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Objective: The association between Helicobacter pylori (H. pylori) infection and serum lipid profile is still controversial. The aim of this study was to determine any possible relationship between H. pylori infection and the lipid profile of patients with upper gastrointestinal symptoms., Material and Methods: Consecutively selected 20-70 year-old dyspeptic patients who had undergone esophagogastroduodenoscopy were evaluated for H. pylori infection using both the CLO test and Giemsa staining. Serum total cholesterol (C), HDL-C, LDL-C, apo-A1, apo-B and triglyceride levels were measured., Results: A total of 137 patients (median age 52.0 years) were studied. Total cholesterol levels were lower in H. pylori-infected patients than in H. pylori-negative patients (mean +/- SEM: 199.3 +/- 5.9 versus 212.6 +/- 4.6 mg/dl, p = 0.08). Patients with duodenal ulcer (DU) had significantly lower levels of all measured lipidemic parameters including cholesterol, with the exception of triglycerides, in comparison with either H. pylori-positive or -negative dyspeptic patients (cholesterol: 177.6 +/- 6.5 versus 214.6 +/- 4.2 mg/dl, p < 0.0001). However, there was no difference in the total cholesterol/HDL-C ratio between DU patients and the rest of the dyspeptic patients., Conclusions: Among H. pylori-positive and H. pylori-negative patients there was no difference in lipid profile apart from a trend towards total cholesterol levels being lower in H. pylori-positive patients. However, cholesterol, HDL-C, LDL-C, apo-A and apo-B were all decreased in DU patients even though this reduction did not result in a fall in the total cholesterol/HDL-C ratio. The etiologic factor differentiating the lipid profiles among dyspeptics only in H. pylori-positive patients carrying a DU could be dietetic, microbial, genetic or a combination of all three.

Objective: The objective of this endoscopic study was to compare the effects on the gastroduodenal mucosa of healthy volunteers of different doses and dosing regimens of AZD3582, a cyclooxygenase-inhibiting nitric oxide donator (CINOD), with equimolar doses of naproxen., Material and Methods: Healthy volunteers were enrolled in a single-centre, randomized, double-blind, crossover trial consisting of two 12-day treatment periods and employing six sequences. The groups were: AZD3582 750 mg daily versus 375 mg twice daily (n=25), AZD3582 375 mg twice daily versus 750 mg twice daily (n=25) and naproxen 250 mg twice daily versus 500 mg twice daily (n=25)., Results: Gastroduodenal tract damage was similar with AZD3582 375 mg twice daily and 750 mg twice daily (mean number of erosions and ulcers+/-SD: 2.88+/-3.95 versus 3.08+/-2.80, respectively; p=0.824; 1 ulcer counted as 10 erosions). There was an indication of decreased gastroduodenal toxicity with AZD3582 750 mg daily compared with 375 mg twice daily (0.92+/-2.08 versus 2.71+/-4.75, respectively; p=0.068). Gastroduodenal toxicity was significantly lower with AZD3582 375 mg twice daily than with naproxen 250 mg twice daily (2.88+/-3.95 versus 6.16+/-9.36; p<0.05), and with AZD3582 750 mg twice daily versus naproxen 500 mg twice daily (3.08+/-2.80 versus 6.68+/-6.97; p<0.05). Equimolar twice-daily doses of AZD3582 and naproxen resulted in similar naproxen plasma levels and serum thromboxane B(2) inhibition., Conclusions: AZD3582 has an improved gastroduodenal safety profile compared with equimolar doses of naproxen. The gastroduodenal effects of AZD3582 375 mg and AZD3582 750 mg twice daily are similar. A once-daily regimen of AZD3582 might be less gastrotoxic than a twice-daily regimen.

Background: Although the association between Helicobacter pylori infection and gastric autoimmunity is now well established, to date little is known about the significance of anticanalicular autoantibodies in patients with duodenal ulcer (DU). We therefore investigated the prevalence of serum antiparietal cell autoreactivity in DU patients as well as the relationship between these autoantibodies, gastric histopathology and gastric secretory function in this setting., Methods: Forty-one consecutive patients with H. pylori-positive DU were initially recruited. In all patients, basal (BAO) and pentagastrin stimulated acid output (PAO), fasting and meal-induced serum gastrin levels, as well as serum pepsinogen I concentrations, were measured. Antral and body gastritis was evaluated according to the Sydney system. Serum anticanalicular autoreactivity was determined by the indirect immunoperoxidase technique., Results: Serum anticanalicular autoantibodies were found in 7 out of 34 patients (20%). The presence of these antibodies was associated with a significantly higher grade of body gastritis (activity: 1.9 versus 0.9) as well as with significantly higher fasting and meal stimulated gastrin levels (mean fasting gastrin, 76.4 (15.2) microg/ml versus 59.3 (20.5) microg/ml). In addition, PAO values were significantly lower in patients with gastric autoantibodies than in those without this autoreactivity (mean 0.35 (0.16) mmol kg(-1)h(-1) versus 0.49 (0.16)mmol kg(-1)h(-1)). In contrast, no significant differences were found between patients with and without anticanalicular autoantibodies as regards fasting serum pepsinogen I concentrations., Conclusions: Serum anticanalicular autoantibodies can be detected in 20% of patients with DU and are associated with a more severe pattern of body gastritis, higher gastrin levels and decreased peak acid secretion values. Their presence could account for the normal or reduced acid output which can be seen in a subset of DU patients.

