gastrins and Duodenal-Ulcer

Helicobacter pylori (H. pylori) have long been associated with a spectrum of disease outcomes in the gastro-duodenal system. Heterogeneity in bacterial virulence factors or strains is not enough to explain the divergent disease phenotypes manifested by the infection. This review focuses on host genetic factors that are involved during infection and eventually are thought to influence the disease phenotype. We have summarized the different host genes that have been investigated for association studies in H. pylori mediated duodenal ulcer or gastric cancer. We discuss that as the bacteria co-evolved with the host; these host gene also show much variation across different ethnic population. We illustrate the allelic distribution of interleukin-1B, across different population which is one of the most popular candidate gene studied with respect to H. pylori infections. Further, we highlight that several polymorphisms in the pathway gene can by itself or collectively affect the acid secretion pathway axis (gastrin: somatostatin) thereby resulting in a spectrum of disease phenotype.

Topics: Animals; Cell Transformation, Neoplastic; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Interleukin-1beta; Molecular Mimicry; Phenotype; Polymorphism, Genetic; Risk Factors; Signal Transduction; Somatostatin; Stomach Neoplasms; Virulence

A 61-year-old woman was referred to our hospital for a double balloon endoscopy (DBE) examination of small intestine. She had undergone laparotomy for a perforated ulcer of the 3rd portion in the duodenum 3 years prior to this admission. Esophagogastroduodenoscopy at the previous hospital revealed multiple ulcers in the 2nd and 3rd portions in the duodenum. DBE revealed multiple ulcer scars in the proximal jejunum. Zollinger-Ellison syndrome was suspected from the distribution of the ulcers and scars. Serum gastrin was high and a selective arterial calcium injection test showed a step up of gastrin level only in the gastroduodenal artery area. We diagnosed a gastrinoma located on the ventral side of the 2nd portion of the duodenum from imaging studies. The tumor was extirpated and histologically found to be a neuroendocrine tumor in a lymph node. Serum gastrin level decreased to the normal range a day after surgery.

Topics: Biomarkers, Tumor; Diagnostic Imaging; Duodenal Ulcer; Endoscopy, Digestive System; Female; Gastrins; Humans; Middle Aged; Peptic Ulcer Perforation; Time Factors; Zollinger-Ellison Syndrome

Recent milestones in the understanding of gastric acid secretion and treatment of acid-peptic disorders include the (1) discovery of histamine H(2)-receptors and development of histamine H(2)-receptor antagonists, (2) identification of H(+)K(+)-ATPase as the parietal cell proton pump and development of proton pump inhibitors, and (3) identification of Helicobacter pylori as the major cause of duodenal ulcer and development of effective eradication regimens. This review emphasizes the importance and relevance of gastric acid secretion and its regulation in health and disease. We review the physiology and pathophysiology of acid secretion as well as evidence regarding its inhibition in the management of acid-related clinical conditions.

Topics: Acetylcholine; Animals; Anti-Ulcer Agents; Digestion; Duodenal Ulcer; Eating; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gastrointestinal Diseases; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Histamine; Histamine H2 Antagonists; Humans; Ion Channels; Paracrine Communication; Proton Pump Inhibitors; Somatostatin; Stomach; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-8

Topics: Anemia; Anti-Bacterial Agents; Anti-Ulcer Agents; Comorbidity; Disease Susceptibility; Drug Therapy, Combination; Duodenal Diseases; Duodenal Ulcer; Enzyme Inhibitors; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Malabsorption Syndromes; Prevalence; Proton Pump Inhibitors; Renal Dialysis; Stomach Diseases; Stomach Ulcer; Urea

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Methylhistamines; Somatostatin; Tumor Necrosis Factor-alpha

Topics: Animals; Cell Division; Chronic Disease; Duodenal Ulcer; Enterochromaffin-like Cells; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Histamine Release; Humans; Somatostatin

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment.. Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Cytochrome P-450 Enzyme System; Drug Administration Schedule; Drug Costs; Drug Interactions; Duodenal Ulcer; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Rabeprazole; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Stomach Ulcer; Zollinger-Ellison Syndrome

Duodenal ulcer patients are characterized by an antrum-predominant, body-sparing, nonatrophic Helicobacter pylori (H. pylori) gastritis, which results in increased gastrin release and increased acid secretion. The increased gastrin release is caused by the infection impairing the acid-mediated inhibitory control of gastrin release. The elevated levels of the gastrin stimulate the healthy uninflamed, non-atrophic acid-secreting region of the stomach to secrete excess amounts of acid. The increased gastrin also exerts trophic effects on the oxyntic mucosa, causing hyperplasia of both the enterochromaffin-like cells and the parietal cells. These trophic changes in the mucosa further enhance its ability to secrete acid. The increased acid secretion results in an increased duodenal acid load, causing gastric metaplasia of the duodenal bulb and eventually the development of ulceration. In H. pylori-infected subjects without duodenal ulceration, a different pattern of gastritis is seen. This includes atrophy of the antrum, which reduces the number of G-cells and thus the degree of hypergastrinaemia induced by the antral infection. There are usually also varying degrees of inflammation and atrophy of the acid-secreting mucosa, which impair its ability to secrete acid in response to gastrin stimulation. The combined effects of the atrophy of the antrum and the inflammation of the antrum of the body mucosa therefore prevent H. pylori-induced acid hypersecretion and may result in varying degrees of hypochlorhydria. The particular pattern of gastritis that a subject develops in response to H. pylori infection and their likelihood of developing a duodenal ulcer is likely to be determinded by host genetic factors plus dietary factors.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Parietal Cells, Gastric

Topics: Duodenal Ulcer; Duodenum; Gastric Acid; Gastrins; Gastroesophageal Reflux; Gastrointestinal Neoplasms; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Stomach Ulcer

Helicobacter pylori is the cause of chronic type B gastritis and occurs in almost all patients with duodenal ulcers. Infection with H. pylori is characterized by an increased production of several inflammatory cytokines. Increasing evidence suggests a central role of these cytokines in the pathogenesis of H. pylori-associated gastritis and peptic ulcer disease. Cytokines may be crucial in the recruitment and activation of inflammatory cells and in stimulation of gastrin release. In addition to their proinflammatory properties, cytokines may also inhibit the ulcer occurrence by stimulation of prostaglandins and somatostatin release and by direct impairment of acid secretion. The balance of these factors may determine the clinical outcome of H. pylori infection.

Topics: Animals; Cytokines; Duodenal Ulcer; Gastrins; Gastritis; Genes, MHC Class II; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Intestinal Mucosa; Peptic Ulcer; Somatostatin

It is now widely recognized that H. pylori gastritis can produce marked alterations in gastric acid secretion. In subjects with an antral predominant gastritis there is increased release of gastrin and consequently increased acid secretion. Such subjects are at risk of developing duodenal ulcers. In other subjects the infection produces a marked body gastritis and this is associated with marked hyposecretion of acid or complete achlorhydria. These subjects have an increased risk of developing gastric cancer. Between these two ends of the disease spectrum lie the majority of H. pylori-infected subjects who have gastritis of both the antrum and body and no overall change in acid secretion. The reason why the infection exerts these divergent effects on gastric morphology and function remains unclear and is a challenge for ongoing research.

Topics: Cell Count; Duodenal Ulcer; Gastric Acid; Gastric Fundus; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum; Risk Factors

Topics: Betazole; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastritis; Humans; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Helicobacter pylori infected patients have increased gastrin release which shows a marked fall after cure of the infection. Recent studies indicate that inflammatory cells and cytokines play an important role in the pathogenesis of Helicobacter-associated hypergastrinemia. Views differ regarding the impact of gastrin on acid secretion. Current evidence suggests that gastrin is responsible for at least some of the increased acid secretion seen in duodenal ulcer patients.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Somatostatin

Helicobacter pylori infection is now recognized to be an important acquired factor in the pathogenesis of duodenal ulcer disease. There is also an association between H pylori and the subsequent development of gastric cancer. The mechanism of the association between the infection and those disorders is incompletely understood but there is increasing evidence that H pylori-induced disturbances of gastric function play a pivotal role. In this article we review the role of H pylori infection in the pathophysiology of these important upper gastrointestinal diseases.

Topics: Ascorbic Acid; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms

The discovery of H. pylori infection and the recognition of its effects on gastric physiology has significantly advanced our understanding of the pathophysiology of ulcer disease, In DU patients H. pylori gastritis is mainly confined to the antral mucosa. It stimulates increased release of gastrin by the antral mucosa and this is accompanied by high acid output by the oxyntic mucosa. This high acid response to gastrin stimulation by the oxyntic mucosa in DU patients is due to the combination of a high parietal cell mass and the fact that the function of these parietal cells is not impaired by any body gastritis. The increased acid secretion results in an increased duodenal acid load with the development of gastric metaplasia within the duodenal bulb and then actual ulceration. The reason why only some subjects develop this antral predominant pattern of H. pylori gastritis and associated acid hypersecretion is unclear but may be explained by a premorbid high acid output protecting the oxyntic mucosa form H. pylori gastritis.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum

Helicobacter pylori is highly adapted to its unusual ecological niche in the human stomach. Urease activity permits H. pylori survival at a pH of <4 in vitro and is required for the organism to colonize in animal models. However, urease does not play an important role in the survival of the organism in a pH range between 4 and 7. Other mechanisms of pH homeostasis remain poorly understood, but preliminary studies indicate that novel proteins are produced when H.pylori cells are shifted from pH 7 to 3, and the gene encoding a P-type adenosine triphosphatase that may catalyze NH4+/H+ exchange across the cytoplasmic membrane has been cloned. Mechanisms of pH homeostasis in other enteric bacteria are reviewed and provide insight into additional pathways that may be used by H. pylori. An important adaptation of H. pylori to the gastric environment may be its ability to alter gastric acid secretion. Acute infection is associated with transient hypochlorhydria, whereas chronic infection is associated with hypergastrinemia and decreased somatostatin levels. Thus, the survival of H. pylori in the gastric environment may be attributed to both the development of specialized intrinsic defenses and the organism's ability to induce physiological alterations in the host environment.

Topics: Acute Disease; Chronic Disease; Cytoplasm; Duodenal Ulcer; Enterococcus faecalis; Escherichia coli; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Salmonella; Somatostatin; Urease

The dictum "no acid-no ulcer" had, in the past, summarized the thinking concerning the pathogenesis of peptic ulcer disease. It is now recognized that infection with Helicobacter pylori is the major causal factor leading to both duodenal and gastric ulceration. Infection is associated with many of the acid secretory abnormalities that have traditionally characterized peptic ulcer disease; indeed, acid secretory physiology returns to normal following bacterial eradication. Since not all individuals infected with H. pylori develop ulcers, host susceptibility, bacterial virulence, and/or specific environmental factors must determine the response to infection and the ultimate clinical outcome. The relative importance of these factors and their complex interactions remain to be determined. H. pylori infection produces tissue damage indirectly because the organism does not directly invade gastroduodenal tissue. A variety of bacterial enzymes, toxins, and inflammatory mediators produced in response to bacterial colonization challenge the integrity of host mucosal defenses. In a susceptible host, breached defenses render epithelium more vulnerable to acid injury and ulcer development. Eradication of H. pylori leads to rapid ulcer healing and reversal of tissue injury, thereby obviating ulcer recurrence.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Stomach Ulcer

Helicobacter pylori is now recognized as the major acquired factor in the pathogenesis of duodenal ulcer disease (DU). There is also an association between H. pylori infection and the subsequent development of gastric cancer. The mechanisms by which such infection predisposes the host to these diseases are incompletely understood, but disorders induced by the bacterium in gastric function play a pivotal role. In most patients, H. pylori infection stimulates acid secretion, leading to a predisposition to DU development. However, in some patients, the infection is associated with a significant decrease in acid secretion, a predisposition to gastric cancer. These divergent effects of H. pylori on gastric acid secretion explain the early conflicting reports on changes in acid secretion associated with the infection. The reason why H. pylori infection produces divergent effects on gastric acid secretion is unclear, but may be related to differences in bacterial strains or genetic, dietary or other environmental factors.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach; Stomach Neoplasms

Topics: Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Ulcer

Topics: Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Ulcer; Virulence

Gastrin is a well known endogenous stimulator of gastric acid. In addition, recent studies have revealed that gastrin has a growth promoting effect on gastric ECL cells. Indeed, development of ECL carcinoid tumor occurs almost exclusively in patients with hypergastrinemia such as autoimmune gastritis and Zollinger-Ellison syndrome with MEN type I. We have recently cloned human gastrin receptor gene, and by using it, we found that both gastric carcinoid tumor and endocrine cell carcinoma of the stomach express significant amount of gastrin receptor gene whereas none of gastric cancer tissue shows gastrin receptor gene expression. Thus, it is clear that gastrin plays important roles in the development of gastric carcinoid tumor as well as endocrine cell carcinoma of the stomach.

Topics: Animals; Carcinoid Tumor; Duodenal Ulcer; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Receptors, Cholecystokinin; Stomach Neoplasms

Before the discovery of Helicobacter pylori, duodenal ulcers were thought to be caused by excessive acid secretion. Duodenal ulcer patients have more parietal cells than controls. In addition, they cannot suppress their acid secretion when the gastric lumen is empty or acidic. These changes, plus an increase in the release of gastrin were attributed to a paucity of the inhibitory peptide somatostatin in the gastric mucosa. It has now been established that the paucity of somatostatin and the failure to suppress acid secretion are actually the result of H. pylori infection. In patients without duodenal ulcers H. pylori infection is often associated with decreased acid secretion. This occurs on first infection and also later because H. pylori gastritis predisposes to gastric atrophy.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Unlike the stimulation of gastric acid secretion, which clearly involves the release of gastrin, the mechanisms of inhibition of this secretory process are poorly defined although recent studies in animals with the use of highly selective cholecystokinin (CCK) antagonists indicate that CCK may play a crucial role in this inhibition. Duodenal ulcer patients (DU) differ from healthy controls by higher total acid secretory rates and diminished inhibition of acid secretion. Several possible pathomechanisms of the abnormal gastric secretory function in DU patients were previously proposed. The deficiency of CCK-induced gastric inhibition in DU patients together with the somatostatin hypothesis appear to be attractive, particularly so the suggestion that a deficiency of somatostatin activity exists in DU patients.

Topics: Animals; Cholecystokinin; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Humans; Reference Values; Somatostatin

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens

Gastrin releasing peptide (GRP) has proved to be a particularly valuable tool in detecting disturbances of gastric secretory function associated with duodenal ulcer disease and Helicobacter pylori infection, and it has furthered understanding of the pathophysiology of these conditions. Its attractiveness lies in the fact that it simultaneously activates many physiological control processes, both stimulatory and inhibitory. This facilitates the detection of a defect in any of the many controls involved in regulating biological function. Other gastrointestinal functions such as gall-bladder contraction, pancreatic secretion and gastrooesophageal motility are also subject to complex regulatory controls, and GRP may also be of value in investigating disturbances of these processes.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter pylori; Humans; Peptic Ulcer; Peptides; Receptors, Bombesin

Helicobacter pylori is the new-found cause of duodenal ulcers (DU), but acid secretion remains necessary and is elevated in DU patients. My group and others have asked whether H. pylori itself alters gastric physiology. This infection has been found to decrease local expression of the inhibitory peptide somatostatin, and to increase release of the acid-stimulating hormone gastrin. H. pylori infection can alter acid secretion in both directions. Acid disappears temporarily on first infection, and may dwindle later if H. pylori causes gastric atrophy. DU patients have approximately twice the normal parietal cell mass, which increases their maximal secretory capacity, but it is not clear whether or not this is due to H. pylori. However, the infection certainly does change physiological control of acid secretion, as expected from the endocrine changes. Acid secretion is elevated during fasting, during stimulation with an acidic meal and during infusions of gastrin-releasing peptide. The balance between these opposing effects of H. pylori on acid may be crucial in determining the clinical outcome of H. pylori infection. High-acid secretion leads to DUs whilst low acid secretion is found in patients with gastric ulcers and gastric cancer. Inflammatory cytokines released in H. pylori gastritis may cause some of these changes in gastric physiology.

Topics: Animals; Cytokines; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Somatostatin; Urease

Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown.. In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays.. In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.

Topics: Adult; Anti-Bacterial Agents; Cholecystokinin; Dietary Fats; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Hormones; Humans; Hydrogen-Ion Concentration; Male; Proglumide; Reference Values; Somatostatin

Etiologic role for HP appears to be best established in histologically proven gastritis. The major factors mediating gastritis induced by the colonization of the "gastric type" mucosa with HP are probably cytotoxins, cytokines and free radicals activated by this organisms. The deficiency of negative feedback in somatostatin-gastrin link in antral gastritis may result in an excessive gastrin release and increased gastric acid secretion with increased duodenal acid load under basal state and after meal. Recent NIH consensus 1994 proposes that: (1) ulcer patients with HP require treatment with antimicrobial agents whether on first presentation or on recurrence; (2) the value of treatment of HP infection in non-ulcer dyspepsia remains to be determined and (3) the asymptomatic subjects with HP infection do not require treatment with antimicrobial agents.

Topics: Bacteriological Techniques; Bicarbonates; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer

In summary, it appears that the role of H. pylori in duodenal ulcerogenesis is not directly associated with acid hypersecretion. Similarly, it seems unlikely that H. pylori-induced autoimmune injury is an important mechanism in duodenal ulcerogenesis. An essential question remaining is whether H. pylori infection of areas of gastric metaplasia in the duodenum is essential to ulcer pathogenesis. The low yield of H. pylori in duodenal biopsy studies argues against this mechanism. It is possible that H. pylori gastritis (present in greater than 90% of duodenal ulcer patients) results in the release of inflammatory mediators into the gastric lumen that wash down to the duodenum with gastric emptying. Such a mechanism would explain both the low recovery rate of H. pylori from duodenal biopsies in ulcer patients and the local IgA response seen in the first part of the duodenum in response to H. pylori antigens. This could also explain the high incidence of H. pylori gastritis in patients with duodenal ulcers. Obviously the four theories discussed in this review are not mutually exclusive. Significant interaction may occur between the mechanisms described. In addition, bacterial strain differences may be more important than variations in host response to H. pylori infection. Genetic studies focused on strain differences regarding mediator production and release will help clarify these issues. In the vast majority of patients with duodenal ulcer, H. pylori infection appears to be required but is not sufficient for pathogenesis of the disease. The mechanisms of ulcerogenesis related to H. pylori remain incompletely understood. Several recently identified animal models including the gnotobiotic piglet and the naturally occurring H. mustelae infection in ferrets hold substantial promise for solving the puzzle of H. pylori disease.

Topics: Animals; Antibody Formation; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Models, Biological; Stomach

Topics: Duodenal Diseases; Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Models, Biological; Somatostatin; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer

All vertebrates secrete gastric acid. Acid denatures the proteins in the food and thus makes them more accessible to proteolytic enzymes, and it kills swallowed micro-organisms. Gastric acid plays an important pathogenetic role in peptic ulcer disease and reflux oesophagitis. In these diseases, drugs that inhibit secretion of gastric acid will heal the lesions and suppress the symptoms. However, both reflux oesophagitis and peptic ulcer tend to recur when the acid-inhibitory treatment is stopped. Therefore, these patients often require long-term treatment with acid-inhibitors. In this overview the potential risks of long-term profound inhibition of acid secretion, raising the pH above 4 for a considerable time, resulting in reduced killing of micro-organisms and secondary hypergastrinaemia, are discussed. Gastrin regulates both the function (production and release of histamine) and growth of the enterochromaffin-like (ECL) cell. Hitherto, the role that this cell plays in gastric carcinogenesis appears to have been underestimated.

Topics: Animals; Antacids; Anti-Ulcer Agents; Duodenal Ulcer; Enterochromaffin Cells; Esophagitis, Peptic; Gastric Acid; Gastrins; Histamine; Histamine H2 Antagonists; Humans; Stomach Ulcer

Topics: Animals; Cholecystokinin; Dogs; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Proglumide; Receptors, Cholecystokinin; Somatostatin

Topics: Duodenal Ulcer; Eating; Gastrins; Humans

Although Helicobacter pylori is now accepted as the major aetiological factor in chronic gastritis in man, many of the factors which determine its pathogenicity are unknown. The organism has adapted to survive in the low-pH environment of the stomach, partly through its ability to buffer hydrogen ion by the hydrolysis of urea and by the presence of lectins on its surface, which bind to gastric mucosa and epithelial cells. After attachment, harmful toxins and enzymes have access to the gastric cells and cellular damage and an immune response ensues. In patients with duodenal ulceration, Helicobacter pylori-related gastritis predominantly affects the gastric antrum and has a high prevalence. Excessive gastrin production has been suggested as a potential aetiological factor linking infection with duodenal ulcer development. Perhaps more important is the association between gastric metaplasia of the duodenal epithelium, which is correlated with acid load and is more extreme in H. pylori positive patients with duodenitis. Organisms may subsequently spread from the gastric antrum into areas of gastric metaplasia in the duodenal bulb, leading to areas of chronic duodenitis and ultimately frank ulceration. It should not be overlooked, however, that other factors such as genetic predisposition, blood group, stress, drugs and smoking all have a role to play in the outcome, given the comparatively small number of patients in the general population infected with H. pylori who develop ulcer disease.

Topics: Duodenal Ulcer; Duodenitis; Duodenum; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa

The response of serum gastrin, insulin and glucagon to administration of sodium bicarbonate (SB) followed by cimetidine was studied in 35 duodenal ulcer patients. Relevant measurements were made using radioimmunoassay kits "Diagnostic" (USA) and "Oris" (France). It was established that SB administration induced a significant rise in gastrin levels while those of insulin, glucagon and gastrin lowered significantly following cimetidine treatment (gastrin levels progressed to baselines). This marked effect of cimetidine on the gut hormone production is not always due to its adverse action being rather of compensatory nature and directed at enhancement of cytoprotection and normalization of gastric secretion.

Topics: Bicarbonates; Cimetidine; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Sodium; Sodium Bicarbonate

Two hundred and thirty-eight patients with duodenal ulcer were subjected to vagotomy. According to the clinical manifestations and the results of gastric acid secretion test, parietal cell vagotomy was done in 100 patients and selective vagotomy plus antrectomy in 138 patients. Follow-up after operation for 10 years showed that 96% and 97% of patients belonged to Visick Grade I and II respectively. The recurrence rate for parietal cell vagotomy was 1.96%, but no recurrence was seen in the group of selective vagotomy plus antrectomy. Long-term side-effects were rarely found in the patients. They had good nutritional states. The follow-up data showed that the recurrence rate could be greatly reduced if the modality of vagotomy was selected according to the type of gastric acid secretion test. The importance of surgeons experience and careful manipulation was emphasized.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pyloric Antrum; Recurrence; Vagotomy, Proximal Gastric

Topics: Cimetidine; Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Ranitidine; Recurrence

Topics: Cimetidine; Duodenal Ulcer; Esophagitis; Gastric Mucosa; Gastrins; Humans; Omeprazole; Ranitidine; Vagotomy, Proximal Gastric

Topics: Acute Kidney Injury; Duodenal Ulcer; Gastrinoma; Gastrins; Humans; Kidney Failure, Chronic; Pancreatic Neoplasms; Pyloric Antrum; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Parietal Cells, Gastric; Peptic Ulcer; Vagus Nerve

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Duodenal Ulcer; Enprostil; Gastric Juice; Gastrins; Humans; Misoprostol; Omeprazole; Prostaglandins E, Synthetic; Stomach Ulcer

The purpose of this short review is to reveal new aspects of nerval regulation of gastric acid secretion. The complex interactions between humoral, paracrine, neurocrine, neuroendocrine, vagal and sympathetic mechanisms are underlined. The finding that stimulation of the vagus nerves releases bombesin from peptidergic nerve fibers, which causes release of gastrin from endocrine cells in the stomach, demonstrates the complex interaction between nerves and hormones. The target organ, the parietal cell, has receptors for gastrin, acetylcholine and histamine, which potentiate each other regarding stimulation of acid secretion. New findings about the pathophysiology of acid secretion in duodenal ulcer patients are emphasized.

Topics: Animals; Duodenal Ulcer; Feeding Behavior; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Parietal Cells, Gastric; Pyloric Antrum; Sympathetic Nervous System; Vagus Nerve

Serum gastrin levels were measured preoperatively and at several intervals postoperatively in 262 patients who underwent highly selective vagotomy for duodenal ulcer. An increase of serum gastrin levels was demonstrated postoperatively in all patients, irrespective of sex, length of history, acid secretion data or recurrence. At several years postoperatively, a highly significant secondary rise in serum gastrin levels was observed, which corresponded well to recent physiologic and morphologic data. The most suitable explanation appeared to be that the proximal gastric vagotomy (vagotomy of the fundus and corpus) abolished the vagally mediated inhibition of the G-cells in the antrum (disinhibition of the oxyntopyloric reflex). The serum gastrin values were always higher and the secondary postoperative increase was earlier for patients who had taken cimetidine preoperatively. Contrary to traditional expectations, no correlation at all was found between serum gastrin levels and acid secretion data. Recurrence could not be predicted on the basis of serum gastrin levels.

Topics: Adult; Chronic Disease; Cimetidine; Duodenal Ulcer; Evaluation Studies as Topic; Female; Follow-Up Studies; Gastrins; Humans; Male; Middle Aged; Premedication; Recurrence; Sex Factors; Vagotomy, Proximal Gastric

Greatly improved understanding of the cellular basis for gastric acid secretion and gastroduodenal mucosal defense has led to a dramatic improvement in the pharmacologic treatment of peptic ulcer disease. The advances produced by cimetidine and ranitidine are being continued by a new generation of histamine receptor antagonists, as well as by other anti-ulcer agents. These new drugs, when used appropriately, will greatly expand the surgeon's ability to treat patients with peptic ulcer disease. A knowledge of the pathophysiologic characteristics of peptic ulceration and of the inherent limitations of each agent will become increasingly important for surgeons who treat these patients.

Topics: Acetylcholine; Benzimidazoles; Chemical Phenomena; Chemistry; Cimetidine; Disease Susceptibility; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Histamine H2 Antagonists; Humans; Imidazoles; Intestinal Mucosa; Peptic Ulcer; Ranitidine; Receptors, Muscarinic; Stimulation, Chemical; Stomach Ulcer

Topics: Animals; Diagnosis, Differential; Digestive System; Duodenal Ulcer; Enterochromaffin Cells; Fluorescent Antibody Technique; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Histocytochemistry; Humans; Hyperplasia; Immunologic Techniques; Intestinal Mucosa; Microscopy, Electron; Neural Crest; Regeneration; Stomach Neoplasms

Topics: Animals; Digestive System; Digestive System Physiological Phenomena; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Histamine; Histamine H2 Antagonists; Humans; Intrinsic Factor; Liver Circulation; Pepsinogens; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Regional Blood Flow; Stomach; Stomach Ulcer; Zollinger-Ellison Syndrome

Recent advances in the medical therapy of duodenal ulcer support the long held concept that acid hypersecretion is an important pathophysiological abnormality in the majority of patients with duodenal ulcer. The origin of acid hypersecretion is heterogeneous (Table 1). Certain specific physiologic abnormalities that lead to acid hypersecretion may have a genetic basis. The various physiologic abnormalities, alone or in combination, may lead to two final common pathways: abnormally large meal-stimulated and nocturnal acid secretion. Indeed, the success of medical therapy aimed at the control of postprandial acid secretion alone or that of nocturnal acid secretion alone strongly support the significance of these two final acid hypersecretory pathways.

Topics: Circadian Rhythm; Duodenal Ulcer; Eating; Enterochromaffin Cells; Ethnicity; Gastric Acid; Gastrins; Gastrointestinal Motility; Humans; Hypertrophy; Parietal Cells, Gastric; Pyloric Antrum; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Enterochromaffin Cells; Food; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Hyperplasia; Vagus Nerve

Several different disturbances in the regulation of acid secretion have been found in persons with duodenal ulcer disease (DU). This paper examines the possibility that some of these regulatory disturbances might arise during postnatal development. The regulation of acid secretion is not fixed in adult form at birth, in either animals or humans. Instead, these regulatory processes continue to change during postnatal development. Examples are developmental changes in the responsiveness of the stomach to parietal cell stimulants and developmental increases and decreases in basal and maximal acid output. The unfolding of these developmental changes requires complex regulatory adjustments. It is possible that untoward environmental circumstances could induce "errors" in these regulated changes or adjustments. Some errors might persist as disturbances in the regulation of acid secretion seen in patients with DU.

Topics: Adult; Aging; Animals; Bethanechol; Bethanechol Compounds; Cold Temperature; Duodenal Ulcer; Gastric Acid; Gastrins; Histamine; Humans; Infant, Newborn; Models, Biological; Pentagastrin; Rats; Rats, Inbred Strains; Stomach; Weaning

Topics: Burimamide; Chemical Phenomena; Chemistry; Cimetidine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Acid; Gastrins; Gastrointestinal Hemorrhage; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Hypersensitivity; Intrinsic Factor; Kinetics; Malabsorption Syndromes; Metiamide; Pancreas; Pepsin A; Ranitidine; Receptors, Histamine H2; Stomach Ulcer; Stress, Psychological; Zollinger-Ellison Syndrome

Topics: 3,4-Dihydroxyphenylacetic Acid; Amylases; Animals; Brain Chemistry; Cysteamine; Dopamine; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Hormones; Humans; Mice; Nitriles; Norepinephrine; Rats; Secretin; Terminology as Topic; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

The Zollinger-Ellison syndrome (ZES) is caused by mainly pancreatic, gastrin-producing tumours, which show a high rate of malignancy. The clinical picture is dominated by gastric hypersecretion, which results in the development of peptic ulcerations of the stomach and duodenum, reflux esophagitis, or diarrhea. The differentiation from other types of hypergastrinemia is done by provocative tests, mainly the secretin-test. Because of the high malignancy rate, therapeutically, a symptomatic treatment of gastric hypersecretion by H2-receptor antagonists or in cases of ineffective conservative treatment total gastrectomy is performed. In patients with duodenal gastrinomas or in the rare cases with benign pancreatic tumours resection of the tumours is the therapy of choice.

Topics: Benzimidazoles; Calcium; Cimetidine; Diarrhea; Duodenal Ulcer; Female; Fluorouracil; Gastrectomy; Gastric Acid; Gastrins; Glucagon; Humans; Male; Middle Aged; Omeprazole; Pancreatic Neoplasms; Prognosis; Ranitidine; Secretin; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Animals; Benzyl Alcohols; Child; Cimetidine; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Middle Aged; Rats

Much epidemiological, clinical, and pathophysiological evidence has accumulated to indicate that the aetiology of duodenal ulcer is heterogeneous (Table 8). Recent advances in the medical therapy of duodenal ulcer support the long held concept that hyperacidity is an important physiological abnormality in the majority of patients with duodenal ulcer. It can also be shown that the origin of hyperacidity is heterogeneous. Certain specific physiological abnormalities that lead to hyperacidity may have a genetic basis. The various physiological abnormalities, alone or in combination, may lead to two final common pathways: abnormally large meal-stimulated acid secretion, and nocturnal acid hypersecretion. Indeed, success of medical therapy aiming at the control of postprandial acid secretion or of nocturnal acid secretion strongly supports their significance. It is possible that hyperacidity occurs as a temporary phenomenon and is associated with stressful life events. However, it is also possible that it occurs as a constant abnormality, bestowed perhaps genetically on the duodenal ulcer patient. In the presence of hyperacidity, mucosal repair may be affected adversely. In either situation, an acute ulcer, such as that associated with stress, is allowed to develop into a full-blown ulcer. Healing takes place if the hyperacidity recedes or is reduced therapeutically, allowing normal mucosal repair to take place.

Topics: Age Factors; Analgesics; Cell Count; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; HLA Antigens; Humans; Intestinal Mucosa; Kidney Failure, Chronic; Lung Diseases; Parietal Cells, Gastric; Sleep; Smoking; Stress, Psychological

In contrast to healthy subjects, duodenal ulcer patients in the active phase contain large amounts of a peptide in serum and antrum which react with antiserum specific for the N-terminus, but not the C-terminus of gastrin-17. The immunochemical and chromatographic properties were similar to that of the N-terminal tridecapeptide sequence of gastrin-17. The peptide follows the clinical course of duodenal ulcer disease, as it disappears when the ulcer heals. The N-terminal tridecapeptide - lacking the bioactive tetrapeptide of gastrin-17 - is a potent inhibitor of gastric acid secretion, presumably by way of competitive antagonism to gastrin. It is suggested to participate in the regulation of gastric acid secretion in patients with active duodenal ulcer disease. To confirm the chemical structure of the peptide, antral and gastrinoma extracts were used for isolation, purification and amino acid analysis. We found two different peptides with the same N-terminus as gastrin-17, namely the previously known N-terminal tridecapeptide fragment of gastrin-17 and a new gastrin component, identical with a C-terminal glycine extended gastrin-17. Furthermore, a C-terminal glycine extended component, corresponding to each of the other molecular forms of gastrin were present. Thus, a variety of abnormally processed gastrins are synthesized and released to the circulation during the active period of duodenal ulcer disease.

Topics: Amino Acid Sequence; Animals; Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastrins; Humans; Species Specificity; Terminology as Topic; Tissue Extracts

The past 20 years have seen gastrin attain true hormonal status. Its structure has been characterized, it has been synthesized, radioimmunoassays for its measurement in blood and tissues have been developed and its physiology and metabolism elucidated. Of much interest to clinicians has been the association between gastrin and tumours of the pancreas (gastrinomas) and atrophic gastritis. The advent of gastrin measurement has facilitated the diagnosis of gastrinoma and the availability of powerful acid suppressants has altered the therapy of gastrinoma.

Topics: Duodenal Ulcer; Gastrins; Gastritis, Atrophic; Humans; Kidney Failure, Chronic; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Calcium; Diagnosis, Differential; Duodenal Ulcer; False Negative Reactions; False Positive Reactions; Gastrectomy; Gastrins; Humans; Infusions, Parenteral; Injections, Intravenous; Jejunal Diseases; Peptic Ulcer; Secretin; Stomach Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Duodenal Ulcer; Endoscopy; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Insulin; Intraoperative Period; Male; Middle Aged; Postoperative Complications; Pyloric Antrum; Recurrence; Stomach Ulcer; Time Factors; Vagotomy; Vagotomy, Proximal Gastric

Topics: Chromaffin System; Cytoplasmic Granules; Duodenal Ulcer; Enterochromaffin Cells; Gastrins; Humans; Hyperplasia; Immunologic Techniques; Pepsinogens; Pyloric Antrum; Zollinger-Ellison Syndrome

The procedures of radioimmunoassays for gastrin are presented in this paper. Techniques are described and evaluated with special reference to preparation of radioiodinated gastrin, purification of monoiodinated gastrin, characterisation of the immunochemical properties of radiolabelled gastrin, raising and characterisation of specific antibodies, incubation conditions, separation of bound and free hormone and treatment of data. Factors contributing to discrepancies of radioimmunoassay results and problems encountered are discussed. Methods employed by the authors in gastrin radioimmunoassay are described. Commercially available gastrin kits are also compared.

Topics: Animals; Antibody Formation; Cattle; Chromatography, Gel; Chromatography, Ion Exchange; Duodenal Ulcer; Gastrins; Humans; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Reagent Kits, Diagnostic; Secretin; Swine; Zollinger-Ellison Syndrome

Topics: Acromegaly; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hyperparathyroidism; Ileal Diseases; Pyloric Antrum; Stomach Ulcer; Zollinger-Ellison Syndrome

Progress in gut hormone research has considerably increased our knowledge in gastrointestinal physiology. However, this knowledge has not yet helped the understanding of common gastrointestinal diseases. A pathophysiological role of gut hormones has been established only for rare conditions This is because the clinical significance of the gut hormones is difficult to evaluate. Morphological and biochemical methods used in classical endocrinology can rarely be applied to gastrointestinal endocrinology because of the special design of the gut hormone system. Also gut hormones and autonomous nervous system overlap in their function. A defect of one system can be compensated by the other. Since the hormone-producing cells of the gut are stimulated by food ingestion, any functional or organic change of the digestive tract will alter gut hormone response. Accordingly, most changes of gut hormone levels are secondary. In some--apparently rare--instances such secondary changes contribute to the symptomatology of a pathological condition. In other instances gut hormone abnormalities mimic common diseases, thus demonstrating the heterogenecity of these conditions. More specific and reliable methods are needed to prove or to exclude the participation of gastrointestinal peptides in the pathogenesis of gastrointestinal disease. Gut peptides are an important link between nutrient entry and metabolism. This is realized by a hormonal gut factor (incretin) which augments glucose-induced insulin release. GIP is the most thoroughly investigated but not the only incretin. In addition, GIP seems to have direct effects on lipid metabolism. This would explain why fat releases more GIP than glucose. Except in the case of the metabolic hormones insulin and glucagon the therapeutic usefulness of gastrointestinal peptides has not yet been established.

Topics: Autonomic Nervous System; Duodenal Ulcer; Endocrine Glands; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Insulin; Insulin Secretion; Intestinal Absorption; Peptide Fragments; Peptides

Topics: Catecholamines; Duodenal Ulcer; Gastrins; Humans; Somatostatin; Vagotomy

The value of cimetidine in treatment of duodenal ulcer and the Zollinger-Ellison syndrome appears to be well established. The drug has been enthusiastically embraced and widely used by practicing physicians. As with virtually all drugs used in the practice of medicine, cimetidine is not without its adverse effects. In some instances these effects may result from actions of cimetidine on H2-receptors on many widely distributed and diverse cells other than parietal cells, to which its potent acid-inhibiting properties are directed. Other adverse effects of cimetidine may be idiosyncratic, and, therefore, not predictable on a pharmacologic basis. In some instances the mechanisms responsible for cimetidine's adverse effects hav e yet to be defined. An assortment of abnormalities reported in patients receiving cimetidine have been suggested, but not proven, to represent adverse effects of the drug. Considering its extremely wide use, serious toxicity with cimetidine is rare. However, no potent drug, including cimetidine, used in the practice of medicine is without its adverse effects. Recognizing the present and projected extensive and probably long-term use of cimetidine, physicians and surgeons treating patients with cimetidine must maintain continued surveillance in order to detect and clarify potential undesired consequences of cimetidine administration.

Topics: Agranulocytosis; Animals; Bone Marrow; Central Nervous System; Chemical and Drug Induced Liver Injury; Cimetidine; Creatinine; Duodenal Ulcer; Endocrine Glands; Gastric Juice; Gastrins; Guanidines; Humans; Immunity, Cellular; Intrinsic Factor; Liver; Pancreatitis; Receptors, Histamine H2; Risk; Stomach Neoplasms; Transaminases

Parietal cell vagotomy (PCV) without drainage is associated with the lowest mortality of any operation currently being widely used for the elective treatment of duodenal ulcer. There are fewer gastrointestinal complaints of the type observed after more orthodox gastric operations. Diarrhea and dumping may occur after PCV in approximately 5 percent of patients, and when these complaints do occur they are milder and more easily controlled than after other types of operation. This improvement is attributed to retention of the peristaltic action of the antrum and an intact pyloric sphincter, which together, permit gastric emptying that is more normal than that which occurs with any other gastric procedure. There is insufficient evidence to indicate that retention of antral innervation exerts an inhibitory or a stimulatory effect on acid secretion which would be either beneficial or detrimental to the duodenal ulcer patients. The acid secretory rates are reduced effectively by PCV and equal the reductions that follow truncal vagotomy and drainage. Acid secretory rates increase during the first postoperative year and then remain rather constant with time. This observation and the reports that the rate of recurrent ulcers after 2 to 4 years follow-up is two to four percent, suggests that PCV is a highly effective procedure.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Emptying; Gastrins; Humans; Pancreatic Polypeptide; Pyloric Antrum; Recurrence; Vagotomy; Vagotomy, Proximal Gastric

Topics: Animals; Atropine; Cats; Cimetidine; Dogs; Duodenal Ulcer; Ethanol; Food; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Stomach; Vagotomy; Vagus Nerve

Patients with duodenal ulcer may have one or more of the following abnormalities: (1) larger than normal volume of gastric mucosa containing correspondingly more acid and pepsin secreting cells which is reflected in (2) increased mean concentration of pepsinogen-I in plasma, and (3) increased maximal rates of secretion of acid and pepsin in response to stimuli such as histamine, gastrin, insulin, or food; (4) increased sensitivy to stimulation by gastrin as reflected by decreased dose of gastrin needed to evoke half maximal response; (5) increased gastrin response to meals; (6) decreased inhibition of gastrin release and of acid secretion in response to acidification of the gastric contents; and (7) increased rapidity of gastric emptying. Items 2, 5, and 7 are heritable autosomal dominant traits in at least some patients. Although mean values of each of these 7 items are significantly different from normal, the range is wide and most individual duodenal ulcer patients fall within the normal range. The diversity of physiological abnormalities found in patients with duodenal ulcer shows that it is a heterogeneous disease with many different factors operating in its pathogenesis.

Topics: Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Pepsin A; Pepsinogens

Topics: Cimetidine; Duodenal Ulcer; Gastric Acid; Gastrins; Guanidines; Humans; Kinetics; Pancreatitis; Time Factors; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Animals; Duodenal Ulcer; Duodenum; Gastric Juice; Gastrins; Histamine Release; Humans; Secretin; Stomach

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Catecholamines; Circadian Rhythm; Dogs; Duodenal Ulcer; Gastrins; Humans; Hypoglycemia; Physical Exertion; Receptors, Adrenergic, beta; Smoking; Vagotomy

Topics: Animals; Deoxyglucose; Dogs; Duodenal Ulcer; Eating; Electric Stimulation; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Insulin; Pepsin A; Vagotomy; Vagus Nerve

Topics: Animals; Celiac Disease; Child; Duodenal Ulcer; Duodenum; Esophageal Diseases; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Intestinal Mucosa; Intestine, Small; Stomach; Zollinger-Ellison Syndrome

Development of histamine H2-receptor antagonists has enhanced the understanding of histamine physiology and pharmacology. The effect of H2-receptor antagonists on gastrointestinal physiology has been studied extensively. These compounds inhibit gastric acid secretion in response to all known secretagogues and, in contrast to anticholinergic drugs, markedly inhibit food-stimulated acid secretion in duodenal ulcer patients. The relative roles of H2-receptor antagonists, anticholinergic drugs and antacids in the treatment of duodenal ulcer remain to be defined. Cimetidine currently is under investigation for the treatment of duodenal ulcer, gastric ulcer, reflux esophagitis, gastrointestinal bleeding and hypersecretory states. Although the long-term safety of cimetidine has not been established, in short-term clinical trials there have been no significant subjective or objective side-effects. Assuming that toxic effects do not develop, H2-receptor antagonists should improve the treatment of acid-peptic disease.

Topics: Cimetidine; Cyclic AMP; Duodenal Ulcer; Esophagitis, Peptic; Gastric Juice; Gastrins; Gastritis; Gastrointestinal Hemorrhage; Histamine; Histamine H2 Antagonists; Humans; Intrinsic Factor; Metiamide; Pepsin A; Stomach Ulcer

Topics: Adult; Aged; Antacids; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Histamine Antagonists; Humans; Male; Parasympatholytics; Peptic Ulcer; Stomach Ulcer; Zollinger-Ellison Syndrome

Cimetidine is a specific competitive histamine H2-receptor antagonist which effectively inhibits gastric acid secretion and is advocated for the treatment of chronic peptic ulceration, haemorrhage from erosive gastritis, and the control of gastric hypersecretion and peptic ulceration in the Zollinger-Ellison syndrome. Placebo-controlled trials in outpatients have demonstrated its efficacy in promoting the healing of endoscopically diagnosed duodenal ulceration, during a period of 4 to 6 weeks, but its role in the treatment of gastric ulcer is less clear. Preliminary evidence suggests that maintenance therapy with cimetidine reduces the rate of recurrence of duodenal ulcer, but further studies are required to clarify its role in this situation and in the treatment of oesophagitis and acute gastrointestinal haemorrhage. Cimetidine controls the peptic ulceration of Zollinger-Ellison syndrome in most patients when given continuously for up to 2 years. Side-effects have generally been trivial and have very seldom necessitated withdrawal of therapy except in the rare occurrence of gynaecomastia. The haematological abnormalities particularly agranulocytosis, which lead to the withdrawal from clinical use of metiamide, have not been reported with cimetidine, except for 1 case of transient neutropenia. The safety of long-term cimetidine administration has yet to be determined.

Topics: Acute Disease; Animals; Cimetidine; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Hemorrhage; Guanidines; Humans; Intrinsic Factor; Recurrence; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Cimetidine; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Glycoproteins; Humans; Intestinal Mucosa; Peptic Ulcer; Receptors, Histamine; Secretin; Secretory Rate; Somatostatin; Stomach Ulcer; Vasoactive Intestinal Peptide

The familial aggregation of peptic ulcer disease has been well established, as has its association with such clear-cut genetic factors as blood group O and nonsecretor status. However, the genetics of this disorder, or group of disorders, is still in question. Polygenic inheritance is the prevailing hypothesis that has been proposed for peptic ulcer. This hypothesis was based primarily on the exclusion of a simple mode of inheritance for all ulcer disease. Genetic heterogeneity is an alternative hypothesis that can explain both the familial aggregation of peptic ulcer disease and the lack of a simple Mendelian pattern of inheritance. The evidence for genetic heterogeneity in peptic ulcer disease is reviewed, and studies are proposed to test this hypothesis.

Topics: ABO Blood-Group System; Antigens; Chromosome Aberrations; Chromosome Disorders; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pepsinogens; Peptic Ulcer; Phenotype; Pituitary Neoplasms; Stomach Ulcer; Werner Syndrome

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable elect

Topics: Adenoma, Islet Cell; Anemia, Pernicious; Chromaffin System; Digestive System; Duodenal Ulcer; Endocrine System Diseases; Enterochromaffin Cells; Esophagitis, Peptic; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Intestinal Mucosa; Metabolic Diseases; Serotonin; Somatostatin; Stomach Neoplasms; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Calcium; Dietary Proteins; Duodenal Ulcer; Gastric Juice; Gastrins; Gastritis; Glucagon; Humans; Hyperplasia; Intestine, Small; Kidney Failure, Chronic; Pyloric Antrum; Pyloric Stenosis; Secretin; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Animals; Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Radioimmunoassay; Stimulation, Chemical; Stomach; Structure-Activity Relationship; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Anemia, Pernicious; Duodenal Ulcer; Gastrectomy; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Liver; Molecular Weight; Peptic Ulcer; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

15-Methyl PGE2 and 16,16-dimethyl PGE2 were found (1) to be 40 and 100 times, respectively, more potent than PGE2 after intravenous administration in inhibiting histamine-stimulated gastric secretion in dogs with a denervated (Heidenhain) gastric pouch, (2) to be active orally and intrajejunally, whereas PGE2 was inactive, and (3) to exert antisecretory activity for longer duration than PGE2. 16,16-Dimethyl PGE2 was about 2.5 times more potent than 15-methyl PGE2. Volume, acid concentration, and output, and pepsin output (but not concentration) were reduced in a dose-dependent manner. In the rat, 16,16-dimethyl PGE2 also inhibited gastric secretion and prevented the formation of ulcers produced by various methods: gastric ulcers (Shay, and steroid induced) and duodenal ulcers (secretogogue induced). In this species, 1l816-dimethyl PGE2 was 2 to 50 times more potent than PGE2, depending on the endpoint, and was active orally. These prostaglandins appear to inhibit gastric acid secretion by acting directly on the parietal cells, and making these unresponsive to most stimulants. Vomiting was a side effect of the prostaglandin analogues in the dog, but almost exclusively when these were given orally. After intravenous or intrajejunal administration at doses inhibiting gastric secretion by 80%, vomiting was seen only once. These results suggest that 15-methyl PGE2 and 16,16-dimethyl PGE2 may be of value in the treatment of peptic ulcer.

Topics: Administration, Oral; Animals; Carbachol; Cyclic AMP; Depression, Chemical; Dogs; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Infusions, Parenteral; Jejunum; Male; Prednisolone; Prostaglandins E; Prostaglandins E, Synthetic; Pylorus; Rats; Stomach; Stomach Ulcer

Topics: Amino Acid Sequence; Animals; Cholecystokinin; Duodenal Ulcer; Gastrins; Gastrointestinal Hormones; Humans; Secretin; Stomach Ulcer

In a short survey recent results of research on gastrin are presented. Special stress is laid upon the mechanism of liberating gastrin, the role of the vagus in this process and the consequences of gastric surgery on serumgastrin. In clinical practice the differential diagnosis of hypergastrinemia in ulcer disease is very important, for it will have a decisive influence on the therapeutic decisions and the specific kind of surgical treatment.

