Sixteen men who were not treated with T served as controls. T administration was followed by an increase in serum concentrations from 17.7 +/- 1.1 to 32.6 +/- 1.8 nmol/L (P0.001) and a marked (50%) reduction compared with controls in lipid radioactivity in omental and retroperitoneal adipose tissues, but not in sc adipose tissue. In controls, sc, visceral, and retroperitoneal adipose tissues assimilated 59.2 g (73.4%), 16.9 g (20.9%), and 4.6 g (5.7%), respectively, of the orally administered fat. In the T-treated men, this was changed to 73.5 g (88.8%), 6.4 g (7.7%), and 2.9 g (3.5%), respectively. It was concluded that T inhibits triglyceride assimilation in intra-abdominal depots and apparently directs this lipid to sc fat in men.

The present paper describes and evaluates a methodologic approach for registration of the fast, interdigestive, motility-related changes in gastric acid and bicarbonate outputs seen in man.The technique is based on continuous gastric luminal perfusion and measurements of pH and PCO2 in gastric effluent and concomitant intragastric/duodenal manometry. Fourteen healthy volunteers participated.Direct acid secretory estimations from pH recordings, corrected for hydrogen ion activity, correlated closely with values obtained by conventional titration. After intragastric infusion of bicarbonate, 96 +/- 5% of the newly measured steady-state value was registered virtually instantaneously provided that corrections for the PCO2 electrode time constant and the perfusion/aspiration time were made. In the neutral pH range (pH 5-7), practically full quantitative recovery of intragastrically infused bicarbonate was obtained. In the acid pH interval (pH 2-5) the recovery was significantly lower (53 +/- 6%; p0.01). With an aspirate without air admixture and during high perfusion rates (31 and 46 ml/min), full recovery of bicarbonate was obtained also at an acid pH, whereas a reduced perfusion rate (16 ml/min) significantly (p0.05) reduced the recovery rate.With the pH/PCO2 technique both acid and bicarbonate assessments have a close to on-line time resolution. Acid output is measured accurately, but the method potentially underestimates actual bicarbonate levels in the acid pH range, a combined effect of diffusion of CO2 into air bubbles in the aspirate and into the gastric mucosa from the lumen. A high gastric perfusion rate minimizes this source of error. The pH/PCO2 technique is well suited for studies of the interaction between secretion and motility in the human stomach.

The bicarbonate ion seems to play a crucial role in mucosal acid-base regulation by generating a pH gradient that is regarded as a 'first line of defense' against acid back-diffusion. The aim of this study was to determine the effects of hypovolemia on gastric mucosal buffering capacity, as reflected by luminal HCO3- release, in human volunteers.Central hypovolemia was induced by lower-body negative pressure (LBNP), and HCO3- release was measured by using a perfusion system based on continuous recording of the pH and PCO2 of gastric aspirate. The response to LBNP was related to concomitant cardiovascular effects, to gastric pH, and to the current phase of the migrating motor complex (MMC).At an acid gastric pH, LBNP induced a slight but statistically significant reduction in luminal HCO3- release (-27 +/- 10%, p0.05). The magnitude of the response was significantly correlated with the degree of reflex tachycardia. A larger and less variable response (-78 +/- 4%, p0.01 versus control group) was seen when luminal pH was increased by ranitidine pretreatment. The effect of LBNP on HCO3- release was statistically significant only during the early and middle parts of the MMC cycle.The results indicate that hypotension may reduce gastric mucosal buffering capacity, probably by activation of a sympathetic reflex. The magnitude of this response seems to depend on: 1) the degree of baroreceptor unloading; 2) luminal pH; and 3) the current phase of the MMC.

In 26 patients with carcinoma of the esophagus or gastroesophageal junction, intestinal interposition was performed in post-resection reconstruction, using left colon in 21 cases, right colon in one and a long jejunal segment in four cases. The tumor involved the gastric cardia in 16 patients with colonic interposition and five underwent palliative resection. Infectious pulmonary and abdominal complications were common. Three patients required reoperation, for empyema, ischemic colonic segment and subphrenic abscess, respectively. Ischemia of the interposed segment occurred in two patients, necessitating removal of the segment in one. There was no anastomotic dehiscence and no tumor in the margins of the resected tissue. The 30-day postoperative mortality was 1/22 and the mean postoperative hospital stay 24 days, with 11 patients discharged directly to their homes. The functional results 6 months postoperatively were favorable in most survivors, and only three complained of dysphagia.