Background: In this study we assessed the accuracy of IgG serology and other tests in confirming Helicobacter pylori eradication., Methods: The outcome of anti-H. pylori therapy was established by at least two of the following tests: rapid urease test (RUT), culture, 14C urea breath test (non-capsule or capsule UBT), and IgG serology (Orion Diagnostica Pyloriset New EIA-G)., Results: Successful H. pylori eradication was confirmed in 698 of 794 patients (88%). The percentage decrease in IgG antibody titre was related to the patients' pre-treatment IgG titre and time interval after treatment. A decrease in IgG titres of 40% or more confirmed H. pylori eradication with 100% specificity, whereas the sensitivity was 82%, 90%, 98%, and 98% 3, 4, 5, and 6 months after therapy, respectively. The 40% cut-off confirmed eradication 3 to 6 months after therapy in 328 of 339 patients (97%) with pre-treatment IgG titres of >700, in 36 of 45 patients (80%) with pre-treatment titres of 300-700, and in 5 of 12 patients (42%) with pretreatment titres of <300. The sensitivity and specificity of the other tests 2 months after treatment were as follows: RUT, 84% and 100%; culture, 88% and 100%; non-capsule UBT, 100% and 89%; and capsule UBT, 100% and 97%., Conclusion: A decrease in IgG antibody titre of 40% or more 3 to 6 months after therapy and the capsule 14C UBT at the 2-month follow-up were both highly accurate in confirming H. pylori eradication.

Objective: In healthy subjects a gastric meal at low pH inhibits gastric acid secretion, possibly by reducing gastrin release, whereas duodenal ulcer (DU) patients have been reported to show a lack of this low pH inhibition of gastric secretion., Methods: The intragastric pH profiles were measured in seven healthy subjects and seven DU patients after meals of pH 6.5 and 3.0 without or with pretreatment with loxiglumide (1.2 g orally), a selective antagonist of type-A cholecystokinin (CCK) receptors. During all tests (30 min before and 30, 60, and 90 min after each meal) plasma gastrin, CCK, and somatostatin were determined by specific radioimmunoassays., Results: In healthy subjects a standard meal at pH 6.5 and 3.0 resulted in median 3-h intragastric pH of 3.8 and 2.8, respectively. In DU patients under the same conditions the pH 6.5 meal resulted in median 3-h intragastric pH of 3.4, and the acidified meal in pH 2.2. After pretreatment with loxiglumide the median pH after both meals was significantly lower in healthy controls but not in DU patients. After the pH 6.5 meal, in healthy subjects the plasma gastrin rose by 57%, CCK by 177%, and somatostatin by 39%, and in DU patients by 152%, 367%, and 125%, respectively. Pretreatment with loxiglumide led to a marked increase in plasma gastrin response to the pH 6.5 meal only in healthy controls and not in DU subjects, and it was accompanied by a significant increase in plasma CCK and a decrease in plasma somatostatin. The pH 3.0 meal resulted in a significantly smaller rise in plasma gastrin and a higher increase in CCK and somatostatin in both groups; again, after treatment with loxiglumide only healthy controls and not DU patients showed significant increase in plasma gastrin level., Conclusions: Acidification of meals results in the reduction of plasma gastrin and increase in plasma CCK and somatostatin in both healthy subjects and DU patients. DU patients differ from healthy subjects by virtually unchanged plasma gastrin response to a meal after CCK antagonism with loxiglumide, suggesting a defect in both gastric acid and gastrin inhibition by CCK in these patients.

Background: Many studies have confirmed the close association of Helicobacter pylori with duodenal ulcer (DU) in adults. However, in the subtype of DU known as 'childhood' or 'early onset DU' genetic factors seem to play a prominent role in the pathogenesis. The aim of this study was to investigate the prevalence of H. pylori in teen-age subjects with DU, gastritis, and normal mucosa and to examine the relationship of H. pylori to serum gastrin levels and gastric acid secretion., Methods: Sixty-one teen-age subjects (24 with DU, 14 with gastritis, and 23 normal subjects) were investigated for the presence of H. pylori, antral histology, gastrin levels, basal acid output (BAO), and maximal acid output (MAO)., Results: All 24 patients with DU and 8 of 14 with gastritis were infected with H. pylori; none of the normal subjects were infected. Mean gastritis scores and fasting serum gastrin levels were significantly higher in patients with DU or H. pylori-positive gastritis than in subjects with H. pylori-negative gastritis or normal mucosa (p < 0.05). The difference in serum gastrin levels was also significant when patients with DU were compared with those with H. pylori-positive gastritis (p < 0.05). BAO and MAO were significantly higher in patients with DU than in subjects with H. pylori-positive gastritis or normal mucosa (p < 0.05), but there was no difference between subjects with H. pylori-positive gastritis and those with normal mucosa., Conclusion: H. pylori infection is associated closely with teen-age DU and gastritis and with hypergastrinemia but does not affect BAO and MAO in most infected teen-age subjects.