Topics: Duodenal Ulcer; Gastrins; Humans; Peptic Ulcer; Postoperative Complications; Vagotomy; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Esophagogastric Junction; Gastric Mucosa; Gastrins; Humans; Ileocecal Valve; Liver; Pancreas; Radioimmunoassay; Sphincter of Oddi; Stomach; Zollinger-Ellison Syndrome

Topics: Animals; Dogs; Duodenal Ulcer; Duodenum; Evaluation Studies as Topic; Follow-Up Studies; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Methods; Stomach Ulcer

Topics: Duodenal Ulcer; Gastrins; Humans; Peptic Ulcer; Stomach; Vagotomy

Topics: Animals; Duodenal Ulcer; Eating; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Models, Biological; Stimulation, Chemical; Vagus Nerve

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Duodenal Neoplasms; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Peptic Ulcer; Radiography; Radioimmunoassay; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Amino Acid Sequence; Animals; Catecholamines; Dehydration; Diarrhea; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Intestinal Mucosa; Peptic Ulcer; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Anemia, Pernicious; Atrophy; Calcium; Carcinoma; Catecholamines; Circadian Rhythm; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Diseases; Hormones, Ectopic; Humans; Ligation; Pancreatic Ducts; Secretin; Stimulation, Chemical; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Hypertrophy; Intestinal Mucosa; Pepsin A; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Anemia, Hypochromic; Body Weight; Bone Diseases; Chronic Disease; Diarrhea; Dumping Syndrome; Duodenal Obstruction; Duodenal Ulcer; Female; Follow-Up Studies; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Insulin; Male; Methods; Pentagastrin; Peptic Ulcer; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Postoperative Complications; Recurrence; Stomach Ulcer; Vomiting

Topics: Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Motility; Glucose; Histamine; History, 20th Century; Humans; Insulin; Male; Methylene Blue; Nerve Regeneration; Pentagastrin; Pepsin A; Peptic Ulcer; Postgastrectomy Syndromes; Preoperative Care; Pyloric Antrum; Radioimmunoassay; Recurrence; Sex Factors; Stomach; Sympathectomy; Time Factors; Vagotomy

Topics: Animals; Duodenal Ulcer; Gastrins; Gastrointestinal Diseases; Humans; Intestine, Small; Liver Cirrhosis; Liver Diseases; Peptic Ulcer

Topics: Adult; Amino Acid Sequence; Cholecystography; Cholecystokinin; Duodenal Ulcer; Female; Gastrins; Gastrointestinal Hormones; Humans; Male; Middle Aged; Peptides; Radioimmunoassay; Secretin

Topics: Bile; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Ischemia; Permeability; Stomach Ulcer

Topics: Animals; Cholecystokinin; Dogs; Duodenal Ulcer; Esophagus; Gallbladder; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Pancreatic Juice; Secretin; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Vagotomy; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Animals; Calcium; Cholecystokinin; Duodenal Ulcer; Eating; Gastric Mucosa; Gastrins; Histamine; Humans; Islets of Langerhans; Pentagastrin; Pepsin A; Peptic Ulcer; Prostaglandins; Radioimmunoassay; Rats; Secretin; Vagus Nerve

Topics: Animals; Cats; Chronic Disease; Creatinine; Dogs; Duodenal Ulcer; Esophageal Achalasia; Esophageal Diseases; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Peptic Ulcer; Pyloric Antrum; Rats; Scleroderma, Localized; Stomach Neoplasms; Vagotomy; Zollinger-Ellison Syndrome

Topics: Diarrhea; Drainage; Dumping Syndrome; Duodenal Ulcer; Female; Gallbladder; Gastric Juice; Gastrins; Gastrointestinal Hemorrhage; Gastrointestinal Motility; Humans; Intestine, Small; Male; Pancreas; Peptic Ulcer Perforation; Postoperative Complications; Pyloric Antrum; Pyloric Stenosis; Pylorus; Recurrence; Stomach; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Pepsin A; Peptic Ulcer; Postgastrectomy Syndromes; Postoperative Complications; Stomach Ulcer; Vagotomy; Vagus Nerve

Topics: Anxiety Disorders; Aspirin; Bile Acids and Salts; Blood Group Antigens; Diet; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Histamine; Humans; Hyperplasia; Male; Pentagastrin; Peptic Ulcer; Radioimmunoassay; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastrins; Heparin; Humans; Intestine, Small; Pancreas; Zollinger-Ellison Syndrome

Topics: Dietary Proteins; Duodenal Ulcer; Feedback; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Peptic Ulcer; Radioimmunoassay; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Anemia, Pernicious; Chronic Disease; Duodenal Ulcer; Duodenum; Esophagus; Feedback; Gastric Juice; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Intestinal Mucosa; Jejunum; Muscle Tonus; Pancreas; Pyloric Antrum; Radioimmunoassay; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Biliary Tract Diseases; Ceruletide; Cholangiography; Cholelithiasis; Duodenal Ulcer; Endoscopy; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Hormones; Humans; Intestinal Absorption; Lactose Intolerance; Pancreatic Diseases; Peptic Ulcer; Radionuclide Imaging; Secretin; Stomach Neoplasms

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Hypertrophy; Intubation, Gastrointestinal; Stomach Neoplasms

Topics: Biopsy; Diagnosis, Differential; Diffusion; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Hydrogen-Ion Concentration; Male; Radiography; Recurrence; Stomach Ulcer; Vagotomy

Topics: Age Factors; Anemia, Pernicious; Antigen-Antibody Reactions; Antigens, Neoplasm; Cholecystokinin; Cross Reactions; Digestive System Physiological Phenomena; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hepatitis B Antigens; Hormones; Humans; Hyperglycemia; Insulin; Methods; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Diabetes Mellitus; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Rats; Secretory Rate; Stomach Ulcer

Topics: Achlorhydria; Age Factors; Body Weight; Diagnosis, Differential; Duodenal Ulcer; Ethnicity; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Male; Methods; Pentagastrin; Sex Factors; Stomach Diseases; Stomach Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastritis; Humans; Research; Zollinger-Ellison Syndrome

Topics: Abdomen; Duodenal Diseases; Duodenal Neoplasms; Duodenal Ulcer; Esophageal Achalasia; Esophageal Diseases; Esophageal Neoplasms; Esophagitis; Esophagoplasty; Esophagus; Female; Gastrins; Gastrointestinal Hemorrhage; Hernia, Diaphragmatic; Humans; Male; Peptic Ulcer; Peptic Ulcer Perforation; Postoperative Complications; Rupture, Spontaneous; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Stress, Psychological; Vagotomy

Topics: Antibodies; Duodenal Ulcer; Female; Gastrins; Humans; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Duodenal Ulcer; Feedback; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Absorption; Neurosecretory Systems; Pancreas; Peptic Ulcer; Secretin; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Achlorhydria; Adenoma; Anemia, Pernicious; Atrophy; Duodenal Ulcer; Endocrine System Diseases; Gastrectomy; Gastric Juice; Gastric Mucins; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Intrinsic Factor; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Central Nervous System; Cerebral Cortex; Digestion; Duodenal Ulcer; Eating; Emotions; Endopeptidases; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Pepsinogens; Peptic Ulcer; Psychophysiologic Disorders; Stomach; Stomach Ulcer

Topics: Animals; Bile; Cholangiography; Cholecystography; Cholelithiasis; Dogs; Duodenal Ulcer; Gallbladder; Gastrectomy; Gastric Juice; Gastrins; Humans; Secretin; Vagotomy; Vagus Nerve

Topics: Alcohols; Aspirin; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Parasympatholytics; Peptic Ulcer; Peptic Ulcer Perforation; Sex Factors; Steroids; Stomach Ulcer; Stress, Physiological; Stress, Psychological; Time Factors

Topics: Acetamides; Acetylcholine; Amino Acids; Animals; Antibodies; Bicarbonates; Chemistry Techniques, Analytical; Cholecystokinin; Digestive System; Dogs; Duodenal Ulcer; Enzymes; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Pancreas; Pancreatic Diseases; Pancreatic Juice; Peptides; Secretin; Sheep; Stimulation, Chemical; Swine

Topics: Animals; Cats; Ceruletide; Cholecystokinin; Digestive System; Digestive System Physiological Phenomena; Dogs; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Motility; Glucagon; Guinea Pigs; Humans; Pancreas; Secretin; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestine, Small; Jejunum; Male; Middle Aged; Neoplasm Metastasis; Radiography; Radioimmunoassay; Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Dogs; Duodenal Ulcer; Duodenum; Eating; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Pancreas; Pepsin A; Peptic Ulcer; Secretory Rate; Stomach; Vagotomy

Topics: Animals; Chronic Disease; Dogs; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Homocysteine; Humans; Liver Cirrhosis; Liver Diseases; Stomach

Topics: Antacids; Blood Circulation; Cryosurgery; Duodenal Ulcer; Electrolytes; Gastric Juice; Gastrins; Gastroenterostomy; Gonadal Steroid Hormones; Humans; Insulin; Pancreas; Pathology; Pepsin A; Peptic Ulcer; Pharmacology; Pylorus; Radiation Effects; Radiotherapy; Research; Stomach Ulcer; Stress, Physiological; Vagotomy; Zollinger-Ellison Syndrome

The classic scheme of gastric acid secretion which divided the digestive period into cephalic, gastric and antral phases has become obsolete in the last 10 years. These "phases" are now seen as concurrently acting mechanisms which depend upon one another to be fully efficient. About half of all gastrin released during a meal is dependent upon vagal stimulation of the antrum. Also, vagotomy desensitizes the acid-secreting parietal cells to the effect of all other types of stimuli.The number of parietal cells (parietal cell mass) varies greatly according to the gastric secretory activity of each individual. It is highest with duodenal ulcer and lowest with gastric ulcer.Parietal cell hyperplasia or atrophy can be induced experimentally, but the factors controlling the size of the parietal cell mass in man have not been studied.A scheme of acid secretion which incorporates recent advances is presented.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Juice; Gastrins; Histamine; Humans; Hyperplasia; Male; Parietal Cells, Gastric; Pathology; Physiology; Stomach; Vagotomy; Vagus Nerve

Melatonin (MT) and its precursor L-tryptophan (TRP) are implicated in the protection of gastric mucosa against aspirin-induced lesions and in the acceleration of healing of idiopathic gastro-duodenal ulcers, but no information is available whether these agents are also effective in healing of gastroduodenal ulcers accompanied by Helicobacter pylori (H. pylori) infection. In this study three groups A, B and C, each including 7 H. pylori-positive patients with gastric ulcers and 7 H. pylori-positive patients with duodenal ulcers, aging 28-50 years, were randomly assigned for the treatment with omeprazole 20 mg twice daily combined with placebo (group A), MT administered in a dose of 5 mg twice daily (group B) or TRP applied in a dose of 250 mg twice daily (group C). All patients underwent routine endoscopy at day 0 during which the gastric mucosa was evaluated and gastric biopsies were taken for the presence of H. pylori and histopathological evaluation. The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after the initiation of the therapy. Plasma MT, gastrin, ghrelin and leptin were measured by specific RIA. At day 21, all ulcers were healed in patients of groups B and C but only 3 out of 7 in group A of gastric ulcers and 3 out of 7 in duodenal ulcers. Initial plasma MT showed similar low levels in all three groups but it increased several folds above initial values in ulcer patients at day 7, 14 and 21. Plasma gastrin and leptin levels showed a significant rise over initial values in patients treated with omeprazole and placebo, MT or TRP while plasma ghrelin levels were not significantly affected by these treatments. We conclude that MT or TRP added to omeprazole treatment, significantly accelerates healing rate of H. pylori infected chronic gastroduodenal ulcers over that obtained with omeprazole alone and this likely depends upon the significant rise in plasma MT and possibly also in leptin levels, both hormones involved in the mechanism of gastroprotection and ulcer healing.

Topics: Adult; Anti-Infective Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastroscopy; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Leptin; Melatonin; Middle Aged; Omeprazole; Stomach Ulcer; Treatment Outcome; Tryptophan; Wound Healing

The aim of this study was to assess the gastric histopathology and serum gastrin-17 and pepsinogens profiles in patients with duodenal ulcer before and after Helicobacter pylori eradication in a population with a very high prevalence of H. pylori. At the same time we assessed the role of H. pylori density on these variables.. Eighty Caucasian patients with H. pylori-associated duodenal ulcer before treatment and 1 year after randomized eradication were studied. Among patients with unsuccessful eradication two groups were distinguished according to the data obtained after treatment: the group with negative rapid urease test and decreased bacterial density according to morphological score (partial elimination group); the group with positive rapid urease test and high bacterial density (failed eradication group).. One year after successful eradication, serum levels of gastrin-17, pepsinogen I and pepsinogen II decreased. Similar changes of serum pepsinogen I and pepsinogen II levels were observed in patients with partial elimination of H. pylori infection. In the group with successful eradication, inflammation, activity, atrophy and number of lymphoid follicles in the antral mucosa fell. In the group with partial elimination, antral mucosa activity and H. pylori score reduced. Other morphological changes were statistically non-significant.. Patients with duodenal ulcer after successful eradication have improvement of morphological and functional characteristics of gastric mucosa.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Biomarkers; Down-Regulation; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Proton Pump Inhibitors; Time Factors; Treatment Failure; Treatment Outcome; Urease; Young Adult

The article discloses the results of the duodenal ulcer treatment with a generic of omeprazole (Omizac) in the in-patient hospital and polyclinic conditions, dynamics of the serum gastrin level against the background of the drug application and after its withdrawal, and assessment of the intensity and duration of acid production inhibition in the stomach.

Topics: Adult; Anti-Ulcer Agents; Biomarkers; Dose-Response Relationship, Drug; Drug Administration Schedule; Duodenal Ulcer; Female; Gastrins; Humans; Male; Omeprazole; Treatment Outcome

Increased gastric emptying and defective action of endogenous cholecystokinin (CCK), that is known to inhibit this emptying, have been implicated in the pathogenesis of duodenal ulcer (DU). The aim of this double blind study was to assess whether CCK and somatostatin participate in the impairment of gastric motility in active DU patients before and after Helicobacter pylori eradication.. Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide, a selective CCK-A receptor antagonist, before and 4 weeks after eradication of H. pylori with 1 week triple therapy that resulted in healing of all DUs tested. The gastric emptying rate after feeding was determined using the 13C-acetate breath test. Before each test, samples of gastric juice were obtained by aspiration using a nasogastric tube for determination of somatostatin using specific radioimmunoassay.. Prior to H. pylori eradication gastric emptying half-time was 31 +/- 6 min in placebo-treated DU patients and this emptying rate was not significantly affected in tests after pretreatment with loxiglumide (10 mg/kg i.v.). Following eradication of H. pylori, in tests with placebo gastric emptying half-time was significantly longer (48 +/- 9 min) compared to that prior to H. pylori eradication. Pretreatment with loxiglumide in H. pylori eradicated DU patients significantly enhanced the gastric emptying rate with an emptying half-time of only 33 +/- 4 min. Eradication of H. pylori resulted in a significant increase in somatostatin concentration in gastric juice and loxiglumide significantly reduced this luminal somatostatin in H. pylori-eradicated subjects compared to values before anti-H. pylori therapy.. 1) H. pylori infection in DU patients is accompanied by enhanced gastric emptying and reduction in luminal release of somatostatin; 2) the failure of loxiglumide to affect gastric emptying in H. pylori-infected DU patients might be attributed, at least in part, to the failure of endogenous CCK to control gastric motility due to deficient release of somatostatin; and 3) H. pylori-infected patients appear to exhibit a deficient somatostatin release by endogenous CCK that can be reversed by the eradication of H. pylori indicating that both CCK and somatostatin may contribute to normalization of gastric emptying following H. pylori eradication in DU patients.

Topics: Adolescent; Adult; Analysis of Variance; Cholecystokinin; Duodenal Ulcer; Follow-Up Studies; Gastric Emptying; Gastric Mucosa; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Hormone Antagonists; Humans; Injections, Intravenous; Male; Postprandial Period; Probability; Proglumide; Reference Values; Sensitivity and Specificity; Somatostatin; Sucralfate; Treatment Outcome

To determine which demographic factors may influence serum gastrin and pepsinogen I (PGI) levels in duodenal ulcer patients undergoing omeprazole treatment.. We conducted an outpatient-based prospective study in the Veterans General Hospital, Taipei, to investigate the pharmacological effects on patients with duodenal ulcers receiving omeprazole treatment for 4 weeks. Sixty-eight patients (61 males/7 females, aged 25 73 years) with endoscopically confirmed duodenal ulcer were included. Gastrin and pepsinogen I levels were measured before and after treatment. Demographic factors including age, sex, smoking, ulcer healing and antral Helicobacter pylori colonization/clearance were analyzed, in order to measure their probable influences on serum gastrin and pepsinogen I levels.. Ulcer healing was seen in 92.6% of patients while 48 (70.6%) antral clearances were seen in 66 H. pylori colonized patients at the end of trial. Omeprazole monotherapy led to a marked elevation of serum gastrin (85.8 pg x ml(-1), SD 32.0 pg x ml(-1) vs 133.9 pg x ml(-1), SD 71.6 pg x ml(-1), P < 0.01), and pepsinogen I (111.0 ng x ml(-1), SD 36.7 ng x ml(-1) vs 253.6 ng x ml(-1) , SD 64.8 ng x ml(-1), P < 0.01) levels when measured on day 29. Only patients showing antral H. pylori clearance exhibited an influence on the magnitude of pepsinogen I elevation following omeprazole monotherapy (143.9%, SD 67.3% vs 78.6%, SD 51.2%, P < 0.01). Moreover, the sensitivity and specificity of serum pepsinogen I variations were plotted on a receiving operating characteristic (ROC) curve. The 140% increased pepsinogen I level yielded a maximum accuracy of 80% specificity or 50% sensitivity to predict antral H. pylori clearance.. Antral H. pylori clearance is at least partially responsible for the omeprzaole-induced hyperpepsinogenemia I. The magnitude of hyperpepsinogenemia I probably provides a non-invasive alternative for predicting H. pylori clearance.

Topics: Adult; Age Factors; Aged; Duodenal Ulcer; Female; Gastrins; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Pepsinogen A; Pyloric Antrum; Sex Factors; Smoking

Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active duodenal ulcer.. This randomized, double-blind, multicentre study, conducted at 25 European sites, compared the efficacy and tolerability of rabeprazole and omeprazole in patients with active duodenal ulcers. One hundred and two patients with active duodenal ulcer received rabeprazole 20 mg and 103 patients omeprazole 20 mg once daily for 2 or 4 weeks, with ulcer healing monitored by endoscopy.. After 2 weeks, complete ulcer healing was documented in 69% of patients given rabeprazole 20 mg and in 62% of patients given omeprazole 20 mg (N.S.). After 4 weeks, healing rates were 98% in the rabeprazole group and 93% in the omeprazole group (P = 0.083). Rabeprazole-treated patients had significantly greater improvement in daytime pain symptom relief than those treated with omeprazole at the conclusion of the study (P = 0.038). Both drugs were well tolerated over the 4-week treatment period. Mean changes from baseline to end-point in fasting serum gastrin were significantly greater in the rabeprazole group, but at end-point mean values were well within normal limits for both groups. No clinically meaningful changes or other between-group differences were observed in laboratory parameters.. In this study, rabeprazole produced healing rates equivalent to omeprazole at weeks 2 and 4, and provided significantly greater improvement in daytime pain. Both treatments were well tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole; Rabeprazole

Maintenance antisecretory therapy is often used to prevent duodenal ulcer recurrence and control symptoms. This study compared the efficacy and safety of lansoprazole 15 mg and 30 mg daily with placebo in preventing ulcer recurrence in patients with a recent history of duodenal ulcer disease.. Fifty-six patients were treated with either lansoprazole 15 mg, 30 mg or placebo o.m.. Within 1 month of study initiation, 27% (four out of 15) of placebo-treated patients experienced ulcer recurrence as compared to 13% (two out of 15) and 6% (one out of 18) of lansoprazole 15 mg and 30 mg treated patients, respectively. Median time to first ulcer recurrence was > 12 months in lansoprazole patients. At Month 12, significantly (P < 0.001) more lansoprazole 15 mg patients (70%) and lansoprazole 30 mg patients (85%) remained healed. Eighty-two per cent of lansoprazole 15 mg and 76% of lansoprazole 30 mg patients remained asymptomatic during the entire study period. All placebo patients became symptomatic, experienced ulcer recurrence, or withdrew from the study by month six. The incidence of adverse events was comparable among the three treatment groups.. Lansoprazole safely and effectively reduces duodenal ulcer recurrence and ulcer-related symptoms.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Drug Resistance; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Recurrence; Treatment Outcome; United States

The aim of this randomized, multicenter, double-masked, parallel-group study was to compare the efficacy of lansoprazole with that of omeprazole monotherapy in duodenal ulcer healing and prevention of relapse. A total of 251 patients with duodenal ulcer were treated with either lansoprazole 30 mg/d (n = 167) or omeprazole 40 mg/d (n = 84). Patients with healed ulcers were then randomly allocated to 12 months of maintenance therapy with lansoprazole 15 mg/d (n = 74), lansoprazole 30 mg/d (n = 71), or omeprazole 20 mg/d (n = 73). Healing rates at 4 weeks (intent-to-treat analysis) were 93.9% (95% confidence interval [CI], 90.2% to 97.6%) with lansoprazole and 97.5% (95% CI, 93.7% to 100%) with omeprazole; there were no significant differences between groups. Endoscopic relapse rates after 6 months were 4.5% (95% CI, 0% to 10.6%) with lansoprazole 15 mg, 0% with lansoprazole 30 mg, and 6.3% (95% CI, 1.5% to 12.5%) with omeprazole 20 mg, compared with 3.3% (95% CI, 0% to 8.2%), 0%, and 3.5% (95% CI, 0% to 8.8%), respectively, at 12 months. Again, there were no significant differences between groups. The incidence of adverse events during acute treatment was 6.0% and 7.1% in the lansoprazole and omeprazole groups, respectively; during maintenance therapy, the incidences were 12.2% (lansoprazole 15 mg), 5.6% (lansoprazole 30 mg), and 11.0% (omeprazole 20 mg). Within treatment groups, pain was significantly ameliorated after the acute phase but not after maintenance therapy (P < 0.05); no differences were observed between groups. Gastrin values increased significantly after acute therapy (P < 0.05), persisted at these increased levels during maintenance therapy, and returned to normal after 6-month follow-up. Both lansoprazole and omeprazole were highly effective and well tolerated in the treatment of duodenal ulcer; relapse rates were similar for all doses studied. Thus no additional benefit is to be gained from using a proton-pump inhibitor at a dose > 15 mg lansoprazole to prevent relapse.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Duodenal Ulcer; Endoscopy; Female; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Secondary Prevention; Time Factors

Rabeprazole, a new proton pump inhibitor, was studied in patients with acid-peptic-related diseases (duodenal ulcer, gastric ulcer, GERD) in three placebo-controlled, double-blind, randomized clinical trials. Men and women over the age of 18 were enrolled if the presence of an active duodenal or gastric ulcer or erosive or ulcerative esophagitis was confirmed on upper gastrointestinal endoscopy. Patients were randomly allocated to either placebo or rabeprazole 20 mg or 40 mg in the duodenal and gastric ulcer protocols or to placebo or rabeprazole 10 mg, 20 mg, or 40 mg in the GERD protocol. All doses of rabeprazole in all three studies were statistically significantly superior to placebo in healing acid-related lesions. There were no treatment differences between the rabeprazole doses in healing active peptic lesions. The incidence of positive [13C]urea breath test for H. pylori was 53% in patients with duodenal or gastric ulcers. H. pylori status was not effected by treatment with rabeprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Breath Tests; Dose-Response Relationship, Drug; Double-Blind Method; Duodenal Ulcer; Enzyme Inhibitors; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Proton-Translocating ATPases; Rabeprazole; Stomach Ulcer; Treatment Outcome

We designed this study to follow exocrine, endocrine and microstructural changes in duodenal ulcer patients with H. pylori infection in the course and after quadruple eradication regimen. Quadruple therapy appeared to be highly effective method of both ulcer healing and H. pylori eradication. We observed enhanced regeneration of gastric mucosa in the course of treatment. Almost immediate decrease of plasma gastrin and increase of plasma somatostatin and EGF concentration in gastric juice were noticed.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Somatostatin

Although eradication of Helicobacter pylori cures duodenal ulcer, some patients are not infected and others are treatment failures. This randomized, double-blind, placebo-controlled study assessed the value of treatment with low-dose lansoprazole in preventing duodenal ulcer recurrence. One hundred eighty-six patients with endoscopic documentation of healed duodenal ulcer received 15 mg/day lansoprazole or placebo for 12 months or until ulcer recurred. Endoscopy results, symptom assessment, and fasting serum gastrin levels were obtained at multiple time points. Densities of E, EC, and G cells were assessed by biopsy when the ulcer recurred or at the final visit. Time to ulcer recurrence was significantly longer (P < 0.001) in the lansoprazole group (median >12 months) compared to placebo (median <3 months), and patients taking lansoprazole were asymptomatic longer (P < 0.05). Maintenance therapy with lansoprazole 15 mg/day suppresses acid and controls recurrence of duodenal ulcer disease.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Biopsy; Double-Blind Method; Duodenal Ulcer; Female; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Recurrence

Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional pirenzepine treatment is also effective in suppressing acid secretion.

Topics: Adult; Aged; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Peptic Ulcer; Pirenzepine; Radioimmunoassay; Somatostatin; Stomach Ulcer

Helicobacter pylori (Hp) infection may be associated with duodenal ulcer (DU) and accompanied by increased release of gastrin and deficiency of somatostatin (S-S) but the mechanisms of these changes in DU patients after eradication of Hp have been little studied. Cholecystokinin (CCK) has been implicated in the feedback control of gastric acid secretion in healthy subjects but its contribution to secretory disorders in DU patients has been little examined. This study, therefore, investigated whether CCK participates in the impairment of postprandial gastrin release and gastric acid secretion in active DU patients. Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide (LOX), a selective CCK-A receptor antagonist, before and 4 wk. after eradication of Hp with triple therapy (omeprazole, amoxycillin and bismuth). In Hp positive DU patients, the postprandial acid secretion (measured by continuous intragastric pH monitoring) was accompanied by a pronounced increment in plasma gastrin with negligible increase of intraluminal release of S-S. The administration of LOX in these patients did not affect significantly the postprandial pH profile and the rise in plasma gastrin. After eradication of Hp the median postprandial intragastric pH increased to about 4.3 (compared to 3.5 before the Hp eradication); the postprandial gastrin concentration was reduced by about 40%, while luminal release of S-S was increased 2 folds. The administration of LOX resulted in significantly greater decrease in median pH (3.1) and higher rise in postprandial plasma gastrin in these patients. Also the postprandial plasma S-S showed a small, but significant decline (by about 25%) as compared to that in placebo treated patients. This study provides evidence that: (1) Hp infection in DU patients is accompanied by enhanced gastrin release and the reduction in luminal release of S-S; (2) The failure of LOX to affect gastric secretion and plasma gastrin DU Hp infected patients could be attributed, at least in part, to the failure of endogenous CCK to control gastric acid secretion via release of S-S; (3) Hp infected patients appear to exhibit a deficiency of S-S release that can be reversed by the eradication of Hp indicating that both peptides may contribute to the acceleration of the ulcer healing following Hp eradication in DU patients; (4) The test with LOX and gastric luminal S-S assay may be useful in identification of Hp po

Topics: Adult; Cholecystokinin; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Hormone Antagonists; Humans; Male; Proglumide; Somatostatin

We defined optimal Helicobacter pylori (Hp) treatment as Hp eradication rate about 90%, well-tolerated with few side-effects. Two centers carried out randomized trials including 90 patients (74% men, 26% women, ages ranging from 18 to 65, mean age 42 +/- 8) with active duodenal ulcers (DU). Patients were treated with the combination of Omeprazole (O) 20 mg bd + Clarithromycin (C) 250 mg bd + Tinidazole (T) (500 mg bd) or with Lansoprazole (L) 15 mg bd + Amoxicillin (A) 750 mg bd + Metronidazole (M) 500 mg bd administered for one week. The DU healing rate was evaluated by endoscopy and the Hp status by rapid urease CLO-test and 14C-urea breath test (UBT). The healing rate of the DU in a group treated with the combination of O + C + T was 91% and in group treated with L + A + M was 93%. The eradication of Hp in group O + C + T and L + A + M averaged 91% and 87%, respectively. There was no statistically significant difference in the DU healing rate and the Hp eradication rate between these two groups. Both treatments were accompanied by a marked rise in the basal and postprandial plasma gastrin levels and the rise in the intragastric pH but these alterations returned to the pre-treatment values 4 weeks after the termination of the therapy. Both treatments were well tolerated and the only side effect was the taste disturbance observed in few patents treated with O + C + T. None of patients discontinued the treatment because of the adverse events. We conclude that one week treatment using O + C + T or L + A + M are highly and equally effective in the healing of DU and in the eradication of Hp.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Antitrichomonal Agents; Clarithromycin; Double-Blind Method; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Tinidazole

About 10% of patients with duodenal ulcers have marked gastric acid hypersecretion with basal acid output (BAO) of more than 15 mmol/h, which is in the range found in Zollinger-Ellison syndrome.. We report long-term, up to 4 years, prospective treatment using lansoprazole in nine male patients with duodenal ulcers and a BAO of more than 15 mmol/h whose results are compared with those in 10 male Zollinger-Ellison syndrome patients with intact stomachs reported in detail in an accompanying paper.. All 19 subjects, except one Zollinger-Ellison syndrome patient who had gastric and oesophageal ulcers, had a history of duodenal ulcers; 22% of those with gastric acid hypersecretion had oesophagitis compared with 60% of those with Zollinger-Ellison syndrome. Each subject had the dose of lansoprazole adjusted to give a BAO of less than 5 mmol/h. At 3-month intervals to 1 year, and then at 6-monthly intervals, basal and pentagastrin stimulated secretions were studied, in addition to gastroscopy with biopsy for gastric mucosal morphology. Basal and maximal acid and pepsin secretions were not different between gastric acid hypersecretion and Zollinger-Ellison syndrome patients before treatment. During treatment, BAO was reduced by over 90% to less than 2 mmol/h, while peak acid output was reduced by 70% in those with gastric acid hypersecretion and 90% in Zollinger-Ellison syndrome patients. Four gastric acid hypersecretion patients had relapses during treatment, three times in one patient and twice in another patient, but all responded to continued treatment with lansoprazole. Of the seven ulcer-related relapses in the gastric acid hypersecretion patients, four occurred with a BAO of less than 2 mmol/h and three with a BAO of 7.1-7.3 mmol/h; five of the seven relapses occurred in the absence of Helicobacter pylori. Lansoprazole remained effective at an average dose of approximately 70 mg/day, without causing any side-effects.. Lansoprazole is apparently safe and effective for treating hypersecretion, whether due to hypergastrinaemia (Zollinger-Ellison syndrome) or not (non-Zollinger-Ellison syndrome hypersecretors).

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Duodenal Ulcer; Enzyme Inhibitors; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Patient Dropouts; Prospective Studies; Proton Pump Inhibitors; Zollinger-Ellison Syndrome

The present study was performed in six asymptomatic patients with a history of resistant duodenal ulcers in whom 24 h intragastric pH, gastric juice pepsin and PGE2 concentrations, as well as serum gastrin concentrations, were measured. We wanted to compare the effects on these parameters of a single night time (q.h.s.) dose of nizatidine 300 mg (N1), nizatidine 300 mg b.i.d. (N2), ranitidine 300 mg q.h.s. (R1) or ranitidine 300 mg b.i.d. (R2) compared with placebo (P). During the night (22.00-08.00 h), all treatments gave a higher mean pH than P, but during the day (08.00-22.00 h) the mean pH was higher than P only for patients administered R2 and N2. Doubling the dose of nizatidine (N2 vs N1) or ranitidine (R2 vs R1) increased the mean daytime pH, but had no effect on night time pH. The daytime pepsin concentration was unaffected by H2-receptor antagonists, while night time pepsin was lower with R1 and R2, but not with N1 or N2. The night time gastrin concentration was unaffected by H2-receptor antagonists; doubling the dose of the H2-receptor antagonist (R2 vs R1 and N2 vs N1) increased daytime gastrin concentration. During the night, each treatment increased PGE2 concentration by at least six-fold compared with P. Thus, where it is therapeutically indicated to achieve greater suppression of acid secretion, doubling the total daily dose by dosing with twice daily versus once daily night time nizatidine or ranitidine is efficacious.

Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Dinoprostone; Drug Administration Schedule; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Nizatidine; Pepsin A; Ranitidine

We studied the effects of lansoprazole with or without amoxicillin on the quality of ulcer healing in relation to eradication of Helicobacter pylori. Ulcer healing rates for lansoprazole 30 mg q.d. alone (group A) were 100% for duodenal ulcers (DU; n = 20) and 92% for gastric ulcers (GU; n = 15). The healing rates for lansoprazole 30 mg plus amoxicillin 1-2 g q.d. (group B) were 100% for both DU (n = 20) and GU (n = 12). Endoscopic findings after treatment showed that the red scar/white scar ratio in group A was 16/4 for DU and 12/1 for GU. The red scar/white scar ratio in group B was 4/16 for DU and 6/6 for GU. The numbers of H. pylori in gastric mucus did not change throughout the course of treatment in group A but decreased significantly, without H. pylori relapse, in group B. Changes in ammonia concentration in gastric juice, as well as serum gastrin and pepsinogen I and II levels, differed between group A and group B. Concomitant treatment with lansoprazole and high-dose amoxicillin eradicated H. pylori and modified gastric secretory function, resulting in high-quality ulcer healing.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Ulcer Agents; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter pylori; Humans; Lansoprazole; Omeprazole; Penicillins; Pepsinogens; Peptic Ulcer; Proton Pump Inhibitors; Stomach Ulcer

Combination therapy with lansoprazole (LPZ) and amoxicillin (AMPC) was administered to eradicate Helicobacter pylori. Changes in eradication rates were monitored and serum antibody titers, levels of pepsinogens I and II (PI and PII), and gastrin were measured. The 40 subjects were divided into two groups: one group received LPZ 30 mg alone, and the other received LPZ 30 mg and AMPC 1,500 mg concomitantly. AMPC was administered for 2 weeks before completion of LPZ treatment. Maintenance therapy was cimetidine 400 mg. The presence of H. pylori was evaluated using the urea breath test (UBT). The clearance rate was 12.5% and the eradication rate was 0% in the LPZ group, and the corresponding rates in the LPZ with AMPC group were 41.6 and 25.0%, respectively. Serum monoclonal H. pylori antibody titers decreased in patients in whom bacterial eradication had been achieved. Serum PI was significantly reduced in those patients in whom eradication had been achieved. Serum PII and gastrin levels also tended to decrease in patients in whom eradication had been achieved, but no such changes were observed in the other patients. Further research into drug treatment and evaluation methods for bacterial eradication is required.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Ulcer Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Breath Tests; Drug Therapy, Combination; Duodenal Ulcer; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Monitoring, Physiologic; Omeprazole; Penicillins; Pepsinogens; Stomach Ulcer; Urea

To compare the efficacy and safety of ebrotidine and ranitidine administered once daily in equimolar doses of 800 and 300 mg, respectively.. A total of 298 duodenal ulcer patients were studied.. A multicentre, parallel, randomized clinical trial.. Of the 298 patients studied, 150 were randomly assigned to ebrotidine and 148 to ranitidine treatment. Digestive endoscopy was performed at enrolment and at weeks 4, 6 and 8 unless the ulcer had healed before. Endoscopic findings were the main parameter for the assessment of treatment efficacy. Plasma gastrin and pancreatic polypeptide concentrations were also measured before and after termination of the therapy.. Ebrotidine achieved a duodenal ulcer healing rate comparable to that of ranitidine, and no statistically significant difference was found between the two drugs. The drugs were equally effective in improving ulcerous dyspeptic symptoms and in relieving gastric pain. Both tobacco and ethanol consumption influenced ulcer healing adversely, but healing in smokers was more pronounced in patients treated with ebrotidine, possibly because of its cytoprotective activity.. Ebrotidine 800 mg is as effective and safe as ranitidine 300 mg in healing duodenal ulcer, but ebrotidine appears to be superior in promoting the healing of duodenal ulceration in smokers.

Topics: Adult; Anti-Ulcer Agents; Benzenesulfonates; Double-Blind Method; Duodenal Ulcer; Female; Gastrins; Humans; Male; Pancreatic Polypeptide; Ranitidine; Thiazoles

In this study, 36 patients undergoing extended parietal cell vagotomy (EPCV) were compared with 30 patients with subtotal gastrectomy 7-14 years after surgery. The patients' nutritional status, gastric sectretion, gastrointestinal motility and intestinal absorption function were evaluated. The nutritional status was generally less satisfactory in 33. 3% patients with anaemia after gastrectomy and decrease of body weight in 54%. The patients after EPCV were all in good nutritional status, with no anemia; 56% of them had a body weight increase of more than 3kg. Therefore, the rationality of EPCV was estalished.

Topics: Adult; Aged; Duodenal Ulcer; Female; Follow-Up Studies; Gastrectomy; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Humans; Intestinal Absorption; Male; Middle Aged; Nutritional Status; Vagotomy, Proximal Gastric

Lansoprazole is a new proton pump inhibitor for the treatment of peptic ulcer disease.. A double-blind, multicentre study was undertaken in 296 patients with endoscopically proven duodenal ulcer to compare the efficacy and safety of lansoprazole 15, 30 or 60 mg with placebo. Ulcer healing was documented by endoscopy at 2 and 4 weeks; patients whose ulcers healed after 4 weeks were followed for up to 6 months post-treatment.. Four-week healing rates of 89.4%, 91.7% and 89.9% were obtained with lansoprazole 15, 30 and 60 mg, respectively, compared with 46.1% on placebo (P < 0.001). All three doses of lansoprazole produced rapid symptom relief, although patients taking 60 mg lansoprazole required fewer antacids than did those taking 15 mg. At 6 months, the percentages of patients healed were 45.3%, 40.0% and 38.4% in the lansoprazole 15, 30 and 60 mg dosage groups, respectively, and 25.3% for the placebo group. No significant adverse events were documented during the period of this trial.. Lansoprazole is an effective and safe treatment for duodenal ulcer and the 15 mg dose is as effective as 30 or 60 mg.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Abdominal Pain; Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Duodenal Ulcer; Duodenoscopy; Female; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Treatment Outcome; Wound Healing

A higher incidence of gastric and duodenum ulcer was well recognized in patients with liver cirrhosis, but the mechanism has not been fully identified. In this study, serum gastrin, free portal pressure (FPP) were measured in 24 consecutively admitted cirrhotic portal hypertensive patients, and preoperative basic acid output (BAO) was measured in 13 randomized patients. Among the 24 patients, concomitant duodenal ulcers were found in 3 by both gastroduodenoscopy and barium series, and gastritis was found in all patients. It was found that most patients (71%) with liver cirrhosis have a elevated level in serum gastrin, whereas BAO is lower than normal in all patients, and the higher the FPP, the lower the BAO is. We believe that the congestive gastroduodenal mucosal lesion was underlying the ulceration most often seen in patients with portal hypertension.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Stomach Ulcer

The aim of this study was the effect of antacids containing inorganic bismuth compounds on the morphology of the gastric mucosa and healing of the duodenal ulcer (DU) in patients with exacerbation of the ulcer disease. 169 patients were treated for four weeks with low-dose antacids (two drugs containing bismuth subnitrate--Gastrin and Wikalina, with buffering capacity below 200 mmol HCl per day) and for comparison with ranitidine, colloidal bismuth subcitrate and placebo. We evaluated the effect of these drugs on the morphology of gastric mucosa using endoscopic, histologic and morphometric methods, as well as healing of DU, ulcer symptoms and drug tolerance. Antacids and colloidal bismuth subcitrate decreased both the chronic active gastritis of praepyloric region and frequency of Helicobacter infection, however without the full eradication. Antacids, ranitidine and colloidal bismuth subcitrate did not affect the height of surface epithelium, thickness of foveolar and glandular mucosa as well as the number and size of parietal cells, thus they were without any trophic effects on the gastric mucosa. All mentioned drugs healed DU in 68-73% of patients and significantly better than placebo (46%). These drugs were well tolerated by patients, however antacids caused slight increase in pH of urine and transient hipermagnesemia. Because the etiopathogenese of ulcer disease is still unclear, its therapy is unsuccessful in many cases. We should stress that the treatment with antacids in some cases can be a good and safe alternative therapy in spite of many other currently used medications.

Topics: Adult; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Organometallic Compounds; Ranitidine

Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown.. In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays.. In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.

Topics: Adult; Anti-Bacterial Agents; Cholecystokinin; Dietary Fats; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Hormones; Humans; Hydrogen-Ion Concentration; Male; Proglumide; Reference Values; Somatostatin

Radioimmunoassay and immunomorphological methods were used in the study of pepsinogen 1, basal and food-stimulated gastrin and somatostatin blood levels, the number of gastroduodenal G- and D-cells as well as gastric secretion during routine-dose treatment with gastrozepin and ranisan of 45 gastroduodenal ulcer patients versus 15 controls. The patients were divided into 2 types according to blood gastrin levels and the number of pyloric G-cells: with hypergastrinemia and/or hyperplasia of the G-cells, with normogastrinemia and normal number of G-cells. A course treatment with gastrozepin of type 1 patients brought about normalization of serum gastrin and the number of the G-cells with elevation of blood somatostatin levels. In patients of type 2 the above parameters did not change. The same picture in them remained after ranisan treatment, though they developed hypergastrinemia. In patients of type 1 after ranisan treatment the above parameters did not change. The data obtained demonstrate once more heterogeneity of duodenal ulcer.

Topics: Adult; Duodenal Ulcer; Duodenum; Follow-Up Studies; Gastrins; Humans; Male; Pirenzepine; Ranitidine; Somatostatin; Stomach; Time Factors

The role of prostaglandins in peptic ulcer disease and their relation to Helicobacter pylori infection remain controversial. This study sought to compare the effects of oral nizatidine and ranitidine on the gastric mucosal release of prostanoids in duodenal ulcer (DU) patients and to correlate prostanoid concentrations with H. pylori status. Twenty-eight patients with DUs were randomized to receive either nizatidine or ranitidine. Nizatidine 300 mg at night elevated intraluminal PGE2 concentrations; 6-keto-PGF1 alpha concentrations also rose, but did not reach statistical significance. Ranitidine induced non-significant falls in PGE2 and 6-keto-PGE1 alpha concentrations. Patients with H. pylori infection had lower PGE2 and 6-keto-PGF1 alpha concentrations than non-infected patients, but nizatidine was equally effective in increasing prostanoid levels in both groups. These findings may be considered as favourable side effects of nizatidine with uncertain clinical significance. Further studies are needed to elucidate the synergism between prostanoids, eradication of H. pylori and nizatidine in the treatment of DU.

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Nizatidine; Pepsinogens; Prostaglandins; Ranitidine

The aim of this study was to compare omeprazole 10 mg o.m. (daily) with omeprazole 20 mg o.m. on Friday to Sunday inclusive (weekend) in the prevention of duodenal ulcer relapse over a 6-month period.. After an open healing phase (4 to 8 weeks) with omeprazole 20 mg o.m., 81 patients entered the follow-up phase. Forty-two were randomized in a double-blind double-dummy technique, to omeprazole 10 mg o.m., and 39 to omeprazole 20 mg at weekends. At 3 and 6 months or on symptomatic relapse the patients underwent endoscopy with gastric biopsies (quantitative assessment of argyrophilic and gastrin cells), symptom evaluation, and laboratory screening with fasting serum gastrin.. Five patients in the 10 mg group and four in the weekend group were lost to follow-up. The estimated relapse rates over six months in the two groups receiving 10 mg daily or 20 mg at weekends were 19% and 31%, respectively (95% CI of percentage difference: -33% to 8%: intention-to-treat analysis, P = N.S.). During the follow-up phase, symptoms tended to be milder in the omeprazole 10 mg daily group compared to the weekend group. Gastrin levels increased significantly during the healing phase but then stayed almost constant in the omeprazole 10 mg group, and significantly decreased with weekend treatment. The median number of argyrophilic cells showed a slight but statistically significant increase in the omeprazole 10 mg daily group, but did not change in the weekend group. Both the healing and long-term therapies were well tolerated.. Our data do not show a clear difference between the two treatment regimens, but there was a tendency towards a lower recurrence rate with omeprazole 10 mg daily compared with 20 mg weekend therapy.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer; Fasting; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Omeprazole; Pyloric Antrum

Duodenal and gastric content of mucosal enzymes in duodenal ulcer (DU) patients differs from that of controls. The purpose of this study has been to examine the effect of omeprazole and eradication of Helicobacter pylori on mucosal enzymes in DU patients.. The enzyme activities of seven gastric and duodenal mucosal marker enzymes from the brush border, lysosomes, and mitochondria have been studied. In study I the measurements were made in 29 patients with an active DU before and after 14 days of omeprazole treatment. In study II 22 duodenal ulcer patients were given bismuth subnitrate, oxytetracycline, and metronidazole (triple therapy) for 2 weeks to eradicate H. pylori. Biopsy specimens were taken from the duodenum and the stomach for enzyme measurements and histologic assessment. In study II additional specimens were obtained from the prepyloric region for urease tests and culture of H. pylori.. The ulcer healing rates were more than 90% after both omeprazole and triple therapy. H. pylori was eradicated in 86% after triple therapy. The activities of the brush-border enzymes lactase, neutral-alpha-glucosidase, alkaline phosphatase, leucyl-beta-naphthylamidase, and gamma-glutamyltransferase (gamma-GT) increased significantly in the duodenal bulb and the descending duodenum during treatment with omeprazole. No changes in duodenal enzyme activity were detected after triple therapy, whereas a significant fall in gamma-GT and acid phosphatase activities was seen in the stomach. The mucosal DNA in the gastric antrum decreased both after treatment with omeprazole and after triple therapy.. A similar decrease in mucosal DNA of the gastric antrum was demonstrated after both omeprazole and triple therapy with bismuth subnitrate, oxytetracycline, and metronidazole. Omeprazole also affects the content of duodenal mucosal enzymes, whereas triple therapy particularly affects the gastric mucosal enzyme activity.

Topics: Antacids; Biopsy; Bismuth; DNA; Drug Therapy, Combination; Duodenal Ulcer; Duodenum; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Metronidazole; Middle Aged; Omeprazole; Oxytetracycline; Stomach

Enprostil, a synthetic E2-prostaglandin efficacious for duodenal ulcer healing, presents both antisecretory and antigastrinic effects. This is at variance with the elevation of plasma gastrin observed with ranitidine. OBJECTIVE--This leads us to compare enprostil and ranitidine on the following points: a) variations of plasma gastrin (basal and postprandial) parameters over a 6-week conventional treatment; b) correlation studies between ulcer relapses (frequency and temporal evolution) after treatment discontinuation and various gastrinic criteria. METHODS--Among a group of 642 patients followed for ulcer relapse, 165 were considered for gastrin (78 of the "Enprostil" group and 87 of the "Ranitidine" group). RESULTS--Initially, both populations were comparable for clinical and plasma gastrin parameters. After 6 weeks of treatment, the increases in the various gastrin parameters (basal, postprandial, peak, integraded) were significantly greater and the absolute values higher (Wilcoxon, P < 0.001) with ranitidine than with enprostil. No correlation was found between relapse occurrence after drug discontinuation and these gastrin parameters. CONCLUSIONS--Ranitidine hypergastrinemia seems directly related to gastric hyposecretion whereas its absence with enprostil is likely more dependent upon a specific antigastrinic activity than on a reduced antisecretory activity. Those differences in mechanism of action have no consequence on the stability of ulcer obtained by either drug.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Enprostil; Female; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Ranitidine; Recurrence

Exogenous cholecystokinin (CCK) is known to affect gastric motor and secretory activities, but its physiologic role in the control of gastric functions is unknown.. In this study involving 10 young healthy subjects and 10 duodenal ulcer (DU) patients, 500 ml of a standard meal without or with addition of 15% soybean oil was given, and the gastric emptying rate and the pH profile and plasma levels of gastrin, CCK, pancreatic polypeptide (PP), and somatostatin were determined in separate tests with placebo or with antagonism of type-A CCK receptors (loxiglumide, 1200 mg orally).. In healthy controls and DU patients the emptying half-time was 44 and 34 min, respectively, and the addition of oil prolonged the emptying by about 50%. Pretreatment with loxiglumide significantly reduced fat-induced retardation of gastric emptying in both healthy controls and DU patients. A standard meal in healthy subjects resulted in an immediate rise in median gastric pH to about 6.0, and this was followed by gradual decrease within about 3 h to premeal values of about 2.0. After the meal, plasma gastrin rose by 57%, CCK by 177%, PP by 100%, and somatostatin by 39%. Addition of fat significantly attenuated and prolonged the pH decrease after the meal while reducing the increment in plasma gastrin and enhancing plasma CCK and PP levels. Loxiglumide significantly reduced the median postprandial pH (from control 4.8 to 2.5) and reversed the changes in the pH profile caused by the addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin and PP were significantly attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin in DU patients.. These results indicate that endogenous CCK released by a fatty meal delays gastric emptying and inhibits gastric acid and plasma gastrin responses in healthy subjects, but in DU patients the inhibitory effect of CCK is less pronounced, suggesting a defect in the action of this hormone on gastrin release and gastric acid secretion.

Topics: Adult; Cholecystokinin; Dietary Fats; Duodenal Ulcer; Gastric Acid; Gastric Emptying; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Pancreatic Polypeptide; Proglumide; Receptors, Cholecystokinin; Somatostatin

Serum gastrin levels in 44 peptic ulcer patients (26 gastric ulcer patients and 18 duodenal ulcer patients) were determined after they had been treated with omeprazole (OPZ) (20 mg/day) alone or in combination with pirenzepine (PZP) (100 mg/day). Serum gastrin levels were measured before, as well as 2, 4, and 6 weeks after administration, and the changes were compared. The levels were significantly elevated (twofold) at 2 weeks of treatment in both the OPZ and OPZ plus PZP groups. In patients taking OPZ alone, the levels rose up to 6 weeks, while in those taking OPZ plus PZP the levels decreased at 4 and 6 weeks. At 4 weeks, serum gastrin levels in the OPZ plus PZP group were lower (although not significantly) than those in patients taking OPZ alone. In gastric ulcer patients, serum gastrin levels in the OPZ group were significantly elevated, while in the OPZ plus PZP group, these levels were only slightly, but not significantly elevated. There was no significant difference between the two gastric ulcer groups at any time. In duodenal ulcer patients, serum gastrin levels increased significantly at 2 weeks of treatment in both groups. At 4 weeks and thereafter, the serum gastrin levels remained significantly high in patients taking OPZ alone, while they decreased at both 4 and 6 weeks in patients taking OPZ plus PZP. Thus, serum gastrin levels in duodenal ulcer patients were markedly decreased by the addition of PZP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Drug Therapy, Combination; Duodenal Ulcer; Gastrins; Humans; Omeprazole; Peptic Ulcer; Pirenzepine; Stomach Ulcer

To verify the effect of age on gastric secretions in gastric (GU) and duodenal ulcer (DU) patients, we carried out a retrospective study evaluating basal and stimulated gastric acid secretion in 427 peptic ulcer subjects aged between 12 and 73 years (GU = 74, DU = 353) in addition to studying gastric juice pepsin, serum pepsinogen group A (PGA) and gastrin in 175 patients (GU = 28, DU = 147). All subjects were then divided into groups according to their sex and age (< 30, 30-39, 40-49, 50-59 and > 60 years). Basal, maximal and peak acid outputs (BAO, MAO, PAO) were unchanged in the various age groups, though MAO and PAO were higher in males than females and in DU than in those with GU, even in the elderly (> 60 years). Pepsin and gastrin levels were unchanged at the various ages in GU and DU, while PGA was higher in males with DU aged 50 or over. This demonstrates that acid, pepsin and gastrin secretions do not change with age in ulcer patients. Acid secretion retains its typical distribution according to pathology (DU > GU) and sex (males > females), and also appears to have a fundamental pathogenetic role in peptic ulcer in the elderly.