Volume and pressure characteristics as a measure of reservoir function were studied in three patient groups greater than 1 year after gastrectomy for cancer, one group with straight Roux-en-Y esophagojejunostomy, one with an s-shaped gastric substitute after total gastrectomy, and the third group with subtotal gastrectomy. A large latex balloon was introduced into the proximal jejunum, gastric substitute or gastric remnant and then filled with water at a constant, slow rate. The maximal volume capacity was 400 ml at basal pressure 13.9 cmH2O in the remnant after subtotal gastrectomy and 475 ml at 10.4 cm in the gastric substitute, but only 180 ml at basal pressure 40.4 cmH2O in the proximal Roux limb of the straight esophagojejunostomy. Maximal basal pressure and maximal pressure amplitudes throughout the study period were significantly higher in the patients with straight Roux-en-Y esophagojejunostomy. The results suggest that a gastric substitute constructed as an s-shaped pouch is characterized by pressure and volume typical of a low-pressure reservoir, similar to that achieved by leaving the proximal part of the stomach intact.

Forty-one patients admitted with first episode of bleeding from esophageal varices were enrolled in a trial of the efficacy of oral propranolol to prevent rebleeding during the course of endoscopic sclerotherapy until obliteration. Single-blind randomization to sclerotherapy alone or with propranolol was used. At monthly endoscopy the varices were injected with 1% Aethoxysclerol until obliteration. If bleeding recurred, additional sclerotherapy was given. There was no intergroup difference in time to eradication of varices (8.1 vs. 7.7 months). The cumulative number of bleedings from varices and from distal esophageal ulcerations was identical in the two study groups. Five patients in the control group but only one in the propranolol group died of bleeding in the study period, a difference of only borderline significance (chi 2 = 4.08, df = 1). There were no specific side effects of propranolol. Thus propranolol did not significantly reduce the frequency of rebleeding until variceal obliteration, but could have had some influence on the gravity of rebleeding.

The metabolism of histamine in the human gastric mucosa was studied in the basal state and during pentagastrin stimulation. Studies were made in healthy volunteers and in patients with peptic ulcer disease. Mucosal biopsies were taken from antral and oxyntic gland areas whereupon histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Histamine content of the oxyntic gland mucosa was decreased as a consequence of pentagastrin administration in all groups studied, and this decrease was numerically largest in patients with duodenal ulcer disease. Pentagastrin induced a significant increase in histidine decarboxylase activity of the oxyntic gland mucosa with the most profound increase seen in patients with duodenal ulcer. The highest rates of histamine formation were present in the oxyntic mucosa of patients with Zollinger-Ellison syndrome. The activity of histamine methyltransferase was the same in all groups studied and was not changed by pentagastrin. In conclusion, pentagastrin administration in humans is followed by a significant mobilization of histamine only from the oxyntic gland mucosa, an effect that is more pronounced in patients with duodenal ulcer disease.

Body compositional changes during rapid weight loss and after weight stabilization were prospectively studied in morbidly obese patients undergoing gastroplasty operations. Body composition was studied preoperatively and 6 and 24 months postoperatively in 23 patients by use of a total body counter (40K) and an isotope dilution technique. The mean fat mass, cell mass, and intracellular water (ICW) decreased during the first 6 months (p less than 0.001) and remained unchanged at the 24-month test. However, the mean liters of extracellular water (ECW) did not change. Consequently, the ECW/ICW ratio, high in states of malnutrition, rose above postoperative levels. A strong correlation was found between decreases in cell mass and increases in the ECW/ICW ratio.