Plasma concentrations of oxyntomodulin-like immunoreactivity, a group of intestinal peptides capable of mediating an enterogastrone signal, were measured during a 24-h period in 6 duodenal ulcer patients and compared with those of 16 age-matched controls. Each subject was submitted to 18 oxyntomodulin-like immunoreactivity determinations. Four standardized meals were given during the test. Furthermore, each patient was evaluated for peak acid output after pentagastrin stimulation. The values of the duodenal ulcer subjects were predominantly within normal acid secretion limits. Fasting levels, meal-induced variations, and nocturnal production of oxyntomodulin-like immunoreactivity were similar in the two groups. A negative correlation was observed between peak acid output and oxyntomodulin-like immunoreactivity evaluated either as nocturnal production or as maximum nyctohemeral concentration. We conclude that, taken as a whole, duodenal ulcer disease is not caused by a defect in oxyntomodulin-like immunoreactivity secretion. However, this study does not rule out the possibility of a selective deficiency of these peptides in some duodenal ulcer subgroups such as hypersecretory patients.

Omeprazole may exert an effect on gastric mucosal proliferation by inhibiting gastric acid secretion and increasing serum gastrin levels. It may also influence the kinetics of endocrine cells and the oxyntic mucosa. The aim of the present study was to evaluate the cell cycle in different gastric compartments following short- (1 month) and long-term (6 months) administration of two different dosages of omeprazole by means of a flow cytometric method. We also determined serum gastrin levels at the same time. No differences in cell cycle distribution of the antrum, body, and fundus were found in the two different dosage groups after 1 month of therapy, considering the synthetic phase (S-phase) of the cell cycle. A statistically significant increase in S-phase was reported after long-term therapy in the mucosa of the fundus and body of the stomach in both groups. Gastrin levels showed no clear correlation with cell cycle distribution variables. We postulate a proliferative adaptation of the oxyntic mucosa to long-term drug administration not mediated by gastrin influence.

We have investigated the possibility that hypergastrinaemia in chronic Helicobacter pylori infection is a compensatory response to reduced parietal cell sensitivity to gastrin. The acid response to 45-min infusions of pentagastrin at sequential doses (micrograms/kg/h) of 0, 0.031, 0.062, 0.124, and 0.6 was compared before and 1 month after eradication of H. pylori in eight duodenal ulcer patients. The median acid outputs (mmol/h) with the respective infusions were 5.0, 7.5, 26.5, 30.8, and 37.0 when H. pylori-positive and similar at 4.5, 7.1, 22.7, 28, and 31.5 when H. pylori-negative. The median estimated dose of pentagastrin required to produce 50% maximal response (D50) was similar before (0.060 micrograms/kg/h) and after (0.057 micrograms/kg/h) eradication of H. pylori. The median estimated maximal response to pentagastrin (mmol/h) was also similar before (39.2) and after (32.3) treatment. The median basal gastrin concentration was 48 ng/l (range, 22-77) before treatment and fell to 33 ng/l (range, 8-37) after eradication of H. pylori (p = 0.03). These findings show that the parietal cell sensitivity to pentagastrin is unaffected by chronic H. pylori infection in duodenal ulcer subjects and that the hypergastrinaemia cannot be attributed to the bacterium inhibiting parietal cell function.

It has been postulated that Helicobacter pylori-related hypergastrinaemia is due to bacterial ammonia raising antral surface pH and thus preventing acid inhibition of gastrin release. If true, the infection should not alter gastrin release at neutral intragastric pH. To test this, we have studied basal and meal-stimulated gastrin at uncontrolled pH and at pH greater than 6 in duodenal ulcer patients before and after eradication of H. pylori. The median integrated gastrin response to the meal alone was 2525 ng/l.min (range, 550-8725) before and 725 ng/l.min (range, 250-2925) after eradication of H. pylori (p less than 0.01). The corresponding values when intragastric pH was maintained above 6 were 3700 ng/l.min (range, 1900-14,100) and 1400 ng/l.min (range, 400-3400) (p less than 0.01). The median reduction in gastrin after eradication of H. pylori was thus similar when the meal was taken at uncontrolled pH (61%; range, 0-97%) and at pH greater than 6 (69%; range, 36-89%). Likewise, 5 h of gastric alkalinisation did not cause the basal gastrin values when H. pylori was eradicated to increase to those observed when H. pylori was present. These findings indicate that the hypergastrinaemia is not due to elevated antral surface pH.

The rise in serum gastrin and pepsinogen I after 5 days' treatment with the proton pump inhibitor pantoprazole (40 mg/day) was examined in eight duodenal ulcer patients with Helicobacter pylori infection and compared with eight in whom it had been eradicated. Before treatment, the post-prandial serum gastrin concentrations were higher in the H. pylori-positive than -eradicated patients (p less than 0.05). The median rise in pre-prandial serum gastrin concentrations on treatment was similar in the H. pylori-positive (41%) and -eradicated patients (45%). The rise in post-prandial serum gastrin was also similar in the H. pylori-positive (81%) and -eradicated patients (69%), resulting in significantly higher gastrin concentrations during treatment in the former. The median rise in serum pepsinogen I on treatment was greater in the H. pylori-positive (114%) than in the -eradicated patients (8%), resulting in significantly higher concentrations during treatment in the former. These observations indicate that eradication of H. pylori may be a means of moderating the hypergastrinaemia caused by acid-inhibitory therapy. They also indicate that H. pylori-related hypergastrinaemia is not due to an increase of the antral surface pH by the bacterium's urease activity.