Topics: Adolescent; Adult; Aged; Aging; Child; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Pepsin A; Pepsinogens; Peptic Ulcer; Retrospective Studies; Stomach Ulcer

Microwave resonance treatment (MRT) of duodenal ulcer leads to normalization of relationships between aggressive and defense ulcerogenesis factors. This combines with activation of reparative regeneration of the ulcer lesion. There appears a tendency to a decline in pepsin and hydrochloric acid secretion in the gastric juice, plasmic gastrin concentrations decrease more noticeably, production of protective glycoproteins of the gastric mucus grows as well as of E 2 prostaglandins and plasmic secretin. Typical changes in the quantities of plasmic bombesin, vasoactive intestinal polypeptide (lowering) and gastroinhibitory polypeptide (rising) in the MRT course allow prognostication of case-by-case responses. The highest sensitivity to MRT was observed in functional regulatory biochemical systems (neuropeptides, hormones) of the APUD series. Their reaction to MRT served the basis for biochemical typing of the patients and MRT outcome prognostication.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Humans; Male; Microwaves; Middle Aged; Neuropeptides; Prognosis; Secretin; Treatment Outcome

To study in a double-blind controlled manner the effects of lansoprazole 15 mg or 30 mg daily compared with ranitidine 300 mg once daily and placebo in the relieving of symptoms and healing of acute duodenal ulceration.. Two hundred eighty patients with duodenal ulcer entered in to the study from 30 centers. They were randomized in a double-blind manner into four groups with 80 patients entered into each active treatment group and 40 patients into the placebo group. Endoscopy was performed at 2- and 4-wk intervals to assess healing. Symptom relief was recorded, serum gastrin levels were measured, and gastric mucosal biopsies were obtained to evaluate for the presence of acute and chronic inflammation, the presence of neoplasia, and the extent of gastric endocrine growth at the time of endoscopy.. After 4 wk of treatment using per protocol analysis, 19 of 40 (47.5%) patients receiving placebo had healed compared with 55 of 78 (70.5%) receiving ranitidine (p < 0.05 vs. placebo), 61 of 76 (80.3%) receiving lansoprazole 30 mg (p < 0.05 vs. placebo), and 72 of 78 (92.3%) receiving lansoprazole 15 mg (p < 0.05 vs. placebo and ranitidine). In patients with evaluable data, lansoprazole 30 mg and ranitidine produced greater relief of night-time symptoms and lansoprazole 15 mg produced greater relief of both day- and night-time symptoms than did placebo after 4 wk of treatment. Ranitidine increased fasting serum gastrin levels (22%; p < 0.05 vs. placebo), whereas both lansoprazole regimens produced more marked rises in serum gastrin (54% and 60%; p < 0.05 vs. placebo and ranitidine). Lansoprazole 15 mg and 30 mg also increased the density of antral G-cells (105.8% and 128.80%; p < 0.05 vs. baseline) and greater curvature Grimelius-positive cells (20.33% and 28.8%; p < 0.05 vs. baseline); there were no increases in the density of antral EC- or D-cells, and there was no alteration of gastric endocrine growth as judged by the Solcia classification. Both ranitidine and lansoprazole were associated with decreased antral Helicobacter pylori density accompanied, in the lansoprazole groups, by decreased antral inflammation scores. All antisecretory regimens were associated with increased inflammatory scores in the greater curvature.. In acute duodenal ulceration, treatment with lansoprazole 15 and 30 mg produced 4-wk healing rates and symptom relief superior to those produced by placebo and the 15-mg dose similar to those produced by placebo. The 15-mg dose of lansoprazole was also superior to ranitidine in healing duodenal ulcer after 4 wk of therapy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acute Disease; Adult; Anti-Ulcer Agents; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Helicobacter pylori; Humans; Lansoprazole; Male; Omeprazole; Ranitidine

The experience with long-term treatment of peptic ulcer with omeprazole is still scant, but the possibility cannot be excluded that its better pharmacodynamic effect on gastric acidity also has a positive result in the relapse rate. Moreover, this drug acts via a mechanism other than receptorial binding, and therefore its efficacy should not dissipate with time. This study was carried out to assess the pharmacodynamic properties and the possible changes with time of two dose regimens of omeprazole that could be suitable for long-term treatment in duodenal ulcer.. Twenty patients with endoscopically proven duodenal ulcer were studied by means of 24-h gastric pH-metry both in basal conditions and on the 5th day of acute treatment with 40 mg omeprazole in the morning. All the ulcers healed after 4 weeks, and thereafter 10 patients were randomized to receive orally 20 mg omeprazole daily at 0800 h in single-blind fashion (group A) and 10 to receive 20 mg omeprazole every other day (group B) for up to 6 months. At the end of the 1st, 3rd, and 6th month of these maintenance treatments 24-h gastric pH-metry was repeated to assess the antisecretory effect of each regimen over time. In group-B patients the test was performed on 2 consecutive days (without and with medication) at each time interval. The fasting gastrin values were also determined. The patients underwent esophagogastroduodenoscopy every 2 months.. Three patients in group B were lost to follow-up for various reasons, and only seven remained eligible for final analysis. The two long-term regimens of omeprazole were able to increase significantly pH values (p < 0.02-0.001) and the times spent at and above pH 3.0 (p < 0.001) over 24 h compared with basal conditions. In group A the 24-h pH value obtained in the 6th month was higher (p < 0.02) than that in the 3rd month of maintenance treatment. In group B the pharmacologic effect tended to decrease on the day without medication compared with the day with medication, but the difference between them was significantly (p < 0.05) only at the 6-month interval. There was no significant difference between the gastrin levels of the two groups in the long-term treatment. No ulcer relapse was detected at any long-term endoscopic control in the two groups of patients.. The two omeprazole regimens we tested are effective in reducing gastric acidity, and their pharmacodynamic action does not decrease with time. They are therefore suitable for maintenance treatment in acid-related disorders.

Topics: Adult; Aged; Drug Administration Schedule; Duodenal Ulcer; Endoscopy, Digestive System; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Omeprazole; Treatment Outcome

Patients (106) with peptic ulceration of the oesophagus, stomach and duodenum, unresponsive to 3 or more months of high-dose treatment with ranitidine, were initially given pantoprazole (40-80 mg, p.o.) daily. In 96.7% of the patients ulcers healed within 2 to 8 weeks, and in 2.3% of patients the ulcers healed within 12 weeks. In just one patient with severe oesophagitis, the lesion took more than 6 months to heal. After ulcer healing, patients (98 to date) were treated with pantoprazole (40 mg/day) as long-term maintenance therapy. Eighty-eight of the 98 patients have been taking pantoprazole for 6 months to 3 years. During maintenance therapy, peptic disease was kept in remission in most patients with 40 mg pantoprazole. Twelve patients with oesophagitis and two patients with gastric ulcers needed higher doses (80-120 mg) to control the disease. One female patient developed peripheral oedema which disappeared quickly after stopping treatment. No further drug-related adverse effects were observed. Seven patients withdrew from the study and two patients died, all for non-drug-related reasons. Routine laboratory tests remained without significant changes in all patients. Mean (+/- S.E.M.) serum gastrin levels were already elevated during the initial high-dose ranitidine treatment (128 +/- 23 pg/ml). Within one year of the start of the pantoprazole treatment, serum gastrin levels rose to 3 times normal values (189 +/- 32 pg/ml). Thereafter, no further increases in serum gastrin were observed for up to 2.5 years. Enterochromaffin-like (ECL) cell density increased very slightly from 0.19% to 0.24% within one year.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; Duodenal Ulcer; Enterochromaffin Cells; Esophagitis; Female; Gastrins; Humans; Longitudinal Studies; Male; Omeprazole; Pantoprazole; Peptic Ulcer; Proton Pump Inhibitors; Ranitidine; Stomach Ulcer; Sulfoxides

In 12 duodenal ulcer patients, gastric emptying (GE) of a radiolabelled solid meal, gastric acid secretion, and gastrin release were examined before and during the early postoperative period (median 13.5 days) after a highly selective vagotomy (HSV). HSV significantly delayed GE; the median slope of GE curves (K) decreased from 11.86 to 6.52 min-1 x 10(-3) (p < 0.01). A significant inhibition of the late phase of GE was reflected by a diminution of the curve shape parameter (S) from a median of 1.41 to 0.98 (p < 0.02). A profound impairment of GE after HSV was found in 4 of 12 patients (33%). HSV resulted in a 49% decrease in the basal acid output (6.9 +/- 1.0 before to 3.5 +/- 1.0 mmol.h-1 after HSV, and a 56% reduction in the pentagastrin-stimulated gastric acid secretion (31.1 +/- 5.1 before vs 13.8 +/- 2.4 mmol.h-1 after HSV (p < 0.01). A significant increase in both the fasted serum gastrin (38.9 +/- 3.7 to 66.9 +/- 8.4 ng.l-1, p < 0.05) and the meal-stimulated gastrin release (AUC0-120: 7179 +/- 440 to 11158 +/- 1062 ng.l-1 min, p < 0.05) was observed after HSV.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Time Factors; Vagotomy

Helicobacter pylori (H pylori) raises serum gastrin but it is unclear whether this stimulates increased acid secretion. Gastrin mediated acid secretion and plasma gastrin after the intravenous infusion of gastrin releasing peptide was studied in nine H pylori negative and nine H pylori positive healthy volunteers, and in 11 duodenal ulcer patients. Nine of the last group were re-examined one month after eradication of H pylori. The median acid output (mmol/h) to gastrin releasing peptide (40 pmol/kg/h) in the H pylori positive healthy volunteers was 15.1 (range 3.3-38.3), which was three times that of the H pylori negative healthy volunteers (median = 5.5, range 1.0-9.0) (p < 0.02). The median acid output in the duodenal ulcer patients with H pylori was 37 (range 8.5-57), which was > six times that of the H pylori negative healthy volunteers. Eradication of H pylori in the duodenal ulcer patients lowered their acid secretion by a median of 66% (range 30%-80%) (p < 0.01) and to values equivalent to the H pylori positive healthy volunteers. The pepsin output in response to gastrin releasing peptide followed the same pattern as the acid output. The median plasma gastrin concentrations during gastrin releasing peptide were similar in the H pylori positive duodenal ulcer patients (150 ng/l, range 95-400) and H pylori positive healthy volunteers (129 ng/l, range 23-420) and both were appreciably higher than H pylori negative healthy volunteers (60 ng/l, range 28-135) (p < 0.005 for each). Eradication of H pylori lowered the plasma gastrin in the duodenal ulcer patients to values equivalent to the H pylori negative healthy volunteers. These findings show a threefold increase in acid secretion in H pylori positive healthy volunteers that is explained by H pylori induced hypergastrinaemia and a sixfold increase in acid secretion in the duodenal ulcer patients that is explained by the combination of H pylori induced hypergastrinaemia and an exaggerated acid response to stimulation by gastrin. Eradicating H pylori lowers gastrin mediated acid secretion by 66% in duodenal ulcer patients as a result of the resolution of the hypergastrinaemia. Increased gastrin mediated acid secretion seems to be the key factor in the pathophysiology of duodenal ulceration and explains the role of H pylori infection in the disorder.

Topics: Amoxicillin; Anti-Bacterial Agents; Basal Metabolism; Breath Tests; Carbon Radioisotopes; Duodenal Ulcer; Female; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Infusions, Intravenous; Male; Metronidazole; Organometallic Compounds; Pepsin A; Peptides; Time Factors; Urea

The efficacy of lansoprazole (30 mg/d) and omeprazole (20 mg/d) has been assessed in active duodenal ulcer disease in 144 patients included in a multicentric, randomized, double-blind trial. After two weeks, the healing rates were 74% and 58% in the lansoprazole and omeprazole groups, respectively (P = 0.049). After 4 weeks, the healing rates were 94% in each group (NS). The delay to pain relief was 2 days for lansoprazole and 3 days for omeprazole (NS). Minor side effects occurred in 12% of the lansoprazole treated patients and in 13% of the omeprazole treated patients. No severe adverse events were reported. A slight increase in serum gastrin level was observed, similar in both groups (+35 UI/L and +19 UI/L for lansoprazole and omeprazole respectively). This study confirms previous results concerning the efficacy of both treatments in duodenal ulcer disease. The statistical difference observed for healing rates after 2 weeks could correspond to a faster efficacy for lansoprazole (30 mg) than for omeprazole (20 mg).

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Anti-Ulcer Agents; Double-Blind Method; Duodenal Ulcer; Female; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Pain

Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate.

Topics: Adult; Aged; Bismuth; Breath Tests; Citrates; Duodenal Ulcer; Food; Gastrins; Humans; Male; Middle Aged; Organometallic Compounds; Pepsinogens; Ranitidine; Time Factors

Forty-two patients with peptic ulceration of the duodenum, stomach or oesophagus, who had not responded to 3 or more months of high-dose treatment with ranitidine (450 or 600 mg/day), were treated with oral lansoprazole at 30-60 mg daily. In 40 patients (95.2%) the ulcers healed within 2-12 weeks. In the remaining 2 patients healing took several months but eventually all ulcers healed. After healing, 40 patients underwent long-term maintenance treatment with 30-60 mg lansoprazole daily for 1-3 years (continuing). During maintenance therapy with lansoprazole, no endoscopically verified relapses occurred when the drug was taken regularly. In 1 patient treatment had to be discontinued because of a drug-related colitis that disappeared soon after treatment had been stopped. There were no significant changes in routine laboratory tests in any patient. Basal serum gastrin concentrations, which were already elevated by the previous high-dose ranitidine treatment (125 +/- 25 pg/ml), rose to four times the normal values after 4 weeks of treatment with lansoprazole (255 +/- 65 pg/ml). Thereafter no further increases in basal serum gastrin concentrations were observed, even after 3 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased slightly during lansoprazole treatment; until now no dysplasia of the enterochromaffin-like cells has been observed. In conclusion, 30-60 mg lansoprazole daily healed ranitidine-resistant peptic ulcers, and subsequent maintenance therapy with 30-60 mg lansoprazole daily was found to be highly effective and safe over the time observed.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Duodenal Ulcer; Enterochromaffin Cells; Esophagitis; Female; Follicle Stimulating Hormone; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Luteinizing Hormone; Male; Omeprazole; Peptic Ulcer; Pyloric Antrum; Ranitidine; Stomach Ulcer; Testosterone

This study was designed to assess the gastroprotective and secretory effects of ebrotidine, a novel H2-receptor antagonist, in humans. Two groups (A and B) of male subjects with normal gastric mucosa were used. Group A (six subjects) was treated for 3 days with either ebrotidine or placebo in a randomized, crossover study, and on the 4th day 100 ml of 50% ethanol was sprayed on the mucosa via an endoscope. Pretreatment with ebrotidine significantly reduced the endoscopic score of mucosal damage and deep hemorrhagic lesions caused by ethanol as compared with those in placebo-treated subjects. In group B (six subjects) the 24-h pH-metry was assessed with an intraluminal pH electrode placed in the gastric corpus and connected to portable recording apparatus. A single oral dose of ebrotidine (800 mg) caused a significant reduction in circadian acidity and resulted in a marked and significant inhibition of acid secretion for about 6 h on administration. We conclude that ebrotidine is highly effective as a gastroprotective agent, and as an H2-receptor antagonist shows a potent inhibitory effect on gastric acid secretion in humans.

Topics: Adult; Benzenesulfonates; Duodenal Ulcer; Ethanol; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastroscopy; Histamine H2 Antagonists; Humans; Male; Thiazoles

The efficacy and safety of omeprazole, in 241 patients with active recurrent duodenal ulcer from 21 Italian centres, was studied in a multicentre double-blind randomized trial comparing 20 mg omeprazole o.m. or 40 mg famotidine nocte with endoscopic examination, symptom recording, laboratory screening and gastrin assay. In a per protocol analysis, the duodenal ulcer healing rates for omeprazole and famotidine, documented by endoscopy, were 62% (68/109) and 33% (39/117) after 2 weeks of treatment (P less than 0.001), 92% (96/104) and 80% (86/108) cumulative after 4 weeks (P less than 0.05), and 99% (102/103) and 92% (96/104) after 6 weeks (P less than 0.05), respectively. The results of this trial demonstrate that 20 mg omeprazole o.m. is superior to 40 mg famotidine nocte in duodenal ulcer healing.

Topics: Abdominal Pain; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Duodenal Ulcer; Evaluation Studies as Topic; Famotidine; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole

The effects of single doses and of 7 days of lansoprazole 10, 20 and 30 mg PO versus placebo on gastric acid secretion have been evaluated in 8 patients with high gastric acid secretion. The double blind crossover period was followed by a simple blind 7 days on placebo to detect any rebound phenomenon. After the first dose lansoprazole did not modify basal acid output (BAO) but it significantly and dose dependently inhibited peak acid output (PAO) and increased the time during which nocturnal intragastric pH was greater than 3. After 7 days of treatment the same significant, dose-dependent suppression of gastric acid was found, but BAO was also blocked. One week after cessation of lansoprazole administration no rebound increase in gastric acid-secretion was observed. The plasma gastrin concentration remained unchanged throughout the study.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Adult; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Lansoprazole; Male; Omeprazole

The aim of this study was to evaluate changes in peptic acid secretion, and in fasting and meal-stimulated plasma gastrin levels after a 7-day course of omeprazole 30 mg/day or ranitidine 300 mg/day, administered in accordance with a randomized, double-blind, double-dummy protocol. Ten duodenal ulcer patients were studied. Their acid and pepsin output was determined prior to and after treatment. Plasma gastrin levels were also determined under basal conditions on day 7 of treatment, and 24 hours after the last administration of the drug. With regard to acid output, omeprazole resulted in a 98% reduction in BAO and an 80% reduction in PAO, both significantly greater than those achieved with ranitidine (BAO 50%, PAO 25%). No significant changes in pepsin secretion were observed. The increase in fasting plasma gastrin observed after ranitidine and omeprazole was 86% and 242%, respectively, on day 7, and 13% and 103% twenty-four hours after final dose. Increases in meal-stimulated plasma gastrin were, respectively, 126% and 125% on day 7 and 8 after omeprazole, whereas the increase with ranitidine was 62% only on day 7 of treatment, with subsequent normalization. In addition to confirming the well-known effect of omeprazole on the physiology of gastric secretion, our data show that administration of therapeutic doses of traditional H2-antagonists is accompanied by a secondary hypergastrinemia, which is rapidly reversible after discontinuation of therapy.

Topics: Adult; Double-Blind Method; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Pepsin A; Ranitidine; Time Factors

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.

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Parietal Cells, Gastric; Pentagastrin; Stomach Diseases

There were 45 patients suffering from duodenal ulcer in the stage of exacerbation and 15 subjects who served as control. Radioimmunoassay and immunomorphological PAP methods were used to examine the blood PGI and gastrin levels, the number of gastroduodenal G and D cells, the characteristics of basal and stimulated acid production in gastric juice in the treatment with gastrozepin (22 persons) and ranisen (23 persons). Depending on the concentration of gastrin in the blood and the number of pyloric G cells, the patients were distributed into two groups: with hypergastrinemia and/or hyperplasia of G cells (48%) and with normogastrinemia and the normal number of these cells (52%). It has been shown that the continuous treatment with gastrozepin of the patients with hypergastrinemia and/or hyperplasia of pyloric G cells was followed by the normalization of blood gastrin concentration and of the number of pyloric G cells; on the contrary in the patients with normogastrinemia and the normal amount of these cells, the analogous characteristics remained unchanged. After the treatment with ranisan the patients with normogastrinemia and the normal amount of pyloric G cells manifested hypergastrinemia without any changes in the amount of G cells; meanwhile in the patients with hypergastrinemia and/or hyperplasia of G cells, the analogous characteristics were unchanged. In these groups patients, the rate and the times of the relapse occurrence were different throughout the whole year. The data obtained support the nonuniformity of duodenal ulcer.

Topics: Adult; Biopsy; Drug Evaluation; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Pepsinogens; Pirenzepine; Pylorus; Ranitidine; Recurrence; Remission Induction

Although omeprazole has a long duration of action and has usually been given in the morning, there are theoretical advantages in administering antisecretory drugs in the evening as has been shown for the H2-receptor antagonists. The aim of this study was to compare the effects of placebo and 20 mg omeprazole given either in the morning or evening, on gastric acidity, plasma gastrin levels and plasma omeprazole in 6 duodenal ulcer patients. The 24-hour mean pH (+/- S.E.M.) was: placebo 1.7 +/- 0.1; morning doing, 3.9 +/- 1.8 (P less than 0.01); evening dosing, 2.9 +/- 1.1 (N.S.). There was a large inter-individual variability of intragastric acidity in response to omeprazole, which was reflected both in the plasma gastrin and in the area under the plasma omeprazole concentration-time curve. Morning administration of omeprazole is optimal, but variability in the patient response to 20 mg omeprazole is still seen.

Topics: Double-Blind Method; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Omeprazole

Since the Roux-en-Y anastomosis prevents the sequela of postoperative enterogastric reflux after gastrectomy, this approach has been advocated as the primary procedure in patients undergoing gastrectomy for peptic ulcer. We have prospectively followed for 2 years 22 patients, in whom gastrectomy was performed with, at random, either Roux-en-Y (n = 11) or Billroth II (n = 11) anastomosis. Two of the 11 patients who had received the Roux-en-Y procedure had anastomotic ulcers, leading to reresection in one of them. These two patients were found to have the highest values for basal and pentagastrin stimulated gastric acid output. After the Billroth II procedure a single patient had a small anastomotic ulcerative lesion. Apart from differences in intragastric bile acids (p less than 0.0001) and the gastritis activity score (p less than 0.01), no significant differences were found between the patients with Roux-en-Y and Billroth II anastomosis with respect to basal and pentagastrin-stimulated gastric acid secretion, basal, postprandial and bombesin-stimulated serum gastrin secretion, serum pepsinogen A and C concentrations, the serum pepsinogen A/C ratio, postprandial glucose, and for a modified Visick grading. From this small series we conclude that, as compared with the Billroth II-anastomosis, the Roux-en-Y procedure effectively prevents enterogastric reflux, and is associated with a higher gastritis activity score, but not with differences in gastric acid, gastrin, pepsinogens, or Visick grading. Furthermore, inadequate reduction of acid secretion in some patients after the Roux-en-Y procedure may lead to recurrent peptic ulcers.

Topics: Anastomosis, Roux-en-Y; Anastomosis, Surgical; Bile Acids and Salts; Duodenal Ulcer; Female; Gastrectomy; Gastric Acid; Gastrins; Humans; Jejunum; Male; Middle Aged; Peptic Ulcer; Prospective Studies; Random Allocation; Recurrence

Twelve patients with active duodenal ulcer disease and Helicobacter pylori infection were treated with 1 g sucralfate q.d.s. for 1 month. Ulcers healed in 8 of the 12 patients without an alteration in the H. pylori-associated antral gastritis. Sucralfate produced a significant fall in basal acid output in all the patients, from a median of 4.8 (range 2.1-12.1) to 1.6 (0.4-8) mmol/h, P less than 0.01, whereas peak acid output was unchanged from 41 (21-59) before to 38 (24-55) mmol/h after treatment. Basal plasma gastrin concentrations and the meal-stimulated integrated gastrin response were not altered significantly by sucralfate: 8 (2-17) pmol/L and 732 (188-1045) pmol. min/L pre-treatment and 6 (2-17) pmol/L and 600 (140-1302) pmol. min/L post-treatment, respectively. The fall in basal acid output observed may contribute to prolonged duodenal ulcer remission after treatment with sucralfate.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Sucralfate

The effect of duodenal ulcer healing induced by omeprazole on gastroduodenal generation of eicosanoids, platelet-activating factor (PAF), pepsinogen A, and gastrin was evaluated. Sixty patients with endoscopically proven duodenal ulcer were randomized to receive 20 mg omperazole once daily or 300 mg ranitidine at bedtime for 2 weeks. Patients whose ulcers did not heal were treated for an additional 2 weeks. Endoscopic biopsy specimens and serum samples were obtained before and after treatment. There was no significant difference in the healing rate between the two treatment modalities. At 2 weeks healing rates were 60% and 56% in the omperazole and ranitidine groups, respectively, whereas at 4 weeks the respective healing rates were 96% and 86%. Ulcer healing induced by omeprazole and ranitidine was not accompanied by significant changes in mucosal leukotriene B4 or C4 generation. Mucosal PAF significantly decreased in patients treated with omeprazole for 4 weeks. In omperazole-treated patients there was a trend towards increase in mucosal prostaglandin E2 generation which was significant in the fundus after 4 weeks of treatment. After 2 weeks of omeprazole treatment, serum gastrin and pepsinogen A levels almost doubled when compared with their pretreatment levels. In conclusion, duodenal ulcer healing with 20 mg omeprazole daily is not superior to healing rates with 300 mg ranitidine at bedtime after both 2 and 4 weeks of treatment. In omeprazole-treated subjects ulcer healing was accompanied by a significant decrease in mucosal PAF generation and increased levels of serum gastrin and pepsinogen A.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Dinoprostone; Duodenal Ulcer; Eicosanoids; Female; Gastrins; Humans; Intestinal Mucosa; Leukotrienes; Male; Middle Aged; Omeprazole; Pepsinogens; Platelet Activating Factor; Random Allocation; Ranitidine

Our previous study demonstrated rebound nocturnal acid hypersecretion after a 4-week course of nizatidine. Nocturnal acid output was increased by 77% two days after discontinuing treatment compared with pretreatment values. To confirm this effect with other H2-blockers we assessed daytime intragastric pH, fasting and meal-stimulated plasma gastrin and nocturnal acid output in 9 duodenal ulcer patients in remission before, during and two days after treatment with three different drugs. Each patient received 4-week courses of 300 mg ranitidine, 40 mg famotidine or 300 mg nizatidine, taken at 20.00 hours in randomized order with a 'washout' period of 4 weeks between each course of drug. Median nocturnal acid output (mmol/10 h) decreased during treatment with ranitidine to 3 (range 0-17), famotidine to 4 (1-12) and nizatidine 6 (0-40) compared with the respective pre-treatment values, 49 (20-126; P less than 0.01), 52 (22-105; P less than 0.01) and 32 (23-114; P less than 0.01). Two days after discontinuing treatment nocturnal acid output was increased after ranitidine at 77 (28-237; P less than 0.04) and after nizatidine at 64 (17-130; P less than 0.05) compared with pre-treatment values. There was no significant change in nocturnal acid output after famotidine at 57 (27-107) compared with the pre-treatment value. There was no change in daytime intragastric pH with any drug during or after treatment compared with the pre-treatment values. Fasting and meal-stimulated plasma gastrin concentrations were increased on the final treatment day with ranitidine and famotidine but had returned to pretreatment levels two days after treatment. The rebound acid hypersecretion may contribute to the high ulcer relapse rate after discontinuation of H2-receptor antagonists.

Topics: Adult; Aged; Duodenal Ulcer; Famotidine; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Nizatidine; Ranitidine; Substance Withdrawal Syndrome

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.

Topics: Adult; Double-Blind Method; Duodenal Ulcer; Eating; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastric Juice; Gastrins; Humans; Pepsin A; Peptones; Prostaglandins F, Synthetic; Ranitidine; Stomach; Vasodilator Agents

Acid secretory responses and parietal cell sensitivity (PCS) have been studied in 21 duodenal ulcer patients before and after successful treatment with omeprazole (n = 7), sucralfate (n = 7), or Maalox (n = 7). The second study was carried out 3 days after documented healing and withdrawal of treatment in the sucralfate- and Maalox-treated groups and 14 days after documented healing and withdrawal of treatment in the omeprazole-treated patients. Acid output (mmol/hour) was measured as basal secretion, and in response to 0.1 microgram/kg/hour pentagastrin (low-dose) and 6.0 micrograms/kg/hour pentagastrin (high-dose) stimulation. PCS was calculated as the ratio of low dose:high dose acid output (expressed as a percentage). Ulcer healing with sucralfate resulted in significant (p less than 0.05) decreases in low-dose acid output from 36.4% (13.2-51.0) (median [range]) to 8.4% (3.2-45.4) mmol/hour and PCS from 69.1% (44.9-91.4) to 22.0% (16.0-85.6), whereas no significant decreases in any of the measured parameters were noted following ulcer healing with Maalox. Ulcer healing with omeprazole resulted in significant (p less than 0.05) decreases in basal acid output from 6.3 (1.5-22.9) (median [range]) to 2.2 (0-6.9) mmol/hour, and low-dose acid output from 31.0 (6.0-58.0) to 23.0 (1.4-44.8) mmol/hour. These findings suggest that acid secretory responses following ulcer healing vary according to the therapeutic agent used.

Topics: Adult; Aged; Aluminum Hydroxide; Antacids; Drug Combinations; Duodenal Ulcer; Endoscopy, Gastrointestinal; Fasting; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Magnesium Hydroxide; Male; Middle Aged; Omeprazole; Parietal Cells, Gastric; Pentagastrin; Recurrence; Sucralfate; Wound Healing

It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin.

Topics: Adult; Ammonia; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Helicobacter pylori; Humans; Male; Middle Aged; Urea

In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole; Recurrence

To assess the comparative efficacy of omeprazole 20 mg, a proton pump inhibitor, versus ranitidine 150 mg twice a day, an H2-receptor antagonist, in healing duodenal ulcers we performed a randomized, double-blind, multicenter trial in 309 patients with endoscopically diagnosed ulcers. Patients were treated for up to four weeks and were seen at week 2 and at week 4, if unhealed at week 2, for determination of ulcer status by endoscopy, review of daily self-assessment symptom diaries, and clinical laboratory including fasting serum gastrin. Gastrin levels were repeated two weeks after cessation of study medication. Evaluation of baseline demographic and laboratory parameters demonstrated no significant differences between the two groups at entry. At week 2, 42% of the omeprazole and 34% of the ranitidine-treated patients were healed (P = NS). At week 4, there was a 19% advantage in ulcer healing for the omeprazole-treated patients in comparison to those treated with ranitidine (82% vs 63%, respectively, P less than 0.05). Healing of ulcers greater than or equal to 1.0 cm occurred in 83% of those treated with omeprazole versus 37% treated with ranitidine (P less than 0.01). There were no significant differences in rate of pain relief or incidence of clinical laboratory abnormalities. Mean fasting serum gastrin value during treatment increased over the baseline in both groups, (P less than 0.05). The percent change was significantly greater with omeprazole but few patients had elevations above the upper limit of normal for the assay. Both drugs were well tolerated. Omeprazole 20 mg demonstrated superiority in healing duodenal ulcers at four weeks in comparison to ranitidine 150 mg twice daily and was more effective in healing ulcers greater than or equal to 1.0 cm.

Topics: Double-Blind Method; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole; Ranitidine; Wound Healing

In a double blind study, 24 hour intragastric acidity and 24 hour plasma gastrin concentrations were measured simultaneously in seven duodenal ulcer subjects on the fifth day of receiving either sufotidine 600 mg bd or placebo. Compared with placebo, during treatment with sufotidine 600 mg bd the median integrated 24 hour intragastric acidity was decreased by 95% (range 74% to 99%) from 1000 to 51 mmol/h/l, whilst the median integrated 24 hour plasma gastrin concentration increased from 416 to 927 pmol/h/l.

Topics: Adult; Circadian Rhythm; Double-Blind Method; Duodenal Ulcer; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Piperidines; Triazoles

The effect of calcitonin on gastric emptying of a radiolabelled test meal was examined in 10 patients with an endoscopically confirmed duodenal bulb ulcer. According to a double-blind study protocol, the patients were given on two different days placebo or synthetic salmon calcitonin (415 pmol i.v. bolus followed by a 90-min infusion to reach an overall dose of 62.25 pmol.kg-1 body mass)--in randomized order. Calcitonin did not affect the postprandial gastrin release nor did it change significantly the serum calcium or phosphorus concentration. The abolished postprandial insulin release by calcitonin was accompanied by a different pattern of serum glucose concentration, when compared to the situation with placebo. In all patients examined calcitonin evoked a profound delay in gastric emptying--the mean gastric transit time, MTT90: 34.1 +/- 1.4 min (placebo) vs 41.0 +/- 1.1 min (calcitonin), p less than 0.001.

Topics: Adult; Calcitonin; Depression, Chemical; Double-Blind Method; Duodenal Ulcer; Eating; Gastric Emptying; Gastrins; Humans; Insulin; Insulin Secretion; Middle Aged

The aim of this study was to compare the effects upon gastric secretion of therapeutic doses of aminophylline, with doxofylline, a new xanthine derivative proposed for the treatment of chronic asthma. Twelve patients with endoscopically-proven healed duodenal ulcer were studied twice under double-blind conditions in cross-over experiments. In a 1-hour infusion, six patients received either 240 mg aminophylline i.v. or 200 mg doxofylline i.v., and six received either 240 mg aminophylline i.v. or 400 mg doxofylline i.v. Compared with basal gastric secretion, for the hour after the infusion 240 mg aminophylline i.v. stimulated gastric acid output by a mean 213% (P less than 0.01) and mean pepsin output by 129% (P less than 0.01). Intravenous doxofylline did not stimulate a significant increase of either acid or pepsin output (200 mg: acid output +4%, pepsin output +10%; 400 mg: acid output +25%, pepsin output +27%). These findings suggest that doxofylline, unlike aminophylline, has a low secretagogue activity and it may be more suitable for asthmatic patients with peptic ulcer disease.

Topics: Adult; Aminophylline; Asthma; Double-Blind Method; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Theophylline

Topics: Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Ranitidine; Recurrence; Time Factors

The influence of cholinergic blockade as well as vagal denervation of the oxyntic gland mucosa on the gastrin response to gastrin-releasing peptide (GRP) have been studied in patients with duodenal ulcer disease. The gastric luminal content was neutralized during the experiments. GRP induced a substantial increase in gastrin levels with a peak response already after 15 min of infusion. Vagal denervation of the parietal cell area induced a significant increase in basal gastrin concentrations and a significant enhancement of the GRP response. Two different doses of benzilonium bromide were studied and neither influenced the basal concentrations of gastrin. A significantly increased gastrin response to GRP was, however, observed after administration of both a high and a very low dose of the anticholinergic drug. Our results delineate a vagal, noncholinergic inhibitory influence on the basal gastrin release. In addition a vagally dependent oxyntopyloric mechanism inhibits the gastrin release stimulated by GRP. This inhibitory mechanism may hypothetically be a cholinergic reflex mechanism.

Topics: Bombesin; Duodenal Ulcer; Female; Gastrin-Releasing Peptide; Gastrins; Humans; Male; Middle Aged; Parasympatholytics; Peptides; Pyrrolidines; Vagotomy, Proximal Gastric

Antral G cell hyperfunction (AGCH) is a rare condition, often associated with severe duodenal ulcer disease poorly responsive to medical therapy. Up to now, no studies have been designed to investigate a possible role of medical treatment in the management of this syndrome. In this study we treated 9 AGCH patients with duodenal ulcer, unhealed with the prolonging standard doses of H2 antagonists (300 mg/day ranitidine or 800 mg/day cimetidine), with a nonantacid therapy, tripotassium dicitrato bismuthate (TDB). 6 out of 9 patients showed a complete healing after 8 weeks of treatment. The healing was irrespective to eradication of Campylobacter pylori. After 9 weeks' suspension of H2 blockers basal gastrin levels decreased significantly by 31.5%, whereas peak meal-stimulated levels, although decreased in 6 out 9 patients, were not significantly affected by the withdrawal of the H2 antagonists. Nonantisecretory therapy seems to be an efficacious alternative in the management of AGCH patients.

Topics: Adolescent; Adult; Anti-Ulcer Agents; Bismuth; Cimetidine; Duodenal Ulcer; Enterochromaffin Cells; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Ranitidine

Six asymptomatic, non-smoking men with endoscopically proven duodenal ulcer disease received single nocturnal doses of placebo, 40 mg famotidine and 300 mg ranitidine each for 1 week prior to serial measurement of pH, peptic activity and serum gastrin concentrations over 24 h and of acid output. The intragastric pH fluctuated between 1.53 and 5.07 when subjects were given placebo but within 2 h of taking famotidine or ranitidine it rose to 5.57 or higher; the effect lasted for 12 h from midnight. Peptic activity fell during famotidine and ranitidine treatment and the decline was somewhat greater 8-15 h after using famotidine. Serum gastrin levels did not change materially with any treatment. The study shows the equivalent effect of standard bed-time doses of famotidine and ranitidine on intragastric pH, acid output and serum gastrin concentrations in asymptomatic men with duodenal ulcer disease.

Topics: Adult; Double-Blind Method; Duodenal Ulcer; Famotidine; Gastric Acid; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Pepsin A; Ranitidine

A total of 143 patients with peptic ulceration of the duodenum, stomach or oesophagus, who did not respond to 3 or more months high-dose treatment with ranitidine (450 mg or more daily), were admitted to oral treatment with omeprazole, 40 mg/day. In 94.4% of the patients, ulcers healed within 2-6 weeks. After healing of their ulcers, 122 patients were admitted to long-term maintenance treatment with omeprazole, 40 mg/day; 91 patients have been on the drug for 1-5.5 years. During maintenance therapy with omeprazole, 40 mg/day, no relapses (verified by endoscopy) have yet occurred and no drug related adverse effects have been observed. There were no significant changes in routine laboratory tests in any patients, including 27 with concomitant liver cirrhosis. Serum gastrin levels were already elevated approximately 2-fold during the initial high-dose ranitidine treatment and rose a further 2-fold at 2-3 months of omeprazole treatment. Thereafter, no further increase of serum gastrin was observed even after 5.5 years of continuous observation. Volume density of G and D cells in the antral mucosa did not change significantly. The volume density of argyrophilic cells in the oxyntic mucosa was 0.73 +/- 0.1% before the start of omeprazole treatment and 0.85 +/- 0.09% after 17-24 months of continuous treatment with omeprazole (ns). In antrectomized patients the volume density was lower (0.23 +/- 0.04%). No clusters of argyrophilic cells were observed in any of the groups. In a control group of patients with gastrinoma the volume density of these cells was higher (1.3 +/- 0.23%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Clinical Trials as Topic; Duodenal Ulcer; Esophagitis, Peptic; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Long-Term Care; Omeprazole; Ranitidine; Stomach Ulcer

In a double blind placebo controlled study the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in eight patients with duodenal ulcer. Synthetic salmon calcitonin 415 pmol iv was given as a bolus followed by a 90 minute infusion to reach an overall dose of 62.25 pmol/kg. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin markedly delayed gastric emptying in all patients examined. The emptying index (Ix) decreased from 2.979 (0.397)/min after placebo to 0.896 (0.317)/min after calcitonin (p less than 0.001). Calcitonin did not affect significantly postprandial gastrin release: AUC0-90, 8768 (880) pg/l min (placebo) and 7807 (619) pg/l min (calcitonin). Postprandial insulin release was abolished by calcitonin -Auc0-90, 2258 (242) mU/l min (placebo) v 736 (131) mU/l min (calcitonin), p less than 0.001. Parallel to the suppression of insulin release was a steady increase in the serum glucose during calcitonin infusion, with the highest glucose concentration of 5.8 (0.53) mmol/l at the end of infusion of the hormone. Calcitonin did not change significantly serum calcium or phosphorus concentrations. A combination of a delaying effect on gastric emptying with the inhibition of gastric acid secretion elicited by calcitonin warrants further studies of calcinonin in the treatment of duodenal ulcer.

Topics: Adult; Blood Glucose; Calcitonin; Double-Blind Method; Duodenal Ulcer; Gastric Emptying; Gastrins; Humans; Insulin; Male; Middle Aged

Roxatidine acetate is a novel H2-receptor antagonist with a chemical structure different to the earlier drugs of this type. It is a potent inhibitor of histamine-mediated gastric acid secretion and in animal models is 4 to 6 times as potent as cimetidine. In a multicentre double-blind clinical trial of over 700 patients with gastric or duodenal ulcers roxatidine acetate 75 mg twice daily and cimetidine 200mg four times daily produced endoscopically confirmed and subjective and objective healing rates in excess of 90% for both types of ulcer, with no significant difference between the treatments. Roxatidine acetate's efficacy in stomal ulcer (marginal ulcer) and reflux oesophagitis has been confirmed in non-comparative studies of up to 8 weeks' duration. The overall incidence of adverse reactions in 1623 patients treated with roxatidine acetate 75 mg twice daily was 1.7%, with skin rashes and constipation the most frequently reported side effects.

Topics: Adult; Cimetidine; Duodenal Ulcer; Female; Gastrins; Histamine H2 Antagonists; Humans; Japan; Male; Middle Aged; Pepsinogens; Peptic Ulcer; Piperidines; Prolactin; Stomach Ulcer; Time Factors

Mifentidine is a new H2-receptor antagonist with distinct characteristics of potency and long plasma half-life. The aim of this study was to evaluate the effects of mifentidine on peptone meal-stimulated gastric acid secretion. Nine duodenal ulcer patients in remission were enrolled in the study and given in double-blind and at random, on two different occasions, a single tablet of 10 or 20 mg mifentidine or placebo according to an incomplete balanced block design. Ninety min after ingestion of the drug, basal gastric secretion was collected for 30 min and volume, pH and acid output determined. Thereafter, the acid output following peptone meal-stimulation was measured for 2 h by a modified version of the intragastric titration method of Thompson and Swierczek. Plasma samples were collected for gastrin and mifentidine determinations. Basal acid output was strongly inhibited by both the low dose (-78%) and the high dose (-98%) (p less than 0.01). The peptone meal-stimulated acid output was reduced in a dose-dependent manner (-45% by 10 mg and -90% by 20 mg). The drug did not affect the fasting serum gastrin levels but increased, although not significantly, the gastrin response to food. The log of the area under the mifentidine plasma levels correlated linearly with total acid output (p less than 0.01). The results of this study indicate that mifentidine dose-dependently suppresses basal acid secretion and reduces peptone-stimulated gastric acid secretion in duodenal ulcer patients.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Humans; Imidazoles; Male; Middle Aged; Peptones; Random Allocation

A randomized, prospective, crossing-over clinico-pharmacological study was conducted on the tolerability by humans, of TISACID (Al-Mg-hydroxy-carbonate), a new antacid of up-to-date composition produced in Hungary. Even a relatively high dose of the preparation is tolerated by the human organism. During a 6-week continuous treatment neither subjective nor objective side-effects were observed. The tablet is immediately decomposed in the gastric juice, a considerable portion of it will permanently stick to the mucosa of the stomach and duodenum. Depending on the dose, it rapidly and permanently reduces the acidity of the gastric content and increases serum gastrin concentration only moderately and for a short time. Administered together with cimetidine, it promotes healing of duodenal ulcer and the cessation of complaints. It does not increase the aluminium and magnesium concentrations of the plasma not even on prolonged administration, and clinical symptoms and laboratory changes characterizing the phosphate depletion syndrome do not develop either. Based on the results, authors consider Tisacid a beneficial preparation as regards both effectivity and tolerability.

Topics: Aluminum Hydroxide; Carbonates; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Magnesium; Magnesium Hydroxide; Male; Prospective Studies; Random Allocation

The effect of placebos on gastric acid secretion in humans is unknown, even though placebo therapy is relatively effective in ulcer patients. Therefore, we evaluated the effect of a placebo capsule on meal-stimulated gastric acid secretion and serum gastrin concentrations in 10 healthy subjects and also in 10 patients with chronic duodenal ulcer. Each subject and patient was studied twice and in random order, once with placebo therapy prior to the meal and once without placebo. In either healthy subjects or duodenal ulcer patients, meal-stimulated acid secretion and serum gastrin concentrations were not significantly different with or without placebo administration. These studies demonstrate that a placebo capsule, administered by a physician just prior to a meal, has little, if any, effect on acid secretion or gastrin release in response to the meal. Any beneficial effects of placebos in treating patients with peptic ulcer disease are probably unrelated to inhibition of meal-stimulated gastric acid secretion.

Topics: Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Placebos; Random Allocation; Time Factors

A study has been done in 10 duodenal ulcer patients of the effect of a single oral dose of 10 mg mifentidine on the acid and pepsin responses to sham feeding after 1 h 30 min and to pentagastrin after 4 h 15 min. The study followed a double-blind, randomized, placebo-controlled, cross-over design. Gastric juice was collected for 5 h 15 min after treatment. Blood was sampled for up to 3 h 30 min to determine the effects of mifentidine on serum gastrin. Mifentidine suppressed basal acid output by 77% and sham feeding-stimulated acid output by 71% vs the placebo values. Pentagastrin-stimulated acid output was inhibited by 30% throughout the pentagastrin infusion. The suppressant effect of the drug on pepsin output was not as marked as on acid secretion. Mifentidine did not affect the serum gastrin level during the basal and sham feeding phases. No untoward effects were reported by the patients. The results show that 10 mg mifentidine p.o. produced a large reduction in the acid output in response to sham feeding and pentagastrin without affecting the serum gastrin responses.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Imidazoles; Male; Middle Aged; Pentagastrin; Pepsin A

Effects of orally-administered pirenzepine and propantheline bromide on food-stimulated gastric acid secretion, serum gastrin concentration, salivary flow and heart rate were compared in 10 duodenal ulcer patients in a placebo-controlled, double-blind study. Pirenzepine inhibited acid secretion by 25, 36 and 44% at doses of 50, 100, and 150 mg, respectively, while propantheline inhibited acid secretion by 32 and 41% at doses of 15 and 45 mg, respectively. None of the doses of pirenzepine affected food-stimulated serum gastrin concentrations, whereas 45 mg propantheline increased serum gastrin concentration significantly above placebo control. Enhancement of gastrin release by propantheline was not due to its antisecretory effect since intragastric pH after the meal was held constant at 5.0 by intragastric titration in vivo. Pirenzepine had no significant effect on heart rate and little or no inhibitory effect on salivary volume, depending on the dose administered. By contrast, both doses of propantheline increased heart rate and reduced salivary volume significantly (P less than 0.05). Thus, pirenzepine and propantheline in the doses administered inhibited acid secretion to approximately the same extent but pirenzepine had fewer effects on other organs.

Topics: Adult; Double-Blind Method; Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Heart Rate; Humans; Male; Middle Aged; Pirenzepine; Propantheline; Salivation

Duodenal ulcer therapy with H2 antagonists initially aimed to control acid secretion throughout the 24-h period, but recently nighttime suppression has been advocated. The effect of single nighttime regimens of cimetidine 400 mg BID, cimetidine 800 mg HS, ranitidine 150 mg HS, and placebo on 24-h intragastric acidity, nocturnal acid output, and pepsin secretion were studied in four healthy volunteers and four patients with healed duodenal ulcer. A nonrandomized dose of cimetidine 1200 mg HS was also studied. For all four treatments, daytime (0730-2230 h) intragastric acidity was reduced by 4-30% in the normals and by 10-44% in the duodenal ulcer patients (NS), while 24-h intragastric acidity was reduced by 44-46% and 40-64%, respectively (p less than 0.05). Reduction in nocturnal acid output was 82-96% in normals and 91-99% in duodenal ulcer, respectively. Pepsin concentration was unaffected by treatment but pepsin concentration was significantly (p less than 0.05) lower in patients than in normals. Mean 24-h gastric acid secretion was reduced by a single nighttime treatment with an H2-receptor antagonist, while nocturnal acid secretion was virtually abolished. H2 antagonists given only at night deserve further clinical evaluation to determine the minimal effective dose and optimal duration of suppression to achieve ulcer healing.

Topics: Cimetidine; Circadian Rhythm; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Pepsin A; Prolactin; Random Allocation; Ranitidine

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.

Topics: Adult; Bile Acids and Salts; Circadian Rhythm; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Omeprazole

Twenty-four hour intragastric acidity was measured in nine volunteer subjects in a single-blind placebo-controlled cross-over study comparing the effects of famotidine with ranitidine. The volunteer subjects received famotidine (40 mg at night), famotidine (20 mg at night), ranitidine (300 mg at night) or placebo in a predetermined random order. Twenty-four hour intragastric acidity was measured after the seventh dose of each drug or placebo. Famotidine (20 mg), famotidine (40 mg) and ranitidine, all caused a significant decrease of intragastric nocturnal acidity when compared with placebo (P less than 0.01), with no effect during the daytime (P greater than 0.05). Treatment with all the drugs caused a significant rise of fasting plasma gastrin concentration compared with placebo (P less than 0.05).

Topics: Administration, Oral; Adult; Aged; Dose-Response Relationship, Drug; Drug Evaluation; Duodenal Ulcer; Famotidine; Gastric Acid; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Random Allocation; Ranitidine; Secretory Rate; Thiazoles; Time Factors

Serum gastrin has been reported to increase after therapy with some agents effective in the treatment of duodenal ulcer (DU). Misoprostol, a prostaglandin E1 analog, is effective in the treatment of DU, with healing rates similar to those achieved with vigorous antacid therapy or H2-receptor antagonists. Misoprostol reduces gastric acid secretion and also possesses cytoprotective properties. This multicenter study examined serum gastrin levels before and after treatment of DU patients with misoprostol. Sera for gastrin measurement were obtained from DU patients after an 8-hr fast, and 15 and 30 min after a standard mixed meal. DU patients were studied before and after two to four weeks of treatment with placebo or misoprostol: in one study, misoprostol 100 micrograms qid (without antacid) was compared with placebo; in the other study, misoprostol at 50- or 200-micrograms qid dosages (with limited antacid, Amphojel up to 54 meq/day) was compared with placebo. In addition, the serum gastrin values obtained in healthy subjects were compared with those from DU patients. Fasting and postprandial serum gastrin concentrations were essentially similar for DU patients and healthy subjects. There were no significant differences, either in fasting serum gastrin or in integrated gastrin responses, in DU patients after treatment with placebo or misoprostol at 100 micrograms (P = 0.32), 50 micrograms, or 200 micrograms doses (P = 0.85). It is concluded that misoprostol, when administered four times daily for two to four weeks at dosages required for the acceleration of DU healing, does not affect serum gastrin levels.