Background: Helicobacter pylori infection contributes to hypergastrinemia and hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and parietal cells normally activated by antral distention. Our aim was to investigate whether a similar blockade of inhibitory responses could be provoked by inducing gastritis with aspirin, thus implicating a common inflammatory component, possibly a proinflammatory cytokine(s). Methods: We studied the effects of antral distention on stimulated acid secretion and gastrin release in H. pylori

Plasma gastrin concentrations and gastric acid output after modified sham feeding were determined in 20 duodenal ulcer patients. Sham feeding produced an acid response corresponding to 40-68% of the maximal acid output after pentagastrin stimulation, with no significant increase of plasma gastrin concentrations. In eight patients proximal gastric vagotomy almost abolished the acid responses to both insulin hypoglycaemia and sham feeding. Sham feeding in the vagotomised patients did not change the gastrin concentrations in plasma. After pretreatment with benzilonium, an anticholinergic with minimal central nervous effects, plasma gastrin concentrations increased after sham feeding. The study confirms that sham feeding is a poor stimulus for gastrin release in duodenal ulcer patients and supports a cholinergic inhibition of gastrin release. Intravenous injection of benzilonium bromide in a dose close to 70 micrograms/kg, and atropine in the low dose of 30 micrograms/kg inhibited the acid response to sham feeding by about 65%. Atropine in a dose of 50 micrograms/kg virtually abolished the acid sham feeding response, possibly owing to ganglionic or central nervous blockade. Vagal activation of the acid secretory glands does not seem to involve a purely cholinergic neurotransmission.

The effect of cholinergic blockade on the concentrations of pancreatic-polypeptide (PP) in plasma was studied in 19 patients with duodenal ulcer (DU) and 16 control subjects. PP concentrations increased with age both in control subjects and in DU patients. In the DU patients atropine or benzilonium, an antimuscarinic agent with minimal cerebral actions, reduced PP concentrations from 47 (8–220) to 28 (7–53) pmol/liter, n=18, median and total range. In the control subjects atropine suppressed the PP concentrations from 17 (0–257) to 11 (0–41) pmol/liter, n=15. Cholinergic blockade had only a minor effect in 1 patient and 1 control, both with high PP concentrations. Both in the DU patients and in the control group the suppression by the cholinergic blockade was most marked in subjects with elevated PP concentrations. Spontaneous acid and PP secretion were measured simultaneously in 25 DU patients. No correlation was found between median acid secretion and median concentrations of PP. However, in the individual patient a positive covariation was found between fluctuations in spontaneous acid secretion and fluctuations in PP concentration, P

In four healthy subjects and in 12 patients with duodenal ulcer (DU), graded balloon distension of the gastric fundus and body caused increments in acid output related to the distension volumes. The mean peak distension response amounted to about 50% of the mean peak acid output (PAOpg) evoked by intravenous infusion of pentagastrin in a dose of 300 microng/h, eliciting maximum observed secretory response. During distension with the largest balloon volume, 1-0 mg atropine injected intravenously significantly depressed the acid secretory rate, the median inhibition amounting to about 80%. In two patients with DU, 2-5 mg atropine completely abolished acid secretion during fundic distension. In nine subjects with DU, complete proximal gastric vagotomy profoundly depressed the secretory responses to graded fundic distension, eliminating the acid response to the smallest balloon volume used. A slight, but significant, response to the largest distension volume persisted after complete vagotomy. Incomplete proxomal gastric vagotomy was found to reduce only moderately the distension responses in five patients, and the peak acid response to fundic distension as related to PAOpg remained unchanged. In conclusion, distension of the gastric fundus and body in man stimulates acid secretion by means of an atropine-sensitive, presumably cholinergic, reflex mechanism and the findings after vagotomy are in agreement with the concept that this reflex mechanism is conveyed by both short intramural and long vagovagal pathways.

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.

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 sham feeding on pancreatic-polypeptide (PP) secretion was studied in 26 duodenal ulcer (DU) patients and in 8 healthy subjects. Modified sham feeding (MSF) by the 'chew and spit' technique induced a rapid increase in plasma concentrations of PP both in DU patients, 56 (2-138) pmol/l, and in the healthy subjects, 24 (2-45) pmol/l, median peak-increment and range. Four out of 26 DU patients and 2 out of 8 healthy subjects did not show any PP response to MSF. The PP response to MSF was abolished by pretreatment with atropine, or benzilonium, a quarternary anti-muscarinic agent with minimal cerebral actions. The PP response to MSF was not dependent on the gastric acid response, since a PP response to sham feeding was found in 13 out of 17 patients with selectively denervated parietal cell area, and thus, without acid response. During adequate sham feeding, in which the food is also swallowed but does not reach the stomach, the PP increment, 100 (81-129) pmol/l, was larger than during MSF in the same patients, 51 (8-78) pmol/l, median and total range, P less than 0.05, N = 7. No correlation was found between the PP and acid responses to sham feeding. It is concluded that cephalic stimulation provoked by tasting, chewing and swallowing is a major stimulus in the initial, rapid PP response during a meal; and that the PP cells are probably stimulated directly by a cholinergic mechanism.