Duodenal ulcer patients have increased serum pepsinogen I (PGI) concentrations and an increased prevalence of Helicobacter pylori infection. We have examined the effect of eradicating the infection on PGI. In 12 duodenal ulcer patients in whom H. pylori was successfully eradicated, the median basal PGI was 90 ng/ml (range, 37-252) before treatment and fell to 74 ng/ml (28-197) 1 month after treatment (p less than 0.01). In 12 patients in whom therapy failed to eradicate the infection, the PGI was 87 ng/ml (35-128) before treatment and remained unchanged at 83 ng/ml (36-119) 1 month after treatment. In the group with successful eradication the median basal plasma gastrin was 43 ng/l (15-95) before treatment and fell to 30 ng/l (17-75) 1 month after treatment (p less than 0.003), but there was no change in the corresponding values in the group without eradication (55 ng/l; range, 25-120, and 45 ng/l; range, 5-175; p = 0.9). In conclusion, eradication of H. pylori results in a fall in PGI and plasma gastrin, and these changes are not due merely to the anti-H. pylori drugs themselves or to discontinuation of previous ulcer therapy.

The IgG subclass response is determined by the type of bacteria producing the infection and by genetic factors of the host. Patients with a Helicobacter pylori infection develop a specific immune response that is mainly of the IgA and IgG class. We measured the IgG subclass response in 20 patients with chronic active gastritis without a history of duodenal ulcer and 20 patients with chronic active gastritis and duodenal ulcer diagnosed by endoscopy and histology. A control group included 20 H. pylori-negative patients and 60 H. pylori-positive blood transfusion donors. Systemic IgG subclass response was measured with a modified enzyme-linked immunosorbent assay technique, using as antigen a sonicate of six different H. pylori strains. Mouse monoclonal antibodies against each of the four human IgG subclasses (IgG1, IgG2, IgG3, and IgG4) were used. The total IgG anti-H. pylori antibody titres were equal in all three H. pylori-positive groups and significantly different from that of the negative control group (p less than 0.01). The IgG subclass response in persons infected with H. pylori involved all four subclasses but was predominantly of the IgG1 and IgG2 subclasses. All of the groups with H. pylori infection had significantly higher levels of IgG1 than the negative control group, but no differences were detected among the three groups. However, the duodenal ulcer group had a significantly higher IgG2 response than the gastritis group (mean optical density +/- SEM, 0.382 +/- 0.047 versus 0.200 +/- 0.025, respectively; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies in animals and humans demonstrated that nocloprost, a stable prostaglandin E2 analogue, shows very high gastroprotective potency, relatively weak gastric inhibitory activity, and low systemic bioavailability after oral administration. In this study the effects of nocloprost on gastric acid secretion and intraluminal pH and on gastric emptying and plasma gastrin levels were determined in humans. Nocloprost at doses of 50 and 100 micrograms was ineffective, but at a dose of 200 micrograms it reduced the response to pentagastrin significantly and that to a peptone meal by 30-50% and abolished plasma gastrin response without affecting the rate of gastric emptying. Nocloprost given at a dose of 100 micrograms three times daily 30 min before the major meals (breakfast, lunch, and dinner) did not affect intragastric pH significantly as monitored by continuous intraluminal pH-metry. We conclude that nocloprost does not affect gastric acid secretion or intraluminal pH when applied at a dose (50-100 micrograms) that is gastroprotective and that is proposed for peptic ulcer therapy. A higher dose (200 micrograms) of nocloprost causes moderate gastric acid inhibition and suppression of plasma gastrin release without affecting gastric emptying or causing any side effects.

Nine patients with Helicobacter pylori-related antral gastritis and history of duodenal ulceration were studied before and at 1 and 7 months after eradication of the infection by a 4-week course of tripotassium dicitrato bismuthate, metronidazole, and amoxycillin. The median basal gastrin concentration before eradication was 30 ng/l (range, 20-60) and fell to 20 ng/l (5-20) at 1 month (p less than 0.02) and 15 ng/l (5-20) at 7 months (p less than 0.01) after eradication. The integrated gastrin response to a peptide meal was 3650 ng/l.min (range, 1875-6025) before treatment compared with 1800 ng/l.min (range, 1200-3075) at 1 month (p less than 0.01) and 1312 ng/l.min (875-2625) at 7 months (p less than 0.03). Daytime intragastric pH (0900-2100 h) was similar before treatment (median, 1.4; range, 1.1-2.1) and at 1 month (1.4; 1.1-2.3) and 7 months (1.4; 1-2.2) after eradication. In five of the patients nighttime acid output (2300-0900 h) was also studied and was similar before (median, 86 mmol/10 h; range, 52-114) and at 1 month (76 mmol/10 h; 50-143) and 7 months (94 mmol/10 h; 63-106) after eradication. In conclusion, eradication of H. pylori is accompanied by a sustained fall in serum gastrin concentrations but is not accompanied by an early or late reduction of daytime intragastric acidity or nighttime acid output.

Duodenal ulcer is associated with such genetic characteristics as blood group O and secretor status. Since Helicobacter pylori has been proved to be an important factor in the pathogenesis of duodenal ulcer, we wanted to study whether the frequency of H. pylori antibodies would vary in individuals with different blood group antigens. Antibodies against H. pylori were determined in 271 blood donors. Acid glycine extract from an H. pylori strain was used as antigen in enzyme immunoassay. Our results suggested no significant association of increased level of H. pylori antibodies with ABO blood group and secretor status, which implies that H. pylori infection is not associated with the ABO group and secretor status. Thus H. pylori and blood group antigens seem to be independently linked to duodenal ulcer.