Topics: Adult; Alprostadil; Antacids; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Misoprostol; Recurrence

The effect of enprostil, a synthetic dehydro-prostaglandin E2, on meal-stimulated gastric acid secretion and gastrin release was studied in six patients with inactive duodenal ulcer disease. Each subject underwent seven tests in random order on separate days: placebo intragastrically and intraduodenally; enprostil 35 and 70 micrograms both intragastrically and intraduodenally; and ranitidine 150 mg intragastrically. After measuring basal gastric acid secretion and gastrin release, a liquid meal (500 ml, pH 5.5, 40 g protein, 30 g fat, 30 g carbohydrate, 550 Kcal, 768 mOsm) was given. Gastric acid secretion and gastrin release were measured over the next four hours. A second identical meal was instilled and both parameters were measured for an additional four hours. Thirty-five and 70 micrograms of enprostil administered intragastrically reduced total eight-hour gastric acid secretion by 58 percent and 82 percent, respectively (p less than 0.05). The 35 and 70 microgram doses administered intraduodenally decreased gastric acid secretion by 67 percent and 91 percent, respectively (p less than 0.05 compared with placebo). Ranitidine suppressed gastric acid secretion by 95 percent, which was similar to the suppression achieved with the 70 microgram dose of enprostil. The total meal-stimulated integrated gastrin response was significantly suppressed by both intragastric doses of enprostil and by the 70 microgram dose given intraduodenally (p less than 0.05). Compared with placebo, the 35 microgram intragastric and intraduodenal doses decreased the integrated gastrin response by 73 percent and 72 percent, respectively. The 70 microgram intragastric and intraduodenal doses of enprostil reduced the integrated gastrin response by 90 percent and 125 percent, respectively. Ranitidine did not alter the integrated gastrin response. It is concluded that enprostil significantly inhibited both meal-stimulated gastric acid secretion and gastrin release. The response to enprostil occurred in a dose-dependent manner and was similar regardless of the route of administration.

Topics: Duodenal Ulcer; Eating; Enprostil; Fasting; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Ranitidine

The efficacy of and tolerance to omeprazole, 40 mg/day, was studied in an open-label study in 18 patients with endoscopically verified duodenal ulcers. The effects of the drug on the oxyntic mucosa and pentagastrin-stimulated acid secretion during and after treatment were also studied. Fifteen patients completed the final endoscopy. The ulcers were healed in all after 4 weeks' treatment. Both basal and peak acid output were significantly reduced during omeprazole treatment, whereas 4 weeks after the cessation of treatment neither basal nor peak acid output differed from the pretreatment levels. Fasting serum gastrin levels rose by 56% during treatment but had returned to pretreatment values when tested again 4 weeks after the end of the treatment period. Histological examination of the biopsy specimens taken before and after treatment showed that omeprazole had no significant effect on the volume densities of either parietal or endocrine cells. We conclude that omeprazole is of value in the treatment of duodenal ulcer and that the effects of the drug on acid output and serum gastrin levels are fully reversible.

Topics: Adult; Anti-Ulcer Agents; Benzimidazoles; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Omeprazole

The effect of varying oral doses of 11R, 16, 16-trimethyl prostaglandin E2 (TmPGE2) on meal-stimulated gastric acid secretion and serum gastrin concentrations was studied in 10 male subjects with asymptomatic duodenal ulcer disease. A liquid protein meal was infused intragastrically 0.5 h and 3.5 h after drug administration. TmPGE2 inhibited gastric acid secretion in a dose dependent manner during the first meal and no significant effect was observed during the second meal. Except for the highest dose, no TmPGE2 was detected in plasma 3 h after drug administration. The degree of inhibition of meal-stimulated gastric acid was positively correlated with the plasma level of TmPGE2, but it was not due to inhibition of postprandial gastrin release. The results indicate that oral TmPGE2 inhibits meal-stimulated gastric acid secretion but not gastrin release in humans with asymptomatic duodenal ulcer disease.

Topics: Adult; Aged; Analysis of Variance; Dinoprostone; Duodenal Ulcer; Food; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation

The effects of seven days' treatment with omeprazole 5 and 10 mg daily on 24 hours gastric secretion and plasma gastrin concentrations were studied in a randomised double-blinded placebo-controlled study of six male patients with healed duodenal ulcer. Omeprazole 5 mg daily reduced mean daytime and nocturnal intragastric acidity by 31.4 and 40.1%, respectively. Omeprazole 10 mg per day produced very similar reductions of 33.6 and 42.0%, respectively. Total nocturnal acid output was reduced by 63.9% and 63.2%, respectively, by omeprazole 5 and 10 mg daily. There was a large degree of inter-subject variability in response to these low doses of omeprazole. Consequently, neither dose showed a statistically significant antisecretory effect when compared with placebo. Neither dose of omeprazole significantly affected fasting levels of gastrin, but omeprazole 10 mg daily produced a significant (P less than 0.05) increase in the integrated gastrin response to a meal. The lack of consistent antisecretory effect to low dose omeprazole is in accord with previous studies. This suggests that doses of 20 mg per day or greater are required to produce a consistent effect on acid secretion.

Topics: Adult; Circadian Rhythm; Double-Blind Method; Duodenal Ulcer; Fasting; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Random Allocation

The effects of pirenzepine and ranitidine alone and combined, on gastric acid secretion and gastrin release stimulated by liquid peptone meal were evaluated in 12 duodenal ulcer patients. Six patients received placebo and ranitidine 150 mg per os and the other six patients were given placebo, pirenzepine 50 mg and pirenzepine 50 mg plus ranitidine 150 mg per os, according to randomized sequences. In the first experiment ranitidine markedly inhibited (69%) gastric acid secretion for entire two hours period (p less than 0.01). In the second experiment acid secretion after pirenzepine, was reduced by 39% while the combination of pirenzepine plus ranitidine almost completely inhibited the meal stimulated acid secretion (99%). Mean integrated gastrin responses after pirenzepine and ranitidine alone as well as pirenzepine plus ranitidine were not significantly different from placebo. The results of these studies show that in duodenal ulcer patients, the simultaneous block of muscarinic and H2-receptors, suppresses meal stimulated gastric acid secretion, without affecting gastrin release. This therapeutic combination might be used in clinical situations (non-responders, Zollinger-Ellison syndrome) in which complete inhibition of gastric acid secretion is needed.

Topics: Adult; Drug Therapy, Combination; Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptones; Pirenzepine; Random Allocation; Ranitidine

120 patients were randomly allocated to receive ranitidine 150 mg twice daily or a tri-potassium di-citrato bismuthate (TDB) tablet four times a day in a trial comparing the effects of these drugs in the short-term healing and post-healing relapse rates of duodenal ulceration. At 4 weeks 81% of those on ranitidine and 90% of those on TDB had healed ulcer craters. At 8 weeks 97% of those on ranitidine and 97% of those on TDB had healed. These differences are not significant. After ulcer healing, the cumulative rates of relapse, as determined endoscopically, for symptomatic and symptomless ulcers were 74% for ranitidine and 41% for TDB at 4 months (p less than 0.001), 87% for ranitidine and 55% for TDB at 8 months (p less than 0.001), and 89% for ranitidine and 62% for TDB at 12 months (p less than 0.001). Females had significantly lower relapse rates than males. In the ranitidine group smokers had a higher rate of early relapse and failure to remain healed at 12 months than did non-smokers; no such difference occurred in the TDB-treated group.

Topics: Adult; Aged; Antacids; Bismuth; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Organometallic Compounds; Patient Compliance; Pepsinogens; Random Allocation; Ranitidine; Recurrence; Smoking; Tablets

Thirteen male patients with a history of duodenal ulcer were given 150 mg RP 40 749 or placebo tablets at bedtime in a double-blind crossover study. The medication was given for two periods of 10 days with an 11-day wash-out period between. pH and pepsin concentrations were determined each hour in aspirates of gastric juice for 24 h on day 1, 10, 22, 31, and a 2-h collection of gastric juice was examined in the middle of the treatment and wash-out periods. At defined hours blood samples were examined for gastrin, somatostatin, and pancreatic polypeptide (PP) by radioimmunological methods, and concentrations of RP 40 749 were determined in blood and gastric juice. Meals were served at fixed hours on days 1, 10, 22, and 31. After treatment with RP 40 749 a highly significant elevation of pH was found after the 1st day compared with placebo, most pronounced during night hours. The pepsin activity was slightly elevated. The serum concentrations of gastrin were increased and those of somatostatin and PP decreased during the first 3-4 h after medication, with a subsequent normalization. No side effects were observed.

Topics: Adult; Anti-Ulcer Agents; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pancreatic Polypeptide; Pepsin A; Placebos; Somatostatin; Thiophenes; Time Factors

The present study intended to investigate the effect of antroduodenal acidification on gastric acid secretion and emptying, gastrin and somatostatin release in response to food in healthy subjects as well as in duodenal ulcer patients. Ten duodenal ulcer patients and 9 normal controls were studied twice: the same 400 ml liquid protein meal (proteins: 10 g) was introduced into the stomach; then intragastric pH was either maintained at pH 4.5 or allowed to decrease in response to the meal. Acid secretion was calculated using the intragastric titration method (for which the intragastric pH is fixed at pH 4.5) and using the serial dilution indicator method (which allows antral acidification) respectively. Gastric emptying was estimated according to: a) iterative measurements of intragastric meal residual volume; b) volume passing through the pylorus. These two tests were performed in a random order and during each, plasma gastrin and somatostatin responses to the meal were determined. In healthy subjects, antral acidification following the meal was associated with a significantly lower acid secretion (17.3 +/- 0.9 mmol/h; m +/- SEM) than when the pH was maintained at pH 4.5 (20.2 +/- 1.3; p less than 0.05). Moreover, gastric emptying was slower when the pH was allowed to decrease (t 1/2: 26.2 +/- 1.4 min) than when the pH was constant (t 1/2: 20.5 +/- 2.2 min; p less than 0.05). By contrast, in the duodenal ulcer group, neither acid output nor gastric emptying were significantly different in the two situations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Duodenal Ulcer; Duodenum; Female; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach; Time Factors

The aim of this study was to compare the effects of atropine with those of placebo and pirenzepine on food-induced gastrin release, and gastric and acid secretion. Three groups of subjects were studied: 8 healthy volunteers; 8 duodenal ulcer patients, and 6 vagotomized patients. Gastric acid secretion and serum gastrin were studied in each subject on 3 different days, after placebo, atropine or pirenzepine, given in random order. In each group, acid secretion was significantly depressed by atropine and pirenzepine. Unlike pirenzepine, atropine induced a significantly increase in serum gastrin in both healthy volunteers and duodenal ulcer patients. None of the treatments caused differences in gastrin response in vagotomized patients.

Topics: Adult; Atropine; Benzodiazepinones; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Kinetics; Male; Middle Aged; Peptones; Pirenzepine; Vagotomy

This study was designed to compare the effects of enprostil, a synthetic dehydro-prostaglandin E2, on 24-h intragastric pH and serum gastrin profile in patients with duodenal ulcer disease. The dosing regimen included 3 enprostil groups: 35 microgram h.s. (at bedtime), 70 micrograms h.s., and 35 micrograms b.i.d., compared with cimetidine 600 mg b.i.d., and with placebo. Ten patients with inactive duodenal ulcer disease were randomly assigned to all five treatment regimens for 1 wk each according to a Latin Square design. There was a 1-wk washout period between each treatment. Intragastric pH and serum gastrin measurements were carried out on the last day of each treatment week. In placebo-treated patients, intragastric pH rose after each meal and fluctuated between 1.5 and 3.5. Enprostil 35 micrograms b.i.d. and cimetidine elevated pH after breakfast and during the night (p less than 0.05). The single nighttime dose of enprostil had a marked effect on pH only when given in the dose of 70 micrograms and this effect lasted over 13.5 h. The pH values during the night were similar in the groups treated with enprostil 35 micrograms b.i.d. and 70 micrograms h.s. During the daytime, the readings at or above pH 4 were placebo, 5%; cimetidine, 21%; enprostil 35 micrograms b.i.d., 34%. During the nighttime, the readings greater than or equal to 4 were placebo, 12%; cimetidine, 29%; enprostil 35 micrograms b.i.d., 39%; 35 micrograms h.s., 19%, and 70 micrograms h.s., 38%. The postprandial rise in serum gastrin was greatly enhanced by cimetidine, but the change after breakfast was dramatically blunted by enprostil 35 micrograms b.i.d. Gastrin concentration was increased with cimetidine during the night but there was no difference in gastrin concentration overnight between all regimens of enprostil and placebo. This study suggests that (a) enprostil 35 micrograms b.i.d. is as effective as cimetidine 600 mg b.i.d. in suppressing postprandial and nocturnal intragastric acidity; (b) enprostil 35 micrograms b.i.d. and 70 micrograms at night are similarly potent in suppressing nocturnal acidity; and (c) in addition to its cytoprotective effect, enprostil has potent antisecretory and antigastrin properties.

Topics: Adult; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Enprostil; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Prostaglandins E, Synthetic; Research Design; Time Factors

GIH secretin bolus (2 CU/kg) and infusion (3 CU/kg/h) have been randomly compared in 9 ZES patients and 10 age-matched DU patients. Serum gastrin and gastric acid variations were studied before and after either mode of secretin administration in the same individuals. Plasma secretin modifications were monitored in parallel. In both ZES and DU, secretin bolus and infusion induced similar gastrin responses (maximal changes and integrated responses). However, secretin infusion had a greater effect on acid output than bolus: larger inhibition in DU and larger increase in ZES. The additive diagnostic value of gastric acid secretion study during a secretin provocation test, as already reported, favors the use of 3 CU/kg/h secretin infusion over that of 2 CU/kg secretin bolus.

Topics: Administration, Oral; Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Infusions, Parenteral; Secretin; Secretory Rate; Zollinger-Ellison Syndrome

The endoscopic healing rates and factors related to healing of two cimetidine regimens designed to reduce respectively postprandial and nocturnal acid secretions were studied in a randomised trial of cimetidine 200 mg tds with meals, vs 600 mg at bedtime, vs 200 mg tds with meals plus 400 mg at bedtime in 246 patients with duodenal ulcer. The respective healing rates were 62.3%, 63.1%, 77.5% at four weeks and 86.6%, 83.3%, 91.2% at eight weeks. The healing rates at four weeks of both meal time and bedtime regimens were inferior (p less than 0.05) to that of the standard regimen. Analysis of 45 prospectively obtained factors showed that (i) habitual cigarette smoking adversely affected healing with the meal time regimen but not with the others, indicating that its adverse effect disappeared once nocturnal acid secretion was reduced, (ii) habitual use of analgesics impaired and their abstinence favoured healing by both meal time and bedtime regimens but these effects were lost with the standard regimen, suggesting that if analgesics cannot be withdrawn during ulcer treatment, a reduction of both meal time and night time acid secretions should be ensured, (iii) responders with the meal time and bedtime regimens had respectively significantly higher postprandial serum gastrin and higher basal acid output than the corresponding non-responders suggesting that these responders had different pathophysiology, and (iv) high maximal acid output and large ulcers healed less well by any regimen.

Topics: Adult; Analgesics; Cimetidine; Drug Administration Schedule; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Smoking; Wound Healing

We evaluated the effect of 20-, 40-, 60-, and 80-mg doses of SKF 93479, a new H2-receptor antagonist, on food-stimulated gastric acid secretion in duodenal ulcer patients. Medications were given as a single oral dose in the morning with a breakfast meal, and acid secretion was measured by in vivo intragastric titration in response to four blended steak meals infused into the stomach at intervals over a 24-hr period. A breakfast meal was infused immediately after medication; a luncheon meal was given 5 hr after drug, and a dinner meal was instilled 10 hr later. A second breakfast meal was infused 24 hr after medication. For comparison, the effect of 300 mg cimetidine, given as normally prescribed (with meals and at bedtime), on acid secretion was also studied. Food-stimulated acid secretion was inhibited in a dose-related manner by each of the four doses of SKF 93479. The antisecretory effect was most dramatic following the luncheon meal, and there was still significant (P less than 0.05) inhibition of acid secretion at the dinner meal with all doses of SKF 93479. With the second breakfast meal 24 hr after medication, the 80-mg dose alone achieved significant (P less than 0.05) inhibition of acid secretion. Inhibition of acid secretion was correlated positively with blood SKF 93479 levels. When compared with placebo results, serum gastrin concentration, measured 5 and 10 hr after medication, was significantly higher (P less than 0.05) with SKF 93479.

Topics: Adult; Aged; Cimetidine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Pyrimidinones

The effect of 600 mg of cimetidine given twice daily on 24-hour intragastric hydrogen ion (H+) concentration was compared with that of the standard regimen of 300 mg of cimetidine given four times daily in six patients with asymptomatic duodenal ulcer. According to the double-blind, Latin-square, repeated-measures design, all subjects followed each cimetidine regimen and a placebo regimen for one week. Acid secretion studies and determinations of drug and gastrin levels in the blood were carried out on the last day of each treatment week. Although 600 mg of cimetidine BID suppressed H+ after breakfast and during the night, compared with placebo treatment (P less than 0.01), the 300-mg QID regimen suppressed H+ only after breakfast and supper (P less than 0.05). A higher percentage of pH readings greater than or equal to 3.0 were obtained with 600 mg of cimetidine BID than with 300 mg of cimetidine QID during the night (P less than 0.05); compared with percentages when placebo was taken, the percentages of pH readings greater than or equal to 3.0 were greater both overnight and during a 24-hour period only when 600 mg of cimetidine was given BID (P less than 0.01). The observed difference in intragastric H+ suppression after each regimen could not be explained by variations in serum concentrations of cimetidine or serum concentrations of gastrin. Despite similar peaks of serum cimetidine after evening doses of 300 or 600 mg of cimetidine, nocturnal intragastric acidity was lower in subjects given 600 mg BID. Further, H+ levels after lunch were similar in both cimetidine-treated groups, despite markedly higher serum cimetidine concentrations in patients receiving 600 mg BID. Pharmacokinetic studies showed equivalent elimination half-times and 24-hour areas under the curve of serum cimetidine concentration in patients on the two cimetidine regimens. Postprandial integrated gastrin responses were of similar magnitude in patients on either cimetidine regimen. There was no significant difference in mean serum gastrin concentrations during the night in placebo-treated and cimetidine-treated patients. Only a weak correlation was observed between H+ and serum gastrin concentration. Although a fluctuation of the H+:gastrin ratio occurred after each meal in all groups, the ratio was suppressed by both dosages of cimetidine. The findings suggest that a regimen of 600 mg of cimetidine BID is superior to the standard regimen of 300 mg QID in suppressing intragastric ac

Topics: Adult; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Humans; Kinetics; Male; Middle Aged

By means of a Latin square design, the effect of antacid alone and in combination with cimetidine on a 24-hour intragastric hydrogen ion (H+) activity and serum gastrin profiles was studied in eight patients with duodenal ulcer. Antacid given seven times a day (one and three hours after meals and at bedtime) combined with 600 mg BID of cimetidine (C + A7) achieved greater suppression of H+ after breakfast, overnight, and over the 24-hour period than did antacid alone seven times daily (A7). Antacid given four times a day (one and three hours after lunch and after supper) combined with cimetidine BID (C + A4) maintained the neutralizing capacity during this time, but was less effective than the C + A7 regimen. However, C + A4 produced more suppression of nocturnal H+ than did A7. A higher percentage of the readings at or above pH 4.0 were obtained with C + A7 than with A7 or C + A4. A greater postprandial integrated gastrin response was obtained with all active treatments as compared with a placebo regimen. The mean peak cimetidine concentration (Cmax) was higher but the time to peak (Tmax) was shorter after the morning than after the evening dose. The area under the cimetidine concentration-time curve and the Cmax and Tmax values after the morning and evening doses of cimetidine were not affected by the coadministration of antacid.. (1) combination therapy of cimetidine plus antacid is more effective than antacid alone in the reduction of intragastric H+; (2) antacid alone fails to suppress the overnight intragastric acidity; and (3) antacid given concurrently with cimetidine does not interfere with pharmacokinetic determinants of plasma cimetidine concentration.

Topics: Adult; Aged; Antacids; Cimetidine; Clinical Trials as Topic; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Humans; Kinetics; Male; Middle Aged; Time Factors

Both pirenzepine and cimetidine have been shown to be beneficial in the healing of duodenal ulcers. The aim of the present study was to determine the effects of 50 mg of pirenzepine BID and 600 mg of cimetidine BID, either alone or in combination, on 24-hour intragastric acidity, nocturnal gastric secretory volume and acid output, and serum gastrin profile in patients with duodenal ulcers. Eight asymptomatic patients with healed duodenal ulcers received placebo, pirenzepine, cimetidine, or cimetidine plus pirenzepine for one week each in a sequential order. All measurements were performed over a 24-hour period on the last day of each treatment week. Compared with pirenzepine, cimetidine was associated with lower hydrogen ion (H+) activities after breakfast, during the night, and over the 24-hour period. Pirenzepine alone failed to suppress H+, but the combination of cimetidine plus pirenzepine resulted in more prolonged acid suppression, with lower H+ after lunch, than did cimetidine alone. The effect of cimetidine on the suppression of nocturnal acid secretory volume and acid output was further enhanced by the addition of pirenzepine. The fasting serum gastrin concentrations were similar in all treatments, excluding one patient with antral G-cell hyperplasia; the postprandial gastrin responses were similarly higher with cimetidine and cimetidine plus pirenzepine than with pirenzepine. The findings suggest an added benefit of combination therapy with cimetidine and pirenzepine that may be useful in patients who fail to respond to single-agent therapy.

Topics: Adult; Benzodiazepinones; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pirenzepine; Random Allocation; Time Factors

The effects of beta-blockade (propranolol, 100 mg orally) on gastric acid output and on circulating levels of gastrin, adrenaline, noradrenaline, and dopamine during modified sham feeding (MSF) were investigated by a randomized, double-blind method in six patients with asymptomatic duodenal ulcer disease. No differences occurred in peak acid output during MSF, whereas basal acid output was significantly suppressed by beta-blockade and peak acid output was unaffected. Basal gastrin concentration was lower during beta-blockade but rose in response to MSF. Without beta-blockade serum gastrin levels were unaffected by MSF. Plasma catecholamine concentrations were not affected by the beta-blockade. It is concluded that acid output and gastrin release in response to MSF, unlike that to insulin hypoglycaemia, is not influenced by beta-adrenoceptor blockade.

Topics: Adult; Catecholamines; Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Propranolol; Secretory Rate

Topics: Adult; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastrins; Humans; Kinetics; Male; Middle Aged; Ranitidine

In duodenal ulcer, acid and pepsin in greater amounts and at higher concentration enter the duodenum and specific treatment should be directed towards correcting this abnormality. Such treatment is provided by the histamine H2-receptor antagonists. We discuss the first U.S. multicenter trial of the new nitrofuran-based antagonist, ranitidine, in which 382 patients were treated for 4 weeks with either ranitidine 150mg b.i.d. (195 pts.) or placebo (187); both groups were allowed to use antacid for pain. Those treated with ranitidine had significantly less pain and used less antacids than the placebo-treated patients; after 2 weeks, 37% vs 19% were healed, and after 4 weeks, 73% vs 45% were healed (p less than 0.01). After 4 weeks, 124 unhealed patients were randomized to ranitidine vs placebo for another 4 weeks. Ranitidine treatment again produced a greater healing rate (p less than 0.01), regardless of prior treatment. The 3 subsets of the data which contained more than 34 patients were analyzed separately. Each showed 1 or more significant deviations (type I and type II errors) from the overall study, which was in all respects similar to the aggregate results of all similar studies overseas. We emphasize the need for studies of adequate size.

Topics: Antacids; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pepsin A; Random Allocation; Ranitidine

In a prospective randomized clinical trial, gastric acid secretion was compared in patients after simple closure, proximal gastric vagotomy with closure, or truncal vagotomy with pyloroplasty performed for perforated duodenal ulcer. The basal and pentagastrin- and insulin-stimulated acid outputs were similar after either proximal gastric or truncal vagotomy; they were also comparable with the postoperative acid values after corresponding procedures performed electively for chronic duodenal ulcer. Conversely, the basal and maximum acid outputs after simple closure of perforation were no different from the preoperative acid outputs of a group of duodenal ulcer patients matched for age and sex. The efficacy of acid reduction by emergency proximal gastric and truncal vagotomy was shown by the respective ulcer recurrence rate of 3% (1/34) and 6% (2/32) compared with 43% (15/35) after simple closure (p less than 0.01). Acid secretory data and serum gastrin levels did not predict ulcer relapse in patients after simple closure of perforation.

Topics: Adult; Clinical Trials as Topic; Duodenal Ulcer; Emergencies; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer Perforation; Postoperative Period; Prognosis; Prospective Studies; Pylorus; Random Allocation; Recurrence; Vagotomy; Vagotomy, Proximal Gastric

The effect of bombesin, a possible neurotransmitter of gastrin release, upon gastrin and gastric acid secretion was investigated in 25 patients with duodenal ulcer and in 16 normal subjects. In patients with duodenal ulcer bombesin (10 ng/kg/min) produced an increase in plasma gastrin output (median 22.4 (range 7.5-75.8) pmol/l/min) similar to that obtained in normal subjects (median 24.4 (range 5.8-56.5) pmol/l/min), whereas gastrin stimulated by a meal was significantly higher in the group of patients with duodenal ulcer (median 20.7 (range 9.2-42.9) vs 16.2 (range 3.4-22.2) p<0.05). Peak acid output induced by bombesin was significantly higher in patients with duodenal ulcer than in normal subjects (median 24.4 (range 9.0-63.8) vs 14.0 (range 3.0-24.8) mmol/h, p<0.05) despite identical gastrin outputs. The ratio (%) obtained by dividing the acid secretory response to bombesin by the response to pentagastrin, however, was similar in both normal subjects and patients with duodenal ulcer (median 55 (range 20-116) vs 58 (range 31-95) respectively). The difference between the gastrin response to food and bombesin could be explained by the fact that bombesin releases gastrin directly, whereas a protein meal involves several mechanisms (neural, peptidergic, paracrine, endocrine), either stimulatory or inhibitory. The above results indicate that a higher concentration in antral and/or duodenal gastrin is unlikely to be present in patients with duodenal ulcer. An increased parietal cell mass could explain the higher gastric acid response after bombesin infusion in our group of patients with duodenal ulcer.

Topics: Adult; Bombesin; Dietary Proteins; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pentagastrin

Fasting plasma levels of immunoreactive gastrin, somatostatin, and pancreatic polypeptide (PP) were determined in 67 patients with an endoscopically proven duodenal, pyloric, or prepyloric ulcer. Pretreatment gastrin (45.6 +/- 53.6 pmol/l, mean +/- S.D.) and somatostatin (54.5 +/- 27.5 pg/ml) did not differ significantly from those in 22 healthy controls (21.8 +/- 20.2 pmol/l and 64.8 +/- 24.7 pg/ml, respectively). The gastrin and somatostatin levels were not changed by 3 weeks of treatment either with propantheline and antacids or with cimetidine and antacids. The mean PP value before treatment was significantly (p less than 0.01) higher in duodenal ulcer patients (0.76 +/- 0.55 ng/ml) than in healthy subjects of similar age (0.36 +/- 0.26 ng/ml). The increased PP level was not lowered significantly by medical treatment even when this resulted in healing of the ulcer.

Topics: Adult; Aged; Cimetidine; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Pancreatic Polypeptide; Propantheline; Radioimmunoassay; Somatostatin; Stomach Ulcer

The gastric antisecretory activity of etintidine, a new histamine H2-receptor antagonist, was evaluated in 5 patients with quiescent duodenal ulcer disease. Meal-stimulated acid secretion was measured after 100 and 300 mg oral doses of etintidine, 100 and 300 mg oral doses of cimetidine, and placebo. Reductions from placebo in four-hour gastric acid secretion were 49, 65, 80, and 94%, with 100 mg cimetidine, 100 mg etintidine, 300 mg cimetidine, and 300 mg etintidine, respectively. Drug concentrations in plasma were determined by HPLC. The pharmacokinetics of the 2 drugs were similar. We analyzed sigmoid-shaped concentration-response curves to both agents; the concentrations causing 50% inhibition of meal-stimulated gastric acid secretion were 0.44 +/- 0.04 and 0.15 +/- 0.04 micrograms/ml for cimetidine and etintidine, respectively. However, characteristics of these curves were such that the potency difference diminished at higher concentrations.

Topics: Cimetidine; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Imidazoles; Kinetics; Male; Middle Aged

The therapeutic efficacy of ranitidine, pirenzepine, cimetidine and placebo in the 28 day treatment of duodenal ulcer was evaluated through an open randomized study performed in 120 patients. At the end of treatment, ranitidine, pirenzepine and cimetidine demonstrated a significantly higher efficacy on ulcer healing as well as on symptom relief in comparison with placebo (P less than 0.05). Data regarding cimetidine and ranitidine failed to reveal significant differences: pirenzepine, on the contrary, when compared with both the H2 blockers employed showed a slower effect on symptom disappearance. As far as functional data are concerned, placebo administration did not induce any variation of secretory or gastrinemic behaviour: on the contrary, after the end of ranitidine and cimetidine treatment a significant decrease of BAO and of MAO were found, failing to reveal any serum gastrin variation. After pirenzepine therapy no differences in the acid secretory behaviour were seen, while a significant increase of fasting gastrinemia was observed.

Topics: Adolescent; Adult; Aged; Antacids; Anti-Ulcer Agents; Benzodiazepinones; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Endoscopy; Female; Furans; Gastric Acid; Gastrins; Guanidines; Humans; Male; Middle Aged; Pirenzepine; Placebos; Ranitidine

A prospective study of the value of secretin, calcium, and meal gastrin challenge tests for the diagnosis of gastrinoma indicated that the secretin test may be valuable. The calcium test was equally valuable, but it cannot be recommended as enthusiastically because it is time-consuming and may cause side effects. New criteria for interpretation of these tests were based on peak responses to the challenge. Further, the study revealed that patients with hypochlorhydria and hypergastrinemia could be identified without the use of gastric analysis. This prospective study reflects the current pattern of clinical practice at a referral institution where patients with gastrinoma, an unusual condition, are seen with regularity. The criteria we propose for interpretation of these tests are simple and could be applied to individual patients in whom a gastrinoma is suspected.

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Diet; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Secretin; Sugar Acids; Zollinger-Ellison Syndrome

The effects of tiotidine, a new histamine H2-receptor antagonist, and cimetidine on food-stimulated gastric acid secretion were evaluated in duodenal ulcer patients. Homogenized steak meals were infused immediately after, 1 h after, 5 h after, and 10 h after an oral dose of medication, and food-stimulated acid secretion was measured by in vivo intragastric titration. Tiotidine and cimetidine had a similar onset of action; however, tiotidine was more potent and had a longer duration of effect. Increased potency was demonstrated by the fact that from 1 to 2 h after medication 150 mg tiotidine inhibited acid secretion to approximately the same extent as did 300 mg cimetidine, and by the fact that for a given percent inhibition of acid secretion, plasma tiotidine concentration was eight to nine times lower than plasma cimetidine concentration. Longer duration of effect was demonstrated by the fact that from 5 to 7 h after medication, acid secretion was inhibited by 80% and 97% with 150 and 300 mg tiotidine, respectively, whereas 300 mg cimetidine inhibited acid secretion by only 22%. Also, 10-12 h after medication, 150 and 300 mg tiotidine inhibited acid secretion by 22% and 53%, respectively, while 300 mg cimetidine had no inhibitory effect. The long duration of effect was due in part to increased potency and in part to a plateau in plasma concentration of tiotidine, which was maintained from 2 to 6 h after medication. Neither tiotidine nor cimetidine had a significant effect on food-stimulated gastrin release or gastric emptying of a nonabsorbable marker.

Topics: Adult; Cimetidine; Duodenal Ulcer; Gastric Acid; Gastric Emptying; Gastrins; Guanidines; Histamine H2 Antagonists; Humans; Middle Aged; Polyethylene Glycols; Thiazoles

The clinical and physiological relevance of the relationship between gastrin and calcitonin has been investigated in normal subjects and in patients suffering from gastritis or duodenal ulcer. Basal plasma levels of calcitonin are increased in these patients but there is no significant relationship between calcitonin and gastrin levels. Acute pentagastrin injection in normal male subjects increased significantly (P less than 0.05) plasma calcitonin levels whereas lower doses of pentagastrin which are known to stimulate gastric secretion are without effect on calcitonin levels. Moreover, stimulation of gastrin secretion by a protein test meal and by intragastric administration of a calcium chloride solution is not followed by any significant increase of plasma calcitonin levels. These results suggest that the stimulation of calcitonin secretion by gastrin and its synthetic analogue pentagastrin is a pharmacological rather than a physiological phenomenon.

Topics: Adult; Anemia, Pernicious; Calcitonin; Calcium Chloride; Dietary Proteins; Duodenal Ulcer; Gastrins; Gastritis; Humans; Injections, Intravenous; Male; Pentagastrin

The effect of an intravenous infusion of an aminoacid solution (Aminoplex 14) on gastric secretion is compared in healthy subjects and in duodenal ulcer patients. The acid secretory response was twice as high in duodenal ulcer patients than in normal subjects, 60 minutes after starting the infusion. Serum gastrin levels, although initially higher in duodenal ulcer patients, showed no augmentation throughout the infusion. Blood glucose, serum osmolality and PCV estimations did not alter significantly. Serum aminoacid levels showed a pronounced rise, doubling basal values, and tended to parallel the increase in acid output. Cimetidine, administered orally, suppressed the acid secretory response to intravenous aminoacid. The marked stimulation in acid secretion following aminoacid infusion in duodenal ulcer patients was not elicited after truncal or highly selective vagotomy.

Topics: Adult; Amino Acids; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Middle Aged; Secretory Rate

Basal and meal-stimulated serum gastrin with or without prior intake of 100 mcg 15(R)-15-methyl prostaglandin E2 (PG) in encapsulated form were measured in 40 patients with active duodenal ulcer disease at the start and at the end of a 4 week treatment period with 100 mcg PG q i d or placebo (Pl). Basal serum gastrin levels did not change throughout the study. Neither was there a blunting of the meal-stimulated serum gastrin release by PG as has been previously observed. The enhanced healing rate (68.4% during PG compared to 33.3% during Pl) can therefore not be explained by changes in basal or meal-stimulated serum gastrin.

Topics: Adult; Arbaprostil; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Kinetics; Male; Middle Aged; Placebos; Prostaglandins E, Synthetic

Oral 16,16-dimethyl prostaglandin E2 is a potent inhibitor of meal-stimulated gastric acid secretion and gastrin release in humans. Experiments were performed in 5 patients with inactive duodenal ulcer to determine the effect of graded doses of intravenous 16,16-dimethyl PGE2 on meal-stimulated gastric acid secretion and gastrin release to demonstrate whether it is necessary for 16-16-dimethyl PGE2 to come into direct luminal contact with the oxyntic and antral gland portions of the stomach to produce its inhibitory effects. All doses of 16,16-dimethyl PGE2, between 0.01 and 0.1 microgram/kg i.v. and between 0.01 and 1.0 microgram/kg orally produced significant postprandial inhibitory effects on both gastric acid secretion and gastrin release as compared with saline control. 0.1 microgram/kg of intravenous of 1 microgram/kg of oral 16,16-dimethyl PGE2 inhibited meal-stimulated acid secretion and gastrin by 80-90%. In 6 unoperated Zollinger-Ellison syndrome patients, 1 microgram/kg of oral 16,16-dimethyl PGE2 significantly inhibited fasting gastric acid hypersecretion by approximately 85% without significantly altering serum gastrin. Each of the oral doses of 16,16-dimethyl PGE2 (0.01-1 microgram/kg) were without untoward effect, as were intravenous doses of 0.01-01 microgram/kg. Maximal inhibition of acid secretion was found with 0.1 microgram/kg 16,16-dimethyl PGE2 i.v. as compared with 1.0 microgram/kg orally. Since 16,16-dimethyl PGE2, whether given orally or intravenously, is a potent inhibitor of both gastric acid secretion and meal-stimulated gastrin release, without apparent untoward side effects, clinical trials with 16,16-dimethyl PGE2 are indicated in patients with acid peptic disease.

Topics: 16,16-Dimethylprostaglandin E2; Administration, Oral; Adult; Aged; Duodenal Ulcer; Food; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Prostaglandins E, Synthetic; Zollinger-Ellison Syndrome

Combinations of H2-receptor antagonists and classical anticholinergics inhibit stimulated gastric acid secretion more than either drug alone. In double blind, placebo controlled, randomised studies we have compared the effects of single and combined intravenous bolus injections of cimetidine and pirenzepine on peptone-stimulated acid secretion and serum gastrin in man. Combined injection of 3.0 mg/kg cimetidine and 0.3 mg/kg pirenzepine suppressed stimulated acid secretion significantly more than either drug alone, and by 90% in healthy volunteers (n = 8) and patients with duodenal ulcer (n = 5). Side-effects (prolactin stimulation, blurred vision) were diminished by reducing the combined dosages to 1.5 mg/kg cimetidine, to 0.075 and 0.15 mg/kg pirenzepine in another series (n = 10). Postprandial gastrin was not affected by any combination. Combination of cimetidine and pirenzepine suppress food-stimulated gastric secretion more effectively than combination of H2-blockers with classical anticholinergics. Pirenzepine--unlike classical anticholinergics--may distinguish between different subclasses of muscarinic receptors and have a more selective antimuscarinic action. Its interaction with H2-receptor antagonists on parietal cell function seems to be synergistic. Such a combination could be of advantage in patients with gastrinoma, in patients with ulcers and hypersecretion resistant to single drug treatment, and in critically ill patients as prophylaxis of stress ulcer bleeding.

Topics: Adult; Benzodiazepinones; Cimetidine; Drug Interactions; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Guanidines; Humans; Male; Peptones; Piperazines; Pirenzepine; Prolactin

Serum gastrin increased in patients with pernicious anaemia after a beef-meal, but decreased after an oral load of glucose, xylose or sodium chloride. 50 g of glucose and 25 or 75 g of xylose suppressed serum gastrin to approximately 40% of basal values at 60 min and were slightly more effective than 10 g of sodium chloride. There was no rise in beef-meal stimulated serum gastrin concentration in vagotomized patients and only a slight rise in two patients with duodenal ulcer when an oral dose of 10 g of sodium chloride was given together with the beef-meal. 25 g of xylose suppressed basal serum gastrin concentration significantly in six vagotomized patients. Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in six vagotomized patients. Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in all subjects examined. Further studies indicated, however, that vasopressin was only effective when pharmacological plasma concenten orally and intraduodenally were compared in six patients with pernicious anaemia. Serum gastrin concentration decreased approximately to the same extent in both experiments. It is concluded that the inhibitory effect of glucose on gastrin secretion most likely is mediated hormonally via osmo-receptors located in the small intestine.

Topics: Administration, Intranasal; Administration, Oral; Adult; Aged; Anemia, Pernicious; Dietary Carbohydrates; Dietary Proteins; Duodenal Ulcer; Duodenum; Female; Gastrins; Glucose; Humans; Hypertonic Solutions; Injections; Male; Middle Aged; Sodium Chloride; Vagotomy; Vagus Nerve; Vasopressins; Xylose

Topics: Adolescent; Adult; Clinical Trials as Topic; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Propranolol; Time Factors

Thirty outpatients suffering from duodenal ulcer of recent onset were given cimetidine 1 g/day or gefarnate 250 mg/day for 6 weeks in a double blind trial, randomly balances between the groups. Endoscopic assessment was carried out at 4 and 6 weeks; patients healed after 4 weeks were withdrawn from the trial. In all parameters considered, cimetidine showed a highly significant difference. The healing rate at 4--6 weeks was 67--93% after cimetidine treatment and 27--53% after gefarnate treatment. The effect of cimetidine on the disappearance of symptoms, mainly the nocturnal ulcer pain, and on antacid consumption was greater than that after medication wity gefarnate. After 4--6 weeks of a full dose cimetidine regimen, both basal and pentagastrin stimulated gastric acid secretion were reduced and peptone meal stimulated serum gastrin increased; the basal gastrinaemia remained unchanged.

Topics: Adult; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Gefarnate; Guanidines; Humans; Male; Middle Aged; Terpenes; Time Factors

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.

Topics: Adult; Aged; Atropine; Benzilates; Depression, Chemical; Duodenal Ulcer; Eating; Gastric Juice; Gastrins; Humans; Insulin; Male; Middle Aged; Parasympatholytics; Pentagastrin; Pyrrolidines; Stomach; Vagotomy

The purpose of the present series of tests was to measure and compare the effects of ingestion of gelatin capsules containing 15(R)-15-methyl PGE2 (PG) and/or an anticholinergic drug (methscopolamine bromide, Pamine) on meal-induced gastric acid secretion and serum gastrin level. Eleven duodenal ulcer patients were stimulated by a 5% peptone meal. Acid secretion was determined by the intragastric titration technique, and serum gastrin was measured by radioimmunoassay. The tests were randomized and double-blind. PG alone given 30 min before a test meal at a dose of 50 micrograms or 100 micrograms produced no side effects and inhibited meal-stimulated acid secretion by about 43% and 55%, respectively. Gastric acid inhibition after a single dose of PG was most pronounced in the first hour of a test meal and was accompanied by almost complete suppression of the meal-induced serum gastrin level. Pamine alone in a dose of 2.5 mg reduced gastric acid response to a meal by about 29% but caused a further rise of postprandial serum gastrin level over control values. The combination of PG, 50 micrograms, and Pamine, 2.5 mg, did not result in significantly greater acid inhibition (about 48%) than when either compound was given alone. When the higher dose of PG (100 micrograms) was given together with Pamine (2.5 mg), the degree of inhibition produced by PG alone was not changed. It is concluded that PG given orally in capsules is a potent inhibitor of gastric acid and serum gastrin response to a meal and that this effect may be of potential value in the treatment of peptic ulcer disease.

Topics: Administration, Oral; Adult; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Male; Parasympatholytics; Prostaglandins E, Synthetic; Random Allocation; Scopolamine Derivatives

The authors report the results of a randomized study in which comparison was made between two different kinds of treatment in patients affected by uncomplicated duodenal ulcer endoscopically diagnosed. The first group was treated with 1 g of cimetidine per day, during a period of four weeks (200 mg three times a day and 400 mg at bedtime); the second with a liquid Al-Mg antacid compound, 210 ml/day 30 ml, 1 and 3 hr after meals and 30 ml before bedtime) for four weeks. Fity-one patients were studied, 27 treated with cimetidine, 24 with antacids. At the end of the four-week period, 21 patients (77.7%) in the cimetidine group and 18 patients (75%) in the antacid group were completely healed. Benign side effects were remarked in both types of treatment, none of which made it necessary to suspend treatment. No significant variation of the basal and peak acid output before and after each kind of treatment was observed, while a slight but significant increase in fasting serum gastrin concentration was noted after treatment in the antacid group.

Topics: Adult; Antacids; Blood Cell Count; Cimetidine; Double-Blind Method; Duodenal Ulcer; Evaluation Studies as Topic; Female; Gastric Juice; Gastrins; Guanidines; Humans; Male; Middle Aged; Random Allocation

In a double-blind trial 16 persons with gastric ulcer and 35 with duodenal ulcer were treated as out-patients with 1200 mg proglumide daily or 1320 mg magnesium tricilicate daily (as an "active placebo") for four weeks. The ulcers were assessed by endoscopy before and after treatment. The gastric ulcers disappeared in 75% of patients receiving proglumide (six of eight subjects) but in only 25% of those on the placebo (two of eight). There was no significant effect of proglumide on duodenal ulcers (17 in the proglumide and 18 in the placebo groups). Proglumide failed to affect either basal or maximally stimulated acid secretion, nor was there any change in the serum gastrin level. There were no side effects during proglumide administration. This underlines its therapeutic value in the treatment of gastric ulcer, in comparison with cimetidine or carbenoxolone.

Topics: Adult; Aged; Ambulatory Care; Double-Blind Method; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Gastroscopy; Glutamine; Humans; Male; Middle Aged; Placebos; Proglumide; Stomach Ulcer

Cimetidine inhibits basal and nocturnal acid secretion and acid secretion stimulated by histamine, pentagastrin, caffeine, insulin, sham feeding, and food. Cinetidine (300 mg) inhibits basal acid secretion in duodenal ulcer patients by 95% for at least 5 hr. When taken at bedtime, cimetidine inhibits nocturnal acid secretion by greater than 80% for most of the night. Cimetidine markedly inhibits food-stimulated acid secretion and is more effective than anticholinergic drugs. However, to get adequate suppression of food-stimulated acid secretion throughout the day, cimetidine should be given with each meal. Cimetidine has no effect on nocturnal serum gastrin concentration, but, when stimulated by food, serum gastrin concentration is higher after cimetidine than after placebo.

Topics: Cimetidine; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Glycopyrrolate; Guanidines; Humans; Metiamide; Quaternary Ammonium Compounds; Time Factors

A double-blind trial was carried out in 30 patients with peptic ulcers to assess the effects of treatment with a gastrin-receptor antagonist, proglumide, compared with a histamine H2-blocker, cimetidine. Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide.

Topics: Adult; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Glutamine; Guanidines; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Proglumide; Stomach Ulcer; Time Factors

The behaviour of serum gastrin fasting levels was studied in 39 randomized patients with proven duodenal ulcer, 21 receiving cimetidine (1 g/day) and 18 placebo for 28 days. No significant variations of gastrin fasting values were found, but in four patients given cimetidine a relevant increase was observed at the end of the treatment. One out of 6 patients, previously treated with placebo, showed a marked increase of fasting gastrin levels after a second trial of cimetidine. No increase of G-17 was observed in the patients showing fasting hypergastrinemia after cimetidine. The present study seems to confirm some previous observations and it seems to suggest the possibility that in some patients cimetidine could induce hypergastrinemia.

Topics: Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Fasting; Gastrins; Guanidines; Humans

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.

Topics: Administration, Oral; Adult; Alkalies; Aluminum Hydroxide; Anesthetics, Local; Dietary Proteins; Drinking; Duodenal Ulcer; Ethanolamines; Gastrins; Humans; Magnesium Hydroxide; Meat

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

Topics: Adult; Dose-Response Relationship, Drug; Duodenal Ulcer; Epinephrine; Gastrins; Humans; Male; Middle Aged; Norepinephrine; Secretory Rate; Stimulation, Chemical

Histamine H2-receptor antagonists are potentially useful agents in duodenal ulcer and knowledge of their effect on postprandial digestive events will contribute to their clinical application. We studied the effect of 200- and 300-mg doses of cimetidine, an H2-receptor antagonist, taken with an ordinary meal, on gastric, pancreatic, and biliary function. Both doses significantly reduced acid output and its delivery into the duodenum. Gastric secretory volume and pepsin output were less affected. Acid inhibition was related to blood drug levels and was less than that previously found at night in nocturnal fasting studies. As the stomach emptied the food, the gastric pH rose. The fractional gastric emptying rate, pancreatic enzyme, and bile acid outputs were unaltered. Cimetidine taken orally with meals at these doses is a potent gastric antisecretory agent without affecting other postprandial gastric, pancreatic, or biliary functions.

Topics: Adult; Bile Acids and Salts; Clinical Trials as Topic; Duodenal Ulcer; Eating; Female; Food; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Liver; Male; Middle Aged; Pancreas

Fasting serum gastrins were carried out at the beginning and end of a 6-week double-blind trial of cimetidine and placebo in 30 patients with duodenal ulcer. Cimetidine did not cause any significant change in fasting serum gastrin levels after 6 weeks of therapy.

Topics: Clinical Trials as Topic; Drug Evaluation; Duodenal Ulcer; Gastrins; Guanidines; Histamine H2 Antagonists; Humans; Imidazoles; Placebos; Secretory Rate; Time Factors

Cimetidine markedly inhibits gastric acid secretion, but from the therapeutic point of view it is important to know whether concurrent treatment with an anticholinergic increases its effect. This possibility has been investigated by measuring the 24 h intragastric acidity and nocturnal output of acid in four duodenal ulcer patients, each receiving on separate occasions cimetidine 1 g/day and placebo, atropine 2-4 mg/day and placebo, cimetidine and atropine, or two placebos. Cimetidine alone decreased mean hourly hydrogen ion activity by 63% of control values, decreased mean hourly hydrogen ion concentration (total acid) by 41%, inhibited nocturnal acid secretion by 83% and resulted in half the nocturnal samples being anacidic. Atropine alone had no effect when compared with control and combined treatment with both drugs was not superior to cimetidine alone. Atropine did not affect the absorption or urinary excretion of cimetidine. Fasting serum gastrin concentrations were not changed by any of the treatments. At the doses studied, the combination of cimetidine with an anticholinergic appears to offer no advantages over treatment with the H2-antagonist alone. Cimetidine is the only potent anti-secretory drug that does not cause acute side-effects and this important advantage would be lost if it were given with a maximal dose of an anticholinergic.

Topics: Administration, Oral; Adult; Atropine; Circadian Rhythm; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Guanidines; Humans; Imidazoles; Male; Metiamide

Parietal cell vagotomy has been in clinical use for 7 years in elective treatment of nonobstructive duodenal ulcer, and for even a shorter period for complicated cases and for gastric ulcer The evolution of the surgical technique has not yet come to an end and the ability to perform the procedure is still improving. It can therefore be questioned, if this operation is yet ripe for a realistic clinical trial, and the great variation in recurrence rate reported in pilot series as well as in prospective randomized clinical trials points to the possibility that we will have to wait several years before the anticipated mean recurrence rate is known. At present it can be stated that even if gastric emptying is not quite undisturbed, the addition of a drainage procedure in nonobstructive cases is unnecessary. The same may be true in some patients with pyloric obstruction. Furthermore, the mortality rate is very low and the incidence of moderate-to-severe dumping and diarrhea is virtually nil.