In seven duodenal ulcer patients the effect of intraduodenal infusion of 20 ml oleic acid on submaximal gastric acid secretion stimulation by a continuous pentagastrin infusion was evaluated before and after proximal gastric vagotomy. In the control tests 20 ml of saline was given. Before vagotomy, oleic acid evoked a significant inhibition of gastric acid secretion of 25% compared with the controls. This inhibition was abolished after proximal gastric vagotomy. The difference in inhibition before and after vagotomy was significant (P=0.01). It is concluded that the vagus nerve in man plays a decisive role in duodenal fat inhibition of gastric acid secretion.

Sham feeding experiments were performed in 20 duodenal ulcer (DU) patients by using adequate sham feeding and modified sham feeding (the 'chew-and-spit' technique). A 15-min sham feeding induced a marked secretion of gastric acid but only an insignificant increase in total gastrin or in gastrin17 concentrations in plasma. Nor did prolonged sham feeding (30 min) with intragastric neutralization significantly increase the gastrin concentrations. We conclude that sham feeding in DU patients induces a release of recognized gastrin components in amounts that are barely detectable radioimmunologically. Therefore, the acid secretory effects of vagally released gastrins in DU patients remains to be established.

Summary The maximal acid response of the stomach to histamine was determined in 13 duodenal ulcer patients before and after resection of the antrum and duodenal bulb, then again following vagotomy. Antrectomy was done with the guidance of visualization at operation of the antrumcorpus border. For vagotomy, 1 week after the gastric surgery, a special procedure was used which did not necessitate a second laparotomy. The maximal acid response to histamine showed a mean reduction of 51% after resection of the antrum and duodenal bulb. This depressed postresection response was in turn reduced by 67% following vagotomy. In a group of 8 patients with the same disease, pyloroplasty and subsequent vagotomy resulted in a significantly smaller reduction of the maximal response. The results confirm that resection of the antrum and duodenal bulb significantly reduces the maximal acid response to histamine in man and show that subsequent vagotomy causes a further significant suppression of this response, indicating that in man the parietal cell response to maximal histamine stimulation is facilitated both by basal release of gastrin and by direct vagal activation of the parietal cells via a basal flow of vagal impulses.

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.

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 study was performed to determine whether the sympathetic nervous system contributes to the reflex control of gastric HCO3- secretion in humans. Gastric HCO3- secretion was registered by a computerized technique based on measurements of pH and PCO2 in gastric effluent. To minimize formation of CO2 in the stomach, subjects were pretreated with the H2-receptor blocker ranitidine. Compensations were made for HCO3- of nongastric origin. As indicators of cardiovascular sympathetic activity, we measured heart rate, forearm vascular resistance, and plasma catecholamine concentrations. In one series of experiments, peripheral sympathetic activity was enhanced by the application of a negative pressure around the lower part of the body (lower body negative pressure, LBNP), at a rate sufficient to induce a slight decrease in systemic arterial pressure. In another series of experiments, peripheral sympathetic activity was inhibited by elevation of the legs, a procedure that simulates volume loading by redistributing blood volume toward the central circulation. LBNP at -20 mmHg decreased systolic pressure and pulse pressure and significantly increased heart rate, forearm vascular resistance, and plasma catecholamine levels. All these effects were observed in the first 15-min period of LBNP and were well maintained throughout the 45-min observation period. LBNP also inhibited basal gastric HCO3- secretion rate in seven of eight individuals, but this response was slower in onset with a latency of at least 15 min. Elevation of the legs increased pulse pressure and decreased forearm vascular resistance. Catecholamines were not measured in these experiments. Gastric HCO3- secretion tended to increase, but the magnitude of the response was highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)