Detection of gastric Campylobacter by the 14C-urea breath test and serology were correlated to biopsy culture in 25 unselected outpatients referred for gastroscopy. All the 17 culture-positive patients had positive 14C-urea breath test, and 16 had positive serology. Of eight culture-negative patients, six patients had negative breath test and seven negative serology. A high degree of reproducibility was found when two subsequent breath tests were performed in 11 healthy volunteers. The breath test values obtained at 10 min showed a strong correlation (r = 0.97, p less than 0.001) to the accumulated values within 30 min. Breath sampling once, 10 min after intake of 2.5 microCi 14C-urea, seems sufficient for the detection of gastric Campylobacter. The 14C-urea breath test correlates well with biopsy culture and provides a sensitive tool for the detection of gastric Campylobacter. Serology also corresponds well with biopsy culture and should provide a useful tool for epidemiologic studies.

Ninety-seven consecutive patients with gastric surgery for peptic ulcer were studied; 86 had duodenal ulcer (DU), and 11 gastric ulcer (GU). DU patients were surgically treated by proximal vagotomy, proximal vagotomy and pyloroplasty, truncal vagotomy and pyloroplasty, or truncal vagotomy and antrectomy. All GU patients were operated on by the Billroth I method. Serum pepsinogen I(S-PG I), serum pepsinogen II (S-PG II), basal acid output (BAO), and maximal acid output (MAO) were determined before and 3 months and 1 year after the operation. The mean preoperative S-PG I concentration in DU patients (154 +/- 7 micrograms/l; mean +/- SE) was significantly higher than that (97 +/- 9 micrograms/l) in GU patients (p less than 0.001). A significant decrease in the mean S-PG I concentration in DU patients was seen 3 months (92 +/- 6 micrograms/l) and 1 year (66 +/- 4 micrograms/l) after the operation (p less than 0.001). This change did not depend on the type of vagotomy. However, this decrease was not seen in all individual patients as it was in BAO values. Moreover, the mean BAO decrease was much greater at 3 months (7% of the preoperative value) and 1 year (23%) after the operation than the respective decrease in S-PG I concentration. There was also no correlation between S-PG I and acid output (BAO and MAO) before and after the operation. In GU patients the decrease in mean S-PG I value after the Billroth I operation was smaller than in DU patients after vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

The concentration of gastrin in serum from 47 fasting patients with duodenal ulcer was measured with two radioimmunoassays, one specific for the COOH- and the other specific for NH2-terminal sequence of gastrin-17. The COOH-terminal assay measured 13 +/- 2 pmol and the NH2-terminal 42 +/- 7 pmol-equivalent gastrin-17 per litre (mean +/- S.E.M.). This result, corroborated by gel chromatography, shows that an NH2-terminal fragment of gastrin-17, presumably the tridecapeptide, circulates in concentrations higher than those of the four known gastrin components. The abundance of NH2-terminal fragment in serum suggests that the complementary COOH-terminal tetrapeptide fragment of gastrin-17 is also produced in large quantities.

To determine whether the serum pepsinogen I (PG I) level would be a suitable marker for selecting patients at risk for duodenal ulcer recurrence and, thus, would benefit from maintenance therapy, we treated duodenal ulcer patients with H2-receptor antagonists. After healing 140 ulcer patients we assessed the recurrence rate at 1 year with and without maintenance therapy. The annual recurrence rates in duodenal ulcer patients with hyper-PGI (95 ng/ml or more), with 66 ng/ml less than or equal to PGI less than 95 ng/ml, and with PGI less than 66 ng/ml were 87.0%, 27.3%, and 17.9%, respectively, when they did not receive maintenance therapy. In patients with hyper-PGI the recurrence rate was significantly lower in patients receiving maintenance therapy than in patients not receiving maintenance therapy, whereas in patients with PGI less than 66 ng/ml the recurrence rate was as low as 20% regardless of maintenance therapy. These results indicate that maintenance therapy with half the dose of H2-receptor antagonist is not required by patients with PGI less than 66 ng/ml, whereas those with hyper-PGI may be good candidates for long-term maintenance therapy.

In 81 patients with duodenal ulcer, the preoperative basal serum gastrin concentration was positively correlated to basal acid output after proximal gastric vagotomy and negatively correlated to the decrease in basal acid output exerted by the operation. The preoperative basal concentration of gastrin in serum was found to distinguish between high and low basal acid output after operation, 40 pg/ml being the discriminatory level.

The contribution of the different gastrin components to the gastrin response to a protein-rich meal was studied. Pooled or individual samples of venous blood drawn at intervals in 12 normal subjects and 16 patients with duodenal ulcers were fractionated on Sephadex G 50 superfine columns of various lengths. Total gastrin immunoreactivity and concentrations of various components were measured radioimmunochemically. The changes in total serum concentration of immunoreactive gastrin were principally due to changes in component II ('big gastrin') and III ('little gastrin'). The predominant pattern in both groups was an early increase in component III and a later and smaller increase in component II. Total gastrin response was largest in the patients with duodenal ulcer, and this was due mainly to component III. Furthermore, fasting samples also showed a relatively higher concentration of component III in the ulcer patients. This study shows that 'little gastrin' is the more important component in the gastrin response to stimulation by food. Serum concentrations of total gastrin immunoreactivity are alike in normal subject and duodenal ulcer patients, but the findings indicate that increased levels of 'little' gastrin may be characteristic of duodenal ulcer disease. Since 'little gastrin' is more potent than 'big gastrin', this would agree with the hypersecretion of acid in duodenal ulcer.