Topics: Animals; Clinical Trials as Topic; Denmark; Diarrhea; Drainage; Dumping Syndrome; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Motility; Humans; Peptic Ulcer; Pilot Projects; Postoperative Complications; Pyloric Stenosis; Recurrence; Stomach; Stomach Ulcer; Vagotomy

We have studied the gastric response to an ordinary solid-liquid meal in 12 patients with active duodenal ulcer and 8 healthy volunteers. Our method employs gastric and duodenal markers to quantify acid, pepsin, and volume outputs in response to the meal, without manipulating intragastric pH. Intragastric volume, rate of gastric emptying, delivery of acid into the duodenum, and serum gastrin response were also measured simultaneously. On a separate day, peak acid output in response to betazole (1.5 mg per kg subcutaneously) was determined. Our results indicate an inappropriately prolonged gastric secretory response to meals in duodenal ulcer disease, without a concomitant increase in peak postprandial secretory rates or an increase in serum immunoreactive gastrin levels. Further, the stomach in duodenal ulcer disease did not "retain" the additional acid secreted in the later postprandial period, and abnormally high rates of acid delivery into the duodenum occurred. Our data are consistent with a dual defect in the duodenal mechanisms regulating both acid secretion and acid delivery into the duodenum.

Topics: Adult; Betazole; Clinical Trials as Topic; Duodenal Ulcer; Female; Food; Gastric Emptying; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pepsin A

The serum gastrin response to Oxo or to a meal was studied in 35 patients with duodenal ulcers and in 28 control subjects. Neither the integrated gastrin response nor the mean peak gastrin concentration was significantly higher in patients with duodenal ulcers compared with the controls, whatever stimulus was used (Oxo or a meal). Atropine 0,5 mg injected intramuscularly half an hour before the meal did not significantly affect the integrated gastrin response or the peak gastrin concentration of controls or of patients with duodenal ulcers. Metoclopramide 10 mg injected intramuscularly half an hour before the meal significantly reduced the integrated gastrin response and, to a lesser degree, the peak gastrin concentration in controls, but it did not affect these variables in patients with duodenal ulcers. The failure to suppress the gastrin response with metoclopramide in patients with duodenal ulcers has not been explained.

Topics: Adult; Atropine; Depression, Chemical; Dietary Proteins; Duodenal Ulcer; Gastrins; Humans; Metoclopramide

Meal-stimulated acid secretion, measured by in vivo intragastric titration, was progressively inhibited by increasing oral doses of cimetidine (25 to 400 mg). Four hundred milligrams suppressed acid secretion by 73% for the first 3 hr after the meal, whereas it inhibited acid secretion by 94% during the 30-min period of maximal inhibition. The dose of cimetidine required to suppress acid secretion by 50% during the 30-min period of maximal inhibition was 25 mg. The duration of action of a 300-mg dose was at least 7 hr. Cimetidine was equally effective in inhibiting meal-stimulated acid secretion at two physiological intragastric pH levels (5.0 and 2.5). Cimetidine had no effect on serum gastrin concentration when intragastric pH was maintained at 5.0, but when pH was allowed to seek its own level, serum gastrin concentration was higher after cimetidine than after placebo. Cimetidine had no effect on gastric emptying. No side effects were noted in any patients.

Topics: Adult; Amino Acids; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Guanidines; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Placebos; Receptors, Drug; Stomach; Time Factors

The mean antral immunoreactive gastrin (IRG) concentration of 38 duodenal ulcer (DU) patients was significantly higher (35-9+/-5-2 mug/g) than that of 21 controls (15-9+/-2-6 mug/g). Also the mean IRG concentration in the proximal duodenal mucosa of 15 DU patients (3-2+/-0-8 mug/g) was higher (but not significantly) than that of 10 controls (1-8+/-0-5 mug/g). The number of G-cells in the antral mucosa of 58 DU patients and in the duodenal mucosa of 29 DU patients was not larger than that of controls. The distribution of immunoreactivity in gastrin components has been investigated in the antral and duodenal mucosa of six DU patients and six controls. In the antral mucosa the mean percentage of G-17 was 93-3% in DU patients and 92-0% in controls. G-34 amounted to 4-0% in DU patients and to 5-0% in controls. The G-34 percentage in the duodenal mucosa was higher (however not significantly) in the DU patients than in the controls (50-1% versus 35-8%). Ultrastructurally, the antral G-cells of DU patients had a significantly lower density index of their secretory granules suggesting higher functional activity. It is concluded that the exaggerated serum IRG response of DU patients to different stimuli is not a consequence of an increased G-cell mass.

Topics: Adult; Aged; Cell Count; Clinical Trials as Topic; Cytoplasmic Granules; Duodenal Ulcer; Duodenum; Female; Gastric Mucosa; Gastrins; Humans; Male; Microscopy, Electron; Middle Aged; Pyloric Antrum; Radioimmunoassay

Topics: Adult; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Pancreatic Juice; Pyloric Antrum; Secretin; Skin Tests; Time Factors

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

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Isoproterenol; Male; Propranolol; Receptors, Adrenergic

The role of gastrin and of serum gastrin analysis in duodenal ulcer disease and duodenal ulcer surgery is analysed. As far as etiology and pathogenesis are concerned up to now gastrin has never been shown to play a significant role. Neither does it provide any diagnostic help in the typical duodenal ulcer disease (but it will allow for diagnosis of the retained antrum after Billroth II resection and of the Zollinger Ellison syndrome). Gastrin determination therefore is not helpful in the choice of the correct operative procedure for the ulcer disease. In today's clinical practice its major role consists in the control of surgical results. This is illustrated by a prospective randomized study on proximal selective vagotomy with and without pyloroplasty. In these patients serum gastrin analysis has shown that the omission of pyloroplasty is not followed by antral stasis. It furthermore always exhibits the typicel vagotomy profile, although vagotomy is incomplete in the 2-DODG-test.

Topics: Duodenal Ulcer; Gastrins; Humans; Male; Pylorus; Vagotomy

50 consecutive male patients with a proven duodenal ulcer disease without pyloric stenosis were electively treated with a proximal selective vagotomy. They were randomized in a group with and a group without pyloroplast. Up to now (1-3 years follow-up) no recurrences were found, and only two patients have major complaints (Visich grading 3). There are no differences between the two groups, as judged by the clinical result, the pentagastrin test, the Hollander test (2-DODG stimulation), and the gastrin analysis. Pyloroplasty therefore is not needed. Although the vagotomy which completely preserves antral motility is mostly incomplete in the Hollander test, it is sufficient as judged by the clinical results and the acid response.

Topics: Adult; Aged; Duodenal Ulcer; Follow-Up Studies; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Pylorus; Vagotomy

The effects of two dose regimens of cimetidine on 24 h intragastric acidity were investigated in six patients with duodenal ulcer. They received placebo capsules on the first day and cimetidine on the second day. Cimetidine 0-8 g/day decreased 24 h mean H+ activity by 55% but 1-6 g/day decreased it by 67%, the difference being due to a greater nocturnal decrease in the high-dose group. Intragastric pH remained below 2-0 for much of the treatment day but similar values were found in four post-vagotomy patients. Cimetidine 0-8-1-6 g/day results in a decrease of intragastric acidity that is compatible with successful medical treatment of duodenal ulceration.

Topics: Circadian Rhythm; Duodenal Ulcer; Fasting; Gastric Acidity Determination; Gastric Juice; Gastrins; Guanidines; Histamine H1 Antagonists; Humans; Hydrogen-Ion Concentration; Imidazoles; Male; Placebos; Vagotomy

The purpose of the present series of experiments was to measure and compare the effects of an anticholinergic drug (isopropamide) and an antagonist of the histamine H2 receptor (metiamide) on food-stimulated acid secretion. Patients with duodenal ulcers were stimulated by a steak meal, and acid secretion was measured by in vivo intragastric titration. The largest dose of isopropamide that can be taken clinically without producing intolerable side effects (maximum tolerated dose) suppressed food-stimulated acid secretion by 35%. By contrast, metiamide in a 400-mg dose produced no side effects and almost completely abolished food-stimulated acid secretion. A dose-response curve revealed that a 50-mg dose of metiamide was required to suppress food-stimulated acid secretion by 50%. Further studies showed that metiamide and isopropamide are additive in suppressing food-stimulated acid secretion, and that metiamide has no effect on serum gastrin concentration or on gastric emptying.

Topics: Adult; Clinical Trials as Topic; Drug Therapy, Combination; Duodenal Ulcer; Female; Food; Gastric Juice; Gastrins; Gastrointestinal Motility; Histamine; Humans; Imidazoles; Male; Middle Aged; Placebos; Quaternary Ammonium Compounds; Receptors, Drug; Stomach; Sulfides; Thiourea

Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer. Oral doses of 100, 200, and 300 mg were tested. Each dose significantly inhibited basal and meal-stimulated secretion. After 300 mg, basal acid secretion was essentially zero for at least five hours. The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01). Cimetidine did not affect meal-stimulated gastrin release. No toxicity was observed after serial doses given during these tests. Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing.

Topics: Administration, Oral; Adult; Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Eating; Gastric Juice; Gastrins; Guanidines; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Propantheline; Time Factors

The results of highly selective vagotomy without drainage and selective vagotomy with pyloroplasty for duodenal ulcer were compared in a randomized, controlled trial of a series of 100 patients. The frequency of dumping, diarrhoea, and epigastric fullness was significantly lower after highly selective (6, 6, and 8 percent) than after selective vagotomy (30, 20, and 28 percent) one year after the operations. Recurrent and persisting duodenal ulcers appearing from one to four years after the operations were significantly more frequent after highly selective (22 percent) than after selective vagotomy (8 percent). No significant relationships were found between recurrent ulceration and gastric acid secretion measurements after the two operations. The Hollander response was early positive in 28 percent and late positive in 30 percent of the patients subjected to highly selective vagotomy, while the corresponding figures after selective vagotomy were 26 and 32 percent. The overall clinical results of the two operations were not different according to the classification of Visick. Excluding the patients with recurrence resulted in significantly better clinical results after highly selective vagotomy.

Topics: Adult; Clinical Trials as Topic; Diarrhea; Duodenal Ulcer; Female; Follow-Up Studies; Gastric Juice; Gastrins; Histamine; Humans; Insulin; Male; Middle Aged; Postoperative Complications; Pylorus; Recurrence; Vagotomy

This is a report of a prospective randomized study of 3 operations for duodenal ulcer; parietal-cell vagotomy alone (without drainage), selective vagotomy with antrectomy, and truncal vagotomy with antrectomy. All patients in the study have been followed for a minimum of 1 yr and despite the small number of patients (total 23 in this report), there has been a statistically significant return of gastric secretory activity to preoperative levels in the parietal cell vagotomy group, while both other groups maintained decreased acid secretion at the 1-yr period. To date there has been one recurrent ulcer and one other suspected ulcer in the parietal cell vagotomy group, while both other groups have no ulcer recurrence even though morbidity has been higher (bile reflux gastritis, and so forth). This preliminary evaluation suggests strongly that extreme caution be used in applying parietal-cell vagotomy alone as a definite operation for duodenal ulcer, but because of the small number of patients involved no conclusions can be drawn at this time.

Topics: Duodenal Ulcer; Follow-Up Studies; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Prospective Studies; Pyloric Antrum; Recurrence; Stomach; Vagotomy

Topics: Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Gastrins; Histamine H1 Antagonists; Humans; Imidazoles; Male; Middle Aged; Peptones; Receptors, Drug; Sulfides; Thiourea

Topics: Blood Glucose; Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Placebos; Propranolol; Stimulation, Chemical; Stomach Ulcer; Vagotomy

Topics: Blood Glucose; Clinical Trials as Topic; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Infusions, Parenteral; Injections, Intravenous; Insulin; Radioimmunoassay; Vagotomy

Topics: Adolescent; Adult; Aged; Benzamides; Clinical Trials as Topic; Drug Evaluation; Duodenal Ulcer; Female; Gastrins; Gastritis; Gastrointestinal Agents; Glutarates; Humans; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer

Ninety patients with duodenal ulcer, divided randomly into three groups, were treated continuously for one year with either glycopyrronium, 1-hyoscyamine (as a sustained-release preparation) or inert tablets. Dosage with active tablets was so adjusted that the patient experienced definite but tolerable side-effects. Basal and maximal gastric acid secretion were measured immediately before and one week after cessation of treatment. There was no significant change in the means of these measurements in patients who received placebo or 1-hyoscyamine. In those given glycopyrronium, mean basal output was significantly increased. Mean maximal acid output in this group fell, but not significantly.Individual measurements of maximal acid output showed quite marked fluctuations in all groups. It is concluded that spontaneous changes in parietal cell mass may occur in patients with duodenal ulcer, and that prolonged anticholinergic therapy does not reduce parietal cell mass.

Topics: Atropa belladonna; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Male; Mandelic Acids; Parasympatholytics; Phytotherapy; Placebos; Plants, Medicinal; Plants, Toxic; Pyrrolidines; Secretory Rate; Statistics as Topic

Topics: Absorption; Adult; Dosage Forms; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Mouth Mucosa; Pepsin A; Peptides; Stomach Ulcer

Topics: Adult; Clinical Trials as Topic; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Diseases; Histamine; Humans; Methods; Middle Aged; Stimulation, Chemical; Stomach Ulcer

Topics: Adult; Atropine; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Hexamethonium Compounds; Histamine; Humans; Infusions, Parenteral; Intubation, Gastrointestinal; Middle Aged; Vagotomy

Topics: Adult; Aged; Anemia, Pernicious; Carcinoma; Clinical Trials as Topic; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Hernia, Diaphragmatic; Histamine; Humans; Male; Middle Aged; Secretory Rate; Stomach; Stomach Neoplasms; Stomach Ulcer

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Topics: Duodenal Ulcer; Epidermal Growth Factor; Gastrins; Gastrointestinal Hemorrhage; Humans; Stomach Ulcer

Zollinger-Ellison syndrome is a rare cause of tumoral hypergastrinemia; 1 of 5 patients with this syndrome also has multiple endocrine neoplasia type 1. The diagnosis of this disease is complicated by the widespread use of proton pump inhibitors that can elevate serum gastrin levels, the cornerstone for biochemical diagnosis. Abrupt discontinuation of proton pump inhibitors could lead to adverse outcomes. Clinician awareness of the relationship between Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 could lead to a safer diagnostic pathway.. We conducted a retrospective review of a cohort of patients with multiple endocrine neoplasia type 1.. There were 287 patients with multiple endocrine neoplasia type 1 (73 with gastrinoma) evaluated between 1997 and 2014. Two patients experienced adverse events after proton pump inhibitor therapy was discontinued to re-measure serum gastrin level during the evaluation of severe peptic ulcer disease. In both cases, the diagnosis of multiple endocrine neoplasia type 1 was made after proton pump therapy was discontinued.. Abrupt discontinuation of proton pump therapy can lead to adverse outcomes in patients with Zollinger-Ellison syndrome. Clinical assessment for features of multiple endocrine neoplasia type 1 (eg, serum calcium levels, personal and family history of hypercalcemia, pituitary or pancreatic tumors) could identify patients with higher risk for a tumoral source of hypergastrinemia where imaging studies can help support the diagnosis without the potential side effects of abrupt discontinuation of proton pump inhibitor therapy.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Proton Pump Inhibitors; Retrospective Studies; Withholding Treatment; Zollinger-Ellison Syndrome

Vagotomy causes inhibition of basal and post-prandial acid secretion in humans, but the knowledge about the trophic effect of the vagal nerves is limited. Vagotomy is known to induce hypergastrinemia and we aimed to study the long-term effects of proximal gastric vagotomy (PGV) on the oxyntic mucosa and the enterochromaffin-like (ECL) cell density in particular.. Eleven patients operated with PGV because of duodenal ulcer and age- and sex-matched controls were examined 26 to 29 years postoperatively by gastroscopy with biopsies from the antrum and oxyntic mucosa. Neuroendocrine cell volume densities were calculated after immunohistochemical labeling of gastrin, the general neuroendocrine cell marker chromogranin A (CgA) and the ECL cell marker vesicular monoamine transporter 2 (VMAT2). Gastritis was graded and Helicobacter pylori (H. pylori) status was determined by polymerase chain reaction of gastric biopsies. Fasting serum gastrin and CgA were measured.. Serum gastrin was higher in the PGV group compared to controls (median 21.0 [interquartile range (IQR) = 22.0] pmol/L vs 13.0 [IQR = 4.0] pmol/L, p = 0.04). However, there was neither a significant difference in serum CgA or in CgA (neuroendocrine) nor VMAT2 (ECL cell) immunoreactive cell volume density in the oxyntic mucosa. There was significantly more inflammation and atrophy in H. pylori-positive patients, but PGV did not influence the grade of gastritis.. Despite higher serum gastrin concentrations, patients operated with PGV did not have higher ECL cell mass or serum CgA. Vagotomy may prevent the development of ECL cell hyperplasia caused by a moderate hypergastrinemia.

Topics: Aged; Biopsy; Chromogranin A; Duodenal Ulcer; Enterochromaffin-like Cells; Female; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Time Factors; Vagotomy, Proximal Gastric; Vesicular Monoamine Transport Proteins

Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol-derived H(2)O(2) reaction. Cochinchina momordica saponins have been suggested to be protective against various gastric diseases based on their cytoprotective and anti-inflammatory mechanisms. This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine-induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms.. Cochinchina momordica seed extract (50, 100, 200 mg/kg) was administrated intragastrically before cysteamine administration, after which the incidence of the duodenal ulcer, ulcer size, serum gastrin level, and the ratio of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) as well as biochemical and molecular measurements of cytoplasmic phospholipase A(2) (cPLA(2)), cyclooxygenase-2 (COX-2), 5-lipoxygenase and the expression of proinflammatory genes including IL-1β, IL-6, COX-2 were measured in rat model. Additional experiments of electron spin resonance measurement and the changes of glutathione were performed.. Cochinchina momordica seed extract effectively prevented cysteamine-induced duodenal ulcer in a dose-dependent manner as reflected with significant decreases in either duodenal ulcerogenesis or perforation accompanied with significantly decreased in serum gastrin in addition to inflammatory mediators including cPLA(2), COX-2, and 5-lipoxygenase. Cochinchina momordica seed extract induced the expression of γ-glutamylcysteine synthetase (γ-GCS)-related glutathione synthesis as well as significantly reduced the expression of cPLA(2). Cochinchina momordica seed extract preserved reduced glutathione through increased expressions of γ-GCS.. Cochinchina momordica seed extracts exerted significantly protective effect against cysteamine-induced duodenal ulcer by either cPLA2 inhibition or glutathione preservation.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Arachidonate 5-Lipoxygenase; Cell Line; Cyclooxygenase 2; Cysteamine; Disease Models, Animal; Dose-Response Relationship, Drug; Duodenal Ulcer; Duodenum; Enzyme Activation; Enzyme Activators; Gastrins; Glutamate-Cysteine Ligase; Glutathione; Inflammation Mediators; Intestinal Mucosa; Lipoxygenase Inhibitors; Male; Momordica; Oxidation-Reduction; Oxidative Stress; Phospholipases A2, Cytosolic; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Time Factors

We aimed to determine the etiology of patients with duodenal and gastric ulcers.. 140 patients diagnosed with peptic ulcer between April 2002-2009 were enrolled in this prospective study. Two biopsy specimens were collected from the antrum and corpus for histology and one for rapid urease testing, and stool samples were analyzed for Helicobacter pylori antigen. Serum calcium and gastrin levels were also analyzed.. 82 (58%) patients were male, with a median age of 47.70±15.03 years (range: 16-92). The ulcer was located in the duodenum in 96 patients, stomach in 40, and both duodenum and stomach in 4. The rates of patients positive for Helicobacter pylori antigen in stool, positive in urease testing and positive for Helicobacter pylori presence in antral and corpus samples were 48%, 52%, 67%, and 60%, respectively. 107 (76%) patients were positive for Helicobacter pylori in one of the test methods. 64 (46%) patients had a history of nonsteroidal antiinflammatory drug use within the last month. Mean levels of calcium and gastrin were 9.29±0.40 (7.90-10.20) and 73.96±89.88 (12.86-562.50), respectively. Gastrin level was correlated to inflammatory activity (p<0.05). 19 (13.6%) of the patients were negative for Helicobacter pylori, nonsteroidal anti- inflammatory drug use and hypersecretory illness, and were classified as idiopathic.. The most common cause of duodenal and gastric ulcer was Helicobacter pylori, and it was responsible for three-fourths of the cases. About half of the patients had a history of nonsteroidal antiinflammatory drug use, and nonsteroidal antiinflammatory drug and Helicobacter pylori were both responsible for the ulcer in three-fourths of these patients. In about one-tenth of the patients, nonsteroidal antiinflammatory drug use was the cause of ulcer alone, and about one-tenth of the ulcers were classified as idiopathic.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Bacterial; Calcium; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Stomach Ulcer; Urease; Young Adult

Phytochemical investigation of Annona squamosa twigs, resulted in isolation and identification of twelve known (1-12) compounds among them one 1-(4-β-D-glucopyranosyloxyphenyl)-2-(β-D-glucopyranosyloxy)-ethane (11) is synthetically known but first time isolated from natural sources. Their structures were elucidated using 1D and 2D NMR spectroscopic analysis. The isolated compounds (2-8, 11) were evaluated for H(+) K(+)-ATPase activity. Three of these compounds (+)-O-methylarmepavine (2), N-methylcorydaldine (3), isocorydine (6) showed promising anti-secretory activity. Activity of these compounds, comparable to the standard drug omeprazole is novel to our finding. Moreover, there is no information accessible regarding the pharmacological effect of A. squamosa on the gastrointestinal system. This study is the first of its kind to show the significant anti-ulcer effect of A. squamosa. The present study aimed to evaluate the gastroprotective effect of A. squamosa (AS) and to identify its active constituents. Anti-ulcer activity was evaluated against cold restraint (CRU), pyloric ligation (PL), aspirin (ASP), alcohol (AL) induced gastric ulcer and histamine (HA) induced duodenal ulcer model and further confirmed through in vitro assay of H(+) K(+)-ATPase activity and plasma gastrin level. AS and its chloroform and hexane fraction attenuated ulcer formation in CRU, PL, HA model and displayed anti-secretory activity in vivo through reduced free, total acidity and pepsin in PL, confirmed by in vitro inhibition of H(+) K(+)-ATPase activity with corresponding decrease in plasma gastrin level. Cytoprotection of AS was apparent with protection in AL, ASP models and enhanced mucin level in PL.

Topics: Animals; Annona; Anti-Ulcer Agents; Aporphines; Aspirin; Benzylisoquinolines; Berberine Alkaloids; Cold Temperature; Dinoprostone; Disaccharides; Drug Evaluation, Preclinical; Duodenal Ulcer; Ethanol; Gastric Juice; Gastrins; Guinea Pigs; H(+)-K(+)-Exchanging ATPase; Histamine; Ligation; Omeprazole; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Physiological

To investigate the association between the gastric emptying rate and the presence of erosive esophagitis in duodenal ulcer (DU) patients among a population with high prevalence of Helicobacter pylori infection.. Cross-sectional survey was performed in a cohort of 60 male patients with either active or healed DU, with or without the presence of erosive esophagitis. Clinical and social-demographic data, blood level of fasting gastrin, pepsinogen I & I/II ratio, and scintigraphic measurement of half emptying time (t(1/2) ) of the solid phase gastric emptying were evaluated.. Patients with active DU and erosive esophagitis tended to have higher plasma level of fasting gastrin than those without erosive esophagitis (75.11±13.74 vs 45.81±5.06pgmL(-1) , P = 0.059). In the absence of H. pylori infection, patients with healed DU and erosive esophagitis had a trend to have longer half-emptying time (t(1/2) : 96.5±6.4 vs 69.1±11.3min, P=0.0572) than those without erosive esophagitis, and statistically significant longer after excluding those diagnosed with hiatal hernia (t(1/2) : 100.8±7.9min vs 69.1±11.3min, P<0.05) from the former group. Among the healed DU patients, those with negative H. pylori infection, hiatal hernia and overweight (body mass index ≥24) had significantly increased risk of severe esophagitis.. Presence of erosive esophagitis in a subset of Taiwanese patients with healed DU and negative H. pylori status was associated with slower solid phase gastric emptying.

Topics: Adult; Cross-Sectional Studies; Duodenal Ulcer; Esophagitis, Peptic; Gastric Emptying; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Taiwan

to study the specific features of working conditions in workers from the chemical plants manufacturing nitrogen compounds by the groups under study and by the time course of changes in the serum levels of gastrin-17 (G-17) and pepsinogen-1 (P-1) in relation to the chemical composition of noxious substances, the length of service, the stage of the disease, and the performed therapy.. A test GastroPanel was used to study the serum levels of G-17 and P-1 in 54 patients with duodenal peptic ulcer (DPU) who worked at the chemical plants manufacturing nitrogen compounds (a study group) and in 15 healthy individuals (a control group).. The objective data on the time course of changes in the functional characteristics (G-17 and P-1) of the gastric mucosa (GM) in patients with DPU vary with the chemical composition of noxious substances and the length of service in chemical industry. The basic therapy for PDU contributes to a positive change in the functional parameters reflecting the state of GM.. In patients with DPU, the working conditions at the chemical plants manufacturing nitrogen compounds result in changes in the functional parameters reflecting the state of GM

Topics: Adult; Biomarkers; Chemical Industry; Diagnostic Techniques, Digestive System; Duodenal Ulcer; Endoscopy, Gastrointestinal; Follow-Up Studies; Gastric Mucosa; Gastrins; Humans; Male; Nitrogen Compounds; Occupational Diseases; Occupational Exposure; Pepsinogen A; Prognosis; Retrospective Studies; Siberia

A 26-year-old man was admitted to hospital with a 6-month history of diarrhea and abdominal pain. Before admission, upper and lower gastrointestinal endoscopy had shown a mild erosive duodenitis and the patient was started on a proton pump inhibitor. Physical examination and laboratory tests on admission were not constructive. In addition, repeated gastrointestinal endoscopy, cross-sectional imaging and neuroendocrine markers did not point to a specific etiology. Therefore, as a provocation test, the proton pump inhibitor therapy was discontinued. Discontinuation resulted in a progression of the patient's symptoms and an endoscopic detection of duodenal ulcers. Except for the normal serum gastrin levels, this constellation was suggestive of a gastrinoma, so that further investigations were initiated. Subsequently, the diagnosis could be confirmed and the gastrinoma located. After successful pancreaticoduodenectomy, the patient was symptom-free.. As part of a systematic investigation on chronic diarrhea, the work-up for neuroendocrine causes can play an important role. In this context, it should be kept in mind that some gastrinoma patients present without an elevation of serum gastrin levels. Regardless of a negative gastrin test, a typical symptom constellation should therefore prompt further investigations.

Topics: Abdominal Pain; Adult; Chronic Disease; Diagnosis, Differential; Diarrhea; Duodenal Ulcer; Duodenitis; Follow-Up Studies; Gastrinoma; Gastrins; Gastroscopy; Humans; Lymphatic Metastasis; Male; Pancreatic Neoplasms; Pancreaticoduodenectomy

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Prevalence; Wound Healing

The levels of serum gastrin-17 (G-17) and pepsinogen-1 (P-1) were studied in 54 patients with duodenal ulcerative disease (UD) who worked at chemical plants manufacturing nitrogenous compounds and in 15 healthy individuals (a control group). There are objective data on the time course of changes in the functional characteristics (G-17 and P-1) of the gastric mucosa (GM) in the patients with duodenal UD, which vary with the chemical compositions of hazardous substances and the length of service at a chemical plant. Basic therapy for UD causes positive changes in the functional parameters reflecting the state of GM.

Topics: Adult; Chemical Industry; Duodenal Ulcer; Gastrins; Humans; Male; Middle Aged; Nitro Compounds; Occupational Exposure; Pepsinogen A

Morphofunctional state of gastric mucous tunic and neuroendocrine cells, and clinical indices at various stages of gastric and duodenal ulcer disease was studied. It was shown, that in clinico-endoscopic remission stage of disease intensity of pathogenetic mechanisms of some neuroimmune-endocrine and clinical indices remained.

Topics: Adult; Biomarkers; Disease Progression; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Prognosis; Quality of Life; Serotonin; Severity of Illness Index; Somatostatin; Stomach Ulcer

Topics: Aged; Biomarkers; Biopsy; Diagnosis, Differential; Duodenal Ulcer; Duodenitis; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastrins; Humans; Intestinal Mucosa; Risk Factors

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Pyloric Antrum; Retrospective Studies; Stomach Neoplasms; Stomach Ulcer

To study the expressions of gastrin (GAS) and somatostatin (SS) in gastric antrum tissues of children with chronic gastritis and duodenal ulcer and their role in pathogenic mechanism.. Specimens of gastric antrum mucosa from 83 children were retrospectively analyzed. Expressions of GAS and SS in gastric antrum tissues were assayed by the immunohistochemical En Vision method.. The expressions of GAS in chronic gastritis Hp+ group (group A), chronic gastritis Hp-group (group B), the duodenal ulcer Hp+group (group C), duodenal ulcer Hp-group (group D), and normal control group (group E) were 28.50+4.55, 19.60+2.49, 22.69+2.71, 25.33+4.76, and 18.80+2.36, respectively. The value in groups A-D was higher than that in group E. The difference was not statistically significant. The expressions of SS in groups A-E were 15.47+1.44, 17.29+2.04, 15.30+1.38, 13.11+0.93 and 12.14+1.68, respectively. The value in groups A-D was higher than that in group E. The difference was also not statistically significant.. The expressions of GAS and SS are increased in children with chronic gastritis and duodenal ulcer.

Topics: Child; Chronic Disease; Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum; Retrospective Studies; Somatostatin

To study trends in morphological changes of gastric mucosa (GM) and its functional characteristics (serum gastrin-17, pepsinogens I and II) in eradication of Helicobacter pylori (HP) in patients with duodenal ulcer (DU).. HP infection was detected with a rapid urease test, morphological study of gastrobiopsies and polymerase chain reaction in 59 patients with DU. The results of HP eradication were assessed two months after the treatment. Morphological study of gastrobiopsies, assays for gastrin-17, pepsinogens I and II in blood serum were made before the treatment and one year after HP eradication.. By the results of eradication two groups were formed: with effective eradication and uneffective eradication of H. pylori. Examination of GM one year after successful H. pylori eradication in DU patients GM inflammation relieved: reduction in polymorphonuclear (by 42.6%), mononuclear (by 29.3%) infiltration and number of lymphocytic follicules (16.8-fold). GM atrophy decreased by 47.8%. In patients with uneffective eradication the above positive changes were not registered. After H. pylori eradication, serum gastrin-17 lowered by 46. 7%, pepsinogen I--by 30.5%, pepsinogen II--by 36.9%. In uneffective eradication this decrease did not occur.. H. pylori eradication leads to positive changes in morphological and functional indices reflecting GM condition.

Topics: Adult; Anti-Bacterial Agents; Biomarkers; Biopsy; DNA, Bacterial; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Pepsinogen A; Pepsinogen C; Polymerase Chain Reaction; Treatment Outcome

Since application of pediatric gastroscopy in the mid-nineteen nineties, there has been a trend that the prevalence rates of pediatric gastritis and duodenal ulcer (DU) are increasing. The diagnosed rate of pediatric gastritis has accounted for 85% - 95% of the total number of children who received gastroscopy, and the rate of DU accounted for 8% - 22%. Such a high rates of the diseases may influence the development of the children severely. However, the etiology and pathogenesis of pediatric chronic gastritis and DU have not been completely elucidated. The disordered gastrointestinal hormones play a crucial role in the pediatric chronic gastritis and DU. This study focused on the expression of gastrin (GAS), somatostatin (SS) in the mucosa of gastric antrum and PCNA and Fas-L in the sinus ventriculi and their possible roles in the pathogenesis of pediatric chronic gastritis and DU.. The sinus ventriculi mucosal samples of 83 cases were collected via gastroscopic biopsy from the hospital during the recent two years and the cases were divided into five groups: group A, chronic superficial gastritis, Helicobacter pylori (Hp)(+); group B, chronic superficial gastritis, Hp(-); group C, DU, Hp(+); Group D, DU, Hp(-); Group E, normal sinus ventriculi mucosa, Hp(-). Immunohistochemical staining (En Vision) was carried out for GAS, SS, PCNA and Fas-L, and positive cells of each slide were counted (x 400). Statistically significant differences among groups for continuous data were assessed with the software SPSS10.0.. The expressions of GAS and SS in the groups A through E had no significant difference. The expression of PCNA in group A was significantly higher than that in group B (P < 0.05), and no significant differences were found among the other groups. There were no significant differences in expressions of Fas-L among the five groups.. There seems to be an increasing tendency in the expressions of GAS and SS in children with chronic gastritis and duodenal ulcer. Hp infection promotes the multiplication of the sinus ventriculi mucosal epithelium cells in the pediatric chronic gastritis.

Topics: Adolescent; Biopsy; Child; Child, Preschool; Duodenal Ulcer; Fas Ligand Protein; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Proliferating Cell Nuclear Antigen; Pyloric Antrum; Somatostatin

Patients with the Zollinger-Ellison syndrome are characterized by islet-cell tumors, striking gastric acid hypersecretion, and peptic ulcer disease. They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences. It is a rare syndrome caused by non-beta cell islet-cell tumors (gastrinomas) located in or in proximity to the pancreas. These tumors freely secrete gastrin, a peptide hormone that serves as a powerful stimulant of gastric acid secretion. Exuberant secretion of gastrin from the gastrinomas produces severe gastric acid hypersecretion that often leads to impressive peptic ulcer disease and the constellation of symptoms listed above. We describe a patient presenting with clinical manifestations characteristic of the ZES with strikingly elevated gastric acid secretion,multiple ulcers in the first and second portions of the duodenum and diarrhea, but in absence of islet-cell tumor and/or hypergastrinemia.

Topics: Adenoma, Islet Cell; Diarrhea; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Phenotype; Zollinger-Ellison Syndrome

Helicobacter pylori (H. pylori) infection induces both gastric (GU) and duodenal ulcers (DU). We examined whether host immunological response to H. pylori determines different disease outcomes.. Thirty-two GU and 28 DU patients infected with H. pylori, and 24 dyspeptic patients without infection were enrolled. The constituents of cellular infiltrates in biopsies from each patient were determined and lymphokines secreted by stimulated T cells were measured. Serum concentrations of IgG subclasses specific to H. pylori were measured.. Low pepsinogen I and high pepsinogen II levels were observed in GU patients, while a high pepsinogen I level was found in DU patients. T cells predominate over other cell types in both GU and DU patients. GU patients had a higher number of T cells (p < 0.01) and lower plasma cells (p < 0.05) than those in DU patients. T cells from GU patients produced greater amounts of IFN-gamma and less IL-4 than those in DU patients (p < 0.01). GU patients had a higher serum level of IgG2 specific to H. pylori than that in DU patients (p < 0.01).. Th response by gastric T cells in GU patient was more polarized to Th1 as compared with that in DU patients, suggesting that a distinct immune response to H. pylori induces different disease outcomes.

Topics: Adult; Cohort Studies; Cytokines; Disease Progression; Duodenal Ulcer; Female; Flow Cytometry; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Intestinal Mucosa; Male; Middle Aged; Pepsinogen A; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Stomach Ulcer; T-Lymphocyte Subsets

Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients.. Thirty-six children aged 10-17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2-3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication.. H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori-positive patients with duodenal ulcer than in gastritis-only patients or controls [mean +/- standard error (SE): 6.56 +/- 1.4, 3.11 +/- 0.4 and 2.65 +/- 0.2 mEq/10 minutes, respectively; p <.001]. Stimulated acid secretion was higher in H. pylori-positive boys than girls (5.0 +/- 0.8 vs. 2.51 +/- 0.4 mEq/10 minutes, respectively; p <.05). Stimulated acid secretion pre- and post-H. pylori eradication was similar (5.47 +/- 0.8 vs. 4.67 +/- 0.9 mEq/10 minutes, respectively; p =.21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p <.001 and peak from 544 to 133 pg/ml, p <.05).. H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.

Topics: Adolescent; Biopsy; Breath Tests; Child; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Urea; Urease

The effects of a new benzimidazole derivative, ME3407 (n-butyl-2-(thiazolo-[5,4-b]pyrid-2-yl) sulfinylacetate, CAS 133903-90-9), on gastric acid secretion and gastric and duodenal ulcers in rats were examined. ME3407, given orally, inhibited dose-dependently (0.3-30 mg/kg) the incidence of gastric lesions such as Shay ulcers, and water-immersion stress-, acetylsalicylic acid (ASA)- and histamine-induced erosions. In addition, ME3407 showed marked therapeutic effect on HCl- and ASA-induced lesions. In the lumen-perfused rats, oral administration of ME3407 inhibited dose-dependently (1-100 mg/kg) gastric acid secretion induced by histamine and tetragastrin with ED50 values of 3.02 and 3.37 mg/kg, respectively. Oral administration of ME3407 at a dose of 30 mg/kg also inhibited the elevation of serum gastrin level. The development of duodenal ulcers caused by mepirizole and systeamine was also potently inhibited by ME3407 at an oral dose of 0.1-30 mg/kg. However, when given at 30 mg/kg intraduodenally, subcutaneously or intravenously, ME3407 did not inhibit these acutely induced gastric elosion and acid output. ME3407 was not detected in the serum upon oral administration. These results indicated that ME3407 was active only by oral administration, and exerts direct action on the ulcers and acid secretion from the gastric membrane.

Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Aspirin; Benzimidazoles; Cysteamine; Duodenal Ulcer; Epirizole; Gastric Acid; Gastric Fistula; Gastric Mucosa; Gastrins; Histamine; Immersion; Indomethacin; Male; Pepsin A; Pylorus; Pyridines; Rats; Stomach Ulcer; Thiazoles

The prevalence of duodenal ulcer (DU) in adult patients with portal hypertension is higher than in patients without portal hypertension. This study investigates the prevalence and characteristics of DU in children with portal hypertension.. From January 1997 to December 2001, 80 children with portal hypertension who had undergone upper intestinal endoscopic examinations were enrolled. Possible factors contributing to the development of DU including severity of liver disease, portal hypertension, H. pylori, and serum gastrin level were studied. The control group consisted of 80 age-and sex-matched children with gastrointestinal symptoms but no liver disease and who underwent endoscopic examination during the same period.. The prevalence of DU was significantly higher in children with portal hypertension than in children with digestive symptoms only (22.5%v 8.8%; P =0.017). DU was more common and appeared earlier in children with a history of variceal bleeding. The presence of DU was independent of the severity of liver disease, H. pylori infection and serum gastrin level.. DU occurs commonly in children with portal hypertension, especially in those who have had variceal bleeding. It is mandatory to screen a patient with gastrointestinal bleeding for DU even in the presence of esophageal varices. Elevated portal pressure might be a factor contributing to the development of DU.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Duodenal Ulcer; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hypertension, Portal; Infant; Male; Prevalence

The aim of this study was to clarify the pathogenesis of Helicobacter pylori-negative duodenal ulcer (DU) by investigating the meal-stimulated serum gastrin (SG) response. The subjects were 9 patients with H. pylori-negative DU, 28 H. pylori-positive DU, 11 H. pylori-positive volunteers, and 30 H. pylori-negative volunteers. Blood samples were taken before and after consumption of a test meal. The integrated 1-hr gastrin response (IGR) was taken to be the area under the SG time curve, calculated by the trapezoid method. H. pylori infection status was determined by histology, serology, and the [13C] urea breath test. The mean basal SG concentration was lower in the H. pylori-negative DU patients than in the H. pylori-positive DU patients, but an exaggerated IGR was observed in three patients (33.3%) with H. pylori-negative DU. In conclusion, our findings indicate that an exaggerated meal-stimulated gastrin response may contribute to the pathogenesis of H. pylori-negative DU.

Topics: Adolescent; Adult; Breath Tests; Duodenal Ulcer; Duodenoscopy; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Postprandial Period; Risk Factors

Topics: Adolescent; Biopsy; Diagnosis, Differential; Duodenal Ulcer; Endoscopy, Gastrointestinal; Gastrinoma; Gastrins; Hepatectomy; Humans; Liver; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Pancreatectomy; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Reoperation; Splenectomy

Gastrointestinal bleeding caused by peptic ulcer disease is one of the serious complications of living-related liver transplantation (LRLT). The aim of this study was to clarify the factors involved in peptic ulcer formation in adult LRLT recipients. Forty consecutive adult LRLT recipients without a history of peptic ulcer disease were studied. Twenty-five patients (62.5%) tested positive for Helicobacter pylori. After LRLT, duodenal ulcer (DU) developed in six patients, and all of them tested positive for H. pylori. In contrast, none of the H. pylori-negative patients developed DU. Preoperative serum gastrin levels in patients with DU were significantly higher than in those without DU, irrespective of H. pylori infection. Preoperative pepsinogen I levels in patients with DU were significantly higher than in those without DU with H. pylori infection. These data suggest involvement of H. pylori infection in the development of DU after LRLT. Eradication of H. pylori may prevent the development of DU after LRLT particularly in patients with hypergastrinemia and high serum pepsinogen I.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Liver Transplantation; Living Donors; Male; Pepsinogen A

The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1alpha, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H+ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H+ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.

Topics: Adult; Aged; Ammonia; Anti-Bacterial Agents; Anti-Ulcer Agents; Bile Acids and Salts; Cytokines; Drug Administration Schedule; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole

To study the long-term clinical results of 34 chronic duodenal ulcer patients treated with high selective vagotomy plus pylorus-preserved mucosal antrectomy (HSV + PPMA).. Clinical follow-up results of the patients from 8 approximately 14 years were analyzed.. Thirty-tow patients (94.1%) followed-up for 8 approximately 14 years after operation achieved Visick grades I-II. No patient died. Gastric acid secretion and infection rate of Helicobacter pylori in the antral mucosa were significantly reduced after operation. No significant difference was found in bile acids, total bacterial counts in gastric juice, and the level of serum gastrin after operation. Gastric emptying was normal. No ulcer recurrence was found by barium meal and endoscopy.. HSV + PPMA is a better operative treatment for duodenal ulcer, which not only can decrease acid secretion and ulcer recurrence rate but also can preserve the function of antrum and pylorus and prevent post-operation bile reflux and intragastric bacterial overgrowth.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Follow-Up Studies; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Recurrence; Stomach; Vagotomy

We investigated the pattern of changes in serum gastrin level produced by three H2-receptor antagonists (H2RA) in patients with gastric and duodenal ulcers between 1990 and 1999. The subjects were 51 patients (cimetidine: 18 patients; famotidine: 16 patients; ranitidine: 17 patients). The gastrin test (in the fasting and meal-stimulated states) was conducted during drug administration and on the fourth day after drug cessation. After cessation of the drug therapy, the fasting serum gastrin level was significantly lower than that during the drug therapy with the three H2RAs. Gastrin level in the fasting test was significantly higher during famotidine therapy than during cimetidine therapy (p = 0.0123). In the meal-stimulated gastrin test, the AUC of gastrin during treatment with H2RA treatment was significantly higher with famotidine than with cimetidine (p = 0.0024). The results indicate different patterns of change in the serum gastrin level in the fasting and meal-stimulated test according to the H2RA administered. Gastrin level was highest in patients administered famotidine and lowest among those administered cimetidine. The pattern of gastrin change in patients administered ranitidine was intermediate between famotidine and cimetidine.

Topics: Adult; Anti-Ulcer Agents; Area Under Curve; Cimetidine; Duodenal Ulcer; Famotidine; Female; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Multivariate Analysis; Ranitidine; Receptors, Histamine H2; Statistics, Nonparametric; Stomach Ulcer

Topics: Adult; Diagnosis, Differential; Duodenal Ulcer; Female; Gastrinoma; Gastrins; Humans; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Proton Pump Inhibitors

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.

Topics: Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Carcinoid Tumor; Duodenal Ulcer; Female; Gastrins; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Peptic Ulcer; Stomach Neoplasms

Nalpha-methyl histamine is an unusual histamine metabolite which is produced in the stomach infected by Helicobacter pylori and which was shown in animals to stimulate gastric acid secretion and to release gastrin in vitro isolated G-cells, but no information is available regarding its influence on gastric secretion and gastrin release in duodenal ulcer patients before and after H. pylori eradication. In this study, we compared the effects of intragastric administration of single or graded doses of Nalpha-methyl histamine on gastric acid secretion and plasma gastrin levels in 16 male duodenal ulcer patients (aging from 35 to 48 years and weighing 65-82 kg) before and after the eradication of H. pylori. Furthermore, the gastric luminal histamine and gastrin contents were determined before and after H. pylori eradication. In H. pylori-infected duodenal ulcer patients, the intragastric application of Nalpha-methyl histamine failed to affect gastric acid secretion or plasma gastrin levels. Following eradication of H. pylori, gastric luminal histamine and gastrin, and both basal gastric acid secretion and plasma gastrin levels, were significantly reduced. Nalpha-methyl histamine given intragastrically in graded doses to such H. pylori-eradicated duodenal ulcer patients was found to increase dose-dependently gastric acid output reaching at a dose of 5 mg, about 80% of histamine maximum induced by i.v. infusion of 25 microg/kg h of histamine dihydrochloride. We conclude that Nalpha-methyl histamine is a potent luminally active stimulant of gastrin release and gastric acid secretion in H. pylori-eradicated patients when luminal histamine is low but is not effective in H. pylori infected patients when luminal histamine is enhanced, possibly due to desensitization of gastrin (G-cells) and acid-producing (parietal) cells by Nalpha-methyl histamine produced excessively in H. pylori-infected stomach.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine; Histamine Agonists; Humans; Male; Methylhistamines; Middle Aged; Statistics, Nonparametric

In the present study we ascertained whether cagA positive and negative H. pylori strains release water soluble products that can influence the production of gastric mucosal cytokines and endocrine (gastrin) or exocrine (pepsinogen C) secretion in 23 H. pylori positive and 19 H. pylori negative patients. Antral biopsies were obtained to classify inflammation, activity, atrophy, intestinal metaplasia and H. pylori density grade. The cagA gene was identified by means of the polymerase chain reaction (PCR) in H. pylori positive colonies after culture of mucosal samples. Three antral biopsies from each patient were incubated with (1.) Water extracts from cagA positive, (2.) Water extracts from cagA negative strains or (3.) H2O (control) at 37 degrees C in a CO2 incubator for 24 hrs. Gastrin, pepsinogen C, IL-1 beta, IL-8, GMCSF, and TNF alpha were measured in the supernatants and mucosal homogenates. H. pylori infection was significantly associated with an increased antral inflammation and activity (chi 2 = 21.7, p < 0.001 and chi 2 = 42.0, p < 0.001), and increased mucosal levels of IL-1 beta, IL-8 and TNF alpha. Water extracts from cagA positive strains enhanced the release of PGC in mucosal biopsy supernatants (p < 0.05) when patients were considered overall and the release of TNF alpha (p < 0.05) when only patients with duodenal ulcer were considered. Water extracts from cagA negative strains stimulated gastrin secretion (p < 0.05). None of the remaining cytokines were influenced by H. pylori water extracts. In conclusion, pepsinogen C and TNF alpha can be induced by cagA positive water extracts and may contribute to damage the gastric and duodenal mucosa. Our findings indicate that in patients with H. pylori infection the increase of the mucosal levels of IL-1 beta and IL-8 does not depend on H. pylori water soluble products, but probably depends on the entire bacterium.

Topics: Adult; Aged; Antigens, Bacterial; Bacterial Proteins; Cytokines; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen C; Reference Values; Tissue Extracts; Tumor Necrosis Factor-alpha; Water

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.. 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.. 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.. 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.

Topics: Adult; Autoantibodies; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A

Topics: Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Japan

Examination and long-term follow-up covered 95 patients with duodenal ulcer (DU). Mean age of the patients was 32 +/- 1.67 years. The patients were divided into two groups: with rare DU recurrences (n = 36) and with frequent recurrences (n = 59). Diagnostic criteria for development of rarely recurrent DU were the following: blood group A(II), exacerbations in winter, weak symptoms at DU onset, weak abdominal pains, solitary surface ulcers. For development of frequently recurrent DU, diagnostic criteria include O(I) blood group, spring exacerbations, marked symptoms of the exacerbation, severe abdominal pains, multiple deep ulcers.

Topics: Abdominal Pain; ABO Blood-Group System; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pepsinogen A; Predictive Value of Tests; Prognosis; Recurrence; Risk Factors; Seasons; Severity of Illness Index; Somatostatin; Wound Healing

There is interest in the development of GERD after Helicobacter pylori eradication. In contrast, the development of duodenal erosions after therapy has received scant attention. Patients were examined after eradication of H pylori infection to determine the frequency of post-therapy duodenal erosions (primary outcome) and whether there was a relation between development of duodenal and esophageal erosions. Additionally, factors were searched for that would identify patients at increased risk for duodenal erosions.. A single-center, endoscopist-blinded, observational study was conducted of 196 patients in whom H pylori was eradicated. The presence of esophageal or duodenal erosions was evaluated 4 weeks and 6 months after eradication. Serum gastrin and pepsinogen I (PG I) and II (PG II) levels were also determined for 83 patients entering the study during its final year.. Multiple small duodenal erosions developed in 8.6% of patients after H pylori eradication and were more common in patients with pre-eradication duodenal ulcer (27.8%) compared with those with gastric ulcer (6.7%) or atrophic gastritis (1.4%) (p < 0.05). Duodenal erosions were associated with high levels of PG I before and after eradication. The frequency of duodenal erosions decreased over time (3.1% by 6 months).. Duodenal erosions occur after H pylori eradication and appear to be related to duodenal ulcer and increased PG I levels, both of which are associated with increased acid secretion. Measurement of PG I may help to identify patients who have duodenal erosions develop after H pylori therapy for studies of the pathogenesis of these lesions.