Thirty-three duodenal ulcer patients (group A) were examined for gastric acid secretion capacity and serum group I pepsinogens (PG I) under basal conditions. Another group of 36 duodenal ulcer patients (group B), who had undergone proximal gastric vagotomy (PGV) 1 year previously, were similarly examined. Mean basal acid output, mean insulin-stimulated peak acid output, and mean pentagastrin-stimulated peak acid output in the conservatively treated group were 4.5 meq/h, 25.1 meq/h, and 34.4 meq/h, respectively. The corresponding values in the PGV group were 2.5 meq/h, 6.7 meq/h, and 18.5 meq/h. The mean serum PG I concentration in group A was 103.6 ng/ml and in group B 69.9 ng/ml, whereas the mean serum PG I concentration in 34 healthy control subjects was 47.9 ng/ml. The differences in serum PG I concentrations between all three groups were statistically significant (p less than 0.05). An elevated concentration of serum PG I is associated with clinical ulcer disease in unoperated patients, but the wide overlap in the PG I concentration area between duodenal ulcer patients and healthy persons limits the use of PG I determinations in disturbances of gastric acid secretion.

The level of serum group I pepsinogens (PG I) has been studied during the conventional insulin-pentagastrin test in 29 duodenal ulcer (DU) patients before and 2 months after proximal selective vagotomy (PSV) and in 31 unoperated DU patients. The mean basal serum PG I level was 191.6 +/- 15.4 micrograms/l (mean +/- SEM) before and 143.7 +/- 24.0 micrograms/l after PSV. A significant increase in mean serum PG I above the initial value was found both in unoperated DU patients and in patients after PSV 1 h after insulin injection. In 29 PSV patients the mean serum PG I showed a paradoxical decrease during the 2nd h after insulin injection, and the mean postvagotomy serum PG I 2 h after insulin injection was significantly (p less than 0.01) lower than the respective preoperative value in the same patients, and the value was close to the basal serum PG I. The low level of serum PG I 2 h after insulin injection in vagotomized patients may reflect the deprivation of the reduced store of PG I in the absence of normal vagal tone. Both the basal serum PG I and serum PG I response during insulin-induced hypoglycaemia showed an overlap between unoperated and vagotomized DU patients. Therefore, serum PG I analyses during the insulin test cannot replace acid secretion tests in the assessment of the completeness of vagotomy.

Serum gastrin, 24-h intragastric acidity, and bile acid concentrations were measured during physiologic conditions in 10 patients with duodenal ulcer disease. Omeprazole, 20 mg daily, for 8 days reduced acidity by greater than or equal to 99% in six patients and by 47-54% in four patients. The degree of acid reduction was related to the area under the plasma omeprazole concentration time curve (AUC). Serum gastrin levels were not significantly increased by omeprazole. Intragastric bile acid concentrations were increased by omeprazole, but this seems to be of little importance for the healing of duodenal ulcers.

Basal and food-stimulated levels of gastrin and pancreatic polypeptide (PP) were studied in 86 patients with non-ulcer dyspepsia (NUD), defined as chronic or recurrent epigastric pain without anatomical antecedents and without concomitant symptoms of irritable bowel. Thirteen patients with endoscopically confirmed duodenal ulcer disease (DU) and 13 healthy subjects constituted the reference groups. The mean basal gastrin concentration was moderately but significantly (p less than 0.05) higher in the NUD group than in the reference groups (24.3 +/- 1.6 (SEM) pmol/l in NUD, compared with 15.0 +/- 1.5 and 13.6 +/- 1.0 pmol/l among DU patients and healthy subjects, respectively). The well-established postprandial hypergastrinemia in duodenal ulcer patients could be confirmed in this study, and their gastrin response to food was significantly (p less than 0.01) greater than the responses observed both in healthy subjects and in NUD patients. The two latter groups did not differ significantly with regard to gastrin increments, but there was a tendency towards greater increases in the NUD group. A significantly (p less than 0.05) enhanced PP response to the test meal was observed among the DU patients, whereas the response pattern in NUD was closely similar to that in healthy subjects.

In 41 non-dyspeptic volunteers (18 females and 23 males) the fasting and food-stimulated serum gastrin concentration was investigated. No significant sex differences were found in the basal serum gastrin concentration. The integrated postprandial gastrin output, however, was significantly higher in females than in males. In 151 duodenal ulcer patients (31 women and 120 men) significant sex differences were found in both the fasting and the food-stimulated serum gastrin concentration. Women had values approximately 60% higher than men. In 116 of the patients (27 women and 89 men) the basal and pentagastrin-stimulated gastric acid concentrations were investigated. In the basal state no significant sex differences in acid output were found. After stimulation women had significantly lower gastric acidity and gastric acid output than men.

During a 7-year period proximal gastric vagotomy (PGV) was performed in 565 patients. Of these, 210 patients with duodenal ulcer and 14 with dyspepsia without demonstrable ulcer at the time of operation were followed for 5--7 years. Sixty-six percent are symptom-free (Visick I), 23% have no complaints when they take certain dietary measures (Visick II), 3% are improved but still have periods of dyspepsia (Visick III), and 8% are failures because of recurrent ulcer (Visick IV). There were 4 duodenal, 3 pyloric, 5 prepyloric, and 7 lesser-curve gastric recurrences. There were one operative death (0.2%) and one major complication (0.2%). The side effects after PGV are mild, infrequent, and seldom of any significance to the patients. Diarrhoea and dumping are virtually eliminated. Body weight was stable during the whole period of study, and blood chemistry did not disclose any deficiency in haemoglobin, serum iron, or vitamin B12 which might be attributed to PGV. It is concluded that 5--7 years after proximal gastric vagotomy for duodenal ulcer there is a 10% recurrence rate, but the low risk of death and of severe complications and the lack of significant side effects more than outweight the high recurrence rate.