Topics: Duodenal Ulcer; Duodenum; Endoscopy, Digestive System; Esophagus; Female; Follow-Up Studies; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies; Stomach Ulcer; Time Factors

It remains controversial whether or not Helicobacter pylori infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed.. To investigate by EGT the effects of H pylori eradication on the state of gastric acid secretion in patients with peptic ulcer.. Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom H pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication.. In patients with duodenal ulcer, the mean EGT value before H pylori eradication was higher than that in H pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before H pylori eradication was lower than that in H pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value.. The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.

Topics: Adult; Aged; Atrophy; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Stomach Ulcer; Tetragastrin

The mechanism by which Helicobacter pylori causes hypergastrinaemia is not completely understood.. To evaluate whether antral lymphocyte density could play a role in this alteration.. A total of 12 patients with active duodenal ulcer and 10 with non-ulcer dyspepsia were enrolled upon detection of Helicobacter pylori infection at endoscopy Enrolled as controls were 7 matched dyspeptic patients without Helicobacter pylori infection. Biopsy specimens were collected for Helicobacter pylori and histological assessments, and for antral lymphocyte density assessment by a histomorphometric method. A blood sample was obtained from each patient to determine basal gastrin levels. All patients were controlled by a further endoscopy 4 weeks after the end of Helicobacter pylori treatment.. Antral lymphocyte density (5,464 +/- 1,328 and 5,635 +/- 1,186 vs 2,267 +/- 557 lymphocytes/mm2; p<0.001 and p<0.001, respectively) and gastrin levels (66.7 +/- 14.1 and 60.4 +/- 21.7 vs 40.7 +/- 7.8 pg/dl; p=0.004 and p=0.02, respectively) were higher in duodenal ulcer and non-ulcer dyspepsia patients than in controls, while no significant differences emerged between duodenal ulcer and non-ulcer dyspepsia patients. There was a significant direct correlation between antral lymphocyte density and gastrin levels both in duodenal ulcer (r=0.77; p=0.003) and in non-ulcer dyspepsia (r=0.75; p=0.03) patients, while no correlation was found in controls [r=0.12; p=0.8). After treatment, this correlation persisted in 10 eradication failure patients (r=0.68; p=0.027), but disappeared in those successfully cured.. These data suggest that lymphocyte density in the antral mucosa could play a role in the impaired gastrin production occurring in patients with Helicobacter pylori infection.

Topics: Adult; Aged; Biopsy; Duodenal Ulcer; Dyspepsia; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lymphocytes; Male; Middle Aged; Pyloric Antrum

A decrease in gastrin and pepsinogen (PG) levels 1 month after Helicobacter pylori eradication has been described repeatedly, but the long-term progression of such a decrease has been scarcely studied. We therefore studied the effect of H. pylori eradication on basal and stimulated gastrin and PG levels for 1 year. Initially, the usefulness of measuring these parameters for the noninvasive diagnosis of H. pylori eradication was validated. Furthermore, an assessment was made of the association between H. pylori reinfection and a re-increase in gastrin and PG values. Finally, an evaluation was made of the variables influencing gastrin and PG concentration, with particular attention to H. pylori infection and histological lesions of gastric mucosa.. Two-hundred and twenty-two patients with duodenal ulcer were studied prospectively. Exclusion criteria were the administration of antibiotics, H2 antagonists, omeprazole or bismuth prior to endoscopy. In all patients serum basal levels of gastrin, PGI, and PGII were measured before and 1 month after completing eradication therapy. In the successfully eradicated patients, gastrin, PGI, and PGII were also measured at 6 and 12 months. In 80 patients stimulated measurements of gastrin (after ingestion of two beef cubes) and PGI (after injection of pentagastrin) were also performed. H. pylori-negative patients after therapy underwent a urea breath test at 6 and 12 months, and patients who had stimulated gastrin and PG concentration measured had also an endoscopy performed at 6 months.. H. pylori was eradicated in 73% of patients. A histological improvement was observed 1 month after completing H. pylori eradication therapy, both at gastric antrum and body (P < 0.001), while a further improvement at antrum was demonstrated at 6 months (P < 0.01). With regard to the different cut-off points for decreased basal and stimulated measurements for diagnosing H. pylori eradication, the best results were obtained, respectively, with PGII (sensitivity of 90% and specificity of 76%) and PGI 30 min after stimulation (sensitivity and specificity of 82%), with an area under the ROC curve of 0.87 in both cases. In the multiple regressions analysis H. pylori status correlated with gastrin, PGI and PGII after therapy (P < 0.001), while histological lesions correlated only with gastrin levels (P < 0.05). A decrease in basal and stimulated serum parameters was demonstrated immediately after eradication (Wilcoxon test, P < 0.001), and an additional decrease (at 6 months) was observed just in PGI (Friedman test, P < 0.01). However, gastrin and PGII values remained unchanged after the first month post-eradication. Seven patients were reinfected with H. pylori during follow-up. Quantitation of basal and stimulated gastrin and PGI levels was not reliable as a reinfection marker. Regarding basal PGII, the parallelism was strong at 6 months (re-increase in all four reinfected patients), although only in one out of three with reinfection at 1 year did PGII rise at that stage.. (1) Measurement of gastrin and PG levels (especially basal PGII values) is a useful non-invasive method to confirm H. pylori eradication after therapy. (2) H. pylori eradication is associated with a significant decrease in basal and stimulated gastrin levels and in basal PGII levels that is detected immediately (1 month) after finishing treatment, and remains unchanged for 1 year. However, the decrease in basal and stimulated PGI levels occurs progressively for 6 months, although such levels remain also unchanged afterwards. (3) Measurement of gastrin and PGI concentrations has a limited usefulness in the diagnosis of H. pylori reinfections after successful eradication, although PGII determination could be more useful in this situation.

Topics: Breath Tests; Duodenal Ulcer; Eating; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pentagastrin; Pepsinogen A; Pepsinogen C; Prospective Studies; Recurrence; Regression Analysis; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Time Factors; Urea

Intravenously administered secretin stimulates pancreatic polypeptide (PP) release in patients with endocrine enteropancreatic tumors, but data in patients with nontumorous disorders are controversial. Therefore, we aimed to evaluate the plasma PP pattern after secretin administration in healthy subjects and in patients with gastroduodenal diseases investigated for recurrent ulcer disease and/or hypergastrinemia.. Synthetic secretin was given as an intravenous bolus (2U/kg) in ten patients with Zollinger Ellison syndrome, ten with duodenal ulcer, ten with atropic gastritis and ten healthy volunteers. Blood samples were taken before and at regular intervals for 30min after secretin injection. Plasma PP and gastrin levels were measured by radioimmunoassay.. Secretin promptly and significantly (P<0.01) increased PP plasma levels in all groups of subjects without any differences in peak values. There were no significant correlations between PP and gastrin plasma levels.. Secretin at pharmacological doses is a powerful stimulus for PP release.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrins; Gastritis, Atrophic; Humans; Kinetics; Male; Middle Aged; Pancreatic Polypeptide; Secretin; Zollinger-Ellison Syndrome

To determine the association, if any, between H pylori genotype and the gastric mucosal variations in the levels of gastrin, somatostatin, tryptase, and histamine.. 49 patients affected by duodenal ulcer and 48 by non-ulcer dyspepsia were studied. To identify the H pylori genotype, the presence of the cagA gene and vacA alleles m1, m2, s1, and s2 were analysed by polymerase chain reaction. Gastrin, somatostatin, tryptase, and histamine were measured in antral mucosal biopsies.. 57 patients were infected with H pylori (30 with duodenal ulcer and 27 with non-ulcer dyspepsia). Gastrin and tryptase were increased in patients with H pylori infection, although the variations were statistically significant only for gastrin; somatostatin and histamine were not influenced by H pylori infection. In patients with non-ulcer dyspepsia the absence of the cagA gene and the presence of vacA alleles s2 and m2 were associated with higher values of tryptase and to a lesser extent of gastrin. These associations were not found in patients with duodenal ulcer.. The cagA negative s2m2 strain of H pylori may be less dangerous for the gastric mucosa than other H pylori strains since it enhances tryptase production by gastric mucosal mast cells; this enzyme is thought to stimulate tissue turnover and favour wound healing.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antigens, Bacterial; Bacterial Proteins; Chymases; Duodenal Ulcer; Dyspepsia; Enzyme Activation; Female; Gastric Mucosa; Gastrins; Genotype; Helicobacter pylori; Histamine; Humans; Male; Mast Cells; Middle Aged; Polymerase Chain Reaction; Serine Endopeptidases; Somatostatin; Tryptases

Duodenal ulcer (DU) patients exhibit raised postprandial gastrin release as compared to that in healthy controls. It is believed that serum pepsinogen I (PG I) concentration reflects the chief cell mass and that hyperpepsinogenemia I plays an important role in the pathogenesis of DU. Currently, strong evidence suggests that Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of DU.. Subjects consisted of 15 patients with H. pylori-positive DU, 10 H. pylori-positive volunteers, and 35 H. pylori-negative volunteers. Blood samples were taken before and at 15, 30, and 60 minutes after eating the test meal, which consisted of 100 gm rice, 130 gm chicken, and 1 egg. The 1-hour integrated gastrin response (IGR) was taken as the area under the serum gastrin time curve, calculated by the trapezoid method. Serum gastrin (SG) and fasting serum PG I concentrations were measured by radioimmunoassay.. Meal-stimulated SG response and fasting PG I concentration were significantly higher in DU patients than in H. pylori-positive and -negative volunteers. The DU patients were divided into two groups in accordance with their IGR levels as follows: hyper-IGR and normo-IGR. Serum PG I concentration was significantly higher in the hyper-IGR than in the normo-IGR group.. The DU patients differed in some way (other than H. pylori infection) from the H. pylori-positive healthy volunteers. The fact that hyper-IGR DU patients had higher serum PG I concentrations suggests that patients in this group may be acid hypersecretors.

Topics: Adult; Duodenal Ulcer; Eating; Fasting; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pepsinogen A

The effects of Helicobacter pylori infection on gastric acid secretion has not been clarified. The aim of this study was to elucidate the effects of H. pylori infection on gastric juice pH in relation to gene expression of interleukin-1beta (IL-1beta), which is reported to inhibit gastric acid secretion. Gastric juice pH and serum gastrin levels were measured in patients with peptic ulcer disease. The amount of IL-1beta mRNA in gastric fundic gland mucosa was also measured by a competitive reverse transcription-polymerase chain reaction method. These parameters were determined before and after treatment with lansoprazole and amoxicillin. Before treatment a significant positive relation was observed between the amount of IL-1beta mRNA in gastric fundic gland mucosa and gastric juice pH. After treatment significant decreases in the amount of IL-1beta mRNA, gastric juice pH, and serum gastrin levels were observed in patients with eradication of H. pylori, whereas no significant changes were observed in patients without eradication. These results suggest that H. pylori infection induces IL-1beta and suppresses acid secretion, resulting in increases in gastric juice pH and serum gastrin levels. Eradication of H. pylori decreases IL-1beta induction, resulting in an increase in gastric juice acidity and normalization of serum gastrin levels.

Topics: Base Sequence; DNA, Complementary; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Interleukin-1; Male; Middle Aged; Molecular Sequence Data; Peptic Ulcer; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index; Stomach Ulcer

During recent years, gastric ECL cells have attracted much attention, mainly due to the fact that mice and rats were found to develop gastric carcinoids following lifelong treatment with blockers of acid secretion. We present the structure and functions of ECL cells and their influence on physiology and pathology of stomach and duodenum. We describe interactions of enzymes and hormones in histamine-stimulated gastric output.

Topics: Animals; Anti-Ulcer Agents; Chromogranin A; Duodenal Neoplasms; Duodenal Ulcer; Enterochromaffin-like Cells; Gastrins; Histamine; Mice; Pancreatic Hormones; Rats; Stomach Neoplasms; Stomach Ulcer

Helicobacter pylori-induced hypergastrinemia is accompanied by increased acid secretion in patients with duodenal ulcer (DU) but not in infected healthy volunteers. The aim of this study was to investigate the mechanism underlying this difference.. Thirty-four H. pylori-negative and 20 H. pylori-positive healthy volunteers and 15 H. pylori-positive patients with DU were studied. Maximal acid output and sensitivity to gastrin (gastrin concentration required to achieve 50% maximal acid output) were assessed by examining the dose response to gastrin 17. Inhibitory control was tested by comparing the maximal acid response to cholecystokinin octapeptide with that for gastrin 17.. Sensitivity to gastrin was similar in patients with DU (median, 69.5 ng.L-1; range, 26.2-142) and H. pylori-negative healthy volunteers (median, 82.2 ng.L-1; range, 17.7-410); H. pylori-positive healthy volunteers were less sensitive than either (164.5 ng.L-1; range, 44.8 to > 3360 ng.L-1). Patients with DU had higher maximal acid output (51.2 mmol.h-1; range, 30.8-73.7 mmol.h-1) than either infected healthy volunteers (37.8 mmol.h-1; range, 0.0-65.0 mmol.h-1; P < 0.04) or uninfected healthy volunteers (35.3 mmol.h-1; range, 21.3-67.3 mmol.h-1; P < 0.002). The maximal acid output in both groups of healthy subjects was similar. The proportion of maximal acid output to gastrin 17 achieved by cholecystokinin was similar in patients with DU (36.6%; range, 21.5%-58.2%) and H. pylori-negative healthy volunteers (28.7%; range, 5.9%-85.8%).. A combination of decreased sensitivity to gastrin in infected healthy volunteers and increased maximal acid secretory capacity in patients with DU underlies their different acid response to H. pylori-induced hypergastrinemia.

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Epidermal growth (EGF) and transforming growth factor alpha (TGFalpha) are potent gastric secretory inhibitors, mitogens, and mucosal protectors, but the impact of Helicobacter pylori infection on their mucosal expression and luminal release has not been clarified.. In this study, gene and immunoreactive and immunohistochemical expressions of EGF and TGFalpha were assessed in the gastric mucosa of 15 H. pylori-negative healthy normals, in 22 H. pylori-positive duodenal ulcer patients (DU) and in 24 H. pylori-positive non-ulcer dyspepsia patients (NUD). All studies in DU and NUD patients were repeated after 2 weeks of triple therapy (amoxicillin + clarithromycin + omeprazole) and 4 weeks and 2 years later.. Immunohistochemical expression of EGF and TGFalpha in H. pylori-positive DU and NUD was significantly higher than in H. pylori-negative normals, and this increase persisted at 2 and 4 weeks after therapy but normalized 2 years later. EGF mRNA was detected in the gastric mucosa of H. pylori-positive DU before and at 2 and 4 weeks after H. pylori eradication, but it was not found 2 years after the eradication of H. pylori or in gastric mucosa of H. pylori-negative control subjects. TGFalpha mRNA was detected in the gastric mucosa independently of H. pylori status, with the stronger expression observed in the gastric mucosa of H. pylori-positive DU and NUD before eradication than after this procedure. Plasma gastrin, which was significantly increased in H. pylori-positive DU, normalized already after 2 weeks of triple therapy. The eradication rate as determined by histology after triple therapy reached 86.3% in DU patients and 90.5% in NUD patients. Two years after the eradication the H. pylori reinfection rate was 4.5% among DU patients and 4.2% among NUD. Treatment of DU patients with triple therapy resulted in complete ulcer healing.. 1) Chronic H. pylori infection and resulting antral gastritis are associated with increased plasma gastrin and increased mucosal cell proliferation, probably due to enhanced expression of EGF and TGFalpha, and 2) the H. pylori eradication results in a decrease in plasma gastrin, but the increase in gastric TGFalpha and EGF content is sustained, suggesting that they may be involved in ulcer healing.

Topics: Adult; Cell Division; Duodenal Ulcer; Dyspepsia; Epidermal Growth Factor; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Polymerase Chain Reaction; Proliferating Cell Nuclear Antigen; Radioimmunoassay; Transforming Growth Factor alpha

Autoantibodies against epitopes located at the canaliculi of human parietal cells occur in about 30% of Helicobacter pylori-infected patients. This has led to the hypothesis that gastric secretory function could be inhibited by anticanalicular autoantibodies in H. pylori gastritis.. Forty-four H. pylori-infected patients with and without duodenal ulcers were screened for anticanalicular autoantibodies by means of immunohistochemistry. Plasma gastrin levels and basal and maximal gastric acid output were determined.. Fasting gastrin levels were significantly increased in the group with anticanalicular autoantibodies. In the group of patients with non-ulcer dyspepsia the presence of anticanalicular autoantibodies was significantly correlated with an impaired basal acid secretion.. Antigastric autoimmunity in H. pylori gastritis seems to be relevant for gastric hyposecretion either directly by inhibiting the proton pump or indirectly through the development of gastric mucosa atrophy.

Topics: Adult; Autoantibodies; Autoimmunity; Duodenal Ulcer; Dyspepsia; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Stomach

Elucidation of the significance of various factors in prognosis of duodenal ulcer (DU) severity.. The observational study entered 18 new cases of DU and 13 healthy controls. All the patients were followed up for 7 years with annual esophagogastroduodenoscopy.. 10 patients (group 1) had annual exacerbations of DU, 8 patients had rare exacerbations (group 2). Group 1 was characterized by basal acid hyperproduction, hyperpepsinogenemia, hypergastrinemia, marked contamination with Helicobacter pylori. Patients of group 2 had normal basal and pentagastrin-stimulated acid production, normopepsinogenemia, normogastrinemia, mild Helicobacter pylori infection.. The 7-year follow-up of new DU cases allowed demonstration of functional-morphological prognostic criteria for frequently and rarely recurrent DU courses.

Topics: Biopsy; Duodenal Ulcer; Duodenum; Endoscopy, Digestive System; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens; Prognosis; Stomach

Topics: Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Hypoglycemia; Neoplasm Proteins; Thyrotropin; Zollinger-Ellison Syndrome

How Helicobacter pylori infection affects gastric acid secretion is still unclear.. Gastric juice pH, ammonia concentration in gastric juice, serum gastrin level, and grade of gastritis in accordance with the Sydney System were determined for patients with gastric ulcer (GU) and duodenal ulcer (DU) before and after treatment with lansoprazole and amoxicillin, and results were compared with those of H. pylori-negative controls.. Scores for H. pylori density, atrophy, metaplasia, and activity of gastritis in the corpus were higher in patients with GU, especially those with proximally located GU, than in those with DU. Gastric juice pH was significantly higher in GU patients than in DU patients and controls. After H. pylori eradication, gastric juice pH and serum gastrin levels in both GU and DU patients were significantly decreased to control levels. In patients without eradication, no significant changes in these factors were observed.. These findings suggest that H. pylori infection and gastritis in the corpus suppress acid secretion and increase gastric juice pH, resulting in hypergastrinemia, and that eradication of H. pylori normalizes acid secretion and serum gastrin levels.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Ammonia; Amoxicillin; Anti-Ulcer Agents; Case-Control Studies; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Omeprazole; Penicillins; Proton Pump Inhibitors; Stomach Ulcer

The aim of this study was to clarify the mechanism of inappropriate hypergastrinemia in Helicobacter pylori (H. pylori)-infected subjects.. We measured fasting serum gastrin (SG) concentrations, and investigated immunohistochemically G and D cell numbers in 47 subjects with normal mucosa, 24 subjects with chronic gastritis, and 24 subjects with duodenal ulcer (DU). The degree of inflammation and atrophy were classified into four categories based on criteria established in the Sydney System: none, mild, moderate, and severe. Avidin-biotin complex methods were used to identify G and D cells, which were counted per unit square (0.25 mm2) in five random fields from each of two well-oriented antral and fundic biopsies. SG concentrations were measured by radioimmunoassay.. The G cell number was not significantly different between 24 subjects with H. pylori-associated gastritis and those with DU. However, the number of antral D cells was significantly lower and the G/D cell ratio was significantly higher in subjects with DU than in those with H. pylori-associated gastritis (p < 0.01), although the degree of inflammation and atrophy in the antrum and H. pylori status were similar between the two groups. The mean fasting SG concentration was higher in subjects with DU than in those with H. pylori-associated gastritis, but the difference was not statistically significant.. Our results demonstrate that a marked decrease in antral D cell number with a high G/D cell ratio may contribute to hypergastrinemia and the pathogenesis of DU.

Topics: Adult; Antibodies, Bacterial; Atrophy; Cell Count; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Inflammation; Male; Somatostatin-Secreting Cells

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Animals; Cytokines; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Pentagastrin; Peptides

To improve the clinical diagnosis and treatment of gastrinoma.. Twelve cases of gastrinoma found in the recent 30 years in our hospital were analyzed.. The results indicated that in addition to the typical symptoms related to gastric acid overproduction, the frequency of certain uncommon features characteristic of the disease was unusually high in our hands i.e., (1) The majority of them (7/12) had serious diarrhea, even resulting in shock. (2) Multiple endocrine neoplasia type I (MEN) was in 3 out of 12 associated in our series. (3) Multiple nodules in the duodenum (3/12) were found and in two patients were shown to be submucosal gastrinoma confirmed by pathology. (4) Multifocal lesions were found in 9 out of 12 patients, and in 7 cases at least two organs were involved. Most gastrinomas were located in the pancreas, stomach and duodenum. (5) As reported by other authors, multiple hormone secretion was common: in five of six patients the tumor secreted more than two hormones. (6) In some cases, tumors were sensitive to chemotherapy.. In our series gastrinoma was found with the feature of multiple lesions and multiple hormone secretion in addition to the typical symptoms related to gastric acid overproduction.

Topics: Adolescent; Adult; Diarrhea; Duodenal Neoplasms; Duodenal Ulcer; Female; Gastrinoma; Gastrins; Humans; Insulinoma; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Somatostatin; Stomach Neoplasms

Proximal gastric vagotomy (PGV) is a first-choice approach for the surgical treatment of duodenal peptic ulcer. However, a high percentage of recidivism takes place after this surgical strategy. To study the possible involvement of gastrin in ulcer recidivism, serum gastrin levels and gastrin receptors in gastric mucosa were determined at several times after PGV in rats. Gastrin concentration was determined using a commercial radioimmunoassay kit and gastrin receptors were analyzed in oxyntic mucosa membrane preparations using 125I-labeled 15-Leu-gastrin-17 as label. Our results show a significant, time-dependent increase in serum gastrin concentration, reaching highest values at 12 weeks after PGV. Similarly, a significant increase in the number of gastrin receptors (Bmax) and in the dissociation constant (Kd) occurred from 1 to 12 weeks post-PGV. Since gastrin exerts a positive feedback effect on its receptors, the PGV-dependent increase in serum gastrin concentration explains the up-regulation of the gastrin receptors in the rat oxyntic mucosa. Furthermore, an increase in the number of gastrin receptors after vagotomy may be at least partially responsible for the recidivism in duodenal peptic ulcers after this surgical approach.

Topics: Animals; Duodenal Ulcer; Gastrins; Kinetics; Male; Parietal Cells, Gastric; Rats; Rats, Wistar; Receptors, Cholecystokinin; Recurrence; Vagotomy, Proximal Gastric

The rule of Ramadan (1 month of food and water intakes restricted to night hours) is followed by the majority of the Moslem fraction of the human population, but the possible consequences of this long-lasting modification of food intake schedule on public health have not yet been extensively documented. Therefore, a group of healthy control subjects and a group of healed duodenal ulcer patients were studied before (controls), during (both groups), and after (both groups) the month of Ramadan. The time-restricted food and water intakes were associated with variations of gastric pH, plasma gastrin, insulin, glucose, and calcium documented on a circadian basis. All of the studied biological variables, except insulin, underwent changes in their 24-h mean concentration (e.g. decrease in gastric pH, increase in plasma gastrin), some of which were still present 1 month after the end of Ramadan. The circadian patterns of all the studied variables were altered during the month of Ramadan. Some differences between the group of healthy control subjects and the group of healed duodenal ulcer patients may suggest a greater susceptibility of the latter to the modifications of feeding and sleeping schedule, which could possibly be a risk factor for the disease.

Topics: Adult; Blood Glucose; Calcium; Circadian Rhythm; Diet; Duodenal Ulcer; Fasting; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Islam; Male; Reference Values; Wound Healing

Topics: Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Humans; Peptides

Topics: Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Humans; Parietal Cells, Gastric; Peptides

Helicobacter pylori infection is associated with an exaggeration of gastrin release following meals or bombesin stimulation attributed to a defect of somatostatin secretion of antral D-cells. Nevertheless, these modifications of gastric physiology do not explain the increase of gastric acid secretion which is only observed in duodenal ulcer patients. The inhibitory effect of somatostatin secretion of fundic D-cells on parietal cells is well known. The aim of our prospective study was to compare the number of fundic D-cells and likewise the number of antral G-cells and D-cells between patients with duodenal ulcer and healthy subjects with and without H. pylori infection.. The numbers of D-cells and G-cells were compared between 19 infected patients with duodenal ulcer and 20 healthy subjects, 10 with and 10 without H. pylori infection. Fundic mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of somatostatin, antral mucosal biopsy specimens for the presence of gastrin and somatostatin.. The number of G-cells was significantly lower (P = 0.0012) in duodenal ulcer patients by comparison with infected subjects and controls. The number of antral D-cells was significantly less (P < 0.0001) in duodenal ulcer patients (mean of 10 random fields = 0.45 +/- 0.04) than in either asymptomatic infected patients (0.65 +/- 0.07) or uninfected controls (0.88 +/- 0.10). The number of fundic D-cells was significantly lower (P < 0.0001) in duodenal ulcer patients (mean = 0.20 +/- 0.03) than in either asymptomatic infected subjects (0.29 +/- 0.05) or controls (0.73 +/- 0.09); here the difference between the two groups of infected subjects was not significant. Multivariate analysis showed that the presence of H. pylori infection of the fundic mucosa did not influence the number of fundic D-cells.. Changes in the number of fundic and antral D-cells induced by H. pylori infection did not explain abnormalities of gastric acid secretion usually observed in duodenal ulcer patients; it is suggested that pre-existing abnormalities in the regulation of parietal cell or increase of parietal cell mass are involved.

Topics: Adult; Biopsy; Cell Count; Duodenal Ulcer; Female; Gastric Fundus; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Prospective Studies; Pyloric Antrum; Somatostatin

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are potent gastric acid inhibitors and stimuli of mucosal growth and protection but their involvement in Helicobacter pylori associated duodenal ulcer has been little examined.. To assess gastric acid secretion, plasma gastrin concentrations, mucosal content of EGF and TGF alpha, and mucosal expression of these peptides and their receptor (EGFr) as well as salivary and gastric luminal release of EGF under basal conditions and after pentagastrin stimulation in 10 healthy subjects and in 25 H pylori positive patients with duodenal ulcer before and after two weeks of triple anti-H pylori therapy and four weeks after the termination of this therapy.. Pentagastrin stimulation caused a significant increase in salivary and gastric release of EGF both in healthy controls and patients with duodenal ulcers but in the patients, the eradication of H pylori resulted in several fold higher gastric luminal (but not salivary) EGF release than before the anti-H pylori therapy. Mucosal contents of immunoreactive EGF and TGF alpha and mucosal expression of EGF, TGF alpha, and EGFr in H pylori positive patients with duodenal ulcer were significantly higher than those in healthy H pylori negative controls and this increase persisted after eradication of H pylori. Basal plasma gastrin was significantly reduced after two weeks of triple therapy and four weeks after the H pylori eradication all ulcers were completely healed.. (1) H pylori infection in patients with duodenal ulcer was accompanied by enhanced plasma gastrin and increased mucosal content and expression of TGF alpha, EGF, and EGFr; (2) H pylori eradication resulted in ulcer healing, reduction in plasma gastrin, and enhancement of gastric (but not salivary) luminal release of EGF, particularly after pentagastrin stimulation; and (3) enhanced mucosal content and expression of TGF alpha, EGF, and EGFr and increased luminal release of EGF may contribute to ulcer healing after eradication of H pylori.

Topics: Duodenal Ulcer; Epidermal Growth Factor; ErbB Receptors; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pentagastrin; Saliva; Transforming Growth Factor alpha

Topics: Cell Count; Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Parietal Cells, Gastric

This study evaluated the effect of gastric acid secretion and serum gastrin response on tumor differentiation for early gastric cancer according to patients' age. We investigated the association between serum gastrin levels, gastric acid secretion and the histologic types of 335 early gastric carcinomas limited to the mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal ulcers. The preoperatively examined basal acid output, maximal acid output and peak acid output after administration of tetragastrin and serum gastrin levels before and after ingestion of a test meal were determined. Patients with differentiated cancer and duodenal ulcer showed a significant negative correlation between gastric acid secretion and age, while the former group also had a significant positive correlation between serum gastrin levels and age. On the other hand, patients with undifferentiated cancer did not show any such correlation between gastric acid and age, but showed a significant positive correlation between serum gastrin, integrated gastrin response and age. Patients with gastric ulcer did not show any such correlations. These data suggest that both low acid secretion and endogenous hypergastrinemia, especially in the elderly, may play an important role in differentiated and undifferentiated gastric carcinomas.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Aged, 80 and over; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Stomach Neoplasms; Stomach Ulcer

The aims of this study in 50 patients with H. pylori infection and duodenal ulcer were to examine the effect of eradication therapy on the serum levels of gastrin, pepsinogen I, and pepsinogen II and to investigate whether monitoring of the serum changes in these peptides after treatment could predict patient outcome. H. pylori status was assessed at entry and one and six months after therapy by culturing and microscopic analysis of the gastric mucosa and by [14C]urea breath test. Significant decreases were observed in the serum levels of gastrin (-11.4 +/- 3%), pepsinogen I (-28.9 +/- 4%), and pepsinogen II (-40.4 +/- 3%) in the 45 patients whose infection was eradicated, but not in the patients without eradication. Serum values of these peptides were unchanged in an additional group of 10 patients that only received omeprazol, none of whom had H. pylori eradicated. The best cutoff point of the percentage of each peptide to predict patient outcome was 10% for gastrin and pepsinogen I, and 15% for pepsinogen II. A pepsinogen II decrease > 15% resulted in the best marker of H. pylori clearance, accurately identifying patient outcome 86.6% of the time, whereas the diagnostic accuracy of gastrin and pepsinogen I was 61.7% and 76.6%, respectively. Significant correlations were found between the bacterial load assessed by histology with the serum concentrations of pepsinogen I and II and with the urease activity as measured by the amount of 14CO2 excreted. In conclusion, eradication of H. pylori infection is followed by a significant drop in serum levels of gastrin, pepsinogen I, and pepsinogen II. Changes in the latter are the most uniform and may be used as an indirect tool to predict treatment outcome.

Topics: Adult; Aged; Breath Tests; Duodenal Ulcer; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens

The mechanism by which Helicobacter pylori (Hp) predisposes to duodenal and gastric ulcers remains still unclear. It is possible that Hp infection impaires gastric secretion. Evaluation of gastric acid and mucus secretion before and after Hp eradication would let to estimate the influence of Hp infection on gastric secretion. To evaluate the effect of Hp infection on gastric acid and gastric mucous secretion before and one year after Hp eradication. We examined 28 Hp positive peptic ulcer disease patients (10-gastric ulcer GU, 18-duodenal ulcer DU) before and one year after antibacterial treatment. Gastric acid output was examined basely (BAO) and in response to pentagastrin (6 micrograms/kg) (MAO) using Kay's standard method. Some components of gastric mucus as fucose, galactose, hexosamines and sialic acid were measured using calorimetric methods basaly and after pentagastrin stimulation. Plasma gastrin concentration was measured in 20 patients (6-GU, 14-DU) by radioimmunoassay before and one year after eradication. Hp status was determined by rapid urease test (CLO) and histology (Giemsa stain). One year after Hp successful eradication gastric acid secretion was significantly reduced-BAO: 3,31 vs 1,474 mmol/h; MAO: 19,63 vs 14,85 mmol/h, p < 0.05. Plasma gastrin concentration decreased significantly from 9,783 to 6,017 pmol/I, p < 0.05. In patients with ineffective eradication we did not observe any significant changes in gastric acid secretion. An evident, but not statistically significant, decrease of sialic acid output in eradicated patients was noted. The study has shown the significant influence of Hp infection on gastric acid secretion. Those results support the hypothesis that increased gastric acid secretion may be one of the pathogenic mechanism of Hp infection inducing mucosal damage.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Fucose; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Mucus; N-Acetylneuraminic Acid; Stomach Ulcer; Time Factors

Previous study showed that duodenal ulcer (DU) patients infected with Helicobacter pylori (H. pylori) have increased basal and pentagastrin- or GRP-induced gastric acid secretion and that these disturbances reversed fully after eradication of H. pylori. This study was designed to compare the gastric acid secretory profile, plasma gastrin levels and growth factors (EGF and TGF alpha) expression in gastric mucosa in DU patients with those in atrophic gastritis patients before and six months after verified eradication of H. pylori. In DU patients, basal and stimulated (GRP and pentagastrin) gastric acid secretion was significantly higher than in healthy controls. Six months following the eradication of H. pylori with triple therapy (omeprazole+clarithromycin+amoxicillin), this secretion returned to normal value. In contrast, in patients with atrophic gastritis, such eradication of H. pylori resulted in a significant increase in basal and pentagastrin- and GRP-stimulated acid secretion. Mucosal expression of immunoreactive EGF and TGF alpha was significantly enhanced in H. pylori positive DU and atrophic gastritis patients but this elevation disappeared or was markedly decreased 6 months upon the eradication of H. pylori. We conclude that 1) H. pylori infection is accompanied both in DU and atrophic gastritis patients by an enhanced plasma gastrin and increased mucosal expression of EGF and TGF alpha, 2) basal and GRP-induced acid secretion is significantly elevated in DU, whereas that in atrophic gastritis patients is greatly reduced, and 3) the H. pylori eradication restores gastric acid and plasma gastrin release as well as the mucosal expression of growth factors in DU and atrophic gastritis.

Topics: Adult; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Transforming Growth Factor alpha

Topics: Acute Disease; Adolescent; Adult; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Recurrence; Reference Values

Helicobacter pylori infection exerts variable effects on gastric acid secretion. It may increase acid secretion, decrease acid secretion or produce no overall change. The effect of the infection on acid secretion depends upon the relative extent to which the Helicobacter pylori gastritis affects the antral and body mucosa of the stomach. When there is antral predominant, body-sparing gastritis, there is increased gastrin release and this is accompanied by increased acid secretion. When there is a significant body gastritis, acid secretion is reduced and subjects may be completely achlorhydric. The majority of subjects have both antral gastritis and body gastritis and this results in no overall change in gastric acid secretion. There is now increasing evidence that the alteration which Helicobacter pylori infection exerts upon gastric acid secretion is a pivotal factor in determining the clinical outcome of the infection. Subjects in whom the infection produces acid hypersecretion develop duodenal ulcer disease due to the increased duodenal acid load. In subjects in whom the infection induces marked hypochlorhydria, there is an increased risk of gastric cancer. The hypochlorhydria probably plays an important role in the carcinogenic process as high intragastric pH markedly raises intragastric nitrite levels, profoundly lowers gastric juice ascorbic acid and allows colonization by nitrosating bacteria. The reason for the different functional responses to Helicobacter pylori infection is unclear but may be related to the host's pre-morbid acid secretory status.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Stomach; Stomach Neoplasms

The mechanism(s) by which sucralfate heals duodenal ulcers remains unclear. The aim of this study was to determine the effect of sucralfate on Helicobacter pylori infection and on the accompanying hypersecretion of gastric acid the infection induces in patients with duodenal ulcer.. Basal and gastrin-releasing peptide (GRP) stimulated gastrin release and acid secretion. H. pylori density, gastric urease activity, and severity of gastritis were studied in patients with duodenal ulcer who were positive for H. pylori before, during, and after 4 weeks' treatment with sucralfate (2 g twice daily).. The density of H. pylori decreased by 70% during sucralfate treatment and returned to the pretreatment level after discontinuation of therapy. This suppression of H. pylori infection was accompanied by an 80% decrease in gastric urease activity. GRP-stimulated plasma gastrin concentrations, GRP-stimulated acid output, and basal acid output all decreased by approximately 50% during sucralfate therapy and returned to pretreatment levels after treatment was discontinued.. These findings indicate that sucralfate markedly suppresses H. pylori infection and the accompanying hypersecretion of acid the infection induces in patients with duodenal ulcer. These effects are likely to be important mechanisms by which the drug promotes duodenal ulcer healing.

Topics: Adult; Aged; Anti-Ulcer Agents; Breath Tests; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptides; Stomach; Sucralfate; Urease

Helicobacter pylori infection and duodenal ulcer disease are firmly correlated. However, the bacteria do mainly colonize the antrum, indicating an indirect pathogenic mechanism. The aim of this study was to test a concept claiming that H. pylori infection of the antrum selectively blocks normal inhibitory reflex pathways to gastrin and parietal cells.. The effect of antral distention was studied on gastric acid secretion stimulated by pentagastrin and on gastrin release stimulated by gastrin-releasing peptide in H. pylori-infected and noninfected patients with and without duodenal ulcer disease, as well as after eradication of the bacteria.. The inhibitory effect on gastric acid secretion induced by antral distention was absent in H. pylori-infected patients irrespective of whether or not they had duodenal ulcer disease. The inhibitory mechanism was restituted in 8 of 10 patients within 9 months after successful eradication of H. pylori infection. Similar results were obtained in studies on gastrin release.. H. pylori infection blocks normal, physiological inhibitory mechanisms from the antrum to both the gastrin cells and to the parietal cell region, resulting in increased gastrin release and impaired inhibition of gastric acid secretion, which will probably lead to an increased duodenal acid load as a general prerequisite for the development of duodenal ulcer disease.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastric Dilatation; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pentagastrin; Peptides; Pyloric Antrum; Stomach Diseases

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Parietal Cells, Gastric

To study basal gastrin levels in duodenal ulcer patients and in those with normal endoscopy, according to Helicobacter pylori infection.. Eighty-four duodenal ulcer patients and 164 with normal endoscopy were studied. Biopsy specimens were taken from gastric antrum and body, and investigated for microbiology (Gram stain and culture) and histology (hematoxilin-eosin stain). Basal gastrin levels were measured (RIA).. In duodenal ulcer patients the percentage of chronic gastritis was higher (p < 0.001) than in patients with normal endoscopy without H. pylori infection, and similar to patients infected by H. pylori. In patients with normal endoscopy (n = 164), those infected with H. pylori (n = 115) had higher (p = 0.02) gastrin levels (mean +/- SD) than non-infected (64 +/- 34 vs 51 +/- 14 pg/ml) and similar to duodenal ulcer patients (62 +/- 20 pg/ml). In the multiple regression model analysis H. pylori infection was the only variable which correlated with gastrin levels (regression coefficient 9.48 [SE = 4.59]; multiple correlation coefficient 0.22 [p = 0.008]). Additional variables (age, sex, duodenal ulcer) were not correlated with gastrin levels. Patients with chronic gastritis had higher gastrin levels (p < 0.01) than those with normal histologic mucosa.. In patients with normal endoscopy, those infected with H. pylori had significantly higher basal gastrin levels than non-infected individuals, and similar to duodenal ulcer patients. Therefore, hypergastrinaemia seems to be associated with H. pylori infection, and is not a distinctive feature of duodenal ulcer disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Chronic Disease; Duodenal Ulcer; Endoscopy; Female; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Regression Analysis; Stomach

Topics: Adolescent; Adult; Aged; Biomarkers; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens

H. pylori infection, both in normal healthy subjects and patients with duodenal ulcer, results in modest elevations of serum gastrin concentrations in the fasting state and quite substantial elevations after a meal or gastrin releasing peptide (GRP) stimulation. Cure of the infection leads to normalization of gastrin homeostasis. Acid secretion in response to a submaximal infusion of GRP is three-fold higher in H. pylori-infected normal subjects and six-fold higher in DU patients than in non-infected controls. These changes also normalize after cure of the infection. H. pylori infection appears to lead to increased basal acid output in some patients with duodenal ulcer while effects on peak acid output to pentagastrin remain under debate. With the possible exception of peak acid output, the abnormalities of gastrin and acid secretion reported for patients with duodenal ulcer are largely a result of infection with H. pylori.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

Topics: Duodenal Ulcer; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Parietal Cells, Gastric; Somatostatin

The aim of our study was to demonstrate the effect of Helicobacter pylori eradication on basal and stimulated serum gastrin levels and gastric acid output 5 months after therapy of patients with duodenal ulcer. Thirty-two patients (24 men and eight women with a mean age of 45 years) who had had endoscopy and were diagnosed as having duodenal ulcer entered the study. In all patients three biopsy specimens were taken from the duodenal bulb, gastric antrum, body, and fundus. These specimens were then sent for microbiological and histological examination. Triple therapy consisting of bismuth, metronidazole, and tetracycline was administered. Endoscopy was repeated 1 and 5 months after therapy, and biopsy specimens were again taken from the gastric antrum and body. Before treatment, serum samples were taken to measure basal and stimulated (90 min) gastrin levels after ingestion of two beef cubes, and basal and stimulated acid outputs (after pentagastrin) were studied. Measurements of gastrin and gastric acid output were repeated 5 months after therapy. H. pylori was eradicated in 26 patients (81.3%). Basal gastrin levels (mean +/- SD) at diagnosis and after eradication were 44 +/- 12 and 35.8 +/- 2 pg/ml, respectively (p < 0.05). Similarly, stimulated gastrin levels (integrated values) decreased from 5,303 +/- 1,526 pg/ml/min before therapy to 3,779 +/- 1,204 pg/ml/min after eradication (p < 0.001). However, basal (4.9 +/- 4mEq/h) and stimulated (28.5 +/- 10mEq/h) acid output did not vary after eradication (3.9 +/- 4 mEq/h and 26.2 +/- 12 mEq/h, respectively). We conclude that basal and stimulated gastric acid output are not changed by H. pylori eradication in duodenal ulcer patients 5 months after therapy, in spite of its association with a significant decrease in basal and stimulated gastrin levels.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Time Factors

The cure rate of Faeces Trogopterus in treating duodenal ulcer for six weeks was 70.59% and the total effective rate of which was 91.18%. The Shay model of rats was used. The result revealed that Faeces Trogopterus could protect the gastric mucosa. These results preliminarily indicated the mechanism of this drug was inhibiting gastric secretion and regulating gastric mucosal blood flow so as to enhance mucosal defense.

Topics: Adult; Aged; Animals; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Materia Medica; Middle Aged; Rats; Rats, Sprague-Dawley; Regional Blood Flow

To determine the clinical efficacy of once-daily treatment with omeprazole in refractory acid-related diseases in children.. Endoscopic healing and 24-hour intragastric pH values were assessed in 13 patients with refractory reflux esophagitis (n = 5), refractory and/or giant duodenal ulcer (n = 6), or giant gastric ulcer (n = 2). The mean dose of omeprazole was 0.6 mg/kg per day (range, 0.3 to 0.7 mg/kg per day). Pharmacokinetic studies of omeprazole were performed in seven patients.. The cumulative healing rates at 2, 4, 6, and 8 weeks of treatment were 46%, 85%, 92%, and 92%, respectively. Esophagitis in one patient did not heal despite increases in doses of up to 1.6 mg/kg per day (40 mg/day). The mean intragastric pH of omeprazole-treated patients was 5.2 (range, 3.0 to 6.6) and mean hydrogenion activity was 1.78 mmol/L (range, 0.01 to 10.42 mmol/L). There was wide interindividual variation in the reduction of gastric acid production. Mean intragastric H+ activity in omeprazole-treated patients was significantly lower than that of control subjects (p < 0.005) and that of patients treated with histamine type 2(H2)-receptor antagonists (p < 0.05). Mean intragastric H+ activity was not significantly correlated to the area under the concentration-time curve of omeprazole. No severe adverse effects were reported during treatment or at follow-up.. Omeprazole has a potent antisecretory effect and is a suitable alternative for short-term treatment of refractory acid-related diseases; a relatively low dose (0.6 mg/kg per day) appears to be optimal in most patients. Unhealed esophagitis at 8 weeks of treatment was considered to be refractory to omeprazole.

Topics: Anti-Ulcer Agents; Case-Control Studies; Child; Dose-Response Relationship, Drug; Duodenal Ulcer; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Female; Follow-Up Studies; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Omeprazole; Stomach Ulcer; Time Factors

The eradication of Helicobacter pylori (Hp) is known to reduce the recurrence rate of duodenal ulcer (DU) to similar extent as gastrectomy but it is not clear what is the prevalence of Hp in DU patients after surgical interventions such as gastrectomy or vagotomy. The purpose of this study was to evaluate the influence of gastrectomy or truncal vagotomy with pyloroplasty on the prevalence of Hp in 51 DU patients just before and 6-8 months after these procedures. Using C14-urea breath test (UTB), rapid CLO-test and histology of the biopsy samples of gastric mucosa obtained during gastroscopy, the Hp was detected in all DU subjects submitted to operation. Following distal gastric resection (antrectomy) with Billroth II anastomosis (N = 32) due to an ulcer resistance to conservative therapy, peptic ulceration was not observed during 6-8 months in any of the examined subjects and the Hp was only rarely observed (only in 3 out of 32 operated patients). Histologically, in antral biopsies taken prior to surgery, all DU patients presented chronic active gastritis. After the surgery, the absence of Hp was confirmed also by histology. Histological evaluation of gastrectomy stump biopsies revealed typical chronic gastritis with concomitant foveolar hyperplasia and focal gland dilation. Following selective vagotomy and pyloroplasty (N = 19), the scarring of duodenal bulb (without active ulcer) was seen in 4 out of 19 operated patients but the Hp was detected in all (100%) cases. Gastric biopsies prior and after vagotomy revealed chronic active gastritis associated with Hp infection. Basal plasma gastrin was reduced after gastrectomy by about 30% and basal and maximal pentagastrin-induced acid secretion was decreased by about 60% and 70%, respectively. Vagotomy did not reduce activity of the mucosal inflammation and the incidence of Hp. Basal plasma gastrin level was increased by about 60%, while basal and pentagastrin induced acid secretion was decreased by 25% and 40%, respectively. Because of the high ulcer recurrence rate after vagotomy as opposed to low recurrence after gastrectomy, it is reasonable to conclude that (1) the disappearance of Hp and reduction in plasma gastrin and gastric acid secretion were probably the major factors responsible for the high efficacy of gastrectomy in prevention of ulcer recurrence, (2) in non-complicated DU, gastric surgery should be avoided and replaced by conservative anti-Hp therapy involving both antisecretory or bismuth agen

Topics: Adult; Breath Tests; Duodenal Ulcer; Gastrectomy; Gastric Stump; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Urea; Vagotomy

Antral gastrin cell hyperfunction (AGCH), is a rare cause of duodenal ulcer associated with non-tumour hypergastrinaemia and acid hypersecretion.. To investigate the role of Helicobacter pylori in AGCH.. Twelve AGCH patients and eight H. pyloripositive non-hypergastrinaemic duodenal ulcer patients were compared.. Basal and peak acid outputs, gastrin-stimulation (meal and bombesin) tests, and immunohistochemistry for antral G and D cells were performed. One year after H. pylori eradication, six AGCH patients were again investigated with the same tests.. Significantly more basal, and stimulated gastrin and acid secretion, were found in AGCH compared to the H. pylori-positive duodenal ulcer patients (P < 0.01). G cell counts were significantly higher in AGCH than in duodenal ulcer patients (118.8, range 58-192.4, vs. 86.1, range 49-184; P < 0.05), and the resulting G/D cell ratio was also higher in AGCH patients (4.2, range 2.6-5.6, vs. 3.3, range 1.9-4.3; P < 0.05). H. pylori was present in the gastric mucosa of all 12 AGCH patients. Cure of infection in six AGCH individuals resulted in marked a decrease of gastrin levels associated with a significant (23.7%: P < 0.05) decrease of G cell count and an increase (12%; P < 0.05) of D cell count.. The results indicate that AGCH may result from H. pylori overstimulation of gastrin cell function in patients with some presently undefined, familial predisposition and that an imbalance of the G/D cell ratio may have a role in the genesis of hypergastrinaemia.

Topics: Adolescent; Adult; Bombesin; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Pyloric Antrum

To determine the relationship between Helicobacter pylori infection and parietal cell mass and functional status in 10 patients with duodenal ulcer and 22 patients with functional dyspepsia.. We measured pentagastrin-stimulated acid secretion, determined the activity status of parietal cells on the basis of ultrastructural morphological features, and measured parietal cell mass and canalicular area with computerized densitometric morphometry. The number of antral G cells per square millimeter of mucosa was estimated inmunohistochemically, and basal serum gastrinemia was determined.. In patients with duodenal ulcer, acid secretion, the percentage of activated parietal cells, and canalicular area were increased, but there was no difference between patients and dyspeptic controls in parietal cell mass. Helicobacter pylori infection did not modify these parameters, although it was associated with basal hypergastrinemia.. In patients with duodenal ulcer, parietal cells display functional hyperactivity, which causes hypersecretion of acid; this effect is apparently unrelated to Helicobacter pylori infection.

Topics: Case-Control Studies; Duodenal Ulcer; Dyspepsia; Female; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter; Helicobacter Infections; Humans; Male; Microscopy, Electron; Middle Aged; Parietal Cells, Gastric

There is evidence that gastric Helicobacter pylori (Hp) infection promotes duodenal ulceration by releasing gastrin. We therefore asked how Hp releases gastrin. Tumour necrosis factor alpha (TNF-alpha) is up-regulated in Hp gastritis and stimulates hormone release from pituitary cells, so we tested its effect on primary cultures of canine antral G cells and human antral fragments. TNF-alpha pretreatment (100 ng mL-1) of canine G cells significantly increased both basal (by 89%: P < 0.01) and bombesin-stimulated (by 39% P < 0.05) gastrin release. A similar pattern of increase was seen following TNF-alpha (20 ng mL-1) pretreatment of human antral fragments: basal gastrin release was increased by 38% (P < 0.05) and bombesin-stimulated by 26% (P < 0.05). This effect persisted during immunoblockade with anti-somatostatin antibody S6. We propose that TNF-alpha provides the link between Hp infection and gastrin release and thus contributes to duodenal ulceration.