Ten unoperated duodenal ulcer (DU) patients and 11 DU patients 1 year after proximal gastric vagotomy (PGV) were examined for gastric acid secretion and for serum group I pepsinogens (PG I) during basal conditions and after consecutive stimulations with insulin and pentagastrin. In unoperated DU patients insulin stimulation caused a significant increase both in gastric acid secretion and in serum PG I. In these patients a consecutive pentagastrin stimulation elicited a significant increase in gastric acid secretion but not in serum PG I. In patients after PGV, insulin stimulation caused a slight but significant increase in gastric acid secretion but not in serum PG I. In these patients a consecutive pentagastrin stimulation caused a significant increase both in gastric acid secretion and in serum PG I. Two of the operated patients had negative and nine had positive responses to the postoperative insulin test. According to this study, in consecutive stimulation with insulin and pentagastrin the effect of pentagastrin on serum PG I is inhibited by preceding insulin stimulation in DU patients. By PGV the effect of insulin on serum PG I is eliminated. and then a subsequent pentagastrin stimulation elicits a significant rise in serum PG I. As a test of the completeness of PGV, the serum PG I response to insulin-induced hypoglycemia seems to be less sensitive than the gastric acid response.

Fasting and meal-stimulated NH2-terminal gastrin concentrations in serum were significantly higher in patients with active duodenal ulcer than in control subjects and in patients with inactive duodenal ulcer (p less than 0.05). In contrast, the COOH-terminal gastrin concentrations (the bioactive gastrins) did not differ among the groups. Parallel variation in the NH2- and COOH-terminal gastrin concentrations occurred both during meal stimulation and as response to adrenaline or secretin infusion. In a longitudinal study of duodenal ulcer patients, higher NH2- than COOH-terminal gastrin concentrations were associated with the active phase of the disease, whereas this seldom occurred during the inactive phase (p less than 0.001). These data suggest that abnormally large amounts of the NH2-terminal fragment of gastrin-17 are released to the circulation during the active phase of duodenal ulcer.

The effect os somatostatin (0.6 mg/hour) on insulin-stimulated gastrin release and gastric secretion of acid, pepsin, and IF has been examined in 6 unoperated patients with duodenal ulcer. Gastrin release and gastric secretion of acid, pepsin, and IF in response to insulin alone (0.15 IU/kg bw. iv.) were significantly reduced by simultaneous administration of somatostatin. This finding indicates an inhibitory effect of somatostatin on insulin-induced gastrin release and gastrin secretion in addition to the already known effects of somatostatin.

Six duodenal ulcer patients were investigated before and 3 months after truncal vagotomy and pyloroplasty. Plasma concentrations of gastric inhibitory polypeptide (GIP), insulin, and glucose were measured during intrajejunal infusion of 50 g of glucose. The GIP response was significantly diminished postoperatively; insulin and glucose concentrations, however, were unchanged. The reduction of GIP release was positively correlated with the reduction of the peak acid output. The results suggest that a reduced vagal innervation of the intestine is accompanied by reduced GIP release after intrajejunal glucose, depending on the degree of completeness of vagotomy.

Previous studies indicate that the forearm venous plasma norepinephrine (NE) concentration is abnormally high in patients with duodenal ulcer. The aim of the present study was to examine the relationship between age and plasma NE concentration in patients with duodenal ulcer and controls. Eleven male patients with duodenal ulcer and 12 male control subjects were examined. Plasma NE concentration was approximately twofold greater in duodenal ulcer patients in both the resting seated position and during exercise than values obtained in controls (2 p less than 0.02, less than 0.05). There was a strong correlation between plasma NE and age in patients with duodenal ulcer but not in controls (r = 0.69, 2 p less than 0.05). Our results suggest that the increase in plasma NE with age is greater in patients with duodenal ulcer than in normal healthy subjects or in patients with minor surgical diseases. Patients with duodenal ulcer may have a higher functional age than healthy subjects.

In duodenal ulcer patients the effect of vagal activation of gastric acid secretion by the intricate procedure of adequate sham feeding for 15 min has been compared with the effects of vagal stimulation induced by more easily accomplishable methods. The comparison involved modified sham feeding for 15 min by a 'chew-and-spit' technique and insulin hypoglycemia produced by i.v. injected insulin in the doses 0.1, 0.15, or 0.2 U/kg b.w. In 6 patients the peak and 2-hour acid responses to adequate sham feeding (10.7 mmol/30 min and 29.7 mmol) did not significantly differ from corresponding responses to modified sham feeding (9.1 mmol/30 min and 25.2 mmol). The peak and 2-hour acid responses to insulin in a dose of 0.1 U/kg (8 patients) were not significantly different from the sham-feeding responses. The 2-hour acid responses to insulin in the doses of 0.15 (6 patients) and 0.2 U/kg (17 patients) were significantly higher than the sham-feeding response. Furthermore, the peak acid response to insulin in a dose of 0.15 U/kg was significantly higher than the peak sham-feeding response. The gastric acid responses to modified sham feeding and insulin in a dose of 0.1 U/kg b.w. in duodenal ulcer patients seem to satisfactorily reflect physiological vagal activation of acid secretion.