Topics: Animals; Cells, Cultured; Dogs; Duodenal Ulcer; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; In Vitro Techniques; Pyloric Antrum; Tumor Necrosis Factor-alpha

To explore the state of the gastric mucosa in individuals with and without peptic ulcer disease from populations with contrasting peptic ulcer risks.. Pepsinogen A, pepsinogen C, gastrin and Helicobacter pylori antibodies are serological markers of gastritis. A decreasing pepsinogen A-C ratio and pepsinogen A level are known to reflect an increasing severity of corpus atrophy, whereas gastrin levels decrease with an increasing severity of antral atrophy when corpus atrophy is present. Helicobacter pylori-positive men, with and without a peptic ulcer history, were the focus of the study.. In 190 Japanese and 425 Dutch male employees, of similar age (mean age 49 years) and level of occupation, fasting serum samples were analysed in the same laboratory for IgG antibodies to H. pylori, pepsinogen A, pepsinogen C and gastrin. Any history of ulcer disease was verified through case notes.. The H. pylori seropositivity rate was higher in the Japanese men (72%) than in the Dutch (33%). There were 23 (12%) Japanese and 18 (4%) Dutch men with a verified duodenal ulcer history, and 14 (7%) Japanese and two (0.5%) Dutch men with a verified gastric ulcer history. H. pylori-positive men with a duodenal ulcer history differed from the H. pylori-positive men without an ulcer history in that they had a significantly higher mean pepsinogen A level (64 and 51 micrograms/l in Japanese men and 71 and 57 micrograms/l in Dutch men) and also a higher mean pepsinogen A-C ratio, whereas pepsinogen C and gastrin levels did not differ. In H. pylori-positive gastric ulcer patients the mean gastrin level was significantly lower than in H. pylori-positive men without ulcer disease (17 and 37 pmol/l in Japanese men), whereas pepsinogen levels were similar.. This study suggests that in H. pylori-positive duodenal ulcer patients there is less mucosal atrophy of the corpus and in H. pylori-positive gastric ulcer patients more atrophy of the antrum than in H. pylori-positive individuals without peptic ulcer disease.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Case-Control Studies; Chi-Square Distribution; Duodenal Ulcer; Employment; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Japan; Male; Middle Aged; Netherlands; Pepsinogens; Prevalence; Stomach Ulcer

The effects of acid, infectious (Helicobacter pylori) and neuroendocrine factors on the course and outcome of chronic duodenitis were studied in 57 patients aged 15-35 years. Within 5-year follow-up ulcer emerged in 26% of duodenitis patients. Ulceration occurred as a result of high acid production in the basal and stimulated phases, contamination of pyloric-antral mucosa with Helicobacter pylori, unbalance of serum hormones T4, TTH, FSH, ACTH. In risk of ulcerogenesis there were psychological shifts with appearance of pathological reaction to the disease. Consideration of pathogenetic specificity of different duodenitis forms and basing on objective and subjective criteria allow identification of ulcer risk group and early start of optimal therapy.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Chronic Disease; Duodenal Ulcer; Duodenitis; Follicle Stimulating Hormone; Follow-Up Studies; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Risk Factors; Stomach; Thyroid Hormones; Time Factors

A "gastrin link" has been suggested to explain the statistically relevant association between Helicobacter pylori and duodenal ulcer. Given the well known, although not entirely clarified, relationships between gastrin and histamine, the purpose of this study was to assess whether gastric mucosal histamine pathways and, more specifically, histamine-storing cells are involved in the Helicobacter pylori-duodenal ulcer route.. Fasting serum gastrin, gastric mucosal histamine content, and mucosal density of both enterochromaffin-like cells and mast cells were compared in 11 H. pylori-positive, non-duodenal ulcer subjects, in 16 duodenal ulcer patients (all H. pylori positive), and in 11 H. pylori-negative control subjects.. Fasting serum gastrin concentration and mucosal histamine content were significantly higher in the duodenal ulcer group than in controls, whereas H. pylori-positive, non-ulcer subjects had values that were intermediate between those of the other two groups. Enterochromaffin-like cell density was significantly greater in duodenal ulcer patients than in the other groups.. These results demonstrate the involvement of histamine pathways in H. pylori infection and duodenal ulcer. The most original finding in this study was that enterochromaffin-like cell density is three times greater in duodenal ulcer patients than in H. pylori-positive, non-ulcer subjects. This could explain the previous report of an exaggerated acid response to gastrin in duodenal ulcer patients when compared with H. pylori-positive, non-ulcer subjects and thus provide further insight into the pathogenesis of ulcers.

Topics: Biopsy; Case-Control Studies; Cell Count; Duodenal Ulcer; Enterochromaffin Cells; Female; Gastric Mucosa; Gastrins; Helicobacter pylori; Histamine; Humans; Male; Mast Cells; Middle Aged

In rats, changes in gastric nerve fibers containing gastrin-releasing peptide (GRP) in cysteamine-induced duodenal ulcer were investigated in relation to the dynamics of gastrin-producing cells (G-cells). Marked increases in gastric acid secretion and serum gastrin level were observed from 2 h after the administration of cysteamine. The number of G-cells was significantly decreased from 2 h after the injection of cysteamine. Two and 4 h after the administration of cysteamine, the G-cells showed ultrastructural changes characterized by a markedly decreased number of secretory granules. Circulating GRP levels were significantly elevated from 2 h after the administration of cysteamine. In the control group given vehicle only, nerve fibers showing immunoreaction for GRP formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa, located close to capillaries and demonstrated varicosities that contained either small clear vesicles or GRP-immunopositive vesicles with large cores. Eight h after the administration of cysteamine, there was depleted GRP immunoreactivity, evidenced by a markedly decreased number of vesicles, with large electron-dense cores, in the oxyntic mucosa. These findings suggest that, in cysteamine-induced duodenal ulcer, alterations in gastric nerve fibers containing GRP may be related to hypergastrinemia.

Topics: Animals; Cell Count; Cysteamine; Duodenal Ulcer; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Immunohistochemistry; Male; Microscopy, Immunoelectron; Nerve Fibers; Peptides; Radiation-Protective Agents; Radioimmunoassay; Rats; Rats, Wistar; Stomach

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.. 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.. 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.. 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.

Topics: Adult; Case-Control Studies; Cholecystokinin; Duodenal Ulcer; Food; Gastric Acid; Gastrins; Hormone Antagonists; Humans; Hydrogen-Ion Concentration; Male; Premedication; Proglumide; Receptors, Cholecystokinin; Somatostatin; Time Factors

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori.

Topics: Adult; Cholecystokinin; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Monitoring, Physiologic; Proglumide; Somatostatin

The behaviour of basal and stimulated acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids was studied in 19 consecutive patients with Helicobacter pylori positive duodenal ulcer, over a follow up period of six months. Eleven patients were studied before and at three and six months after eradication with lansoprazole plus amoxicillin and tinidazole (case group), whereas the remainder, with persistent H pylori infection, were studied before and after three and six months from ulcer healing, thus constituting the control group. In the case group, three months after eradication, fasting serum pepsinogen I fell from (mean (SEM)) 91.9 (6.9) (pretreatment) to 72.2 (5.1) ng/l and the integrated gastrin response to a meal reduced from 11,470 (1174) (pretreatment) to 8130 (608) pg/ml/h (p < 0.05). Fasting serum gastrin concentrations and maximal acid output reduced significantly only six months after eradication. In contrast, no significant change of any of these measurements was seen in the control group either at three or six months from healing compared with the pretreatment values. Gastric emptying of liquids did not change over the entire period of follow up in both study groups. In conclusion, eradication of H pylori in duodenal ulcer patients is accompanied by a rapid fall in serum pepsinogen I and plasma gastrin concentrations, whereas a slight but significant reduction of maximal acid secretion takes place later on. In contrast, gastric emptying of liquids does not seem to be influenced by H pylori status.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Emptying; Gastrins; Helicobacter Infections; Humans; Male; Pepsinogens; Time Factors

Recent studies on the role of Helicobacter pylori in the pathogenesis of duodenal ulcers have focused on the mechanism by which H. pylori infections cause exaggerated gastrin release.. We determined meal-stimulated serum gastrin concentrations and antral somatostatin content in 24 asymptomatic volunteers (6 H. pylori-infected, 18 H. pylori-uninfected). Somatostatin content was determined by radioimmunoassay in biopsy specimens obtained from the antrum.. Fasting and integrated 2-h gastrin concentrations were significantly higher in H. pylori-positive volunteers than in H. pylori-negative volunteers (fasting, 111 +/- 16.3 pmol/l versus 53.4 +/- 3.5 pmol/l; p < 0.05; integrated 2-h, 267 +/- 41.2 pmol/l versus 70.1 +/- 2.1 pmol/l; p < 0.01). Antral somatostatin content was 0.764 +/- 0.173 ng/mg and 2.931 +/- 0.414 ng/mg in H. pylori-positive and -negative volunteers, respectively (p < 0.01).. Low antral somatostatin content may cause hypergastrinemia in asymptomatic healthy volunteers, and H. pylori may contribute to the pathogenesis of duodenal ulcer, through this mechanism.

Topics: Adult; Biopsy; Duodenal Ulcer; Gastrins; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Pyloric Antrum; Radioimmunoassay; Somatostatin

To evaluate endogenous and exogenous factors affecting the quality of ulcer healing produced by proton pump inhibitors, gastric acid pH, serum gastrin, and serum pepsinogen (PG) I and II were measured in peptic ulcer patients before and after treatment with lansoprazole 30 mg once daily. Lansoprazole achieved more rapid scarring in duodenal ulcer (n = 34), with a healing rate of 97.1% after 6 weeks, than in gastric ulcer (n = 56), with a healing rate of 92.8% after 8 weeks. Scarring was the most rapid in gastroduodenal ulcer (n = 8), with a healing rate of 100% after 8 weeks, but the rate of complete scarring was the lowest (37.5%). Lower gastric acidity and lower PG I:II ratio were associated with poor quality ulcer scarring in patients with gastric ulcers, but the opposite was true for those with duodenal and gastroduodenal ulcers. For gastric ulcers, not only ulcer size but also mucosal atrophy was an important factor in ulcer healing. Smoking and alcohol consumption had little effect on the quality of ulcer healing during treatment. These results suggest that there are a number of differences between gastric ulcers and duodenal ulcers in terms of the quality of ulcer healing after lansoprazole treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Age Factors; Alcohol Drinking; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Pepsinogens; Peptic Ulcer; Proton Pump Inhibitors; Sex Factors; Smoking; Stomach Ulcer

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.. 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).. 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.. 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.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Prevalence; Retrospective Studies

The mechanism by which Helicobacter pylori predisposes to duodenal ulcers (DUs) remains unclear. The aim of this study was to investigate the effect of the infection on acid secretion.. Acid output was examined basally and in response to gastrin-releasing peptide (GRP) and gastrin in healthy volunteers with and without H. pylori infection and in patients with DUs before and after eradication of the infection.. Compared with H. pylori-negative healthy volunteers, patients with DUs with H. pylori had the following abnormalities of acid secretion: (1) threefold increase in basal acid output, (2) sixfold increase in acid response to GRP, (3) increased maximal acid response to exogenous gastrin, (4) increased ratio of basal acid output to maximal gastrin-stimulated output, and (5) increased ratio of maximal GRP-stimulated acid output to maximal gastrin-stimulated output. All of these abnormalities resolved fully after H. pylori eradication except for increased maximal acid output to gastrin, which was unchanged. Infected healthy volunteers showed a threefold increase in acid response to GRP that resolved after eradication of H. pylori infection.. These disturbances in acid secretion caused by H. pylori infection are consistent with impaired inhibitory control and are likely to be relevant to the mechanism by which the infection predisposes to DU.

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Metronidazole; Organometallic Compounds; Peptides; Reproducibility of Results

To examine gastric secretion in duodenal ulcer patients; simultaneous assessment of serum gastrin and pepsinogen I levels and acid secretion.. 32 patients with duodenal ulcer disease were studied (mean age: 44.7 +/- 14 years, 24 males (75%). At endoscopy, biopsy specimens from duodenal bulb, antrum, body and gastric fundus were taken. Basal levels of acid secretion, pepsinogen I and gastrin were measured, as well as stimulated levels (with pentagastrin and beef meal).. Mean (+/- SD) BAO and MAO was 5.5 +/- 4 and 27.7 +/- 10 mEq/h, respectively. BAO in males were higher than in females (p < 0.05). A positive correlation (p < 0.01) was observed between MAO, and basal and stimulated pepsinogen I. Basal and stimulated (integrated-90 min) gastrin levels were 43.4 +/- 12 pg/ml and 5,260 pg/ml min, respectively. No correlation between such levels and acid secretion or pepsinogen I was observed. Mean basal and stimulated (integrated-120 min) pepsinogen levels were 109.3 +/- 35 ng/ml and 4,950 +/- 160 ng/ml min, respectively, and they were higher in males (p < 0.01), and in smokers (p < 0.05).. It was confirmed, in a group of duodenal ulcer patients, that BAO is higher in males than in females. There is a positive correlation between MAO and pepsinogen I levels, although this correlation is not present between gastrin levels and acid secretion or pepsinogen I. Pepsinogen I levels are higher in males and smokers.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Pepsinogens; Radioimmunoassay; Sex Characteristics

Primary endocrine neoplasms of intra- and extrahepatic biliary ducts are very rare. We describe the first case of a primary endocrine tumor of the common bile duct producing gastrin. A 53-year-old woman had a 3-year history of recurrent duodenal and gastric ulcers as well as obstructive jaundice. A small neoplasm was found in the lower third of the common bile duct, which showed diffuse gastrin production and focal synthesis of serotonin and pancreatic polypeptide by immunohistochemistry and electron microscopy. Although serum gastrin was within normal levels (90 ng/ml), symptoms of peptic acid disease could have been related to hypergastrinemia, since gastric and duodenal ulcers healed after surgical removal of the tumor. She has remained asymptomatic for 8 months.

Topics: Cholestasis; Common Bile Duct Neoplasms; Duodenal Ulcer; Female; Gastrinoma; Gastrins; Humans; Immunohistochemistry; Middle Aged; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric

Acid secretion in response to gastrin releasing peptide (GRP) is increased six-fold in Helicobacter pylori positive duodenal ulcer (DU) patients and threefold in H pylori positive healthy volunteers, and this fully resolves after eradication of the infection. This study was undertaken to determine whether a proportion of H pylori positive patients with non-ulcer dyspepsia (NUD) have an acid secretion disturbance similar to DU patients. Basal and GRP stimulated gastrin concentrations and acid output were examined in 25 H pylori positive NUD patients and the results compared with those of 25 H pylori positive healthy volunteers, 25 H pylori negative healthy volunteers, and 25 H pylori positive DU patients. Compared with the H pylori negative healthy volunteers, GRP stimulated gastrin was increased approximately three fold in each of the three infected groups. GRP stimulated acid secretion (median, range) was higher in the H pylori positive NUD patients (29.6 mmol/h (5.2-46.5)) (p < 0.005) than in the H pylori positive healthy volunteers (19.0 (1.0-38.3)) (p < 0.001) or H pylori negative healthy volunteers (6.3 (2.8-20.9)) (p < 0.0001). The H pylori positive NUD patients, however, had lower acid output than the DU patients (39.1 (17.9-64)) (p < 0.005). These findings are consistent with approximately 50% of the NUD patients having a similar disturbance of GRP stimulated acid secretion to DU patients.

Topics: Adolescent; Adult; Duodenal Ulcer; Dyspepsia; Female; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptides; Stimulation, Chemical

Hypergastrinemia has long been considered an important factor in the pathophysiology of duodenal ulcer. Moreover, H. pylori infection has been reported in virtually all duodenal ulcers.. To demonstrate the influence of H. pylori eradication on the basal levels of serum gastrin in patients with duodenal ulcer.. Seventy-six patients with endoscopically proved duodenal ulcer were prospectively studied. At endoscopy three biopsy samples each were taken from duodenal bulb, gastric antrum, corpus and fundus. Two samples from every location were submitted for conventional histological examination and the other for microbiological examination (Gram staining and culture). Endoscopy was repeated one month after the end of therapy, when endoscopy samples were again obtained from the gastric antrum and corpus. Basal levels of gastrin were measured both at initial and repeat endoscopies. Different therapeutic regimes were used: Amoxycillin/Clavulanate plus omeprazole or ranitidine, and triple therapy.. H. pylori eradication was associated with a significant histological improvement (p < 0.001), both in antrum and corpus. In those patients with eradicated H. pylori the differences in basal gastrin levels both at diagnosis and after therapy were 45.4 +/- 11 pg/ml and 36.7 +/- 10 pg/ml, respectively; these differences were statistically significant (p < 0.001). When eradication was not achieved differences were not significant. The area under the ROC curve constructed from the different cutoff points for the gastrin decreases was 0.68 (EE 0.06).. H. pylori eradication in patients with duodenal ulcer was associated with a significant decrease in basal levels of serum gastrin. Although the verification of such a decrease doesn't have an optimal relationship between sensitivity and specificity, it could be an aid as a useful non-invasive method to monitor the efficiency of therapy, both in H. pylori eradication and in the resolution of the associated gastritis. This procedure is also associated with early results and a low cost.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrins; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; ROC Curve; Sensitivity and Specificity

To evaluate the evolution of fundic argyrophil cell density and hyperplasia grading, fundic chronic gastritis grading and serum gastrin levels in patients treated with proton pump inhibitors.. Thirty-two patients treated with proton pump inhibitors for gastroesophageal reflux and/or duodenal ulcer were studied. No patient had a gastric ulcer. The studied parameters were serum gastrin levels, fundic argyrophil cell density, the degree of fundic argyrophil cell hyperplasia, the grade of fundic atrophic gastritis and the presence of Helicobacter pylori. The first point of the study was 7 months (range: 0-42 months) and the last point 33 months (range: 7-72 months) after the beginning of the treatment.. Serum gastrin levels significantly increased with treatment. Fundic argyrophil cell density did not change significantly. In 3 patients (9%), serum gastrin levels were twice the normal upper limit. The highest serum gastrin levels (249 and 665 pg/mL) were noted in the 2 patients treated with the highest doses of proton pump inhibitors. Micronodular hyperplasia of the fundic argyrophil cells was observed in 2 patients treated with omeprazole 20 mg/d for 4 years and lansoprazole 90 mg/d for 6 years, respectively. Non active superficial chronic gastritis was noted in 2 patients. Serum gastrin levels were significantly correlated with cell densities.. There were minor modifications of fundic argyrophil cell population and of gastrinaemia during the study period. They were not related to chronic atrophic gastritis. However, survey is mandatory in patients treated with high dose proton pump inhibitors, in those in whom gastrinaemia is elevated and when treatment duration is longer than 5 years.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Enzyme Inhibitors; Female; Gastric Fundus; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Time Factors

Results of prognostic tests of vagotomy were studied in 365 patients with chronic duodenal ulcers (CDU). It was established that the atropin test can not be taken as the main criterion of prognosis of vagotomy. However, according to its results the patients can be divided into 2 groups: atropin sensitive (69.3%) and atropin-resistant (30.7%). According to the parameters of the atropin test and the night gastric secretion the patients were divided into 3 groups: favorable (45.7%), doubtful (31.0%) and unfavorable (23.3%) prognosis of effectiveness of vagotomy with draining operations of the stomach.

Topics: Atropine; Chronic Disease; Drug Resistance; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Nervous System Physiological Phenomena; Parasympatholytics; Phenylephrine; Prognosis; Recurrence; Reflex; Risk Factors; Sympathomimetics; Vagotomy

Changes in gastric acid secretion and fasting gastrin levels (FGL) during the healing of duodenal ulcers were investigated. Duodenal ulcers were classified into three stages, with regard to healing, active, healing, and healed (scar). As controls, 49 individuals without gastro-duodenal lesions were used. We found that gastric acid secretion was highest during the active stage, thereafter decreasing during the healing and healed stages. Gastric acid secretion was lowest in the normal subjects, and significant differences were found between the 3 stages of the duodenal ulcers. FGL was also highest in the active stage, thereafter decreasing during the healing and healed stages. In the follow-up of 10 doudenal ulcer patients, gastric acid secretion and FGL were higher in the active than in the healed stage. It was concluded that gastric acid secretion and FGL change during the healing of duodenal ulcers. The increase of gastric acid secretion and FGL seen in the active stage appears to be implicated in the pathogenesis of the duodenal ulcer.

Topics: Adult; Duodenal Ulcer; Fasting; Female; Gastric Acid; Gastrins; Humans; Male; Wound Healing

It is well known that acupuncture is effective for treatment of gastric disease in human. We have observed the effect of acupuncturing "Zhongwan" "Neiguan" "Zusanli" on fluorohistochemical changes of G cells of antral mucosa in 42 patients with gastric disease. The results show that after acupuncture treatment the amount of fluorescent G cells and the fluorescent intensity of gastrin in the G cells were obviously decreased in patients with duodenal ulcer, as compared with that before acupuncture treatment. However, the amount of G cells was increased by acupuncture treatment in patients with chronic atrophic gastritis. These data indicate the acupuncture may regulate G cell from abnormal to normal condition in gastric mucosa of gastric disease.

Topics: Acupuncture Therapy; Chronic Disease; Duodenal Ulcer; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Gastritis; Humans; Pyloric Antrum

Topics: Adult; Cimetidine; Duodenal Ulcer; Fasting; Gastrins; Humans; Male; Ranitidine

The synchronous changes in antral gastrin and somatostatin release in anesthetized, nonatropinized duodenal ulcer patients and control subjects were investigated by serial intraoperative blood sampling from the right gastroepiploic vein. The mean basal antral plasma gastrin and somatostatin concentrations of the two groups did not differ significantly. The significantly greater gastric acid secretory response to systemic gastric acid stimulation (pentagastrin stimulation) in duodenal ulcer patients compared with that of control subjects was not linked to any difference in antral somatostatin release pattern. The decrease in antral plasma gastrin release was significantly lower after acid instillation and the increase was significantly higher after alkali instillation in duodenal ulcer patients compared with those of controls, indicating an abnormal gastrin response to intragastric pH changes in duodenal ulcer patients, which was again not found to be coupled to any significant difference in antral somatostatin release. The results suggest that an abnormal somatostatin-mediated inhibition of gastrin release and/or gastric acid secretion does not exist in duodenal ulcer patients.

Topics: Anesthesia; Atropine; Cholelithiasis; Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Hydrogen-Ion Concentration; Pentagastrin; Pyloric Antrum; Somatostatin; Time Factors

Changes in serum gastrin levels in the late postoperative period have been studied in 24 patients with non-stenotic duodenal ulcer who underwent proximal gastric vagotomy. Twenty healthy volunteers were used as a control group. Serum gastrin levels were determined under basal conditions and after a high protein meal stimulation. Both measurements were done in the preoperative, early postoperative (12th day) and late postoperative periods (X = 5.5 yrs.). Regarding basal serum gastrin levels, the results show mean values of 46.2 pg/ml in the preoperative, 61.6 pg/ml in the early postoperative, 73.9 pg/ml in the late postoperative and 51 pg/ml in the control group. Early and late postoperative period values show statistical significant differences when compared with preoperative values (p < 0.05), but not with the control group ones. Stimulated gastrin levels show mean values of 75.7 pg/ml in the preoperative, 99.1 pg/ml in the early postoperative, 134.1 pg/ml in the late postoperative and 73.4 pg/ml in the control group. Late postoperative values show statistical significant differences when compared with preoperative and early postoperative values (p < 0.05), and also when compared with the control group (p < 0.05). Possible causes and the physiopathological effects of these variations are discussed.

Topics: Adolescent; Adult; Aged; Dietary Proteins; Duodenal Ulcer; Elective Surgical Procedures; Female; Gastrins; Humans; Male; Middle Aged; Postoperative Period; Time Factors; Vagotomy, Proximal Gastric

Content of gastrin, glucagon and insulin in the blood of 49 patients with a duodenal ulcer was similar to that in control group patients. Significant increase in gastrin and glucagon levels, decrease in insulin content was noted 14-15 days after the performance of selective proximal vagotomy. At the late period, concentration of the hormones studied was within the limits of physiologic levels. The data obtained permit to assess the completeness of vagotomy and to predict the long-term result of the operation.

Topics: Duodenal Ulcer; Gastrins; Glucagon; Humans; Insulin; Time Factors; Vagotomy, Proximal Gastric

To understand the short-term and long-term effects of the eradication of Helicobacter pylori on serum pepsinogen I, gastrin, and insulin concentration, we studied 53 patients with endoscopically proven duodenal ulceration and H. pylori infection.. All patients received a 2-wk course of colloidal bismuth subcitrate, amoxycillin, and metronidazole, and endoscopy was performed at 1.5, 3, 6, and 12 months after entry. H. pylori status was assessed by a urease test and histology.. Among 43 patients in whom H. pylori was eradicated throughout the follow-up year, the mean basal pepsinogen I was 108 ng/ml at pretreatment, decreasing significantly to 85, 77, 80, and 75 ng/ml at 1.5, 3, 6, and 12 months, respectively, at posttreatment. The basal gastrin was 100 pg/ml at pretreatment and fell significantly to 72, 64, 65, and 59 pg/ml, respectively, posttreatment. Of the four patients in whom the H. pylori was not eradicated, there was no significant change in the median basal pepsinogen I and gastrin concentration. Among the six patients in whom the H. pylori was again detectable within the follow-up year, the fallen serum concentration of pepsinogen I and gastrin returned to the pretreatment level. There was no significant change of basal insulin concentration after triple therapy in either the successfully eradicated or failed group.. We conclude that H. pylori is the leading and direct cause of higher serum concentration of pepsinogen I and gastrin in duodenal ulcer patients.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Insulin; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pepsinogens; Time Factors

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

We measured basal and pentagastrin-stimulated acid secretion, as well as basal and meal-stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin-related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger-Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti-Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger-Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal-stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16% vs duodenal ulcer 2% P = 0.0144). In the presence of duodenal ulcer disease resistant to H2-blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin-related syndromes, Zollinger-Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.

Topics: Adult; Aged; Antibodies, Bacterial; Duodenal Ulcer; Enzyme-Linked Immunosorbent Assay; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Zollinger-Ellison Syndrome

The density of antral gastrin (G)- and somatostatin (D)-immunoreactive cells and the contents of antral gastrin and somatostatin were investigated in endoscopic antral biopsy specimens from patients with duodenal ulcer before and after eradication of Helicobacter pylori. After H. pylori eradication both antral somatostatin concentration (p = 0.0002) and antral D-cell density (p = 0.01) increased significantly. Conversely, although the number of G-cells was unchanged, antral (p = 0.0002) and serum (p = 0.001) gastrin contents decreased significantly. The number of oxyntic D-cells did not change significantly. These results strongly suggest that the hypergastrinaemia observed in H. pylori-positive patients may be due to a deficiency in antral somatostatin, which normally inhibits the synthesis and release of gastrin.

Topics: Adult; Biopsy; Cell Count; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pilot Projects; Pyloric Antrum; Somatostatin; Time Factors

The number, size, and volume density of endocrine cells was determined in biopsies obtained endoscopically in patients after proximal selective vagotomy (PSV; N = 31), antrectomy (N = 9), untreated duodenal ulcer (DU) disease (N = 11), and in controls (N = 15). Serum gastrin was significantly elevated after PSV (mean 60 pg/ml) compared to DU patients (29 pg/ml), controls (26 pg/ml), and after antrectomy (11 pg/ml). Volume density of fundic argyrophil (largely enterochromaffin-like) cells after PSV (0.74%) and in DU disease (0.63%) were significantly (P < 0.001) higher when compared with controls (0.37%) but lower after antrectomy (0.24%; P < 0.02). The density of argyrophil cells was not influenced by the interval following PSV or the magnitude of hypergastrinemia. Antral gastrin cells were increased after vagotomy, whereas the antral and fundic somatostatin cell numbers were reduced after PSV. It is concluded that: (1) a major role of the vagal nerve as a trophic factor for enterochromaffin-like cells could not be demonstrated after PSV, and (2) moderate hypergastrinemia after PSV did not induce proliferation of ECL cells.

Topics: Adult; Aged; Biopsy; Duodenal Ulcer; Enterochromaffin Cells; Female; Gastrectomy; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Vagotomy, Proximal Gastric

Topics: Biopsy; Duodenal Ulcer; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pyloric Antrum; Somatostatin

In order to ascertain possible abnormalities in somatostatin and gastrin secretion in patients with duodenal ulcer, the author compared bombesin-stimulated somatostatin and gastrin secretion by antral mucosal explants in patients with duodenal ulcer, those with atrophic gastritis and normal controls. An organ culture technique was employed. This excluded neurogenic, hormonal and circulatory influences. Bombesin in concentrations of 10(-7) M to 10(-5) M stimulated gastrin and somatostatin secretion at a dose-dependent manner. In all subjects, bombesin (10(-7) M) stimulated antral gastrin release and increased explant gastrin content significantly (p < 0.05). Bombesin significantly increased somatostatin release and explant somatostatin content in normal subjects (p < 0.05) but not in patients with duodenal ulcer (p > 0.05). In the presence of bombesin, the total net increase of gastrin in medium and explants was greater in duodenal ulcer patients (31.57 +/- 5.20 ng/mg wet w.) compared with normal subjects (19.63 +/- 4.50 ng/mg wet w.) (p < 0.01). The total net increase of somatostatin in the presence of bombesin was significantly less in duodenal ulcer patients (0.10 +/- 0.02 ng/mg wet w.) than in normal subjects (1.45 +/- 0.24 ng/mg wet w.) (p < 0.01). The results suggest that abnormalities in somatostatin and gastrin secretion of the antrum contribute to the pathogenesis of increased gastric acid secretion in duodenal ulcer.

Topics: Adult; Bombesin; Culture Techniques; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastrins; Gastritis, Atrophic; Humans; Intestinal Mucosa; Male; Middle Aged; Somatostatin

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.

Topics: Adult; Aged; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Glucagon-Like Peptides; Humans; Male; Middle Aged; Oxyntomodulin; Radioimmunoassay

To compare gastric secretory function in patients with duodenal ulcer and in healthy volunteers with and without Helicobacter pylori infection.. Basal acid output, peak acid output, meal-stimulated acid output, fasting and meal-stimulated serum gastrin concentrations were measured in 136 healthy volunteers (63 H. pylori positive, 73 H. pylori negative) and 52 duodenal ulcer patients, all but one of whom were H. pylori positive.. By multivariate linear regression analysis, H. pylori infection was a significant negative predictor of basal acid output and a positive predictor of fasting and meal-stimulated gastrin concentrations. When compared to truly normal (i.e., H. pylori-negative) control subjects, duodenal ulcer patients had elevated basal acid output, peak acid output, fasting and meal-stimulated gastrin concentrations.. Our results show that in patients with duodenal ulcer disease, hypergastrinemia is largely related to gastric H. pylori infection, whereas acid hypersecretion is due to factors other than H. pylori.

Topics: Adult; Antibodies, Bacterial; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

Helicobacter pylori infection increases the serum concentration of gastrin, and this may be one of the mechanisms by which it predisposes to duodenal ulceration. Different forms of circulating gastrin were studied both basally and postprandially in 13 duodenal ulcer patients before and one month after eradication of H pylori. Three antisera that are specific for particular regions of the gastrin molecules were used. Gel chromatography indicated that > 90% of the circulating gastrin consisted of gastrin (G) 17 and G34 both before and after eradicating the infection. The basal median total immunoreactive gastrin concentration fell from 26 pmol/l (range 11-43) to 19 pmol/l (8-39) (p < 0.05), entirely because of a fall in G17 from 6 pmol/l (< 2.4-25) to < 2.4 pmol/l (< 2.4-23) (p < 0.001). The median (range) basal G34 values were similar before (15 pmol (2-36)) and after (10 pmol (2-30)) eradication. The median total immunoreactive gastrin concentration determined 20 minutes postprandially fell from 59 pmol/l (38-114) to 33 pmol/l (19-88) (p < 0.005), and again this was entirely the result of a fall in G17 from 43 pmol/l (9-95) to 17 pmol/l (< 2.4-52) (p < 0.001). The median postprandial G34 values were similar before (13 pmol/l, range 6-42) and after (15 pmol/l, range 6-30) eradication. Eating stimulated a noticeable rise in G17 but little change in G34, both in the presence and absence of H pylori. The finding that H pylori infection selectively increases G17 explains why the infection causes mainly postprandial hypergastrinaemia. G17 is increased selectively because H pylori predominantly affects the antral mucosa which is the main source of G17 whereas G34 is mainly duodenal in origin. This study also indicates that the increased concentration of gastrin in H pylori infection is the result of an increase in one of the main biologically active forms of the hormone.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Protein Precursors

In the past five years 12 patients have been identified presenting with chronic duodenal ulcer (DU) disease and with no evidence of current or recent Helicobacter pylori (H pylori) infection. Four of them were taking regular non-steroidal anti inflammatory agents, one was subsequently found to have Crohn's disease of the duodenum, and one to have the Zollinger-Ellison syndrome. The remaining six patients with idiopathic DU disease were remarkable for their absence of the A1 blood antigen gene. Detailed studies of gastric function were performed in these six patients and compared with H pylori positive patients with DU and with healthy volunteers. The median integrated gastrin response in the patients with idiopathic DU (2810 (range 750-8750) ng/l min) was similar to that of the H pylori positive patients with DU (3355 (550-8725)) and higher than that of the H pylori negative healthy volunteers (560 (225-1125)). The median peak acid output in the patients with idiopathic DU (37 mmol/h, range 17-52) was similar to that of the H pylori positive patients with DU (40 (15-57)) and higher than that of the non-ulcer controls (22 (16-29)). The median percentage of a liquid meal retained in the stomach at 60 minutes was less in the patients with idiopathic DU (23 (15-33)) than in H pylori negative healthy volunteers (34 (30-53) p < 0.01). The median percentage of a solid meal retained at 60 minutes was less in the patients with idiopathic DU (54 (9-83)) than in either H pylori negative healthy volunteers (87 (49-95) p<0.01) or H pylori positive patients with DU (79 (51-100) p<0.01). In conclusion, three abnormalities of gastric function are prevalent in patients with H pylori negative idiopathic DU disease - hypergastrinaemia, increased acid secretion, and the one feature distinguishing them from H pylori positive patients with DU - rapid gastric emptying of both liquids and solids. Each of these abnormalities will increase the exposure of the duodenal mucosa to acid and thus explain its ulceration. The absence of the blood group A1 antigen gene is consistent with a genetic basis for the disturbed gastric function linked to the ABO blood group antigen genes.

Topics: ABO Blood-Group System; Adult; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastric Emptying; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

The relation between Helicobacter pylori (H pylori) infection and fasting gastrin and pepsinogen-I and -II concentrations was evaluated in 278 volunteers without symptoms and the results were compared with the values obtained in 35 patients with duodenal ulcers. H pylori infection was determined with the 13C-urea breath test in subjects without symptoms and with endoscopy, biopsy (histology and culture), and quick urease test (CLO-test) in patients with duodenal ulcers. Gastrin and pepsinogen-I and -II concentrations were assayed with specific radioimmunoassay systems. The results clearly indicate that fasting gastrin and pepsinogen-I and -II concentrations were significantly higher in H pylori positive compared with H pylori negative subjects. Neither age nor sex affected basal gastrin and pepsinogen concentrations in H pylori negative subjects. Fasting gastrin, pepsinogen-I and -II concentrations in serum samples were similar in H pylori positive persons with no symptoms and those with duodenal ulcers suggesting that similar mechanisms are involved in increasing plasma concentrations of these variables in both populations. Hypergastrinaemia and hyperpepsinogenaemia are therefore probably secondary to active H pylori infection.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Sex Factors

Smoking is associated with an increased incidence of duodenal ulcer with a high relapse rate, and smokers tend to be slow healers. The etiology responsible for this remains unknown, and there is general disagreement as to whether smoking affects gastric secretion. The aim of the present study was to investigate both aggressive and protective factors in response to vagal stimulation induced by modified sham feeding (MSF) in duodenal ulcer patients when smoking versus not smoking. On smoking days, nicotine concentrations in plasma averaged about 15 ng/ml and were extremely high in saliva and gastric juice (> 1300 and > 800 ng/ml, respectively). MSF induced a significant decrease in intragastric pH during non-smoking (p = 0.01) but not during smoking. Acid output 1 h after MSF was lower on smoking than on non-smoking days (p = 0.02), as was volume secretion (p = 0.02). Plasma gastrin concentrations were significantly increased during MSF on non-smoking days (p = 0.04) but not on smoking days, the concentrations during the whole day being lower on smoking days (p = 0.002). Plasma catecholamine levels were unaffected by MSF, whether smoking or not. However, plasma concentrations of noradrenaline decreased during the smoking of a single cigarette (p = 0.03), whereas those of adrenaline were increased on smoking days (p = 0.02). Epidermal growth factor concentrations were decreased in gastric juice after MSF during non-smoking (p = 0.01) but not during smoking. Although prostaglandin E2 (PGE2) concentrations in gastric juice were unaffected by MSF, PGE2 output increased after MSF whether smoking or not, the increment being non-significantly less during smoking (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bile Acids and Salts; Catecholamines; Dinoprostone; Duodenal Ulcer; Eating; Epidermal Growth Factor; Female; Gastric Acid; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Nicotine; Saliva; Smoking; Vagus Nerve

The histamine concentration of the oxyntic mucosa was determined in Helicobacter pylori-positive patients with duodenal ulcer before and after antimicrobial therapy and in H. pylori-negative subjects. Determination of serum gastrin was also performed in duodenal ulcer patients before and after H. pylori eradication. The histamine content of the oxyntic mucosa was lower in patients with duodenal ulcer than in H. pylori-negative subjects, but it increased after H. pylori eradication. Conversely, in patients in whom therapy failed to eradicate the microorganism, the histamine content remained unchanged. Serum gastrin levels fell after microorganism eradication, and the percentage of this fall was correlated with the percentage of increase in gastric histamine. In conclusion, our findings suggest that abnormalities of histamine store present in duodenal ulcer patients might be a feature of H. pylori infection.

Topics: Adult; Amoxicillin; Drug Therapy, Combination; Duodenal Ulcer; Female; Furazolidone; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Male; Metronidazole; Time Factors

The effect of ulcer healing with eradication of Helicobacter pylori (H pylori) on gastric function was investigated in nine patients with duodenal ulcer disease. One month after eradication there were significant reductions in both basal plasma gastrin concentration, from a median (range) of 19 (1-22) to 6 (2-15) pmol/l (p < 0.05), and of basal acid secretion from 8.3 (2.4-24) to 2.6 (1.4-8.1) mM H+/h, (p < 0.01). The peak acid secretion rate was unchanged from 37 (16-59) to 37 (21-59) mM H+/h. After treatment there was no change in the parietal cell sensitivity to stepped infusions of gastrin heptadecapeptide: the median concentration of gastrin required for 50% of maximal acid secretion (EC50) was 41 (14.8-126) before and 33 (23-125) pmol/l after eradication of H pylori. The metabolic clearance rate of gastrin was also unaffected by the eradication of H pylori. Thus eradication of H pylori infection from patients with active duodenal ulcers is accompanied by falls in both basal gastrin release and basal acid secretion without a change in the parietal cell sensitivity to gastrin. Cyclical changes in H pylori infection may cause the variations in basal acid secretion that are seen in duodenal ulcer disease.

Topics: Acute Disease; Adult; Aged; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Parietal Cells, Gastric; Tetracycline

H. pylori infection is associated with acid-peptic disease, although its role in the pathogenesis is unclear. The purpose of this study was to determine if chronic infection in asymptomatic subjects impairs the inhibition of meal-stimulated gastrin and acid secretion that is observed normally at low intragastric pH. Presence of infection was determined by both C-14 urea breath test and serology. Acid secretion was measured under basal conditions and in response to peptone meal stimulation and pentagastrin. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and during peptone meal stimulation. Intragastric titration with 1% peptone during the first hour, and 8% peptone during the second hour, was performed at both pH 7.0 and 2.5 on different days to compare the inhibition of gastrin and acid secretion. Compared to noninfected subjects, asymptomatic individuals infected with H. pylori had significantly increased: (1) basal gastrin values (P < 0.005); (2) 8% peptone-stimulated gastrin responses at both pH 7.0 and 2.5 (P < 0.05); and (3) 8% peptone-stimulated acid output at pH 2.5 (P = 0.01). During the second hour of peptone-stimulation, subjects infected with H. pylori had significantly decreased inhibition of gastrin (52% vs 95%) (P = 0.002) and acid (30% vs 81%) (P = 0.01) secretion from pH 7.0 to 2.5. Thus, chronic infection with H. pylori results in impaired inhibition of gastrin and acid secretion at low intragastric pH during the second hour of peptone meal stimulation. These defects may be unrelated to the pathogenesis of acid-peptic disease, since they occur in asymptomatic subjects infected with H. pylori.

Topics: Adult; Aged; Duodenal Ulcer; Feedback; Food; Gastric Acid; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Peptones

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.

Topics: Adult; Cell Cycle; Duodenal Ulcer; Female; Flow Cytometry; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Omeprazole; S Phase; Time Factors

To investigate whether antral colonization by Helicobacter pylori (Hp) modifies gastrin-cell population, the number of G-cells was evaluated in antral biopsy specimens from 22 apparently healthy subjects and from 48 duodenal ulcer patients using a morphometric method. The level of serum immunoreactive gastrin in a sample of fasting serum obtained at the time of biopsy was also measured. In healthy subjects the G-cell count (evaluated according to G/I index) and the serum gastrin levels were not significantly different than those found in duodenal ulcer patients. When the antral colonization by Hp was assessed, we found that, both controls and duodenal ulcer Hp-positive patients had a mean G-cell count and fasting serum gastrin levels not significantly higher than in patients without Hp.

Topics: Adult; Biopsy; Cell Count; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Helicobacter pylori; Humans; Male; Pyloric Antrum

To study whether the vagus sustains basal secretion and stimulates acid and pepsin differently in duodenal ulcer (DU) and non-DU, we tested 144 patients with DU and 92 nonulcer controls, using 1-hr basal secretion followed by 15 min of modified sham feeding (MSF) and after 1 hr followed by a reference maximum elicited by 6 micrograms/kg pentagastrin given subcutaneously and observed for another 1 hr. Of all subjects, 97.5% responded to MSF by raising basal acid output (BAO) at least 15%. MSF added amounts of acid equal to 26-30% of peak acid output and 30-43% of peak pepsin output, regardless of diagnosis or level of basal secretion (including hypersecretors). Speed and duration of responses were similar in DU and controls. MSF did not substantially alter serum gastrin. Males secreted more acid and pepsin than females under all conditions, differences that persisted in DU but not in controls when outputs were corrected for body weight. Male DU but not female DU patients secreted more than corresponding controls. Sham feeding is an effective stimulus with similar characteristics in controls and DU patients. There was no evidence for saturation of vagal pathways in basal hypersecretors. MSF stimulation does not appear to involve gastrin. Hypersecretion in DU derives largely from responses in male DU.

Topics: Adult; Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Pepsin A; Reproducibility of Results; Sex Characteristics; Vagus Nerve

Topics: Drug Administration Schedule; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Omeprazole

We analyzed environmental factors, family history of peptic ulcer, gastric acid secretion, and serum levels of pepsinogen I (PG I) and gastrin in 56 juvenile patients with duodenal ulcer and 39 normal teenage subjects. Basal acid output and maximal acid output were significantly higher in our duodenal ulcer patients than in controls without ulcer (both, p < 0.01), and patients with duodenal ulcer showed significantly higher serum levels of PG I and gastrin than the controls (both, p < 0.001). There were no significant differences in any environmental factor between the patients and controls. Fifteen of the 17 patients who had one or both parents with hyperpepsinogenemia I had high serum PG I levels. Over half of the duodenal ulcer patients had high serum gastrin levels, irrespective of family history of hypergastrinemia. Our findings suggest that hyperpepsinogenemia I and hypergastrinemia are important characteristics and that genetic background, particularly the inheritance of a gastric mucosal trait expressed as hyperpepsinogenemia I, is frequently involved in the pathogenesis of juvenile duodenal ulcer.

Topics: Adolescent; Child; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Pepsinogens; Risk Factors

A 60-yr-old man with longstanding duodenal ulcer was found to have hyperchlorhydria, moderate fasting hypergastrinemia, and markedly exaggerated meal-stimulated gastrin release. Antral tissue specimens showed the proliferation of gastrin cells and increased gastrin content, and he was found to have Helicobacter pylori infection in the antral mucosa. His illness was diagnosed as primary gastrin cell hyperplasia with H. pylori infection. Eradication of H. pylori normalized not only gastrin hypersecretion but also gastrin cell hyperplasia. These results indicate that H. pylori infection could be one of the causes of this syndrome.

Topics: Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Metronidazole; Middle Aged; Pyloric Antrum; Tetracycline

Topics: Animals; Dogs; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Regional Blood Flow

Hypersecretion of gastric acid, gastrin, and pepsinogen are considered to be causally related to duodenal ulcer diathesis. Until recently, these abnormalities have been considered to be primary and largely genetically determined. However, Helicobacter pylori infection has been shown to be responsible for several of the abnormalities of gastric secretion in duodenal ulcer. H. pylori infection is not only associated with chronic active inflammation but also with a reduction of somatostatin producing D-cells and somatostatin concentrations in the gastric mucosa. The reduced inhibitory action of somatostatin on the secretion of gastric acid, gastrin, and pepsinogen may be responsible for the hypersecretory state of the stomach in duodenal ulcer. These recent findings have drastically changed our understanding of the pathogenesis of duodenal ulcer.

Topics: Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Pepsinogens

To find out if there was a correlation between hydrogen, potassium stimulated ATPase (H,K-ATPase) activity and gastric acid secretion in patients with duodenal ulcers after proximal gastric vagotomy.. Retrospective study.. Regional referral center.. 61 patients with chronic duodenal ulcers divided into three groups: patients who had not been operated on but had exacerbations of their symptoms (n = 39): those who had been treated successfully by proximal gastric vagotomy either less than 1 year ago (n = 7) or greater than or equal to 1 year ago (n = 9): and those patients who presented with recurrent ulceration after proximal gastric vagotomy (n = 6).. Measurement of H,K-ATPase activity and gastric acid secretion.. There was a decrease in H,K-ATPase activity after effective vagotomy, and enzyme activity was the lowest in patients who had been operated on 1 year ago. Both H,K-ATPase and gastric acid secretion were decreased by proximal gastric vagotomy.. There may be a gradual recovery of gastric H,K-ATPase activity with time after proximal gastric vagotomy.

Topics: Adenosine Triphosphatases; Adult; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; H(+)-K(+)-Exchanging ATPase; Humans; Male; Middle Aged; Vagotomy, Proximal Gastric

Ninety patients suffering from peptic ulcer and 25 healthy subjects were examined for the content of gastrin, bombesin and somatostatin in blood and gastric juice. Among patients with duodenal ulcer, 2 groups were distinguished: group I included patients in whom peptic ulcer occurred before 30 years; the majority of the patients manifested blood hypergastrinemia, a decrease of bombesin concentration and normal somatostatin concentration; gastric juice was characterized by a lowering of somatostatin concentration and unchanged gastrin concentration; group II was made up of patients who developed peptic ulcer after 30: in the majority of the patients, gastrin concentration was reduced under basal conditions, after loading it was unchanged; in part of the patients, blood somatostatin concentration was elevated, in 16 in exacerbation and in 19 in remission; in the remainder, it was unchanged. The concentration of bombesin in blood remained unchanged. In gastric juice, gastrin concentration was increased only after histamine administration, somatostatin concentration was unchanged whatever the disease stage. In patients with gastric ulcer, gastrin concentration in blood was elevated only under basal conditions, being unchanged in gastric juice irrespective of the disease stage. Meanwhile, the concentration of bombesin was lowered both under basal conditions and after insulin administration, the concentration of somatostatin was decreased both in blood and gastric juice whatever the disease stage.

Topics: Adult; Bombesin; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Somatostatin; Stomach Ulcer

Infection of the gastric antrum by Helicobacter pylori is associated with recurrent duodenal ulcer disease but the mechanism of ulcerogenesis is unclear. Since pathways inhibiting gastric secretion are defective in patients with duodenal ulcers, we investigated whether H pylori interferes with the normal gastric inhibition that is mediated by somatostatin. We studied 28 patients with active duodenal ulcers in whom H pylori was eradicated successfully. In 18 patients, we measured the density of antral somatostatin-immunoreactive cells and in a further 10 subjects, the amount of somatostatin mRNA before and after eradication of H pylori was determined. After eradication, the median density of somatostatin-immunoreactive cells increased significantly from 9 (range 3-47) to 19 (6-57) cells per mm muscularis mucosa (p = 0.025). The median somatostatin mRNA/rRNA ratio increased from 50 (25-160) to 95 (40-180) (p = 0.01). The number of gastrin cells and quantity of gastrin mRNA did not change significantly. Our results suggest that in duodenal ulcer disease, gastric secretory function is disinhibited through the suppression of mucosal somatostatin.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Somatostatin

This study compares the efficacy and side effects of omeprazole and regular- and double-dose nizatidine in the treatment of duodenal ulcers. Duodenal ulcer healing rates in these three groups (omeprazole, 20 mg qd; nizatidine, 300 mg hs and 600 mg hs) were 81.8%, 19% and 30%, respectively, after two weeks of therapy; and 90.5%, 70% and 84.2%, respectively, after four weeks of treatment. Omeprazole had a significantly better healing rate than nizatidine, 300 mg or 600 mg, after two weeks of treatment (p < 0.01), but not after four weeks of treatment. Omeprazole relieved the ulcer pain sooner than nizatidine (p < 0.05). Smoking decreased the duodenal ulcer healing rate in the omeprazole group, but not in the nizatidine groups. Clinical features, such as sex, age, alcohol consumption, ulcer size, past history of upper gastrointestinal bleeding and duration of peptic ulcer history, did not collate with the healing rate. Patients with double-dose nizatidine did not show any benefits over those with a regular dose in this study. Adverse effects were minor, and there were no significant changes in biochemistry after therapy in these three groups of patients.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Nizatidine; Omeprazole

Thirty patients with active duodenal ulcer who were Helicobacter pylori positive (HP+) by HLO test and by histology (Giemsa stain) were given omeprazole (OME) 20 mg/d for a two-week period. Estimation of fasting serum gastrin concentration (RIA) was performed before treatment and 24 hours after the last dosage of OME, and HP was searched for an antral biopsies at the end of the treatment as well. Mean fasting serum gastrin concentration increased significantly after treatment in all patients studied (p less than 0.05). However, the increase remained significant only in those patients who continued to be HP+ while no significant increase was observed in those who became HP-. The results could be considered as further evidence of the 'clearing' effect of Omeprazole on HP.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole

Topics: Adolescent; Adult; Biopsy; Drug Evaluation; Duodenal Ulcer; Duodenum; Enprostil; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric; Stomach

Patients with duodenal ulcers and Helicobacter pylori infection have elevated plasma gastrin concentrations which fall after suppression of the organism. This may be due to H. pylori elevating the pH of the antral mucous layer, therefore preventing luminal acid from inhibiting gastrin release. To test this idea, we measured the plasma gastrin concentrations under basal conditions and in response to 4% peptone when the gastric lumen was maintained at pH 2.5 and at pH 5.5 by gastric perfusion. We studied 11 duodenal ulcer patients before and after suppression of H. pylori. Gastrin concentrations were significantly higher before suppression of H. pylori than after treatment in all three states; basal gastrin (pmol/l) fell from 9.2 (3.7-23, median and range) to 5.1 (1.7-15) after treatment; from 11.3 (3.8-29) to 5.9 (5.7-6.1) at pH 2.5 and from 15.2 (3.9-32) to 7.15 (6.1-14) at pH 5.5. The ratio of peptone-stimulated gastrin at pH 2.5/pH 5.5 was similar before (0.8; 0.5-1.7) and after (0.8; 0.5-1.1) suppression of H. pylori. These results indicate that infection with H. pylori increases basal and peptone-stimulated plasma gastrin concentrations, and that this response is independent of luminal pH.