The effect of insulin-induced hypoglycemia on serum group I pepsinogens (PG I), gastric H+, and pepsin secretion was studied in 11 duodenal ulcer patients before and 30 days after a proximal gastric vagotomy. The hypoglycemia elicited a significant increase in all the three variables preoperatively but in none of them postoperatively. This suggests that the preoperative increase in serum PG I must be mediated by the vagal nerves. Four of the 11 patients had an incomplete vagotomy by the method of Hollander. Serum PG I did not show any rising tendency in these patients postoperatively. It seems that serum PG I is a less sensitive indicator of the "completeness" of vagotomy than gastric H+ output. The serum PG I response to insulin-induced hypoglycemia can accordingly not be used as a clinical test for completeness of vagotomy.

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.

Simultaneous 50-g oral glucose tolerance tests and measurements of gastric emptying time were performed in 11 duodenal ulcer patients. Gastric emptying time, measured by the gamma-camera technique, and the response of gastric inhibitory polypeptide (GIP) and enteroglucagon to the oral load showed a significant negative correlation. The GIP response and the insulinogenic index were significantly positively correlated. It is concluded that the increased GIP and insulin response to glucose among duodenal ulcer patients may be explained by increased gastric emptying, known to occur in these patients. The study has not given new information on the possible physiological role of enteroglucagon.

A test meal was given to 9 male controls and 9 male patients with duodenal ulcer. The serum gastrin concentrations were determined by radioimmunoassay, and gastric secretion of acid was determined before and after stimulation with 6 mug pentagastrin per kg body weight given subcutaneously. The pattern of gastrin response was found to be biphasic, with an early maximum of the first peak in the patients versus a monophasic response with a maximum in the second hour in the controls. Fasting serum gastrin levels were positively correlated to the basal acid outputs (BAO) in the patients but not in the controls. The mean quotient BAO/Fasting serum gastrin concentration was highest in the patient group, but the quotient of "maximal" acid output (MAO)-BAO/"integrated gastrin response" was equal in the two groups.

In 9 non-diabetic, non-obese patients, oral and intravenous glucose tolerance tests were carried out before and after vagotomy, and the serum insulin was determined. The potentiating effect on insulin release of orally administered glucose was not abolished by total vagotomy, meaning that vagal mechanisms are not likely to play a major role in this potentiation in man.

The fasting serum concentration and the first-hour serum gastric response to a protein-rich meal were related to the antral G-cell population in 14 patients with peptic ulcer. They were divided into a uremic (n=5) and non-uremic group (n=9). Fasting serum gastrin correlated significantly with the total antral G-cell mass only in the non-uremic patients who showed a relatively narrow transitional body-antrum zone. Conversely, the integrated serum gastric response was inversely related to the size of this zone in both groups of patients. A presumptive endocrine G-cell mass was estimated by subtracting the G cells in the transitional zone from the total antral G-cell population. Total gastrin output correlated positively with this estimated mass in the non-uremic group and in the material as a whole. Also, the integrated gastrin response was positively correlated with the presumptive endocrine G-cell mass in the whole material. It was concluded that G cells in the transitional body-antrum zone, where also parietal cells are present, do not release gastrin into the circulation during meal stimulation like G cells in the remaining part of the pyloric antrum. On the basis of these results and our previous morphological observations (19), we propose that the G cells in the transitional zone are involved in a paracrine interrelationship with the surrounding parietal cells rather than contributing to the circulating pool of gastrin.

Gastric acid and serum gastrin (radioimmunoassay) responses to insulin (0.2 U/kg i.v.) and 2-deoxy-D-glucose (2DG) (50 mg/kg i.v.) were determined in 11 male duodenal ulcer patients before and after partial gastrectomy involving complete antral resection. In 8 of the patients the acid response to pentagastrin (6 mug/kg subc.) was also determined. Before operation, 2DG produced higher acid and gastrin responses than insulin. Partial gastrectomy reduced basal acid secretion by 54% but did not alter the basal gastrin level, suggesting that this gastrin is of extra-antral origin. Partial gastrectomy reduced the acid responses to insulin and 2DG by 66% and 78%, respectively; after operation the acid responses to these stimulants were equal. The ratio for the acid response to insulin and pentagastrin was 65% before and 56% after partial gastrectomy; corresponding ratios for 2DG and pentagastrin were 112% and 48%. Partial gastrectomy abolished the peak gastrin response to insulin hypoglycemia and reduced that to 2DG by 64%. The integrated gastrin response to insulin and 2DG was insignificant in the operated patients. Both insulin and 2DG release mainly antral gastrin which appears to be of greater importance for the acid response to 2DG than insulin.

Twelve patients with duodenal ulcers were each given on separate days and in random order an oral local anaesthetic (oxethazaine), an alkali (aluminium hydroxide and magnesium hydroxide), a combination of local anaesthetic and alkali (Mucaine), and a similar volume of water (control) followed one hour later by a solution of meat extract (Oxo). The effect of these treatments on serum gastrin levels was measured. None of the treatments altered the normal basal gastrin levels. The gastrin response to ingestion of protein extract was significantly lower in patients who had been pre-treated with local anaesthetic than those who had received alkali, with or without local anaesthetic, or water.