Topics: Amoxicillin; Anti-Ulcer Agents; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Metronidazole; Middle Aged; Organometallic Compounds

Serum gastrin levels were measured under basal conditions and after hyperproteic meal stimulation in 24 patients with non-stenotic duodenal ulcer, 78% of them were males with a mean age of 36.4 years. Results were compared with those obtained in 20 volunteers. Basal gastrin levels in patients with duodenal ulcer 46.2 +/- 17.5 pg/ml did not show any significant statistical differences when compared with those in the control group (51.01 +/- 28.1 pg/ml). After meal stimulation gastrin levels at different time intervals, were similar in patients with duodenal ulcer and in the control group. We conclude that serum gastrin does not seem to play a relevant pathogenic role in the development of duodenal ulcer; its measurement is of no value as a biological marker of duodenal ulcer disease.

Topics: Adult; Basal Metabolism; Dietary Proteins; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Male; Middle Aged

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.

Topics: Adult; Amoxicillin; Antacids; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Metronidazole; Middle Aged; Organometallic Compounds; Pyloric Antrum

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.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Benzimidazoles; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Omeprazole; Pantoprazole; Pepsinogen A; Pepsinogens; Peptide Fragments; Sulfoxides

To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol.kg-1.h-1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2-8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Peptones

It is known that cysteamine-induced duodenal ulcers in rats are similar to the human duodenal ulcers in some aspects. We investigated their similarities in view of adrenalin-stimulated gastric acid secretion and gastrin secretion in these rats. Acid outputs decreased in the control group by the administration of adrenaline, but in the cysteamine-administered group acid outputs increased dose dependently. Serum gastrin levels and plasma noradrenaline levels increased by cysteamine administration. The abnormal gastric acid secretion by the adrenalin infusion in the process of cysteamine-induced duodenal ulcers in rats, which was resembled to that of duodenal ulcer patients, was recognized.

Topics: Animals; Cysteamine; Duodenal Ulcer; Epinephrine; Gastric Acid; Gastric Mucosa; Gastrins; Male; Rats

Helicobacter pylori increases gastrin release in duodenal ulcer patients. This may be through disruption or changes in the mucus layer affecting the access of luminal stimulants to gastrin releasing cells. The effect of suppressing H pylori on gastrin release stimulated by a non-luminal stimulus, gastrin releasing peptide (GRP), was examined. Eleven patients with active duodenal ulcer disease and colonised with H pylori received an intravenous infusion of GRP (2.9 pmol/kg/minute for 30 minutes) and the plasma gastrin response was measured. Basal and peak pentagastrin stimulated acid output were also determined. Patients were treated with tripotassium dicitratobismuthate (De-Nol) and metronidazole to suppress H pylori and the tests were repeated. Suppression of H pylori decreased plasma gastrin concentrations during GRP infusion, but acid output was not affected. Chromatographic analysis of the forms of gastrin in plasma showed a significant fall in gastrin 17, the predominant form found in the gastric antrum. Gastrin 34 did not fall significantly. This study shows that suppression of H pylori decreases the hypergastrinaemia caused by the nonluminal stimulant, GRP, mainly via decreasing gastrin 17.

Topics: Adult; Duodenal Ulcer; Female; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peptides; Secretory Rate

Basal serum gastrin levels were measured in 237 patients with endoscopically confirmed duodenal ulcer and were higher than normal in 16 cases. Protein meal gastrin stimulation was performed on this group of 16 patients and on a control group of 48 patients with normal basal gastrin concentrations but high rates of either ulcer recurrence or of complications (e.g., bleeding or perforation); 21 patients from the two groups were also tested for serum gastrin inhibition with secretin. Four cases (25%) of antral G-cell hyperfunction were found in the first group, plus 1 case compatible with Zollinger-Ellison syndrome (6.2%). Only 1 case (2%) of antral G-cell hyperfunction was found among the 48 controls. These results suggest the clinical utility of routine basal gastrin measurement in screening for hypergastrinemic patients with duodenal ulcer disease.

Topics: Adult; Aged; Algorithms; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Kinetics; Male; Middle Aged; Syndrome

The gastrin response to a low and a high dose of gastrin-releasing peptide infusion was studied in healthy volunteers and in patients with duodenal ulcer disease. In duodenal ulcer patients, the gastrin response was exaggerated. Cholinergic blockade did not change the gastrin release in healthy volunteers. Antrum distension during neutralization of the gastric lumen was unable to stimulate gastrin release, also under cholinergic blockade. However, in healthy volunteers distension of the antrum significantly inhibited the gastrin response to gastrin-releasing peptide infusion. This inhibitory influence was most pronounced in patients given the lower dose of the neuropeptide. Cholinergic blockade counteracted the inhibitory effect exerted by antral distension. On the other hand, antral distension did not alter the gastrin response to gastrin-releasing peptide in patients with duodenal ulcer disease. These results suggest an additional defective inhibitory mechanism in duodenal ulcer patients.

Topics: Adult; Catheterization; Duodenal Ulcer; Female; Gastric Dilatation; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Humans; Male; Middle Aged; Peptides; Pyloric Antrum; Radioimmunoassay

The role of mood state (affect) and personality on basal acid secretion and basal serum gastrin concentrations were examined in seven healthy men and eight patients with duodenal ulcer. In each subject, gastric secretion and affect were assessed simultaneously on 5 separate days. None of 10 self-reported affect variables correlated with daily fluctuations in basal acid secretion in either group. Three variables (tension, conflict, and anxiety) correlated significantly with serum gastrin fluctuations in normal subjects, but these relationships were not present in patients with ulcer, who were hypergastrinemic regardless of their affective state. The degree to which serum gastrin fluctuated was unrelated to personality, as assessed by Minnesota Multiphasic Personality Inventory. On the other hand, several Minnesota Multiphasic Personality Inventory scales correlated with the degree of variability in basal acid secretion, including scales that measured impulsivity and social isolation/alienation. These studies indicate that serum gastrin concentrations are related to affective state in normal men, that this relationship is altered in men with duodenal ulcer, and that certain personality traits, such as impulsivity and social isolation, are associated with more labile basal acid secretion rates.

Topics: Adult; Affect; Analysis of Variance; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Osmolar Concentration; Personality; Personality Inventory; Reference Values

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.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Middle Aged; Pepsinogens; Time Factors

From Aug. 1977 to June 1988, vagotomy had been performed in 238 patients with duodenal ulcer (DU). According to the clinical signs and the result of gastric acid secretion test, (GAST) parietal cell vagotomy (PCV) and selective vagotomy plus antrectomy (SV+A) were performed in 100 and 138 cases respectively. The patients were followed up for 1 to 10 years. 96% and 97% of them belonged to Visick grade I and II respectively. The recurrence rate was 1.96% in PCV group, while no ulcer recurrence was seen in SV+A group, long-term side effect was rare and the nutritional status was quite good. The follow-up data showed that recurrence rate could be greatly reduced if the mode of vagotomy was selected according to results of GAST.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Follow-Up Studies; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Vagotomy, Proximal Gastric

The authors provide the data on the hormonal spectrum (STH, gastrin, sex hormones) in patients with long unhealing duodenal ulcers. It is shown that changes in the concentrations and ratios of the concentrations of hypophyseal-gonadal hormones may serve as a defensive adaptation reaction of the body and may be due to activation of the adaptation systems that mediate the neurohumoral mechanisms of regulation. Such changes are more remarkable in patients with common peptic ulcer. Apparently, in patients with long unhealing ulcers, these mechanisms tend toward depletion, as a result of which the other mechanisms start prevailing (microcirculatory disorders, immunologic abnormalities, pathological microflora).

Topics: Adult; Chronic Disease; Cyclic AMP; Duodenal Ulcer; Female; Gastrins; Gonadal Steroid Hormones; Growth Hormone; Humans; Male; Ovary; Pituitary Gland; Testis; Wound Healing

We assessed the effect of long-lasting inhibition of gastric acid secretion on basal and meal-stimulated serum gastrin and gastric acid secretion in 37 patients on long-term maintenance treatment with H2 antagonists for severe relapsing and/or complicated duodenal ulcer disease. After a mean of 142 weeks (range, 28-324 weeks) of continuous treatment, gastric acid secretion, basal plasma gastrin, and gastrin response to a test meal were evaluated. All tests were performed a week after drug discontinuation to exclude rapidly reversible hypergastrinemia. Gastrin levels were above the normal range in seven patients (18.9%). After H2 antagonist were stopped for 6 weeks, basal gastrin returned to normal levels in all cases [from a median of 180 (range, 130-350) pg/ml to 58 (25-90) pg/ml] and peak meal-stimulated gastrin significantly decreased from a median of 500 pg/ml to 245 pg/ml (p = 0.02). In patients with hypergastrinemia, the discontinuation of H2 antagonists for 6 weeks led to a significant decrease of gastric acid secretion. Patients who developed hypergastrinemia spent more weeks on full-dose treatment and had more recurrences during therapy. The results of the present investigation demonstrate that a long-lasting inhibition of gastric acid secretion can induce, in a small percentage of patients, a reversible sustained hypergastrinemia and a consequent increase of acid secretion, which conceivably could lead to more frequent relapses of duodenal ulcer disease.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Radioimmunoassay; Recurrence; Time Factors

Single subcutaneous administration of cysteamine (2-aminoethanethiol, CSH) produces duodenal ulceration in rats within 24 h. Depletion of circulating and tissue somatostatin (SOM), hypergastrinemia and gastric acid hypersecretion have all been postulated as the pathophysiological response to CSH leading to ulceration. The purpose of this study was to analyze the synthesis, storage and secretion of gastrin and SOM as well as structural changes in SOM peptide after CSH treatment. Injection of 300 mg/kg (s.c.) of CSH caused macroscopic duodenal ulcers in seven out of eight rats at 24 h. Hypergastrinemia was seen within 30 min (from 23 +/- 4 to 74 +/- 20 pmol/l), and persisted for 4 h. Antral gastrin content was elevated at 30 min (2539 +/- 114 pmol/g) when compared to saline controls (1589 +/- 101 pmol/g). Plasma SOM did not change over the 24 h but antral SOM increased at 30 min (from 120 +/- 3 to 230 +/- 23 pmol/g) and remained elevated at 2 h (374 +/- 48 pmol/g) and 4 h (357 +/- 37 pmol/g). Fundic and duodenal SOM followed a similar pattern. Antral SOM mRNA was also elevated over the first 4 h (3-fold increase, P less than 0.05). HPLC analysis of antral tissue extracts revealed the presence of additional molecular forms of SOM which, however, differed from the major products of in vitro reduction with either CSH or dithiothreitol. Thus, the in vivo effect of CSH on SOM cannot be solely explained by a reductive opening of the disulphide bond. These results suggest that duodenal ulceration in rats treated with CSH is not related in a simple fashion to depletion of immunoreactive SOM. Early induction of hypergastrinemia may be important in the onset of ulceration. The value of CSH as a SOM depleting tool in gastrointestinal tissue must remain in doubt.

Topics: Animals; Base Sequence; Chromatography, High Pressure Liquid; Cysteamine; DNA; Duodenal Ulcer; Female; Gastrins; Kinetics; Molecular Sequence Data; Rats; Rats, Inbred Strains; RNA, Messenger; Somatostatin

The serum gastrin response to an infusion of gastrin-releasing peptide (GRP), with or without simultaneous fundic distension, was studied in healthy volunteers and in patients with duodenal ulcer disease before and after a complete proximal gastric vagotomy (PGV). We also studied the effect of fundic distension alone on gastrin release and intraluminal gastric pressure in healthy volunteers and in patients after PGV. We observed an increased intraluminal pressure in patients after PGV compared with healthy subjects. During fundic distension with 600 ml of air no significant increase in gastrin values was observed in healthy subjects or in duodenal ulcer patients. In healthy subjects fundic distension significantly inhibited the gastrin response to the higher dose of GRP. This inhibitory effect exerted by fundic distension was counteracted by cholinergic blockade. In contrast, fundic distension did not alter the gastrin response to GRP in duodenal ulcer patients, suggesting a defective inhibitory mechanism in duodenal ulcer patients. After PGV, GRP infusion resulted in an enhanced gastrin response, and fundic distension seemed to facilitate the gastrin-stimulatory effect of GRP. This supports the concept of a vagally dependent inhibitory oxyntopyloric mechanism and that fundic distension can elicit both inhibitory and stimulatory secretory mechanisms.

Topics: Adult; Catheterization; Duodenal Ulcer; Female; Gastric Fundus; Gastrin-Releasing Peptide; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric; Peptides; Pressure; Stomach; Time Factors; Vagotomy, Proximal Gastric

The effects of antrectomy and proximal gastric vagotomy on the metabolism of histamine in the human gastric mucosa were studied in the basal state and during pentagastrin stimulation in patients with duodenal or gastric ulcer disease. Mucosal biopsy specimens were taken from the antral and oxyntic gland areas, whereafter histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Vagotomy was followed by a decrease in the acid secretory capacity and an increase in basal serum gastrin levels. Histamine content of the oxyntic mucosa increased after vagotomy, but the ability of pentagastrin to form new amounts of the amine was impaired. Antrectomy caused a decrease in acid secretion and a fall in gastrin concentrations. Basal histamine content and rate of amine formation in the remaining oxyntic mucosa were unaffected by antrectomy. Antrectomy impaired the ability of pentagastrin to release histamine. Histamine methyltransferase was not affected by pentagastrin, vagotomy, or antrectomy. In conclusion, both antral gastrin and the vagus nerve seem to exert a regulatory influence on the metabolism of histamine in the human oxyntic mucosa. The withdrawal of these factors either causes impaired ability of pentagastrin to release histamine from its storage site or counteracts the ability of pentagastrin to accelerate histamine synthesis.

Topics: Analysis of Variance; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Histamine N-Methyltransferase; Histidine Decarboxylase; Humans; Middle Aged; Pentagastrin; Pyloric Antrum; Stomach Ulcer; Vagotomy

Topics: Animals; Chromium Radioisotopes; Dogs; Duodenal Ulcer; Duodenum; Endocrine Glands; Gastric Mucosa; Gastrins; Hormones; Intestine, Large; Liver; Pancreas

Helicobacter infection of the gastric antrum is linked to the development of duodenal ulcer. A key element could be the associated hypergastrinemia. This brief commentary seeks answers to the following questions: 1) Does hypergastrinemia occur? 2) How does it occur? and 3) Does it matter?

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans

The results of gastric secretory studies in 192 cases of recurrent ulcer after surgery for duodenal ulcer were analyzed and compared with the secretory data collected in a control group of 74 duodenal ulcer patients who had undergone various forms of gastric surgery, but who did not develop a recurrent ulcer (controls). The patients studied comprised 46 cases of recurrent ulcer after partial gastrectomy, 10 cases of recurrent ulcer after partial gastrectomy and bilateral truncal vagotomy, 56 cases of recurrent ulcer after truncal vagotomy and drainage, 52 cases of recurrent ulcer after highly selective vagotomy, and finally 28 cases in which the recurrent ulcer led to the diagnosis of the Zollinger-Ellison syndrome. The entire study was based upon an analysis of the basal acid output, the response to maximal stimulation by pentagastrin or by histalog and by insulin in the case of previous vagotomy, and finally on an assessment of basal serum gastrin. The analysis has suggested minimal secretory levels with discriminative values useful for the postoperative diagnosis of recurrent ulcer and for an assessment of the completeness of vagotomy (ratio PAO Insulin/PAO pentagastrin or histalog). Moreover, an analysis of various elements of the sequential basal pentagastrin-insulin test permitted us to approach the pathophysiological mechanism responsible for ulcer recurrence, and to identify suitable criteria for selection of the best treatment.

Topics: Adult; Duodenal Ulcer; Female; Gastrectomy; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Recurrence; Vagotomy; Zollinger-Ellison Syndrome

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.

Topics: Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Bismuth; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Metronidazole; Middle Aged; Organometallic Compounds; Stomach; Time Factors

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Omeprazole; Vagotomy, Proximal Gastric

The serum gastrin content in patients with ulcerous duodenal bleeding was studied in the process of surgical treatment. A significant decrease in the hormone concentration with increase in the volume of acute blood loss was noted.

Topics: Acute Disease; Blood Loss, Surgical; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Peptic Ulcer Hemorrhage; Postoperative Period

The effect of omeprazole on acid secretion and gastrin levels has been investigated in 10 elderly duodenal ulcer patients in remission. Doses of 5, 10, 20 and 40 mg omeprazole were given once daily for 7 consecutive days and the basal (BAO) and peak (PAO) acid output and fasting plasma gastrin concentration were measured 24 h after the seventh dose. Omeprazole suppressed PAO significantly and dose-dependently after doses of 10, 20 and 40 mg, the suppression being 42%, 75% and 85%, respectively. No patient showed complete inhibition of PAO and at least 20 mg had to be given to obtain a marked inhibitory effect in all patients. Increasing the dose to 40 mg had only a slight additional effect compared to 20 mg. There was a relationship between degree of acid inhibition and the increase in fasting plasma gastrin. PAO had to be suppressed by more than 80% before a moderate increase in fasting plasma gastrin was observed. The optimal once-daily oral dose of omeprazole for inhibition of acid secretion in elderly patients appears to be 20 mg. Omeprazole 20-40 mg may cause a moderate increase in fasting plasma gastrin.

Topics: Aged; Aging; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Omeprazole

The mechanism of the hypergastrinaemia associated with Helicobacter pylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We have examined the effect on serum gastrin of inhibiting H pylori urease activity with acetohydroxamic acid in six duodenal ulcer patients. On day 1 the fasted patients received placebo tablets at 8 am, a peptide meal at 10 am, and a 14C urea breath test at 11.30 am. The next day 750 mg acetohydroxamic acid was administered orally in place of the placebo. The median (range) 30 minute breath test value (dose/mmol CO2 X kg body wt X 100) was 152 (111-335) on day 1, but only 22 (14-95) the next day (p less than 0.03). Further studies performed in one subject confirmed that acetohydroxamic acid lowered the ammonium concentration and raised the urea concentration in gastric juice. The inhibition of urease activity and ammonia production did not result in a fall in the basal gastrin concentration or in the median integrated gastrin response to the peptide meal, which was 78 ng/1.h (range 21-222) on day 1 and 79 ng/1.h (33-207) the next day. Ten days after acetohydroxamic acid, the urea breath test values were similar to those before treatment. This study shows that the raised gastrin concentration in patients with H pylori infection is not directly related to the organism's urease activity. It also shows that temporary suppression of H pylori urease activity does not clear the infection.

Topics: Adult; Ammonia; Breath Tests; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Helicobacter pylori; Humans; Hydroxamic Acids; Male; Middle Aged; Urea; Urease

In a prospective study, eight young healthy subjects (five with an active H. pylori infection in the antral mucosa) were treated with a course of tripotassium dicitrato bismuthate, amoxycillin and metronidazole. The triple therapy eradicated infection when assessed 20-24 weeks later by antral biopsy (urease, histology, and 13C urea breath test [4 out of 5 subjects]). Twenty-four hour intragastric acidity and plasma gastrin concentration were measured before treatment, and 4-6 weeks and 20-24 weeks post-treatment. Treatment did not affect acidity in either the H. pylori-positive or H. pylori-negative groups, nor did it affect the plasma gastrin profile in the H. pylori-negative group. Eradication of H. pylori infection in five subjects caused a drop of the median integrated 24-hour plasma gastrin concentration from 558 pmol.h/L before treatment to 307 and 289 pmol.h/L at 4-6 and 20-24 weeks post-treatment, respectively. It is concluded that H. pylori infection is associated with 24-hour hypergastrinaemia, and that in apparently healthy subjects normal gastric physiology can be restored by eradication of the infection.

Topics: Adult; Amoxicillin; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds

Basal and pentagastrin-stimulated gastric acid secretion and basal serum gastrin level were investigated in 55 active duodenal ulcer patients with antral colonization with Helicobacter pylori (HP) and 17 patients without. Our study shows that basal (BAO) and pentagastrin-stimulated gastric acid secretion (MAO and PAO) were significantly higher in HP positive than in HP negative patients with duodenal ulcer disease. There were also a tendency to increase in basal serum gastrin concentration in HP positive patients. We suggest that antral HP increases antral gastrin release and gastric secretion. Increased acid secretion then causes duodenal ulcers by producing a low intraduodenal pH.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

Since Helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that if H. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency of H. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P less than 0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30 min; P less than 0.02) but serum gastrin was correspondingly lower in patients positive for H. pylori (P less than 0.05). H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion.

Topics: Adolescent; Adult; Aged; Child; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Helicobacter pylori (previously Campylobacter pylori) is almost invariably associated with chronic duodenal ulcer disease. The relationship between H. pylori infection and duodenal ulcer in Zollinger-Ellison syndrome is unknown. We investigated the frequency of H. pylori infection in Zollinger-Ellison syndrome and also what effect H. pylori infection had on gastric function in patients with Zollinger-Ellison syndrome. H. pylori infection was diagnosed based on a specific serologic (ELISA) assay based on high-molecular-weight cell-associated proteins of H. pylori. We studied 20 patients with Zollinger-Ellison syndrome; 15 men and 5 women ranging in age from 24 to 71 years, median age 51. Six Zollinger-Ellison syndrome patients had H. pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease (P less than 0.05). Pretreatment basal acid output in Zollinger-Ellison syndrome patients ranged from 7.9 to 95.0 mmol/hr, median 35.2. Pentagastrin-stimulated maximal acid output ranged from 8.5 to 132 mmol/hr; median 52.7. Acid secretion was lower in the H. pylori-infected patients than the uninfected patients (BAO 24.5 +/- 6.5 vs 45.4 +/- 6.6, and MAO 44.3 +/- 11.8 vs 67.9 +/- 10.7, for H. pylori infected vs uninfected patients, respectively). The difference in BAO was statistically significant (P less than 0.05). The present results indicate that H. pylori is not a major contributing factor in duodenal ulcer associated with Zollinger-Ellison syndrome. The association of a reduced BAO with H. pylori suggests that these findings may be related.

Topics: Adult; Aged; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Recurrence; Zollinger-Ellison Syndrome

A different pathophysiological mechanism is widely accepted for gastric and duodenal ulcer. In particular, the exact role of gastrin in the determinism of non hormono-dependent peptic ulcer disease is not completely clarified. Therefore, the aim of present study was to analyse fasting and post-prandial serum gastrin levels in 99 duodenal ulcer patients, 17 gastric ulcer patients and 11 subjects presenting an association of gastric and duodenal ulcer. The possible correlation between post-prandial gastrin concentrations and basal and maximal acid output in the 3 fasting serum gastrin levels appear not different among the 3 classes of patients, while post-prandial gastrin concentrations are statistically higher at 15 minutes in duodenal ulcer patients and in subjects with the association of gastric and duodenal ulcer as compared to gastric ulcer patients. Mean fasting and stimulated gastrin levels are higher in gastric ulcer females than in males during the entire test and with statistically difference at 30 minutes. The concentrations of the hormone are not different in males of the 3 groups of patients at basal time, while are statistically lower at 15 and 30 minutes in gastric ulcer males compared to the males with duodenal ulcer and the association of the localization. Finally, positive correlation has been observed between BAO and MAO and post-prandial gastric concentrations in the 3 groups of patients, while there is an inverse correlation between the previous parameters as regards sex, both in gastric and duodenal ulcer.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Feeding Behavior; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Sex Characteristics; Stomach Ulcer; Time Factors

Recent studies have shown that the exaggerated meal-stimulated gastrin release in patients with duodenal ulcer abates after eradication of Helicobacter pylori infection. Bombesin-stimulated gastrin release was compared in 11 H. pylori-infected patients with chronic duodenal ulcer and 8 uninfected healthy volunteers both before and after therapy to eradicate H. pylori. Bombesin infusion significantly increased the gastrin release both in control subjects and in patients with duodenal ulcer. Antimicrobial therapy (bismuth, tetracycline, and metronidazole) to eradicate the H. pylori infection was associated with a significant reduction in bombesin-stimulated gastrin release in patients with duodenal ulcer (from 116.9 +/- 19 pg/mL to 69.5 +/- 7 pg/mL following 50 pmol.kg-1.h-1 bombesin; and from 158 +/- 29 to 83.4 +/- 10 following 200 pmol.kg-1.h-1 bombesin: P = 0.01 for each). Antimicrobial therapy had no effect on gastrin release in uninfected volunteers, thus excluding a nonspecific effect of antimicrobial therapy on antral G-cell function. Serum gastrin was also not increased by feeding 500 mg of urea to 5 H. pylori-infected volunteers. This suggests that access of hydrogen ion to the pH-sensitive sites governing gastrin release by mucosal ammonia produced by H. pylori urease is not a critical factor. These data suggest that exaggerated gastrin release present in patients with duodenal ulcer disease is secondary to H. pylori infection.

Topics: Adult; Bombesin; Duodenal Ulcer; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Urea

Posttranslational processing is an important phase of the expression of most eucaryotic genes in terms of functional proteins. Among these, secretory proteins and peptides are of particular interest for clinical chemists, since diagnostic measurements of circulating proteins and peptides constitute a major discipline in clinical chemistry. The posttranslational covalent maturation of secretory proteins and peptides involves multiple enzymatic modifications of the corresponding proproteins along the intracellular secretory pathway. During the eighties, an increasing amount of evidence has indicated that sick secretory cells fail to process their secretory products normally. The diseased cells therefore fail to process their secretory products normally. The diseased cells therefore release also incompletely processed precursors and processing-intermediates. In order to measure the degree of disease, assays that measure proteins and peptides independent of the degree of processing are therefore desirable. We have now designed a new analytical principle, according to which secretory proteins, peptides and their precursors can be accurately quantitated irrespective of the degree of processing. This principle, named processing-independent analysis (PIA), is generally applicable to all cellular synthesized substances. The principle has been applied to and developed first for a well-defined secretory peptide system, progastrin and its products. Using this model, the results obtained so far confirm the diagnostic superiority of processing-independent analysis in comparison with conventional assays for bioactive peptides.

Topics: Amino Acid Sequence; Animals; Chemistry, Clinical; Clinical Laboratory Techniques; Duodenal Ulcer; Gastrinoma; Gastrins; Humans; Molecular Sequence Data; Peptides; Protein Precursors; Protein Processing, Post-Translational; Proteins; Radioimmunoassay; Zollinger-Ellison Syndrome

Observations on gastric acid secretion, plasma gastrin and prostaglandin E1 in patients with peptic ulcer disease were made after giving acupuncture with Na Ja Fa. The relationship between the chosen points and their effects was also discussed so as to provide more evidence to evaluate and practice the traditional chronoacupuncture more accurately. The results of this experiment were: (1) The gastric acid output of patients with peptic ulcer disease was decreased, while the plasma gastrin and prostaglandin E1 were increased after puncturing with Na Ja Fa. This reveals that the decrease of acid output was not caused by the change of plasma gastrin, however the plasma prostaglandin E1 may be involved in this process. (2) By using points on Stomach and Spleen meridians, there was a better inhibiting effect in acid output than treating the points of other meridians. This showed that using chronoacupuncture should include choosing points according to differentiation and only by laying stress on the relative specialization of the actions of these points one could expect improvement in efficiency. (3) There were no obvious differences between the standard opening points and the group of points which changed to opening points by Dr Shan Yu Tang. This proves that these two groups of points do have some similar functions and are both effective for clinical use.

Topics: Acupuncture Therapy; Adolescent; Adult; Alprostadil; Circadian Rhythm; Duodenal Ulcer; Electroacupuncture; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged

A number of conditions should be observed when pretreating gastric juice for gastrin measurements, in order to obtain reliable results. The authors compare the results of gastric juice pretreatment by various methods and the results obtained with the use of different radioimmunoassay kits. Calculation coefficients are suggested, based on the results of computer processing of standard curves. Gastrin concentrations in the blood serum and gastric juice (pretreated and untreated) are compared in the same patients.

Topics: Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Radioimmunoassay; Reagent Kits, Diagnostic

It was found that in patients with gastroduodenal hemorrhage the number of serotonin-, histamine-, and melatonin-producing apudocytes in the gastric mucosa increases while the number of cells producing gastrin, adrenaline, and noradrenaline reduces. In timely arrest of hemorrhage, the primarily increased number of melatonin-producing apudocytes diminishes with time from the onset of bleeding and reaches normal values gradually. The essential differences in the content of melatonin- and noradrenaline- producing apudocytes in patients with and without hemorrhage allow this morphological sign to be used as diagnostic and prognostic criteria in gastroduodenal hemorrhages.

Topics: Adult; Aged; APUD Cells; Catecholamines; Cell Count; Duodenal Ulcer; Female; Gastrins; Hormones, Ectopic; Humans; Male; Melatonin; Middle Aged; Peptic Ulcer Hemorrhage; Pyloric Antrum; Stomach Ulcer

Basal serum gastrin, integrated gastrin response to a meal, and integrated gastrin response to insulin induced hypoglycaemia were measured in 60 patients with duodenal ulcer before and after elective highly selective vagotomy to determine whether antral gastrin has a role in resistance to H2 receptor antagonist treatment which the patients had received before surgery or in the development of recurrent ulceration after vagotomy. The basal gastrin, integrated gastrin response to a meal, and the integrated gastrin response to insulin were similar in patients whose ulcers healed after H2 receptor agonist treatment or were refractory to at least three months of this treatment. The same parameters measured before or after highly selective vagotomy were similar in patients who eventually developed recurrent ulceration compared with those who did not. As expected the basal and meal stimulated (but not insulin stimulated) serum gastrin values increased after highly selective vagotomy. Ulcer patients with particularly high gastrin values (whether basal or stimulated) were not more resistant to H2 receptor antagonist treatment or prone to develop ulcer recurrence after highly selective vagotomy. This study suggests that antral gastrin is not important in 'resistance' of duodenal ulceration either to H2 receptor antagonist treatment or to highly selective vagotomy.

Topics: Adolescent; Adult; Aged; Cimetidine; Drug Resistance; Duodenal Ulcer; Female; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Postoperative Complications; Pyloric Antrum; Ranitidine; Recurrence; Vagotomy, Proximal Gastric

Topics: Adult; Bombesin; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Male; Pepsinogens; Somatostatin

The immunoreactive gastrin (IRG) and somatostatin (IRS) contents in gastric mucosa were measured from the same biopsy specimen of the same patients with duodenal ulcer (DU) at the active stage and healing stage, and compared to those of patients with fundic gland polyposis (FP) and endoscopically normal subjects whose gastric mucosa had only slight atrophic change (Control). The IRS in both the antrum and the gastric body of DU were significantly lower than those of the other two groups, and those showed no difference between the two stages. In all groups, there was a significant positive relation between the IRG and IRS in the antrum. In DU, particularly at the active stage, the relative decrease of the IRS against the IRG was prominent compared to the other two groups. In FP, which has similar background gastric mucosa and ability of acid output to those of DU, it was found that somatostatin was secreted sufficient to control gastrin secretion and acid output. Whereas in DU, secretion of somatostatin was reduced and, particularly at the active stage, it was considered that somatostatin, which could control increased gastrin secretion and increased acid output, was not secreted.

Topics: Adult; Duodenal Ulcer; Female; Gastric Fundus; Gastric Mucosa; Gastrins; Humans; Male; Polyps; Radioimmunoassay; Somatostatin; Stomach Neoplasms

Immunomorphological PAP method was used in 20 patients with duodenum ulcer and in 10 control individuals to study gastrin (G)-, somatostatin (D)- and calcitonin-gene-related peptide (CGRP) cells in biopsies of the stomach and duodenum. The gastrin and pepsinogen level in the blood, basal and acid production stimulated by pentagastrin were also studied. All patients are subdivided into two groups by their acid production: those with hypersecretion and those with normal secretion. The group with hypersecretion was not homogeneous: some patients had deficiency of D-cells (sometimes in combination with G-cell hyperplasia) and others had a relative and absolute decrease of the number of CGRP cells in combination with foci of parietal cells in pylorus. These patients showed a tendency to the hypergastrinemia and significant hyperpepsinogenemia I in the blood. Stomach hyperplasia in the duodenum, multiple duodenal ulcers, erosive gastroduodenitis and ulcers in close relatives occurred more frequently in these patients. G- and CGRP cells are found to be similar in the form and localization. It is not excluded that G-cell contains, apart from gastrin 1-17, calcitonin-gene related peptide.

Topics: Adolescent; Adult; APUD Cells; Calcitonin Gene-Related Peptide; Cell Count; Duodenal Ulcer; Duodenum; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pepsinogens; Stomach

Gastrin- and somatostatin-immunoreactive cells in biopsies taken from the prepyloric portion of the antrum from 15 patients with duodenal ulcer, 16 patients with gastric ulcer, and a control group of 19 patients without histopathological alterations of the antral mucosa were studied using peroxidase anti-peroxidase and immunogold-silver staining methods in combination with morphometry. Numerical densities and sizes (immunoreactive areas) of the cells demonstrated were measured and compared between all three groups. Gastrin- and somatostatin-immunoreactive cells were located most frequently in the lower midzone of the gastric crypts. None of the parameters measured showed a correlation with age or sex. The group with duodenal ulcer tended to exhibit gastrin- and somatostatin-cell-hyperplasia whereas the size of both cell types remained unchanged. In comparison with the control group, the numerical density of gastrin-immunoreactive cells was significantly increased in gastric ulcer patients, whereas the numerical density of somatostatin-immunoreactive cells was decreased in this group. Immunoreactive areas of both cell types were significantly increased in patients with gastric ulcer.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Gastrins; Humans; Immunohistochemistry; Male; Middle Aged; Mucous Membrane; Pyloric Antrum; Somatostatin; Stomach Ulcer

Fifty asymptomatic patients with duodenal ulcer disease, aged 31-82 years, who had received ranitidine maintenance therapy continuously for five or more years without a symptomatic recurrence, were studied. Fasting plasma gastrin concentrations were normal (mean 24 pmol/L, S.D. +/- 22) while the post-prandial gastrin response was variable with maximum plasma concentrations ranging from 16 to 309 pmol/L. Endoscopy revealed six asymptomatic peptic ulcers. Histological examination of gastric biopsies showed mild, superficial inflammatory cell infiltration of the fundic mucosa, but more extensive inflammatory cell infiltration with some atrophy of the mucosal glands in the antral mucosa. Patchy intestinal metaplasia was evident in the antral mucosa of 18 patients. No fundic ECL cell hyperplasia was seen. Helicobacter pylori were detected in the corpus and antrum of most patients. These results suggest that maintenance treatment with ranitidine for 5 years is not associated with either significant hypergastrinaemia or with changes in the fundic mucosa which could be interpreted as pre-malignant.

Topics: Adult; Aged; Aged, 80 and over; Campylobacter; Duodenal Ulcer; Female; Food; Gastrins; Gastroscopy; Humans; Male; Middle Aged; Ranitidine; Stomach

By immunocytochemical method and radioimmunoassay, the gastrin secreting cells (G cells) and gastrin concentration in antral mucosa, gastric juice and serum in 20 patients with duodenal ulcer (DU) were studied. The number of G cells and gastrin concentration in antral mucosa showed no significant difference as compared with normal control. The number of G cells in patients with DU and antral atrophy was much higher than those with antral atrophy but with DU. It indicated that G cells were increased in number in DU, and the gastrin concentration in gastric juice (271.11 +/- 255.25 pg/ml) was much higher than in sera (74.71 +/- 43.07 pg/ml). G cells were distributed in different parts of pyloric glands, showing that gastrin in gastric juice should come directly from G cells. The disturbance of feedback mechanism in regulating gastric acidity might be an important role in hypersecretion of gastric acid in DU. The increase of gastrin concentration in gastric juice might be closely related to hyperplasia of parietal cells.

Topics: Adult; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Parietal Cells, Gastric

At present the mechanisms by which the use of tobacco produces a damaging effect on duodenal ulcerous disease are not clearly understood. This paper reports the results of a study of basal and postprandial gastrin and pepsinogen I (PG I) levels of 74 duodenal ulcer (DU) patients and 18 controls in relation to their smoking habits. There was no difference between the UD group and the control group as far as basal gastrin levels were concerned, but there was in the PG I levels (107 +/- 54 ng/ml in UD vs. 69 +/- 30 ng/ml in control) (p less than 0.05). The postprandial gastrin and PG I responses in 34 UD subjects only differed in relation to smoker/non-smoker status; there was no correlation with age less than greater than 35, positive family history or duration of illness. Patients who had had UD less than 10 years showed higher postprandial PG I levels; however, this group included the 83.3% smokers with UD. It was concluded that chronic smoking is clearly related to the existence of hyperpepsinogenemia I, and probably also to postprandial hypergastrinemia in UD sufferers.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Pepsinogens; Smoking

The relationship between suppressed gastric acidity and the increase in plasma gastrin levels after pharmacological and surgical treatment of peptic ulcer disease were compared in this study. Eight patients with chronic duodenal ulcer and referred for proximal gastric vagotomy were studied. 24-hour intragastric acidity and plasma gastrin levels were investigated in the same patients on three consecutive occasions: preentry without any treatment; after 4 weeks of administration of 20 mg of omeprazole daily, and 4-6 months after proximal gastric vagotomy. Intragastric acidity was slightly more reduced by omeprazole (94%) than after proximal gastric vagotomy (78%), with no difference found during the day or night with either. Plasma gastrin levels increased slightly more after proximal gastric vagotomy [284% (median, 2120 pmol.h/L; range, 733-2831 pmol.h/L)] than after omeprazole administration [186% (median, 1586 pmol.h/L; range, 495-2573 pmol.h/L)]. There is strong evidence that the increased plasma gastrin concentration following omeprazole treatment is caused by the reduced intragastric acidity. The slight increase in plasma gastrin concentration following proximal gastric vagotomy despite a lesser reduction in intragastric acidity may be the result of additional effects on gastrin release by the vagotomy. Both treatments resulted in a modest increase in plasma levels of gastrin that were far below the gastrin levels observed in achlorhydric patients, e.g., patients with pernicious anemia.

Topics: Adult; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Omeprazole; Vagotomy, Proximal Gastric

In the experiment on dogs and in patients with duodenal ulcer disease, it was established that the regulation of acid production besides the vagal nerves was mediated by the intragastric gastrin transport with the blood flow. A method of preoperative diagnosis of the intensity of intragastric blood flow permitting to define more accurately the indications for the choice of a method for surgical treatment has been developed. Supplementation of the selective proximal vagotomy with circular mucosectomy at the boundary between the antrum and body of a stomach enhances the effectiveness of operation due to reduction of the antral gastrin influence on the acid-producing zones of the stomach.

Topics: Animals; Dogs; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum; Vagotomy, Proximal Gastric

Antisera were raised against fragment 38-54 of human progastrin. All of eight immunized rabbits responded, but only one (No. 2145) produced high-titer (3.2 x 10(4)) and high-avidity (Keff degrees = 1.2 x 10(12) l/mol) antibodies. A radioimmunoassay based on antiserum 2145 and monoiodinated gastrin-34 was specific for the N-terminal sequence of human gastrin-34. It measured concentrations of 9.7 +/- 1, 18.4 +/- 2 pmol/l (mean +/- SEM) and 1.553 (0.7-476) nmol/l (median (range], respectively, in sera from normal subjects (n = 20), patients with duodenal ulcer (n = 19), and Zollinger-Ellison patients (n = 8). Conventionally measured concentrations of carboxyamidated gastrins in the same sera were 21.4 +/- 1, 23.8 +/- 3 pmol/l (mean +/- SEM) and 0.833 (0.4-214) nmol/l (median (range)), respectively. The results show that radioimmunoassays specific for the N-terminus of human gastrin-34 discriminate between healthy subjects and patients with duodenal ulcer. The improved diagnostic specificity is due to co-measurement of unprocessed and partly processed progastrins that occur in plasma of patients with duodenal ulcer disease and gastrinomas. We suggest that conventional gastrin assays are supplemented with assays specific for the N-terminus of gastrin-34 in studies of duodenal ulcer disease.

Topics: Amino Acid Sequence; Anemia, Pernicious; Animals; Chromatography, Gel; Duodenal Ulcer; Gastrins; Immune Sera; Molecular Sequence Data; Protein Precursors; Rabbits; Radioimmunoassay; Zollinger-Ellison Syndrome

Pretrophic and moderately atrophic gastritis is found in the antrum in patients with noncomplicated duodenal ulcer. Normal mucosa or superficial gastritis were observed in the gastric body. Statistically significant worsening of the gastritis of both stomach areas without pronounced atrophic forms, stable decrease of the acid production and the number of parietal cells with a mild increase of the gastrin-producing cells of the antrum are found 1 to 8 years after the selective proximal vagotomy.

Topics: Adult; Chronic Disease; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Histocytochemistry; Humans; Male; Postoperative Period; Pyloric Antrum; Time Factors; Vagotomy, Proximal Gastric

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.

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histamine; Histamine N-Methyltransferase; Histidine Decarboxylase; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pentagastrin; Stimulation, Chemical; Stomach Ulcer; Zollinger-Ellison Syndrome

Patients with hypergastrinaemic duodenal ulcer disease were studied to determine whether chronic moderate hypergastrinaemia produces hyperplasia of gastric enterochromaffin-like cells in man. Eight patients had peak postprandial plasma gastrin concentrations greater than 200 pmol/l, which is the 92nd percentile for patients with duodenal ulcer disease in this laboratory. The control group was eight patients with duodenal ulcers whose peak postprandial gastrin concentrations were less than 200 pmol/l. Basal and peak postprandial plasma gastrin concentrations were 107 (37) and 306 (66) pmol/l (mean (SEM] respectively in the hypergastrinaemic patients compared with 26 (4) and 137 (14) pmol/l respectively in the controls. There was no significant difference in the density of gastrin enterochromaffin-like cells between the two groups. The number of enterochromaffin-like cells per high power field was 53 (8) in the hypergastrinaemic patients compared with 50 (8) in the controls. We conclude that chronic moderate hypergastrinaemia does not produce hyperplasia of enterochromaffin-like cells in man. Our hypergastrinaemic group had plasma gastrin concentrations similar to, or greater than those reported during treatment with drugs such as omeprazole and histamine H2 receptor blockers.

Topics: Adult; Cell Count; Chromaffin System; Duodenal Ulcer; Enterochromaffin Cells; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged

It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism.

Topics: Calcium; Duodenal Ulcer; Gastrins; Humans; Hyperparathyroidism; Parathyroid Glands; Parathyroid Neoplasms; Stomach Ulcer

An exaggerated increase in meal-stimulated gastrin is a common finding in patients with duodenal ulcer. Duodenal ulcer patients also exhibit an increase in the number of parietal cells, which results in an increase in maximum acid output. There are also data to suggest that acid hypersecretion may not predate the ulcer disease, but is acquired, possibly due to the trophic effects of the exaggerated gastrin release on parietal cells. We investigated meal-stimulated gastrin release in nine Helicobacter pylori-infected individuals; eight patients with chronic duodenal ulcer and one H. pylori-infected healthy control, both before and after therapy designed to eradicate H. pylori infection. We also simultaneously measured intragastric pH in six duodenal ulcer patients. Eradication of the H. pylori infection reversed the exaggerated meal-stimulated gastrin release (gastrin secretion fell from 141 + 16 pg/ml/h before treatment to 98 +/- 7 pg/ml/h after, p less than 0.01) without affecting intragastric pH. Whereas exaggerated meal-stimulated gastrin release may be an important pathogenetic feature of duodenal ulcer disease, we conclude that it is secondary to the H. pylori infection. This study provides further insight into the role of H. pylori in the pathogenesis of duodenal ulcer disease. We postulate that reversal of the abnormalities in gastrin secretion will be associated with a gradual return of gastric secretion to normal.

Topics: Bismuth; Campylobacter Infections; Drug Therapy, Combination; Duodenal Ulcer; Female; Food; Gastrins; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Tetracycline

Anatomically, functionally, and clinically, peptic ulcer patients are a heterogeneous group of subjects. These patients can be classified according to the anatomic localization of the niche. The functional state of the gastric mucosa was studied in 30 gastric ulcer patients, 25 duodenal ulcer patients, and 10 normal controls. The classification of the first group was based on Johnson's criteria, with the following results: 10 individuals were type I, 10 were type II, and 10 were type III. Pepsinogen I levels and gastric acid secretion were measured in all 65 subjects under basal conditions and after subcutaneous pentagastrin stimulation. Both basal and stimulated serum pepsinogen I values were significantly higher (p less than 0.05) in gastric ulcer type III patients than in the other four groups. These values in gastric ulcer type I were similar to those of the controls. Gastric ulcer type II patients showed an intermediate functional state similar to that of duodenal ulcer patients. In both gastric ulcer type II and duodenal ulcer patients, the basal and stimulated pepsinogen I levels were significantly higher (p less than 0.05) than those found in controls, whereas the basal serum gastrin levels were similar in the five groups. In conclusion, different HCl and pepsinogen I secretory patterns, with functional heterogenicity of the gastric mucosa, are shown here for the anatomically defined gastric ulcer subsets.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pepsinogens; Stomach Ulcer

Progastrin and all of its processing products were measured in serum from 48 patients with Zollinger-Ellison syndrome, 42 patients with duodenal ulcers, and 34 normal subjects. A processing-independent gastrin analysis and a conventional radioimmunoassay for the biologically active alpha-amidated gastrins were used. In serum from normal subjects, 87% (median; range, 27%-160%) of all progastrin products were alpha-amidated gastrins, whereas they constituted only 39% (15%-130%) in serum from patients with duodenal ulcers (p less than 0.01) and 46% (16%-100%) in serum from gastrinoma patients (p less than 0.01). A significantly lower percentage of alpha-amidated gastrin was found in patients with hepatic metastases (23%) than in patients with apparently benign tumors (54%). Chromatography of serum showed that large progastrin molecules occurred mainly in patients with malignant tumors, whereas smaller glycine-extended precursors dominated in patients with benign tumors. The results indicate that the total progastrin product reflects tumor synthesis of gastrin better than conventional measurements of alpha-amidated gastrin. Moreover, the results suggest that a low degree of processing of progastrin could serve as a predictor of a malignant clinical course at an early stage of the disease.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Chromatography, Gel; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Humans; Male; Middle Aged; Protein Precursors; Radioimmunoassay; Zollinger-Ellison Syndrome

Vagotomy was performed in 238 consecutive patients with duodenal ulcer since 1977. Electron microscopy of parietal cells from gastric body mucosa, gastric acid secretory test, and serum gastrin evaluation were done in randomly selected 15 PCV and 13 SV+A cases before and after vagotomy. It was found that 2-6 weeks after the surgery, the ultrastructure of parietal cells presented the feature of secretory depression and gastric acid output was decreased. One to ten years after PCV, the ultrastructure gradually regained its preoperative morphology, serum gastrin level was also increased, though acid output remained on low level. During the same period, patients undergoing SV+A were characterized with the feature of depressed secretion in gastric mucosa ultrastructure, and constantly low level of gastric acid output and serum gastrin. These results, in the authors' belief, may explain low gastric acid output after vagotomy and provide theoretical basis for the application of vagotomy in surgical treatment of duodenal ulcer.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Microscopy, Electron; Middle Aged; Parietal Cells, Gastric; Vagotomy

Patients with duodenal ulcer were classified into responders to H2-receptor antagonist and non-responders in whom duodenal ulcer did not heal within three months with the antagonist. In these patients and healthy controls, modified sham-feeding (MSF) test was performed to elucidate the pathophysiological differences between these groups, especially vagal activity of acid output. After tetragastrin 4 micrograms/kg/hr infusion for one hour, MSF was superimposed to the infusion (G + MSF). The acid output of non-responders (8 cases) and controls (8 cases) significantly increased in G + MSF. On the other hand, the acid output of responders (6 cases) significantly decreased. The acid output of non-responders in G + MSF was also significantly higher than that of controls. The results suggest that vagal activity of non-responders is higher than responders, and that there is disturbance of inhibitory mechanism in vagal system.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Tetragastrin; Vagus Nerve

We present 28 children, 4 to 14 year-old, with duodenal ulcer; there were 21 males and 7 females. In 16 cases, after stimulation with pentagastrin, basal pepsinogen I (PG1), basal gastrinemia and basal acid output (BAO) and maximal acid output (MAO) were measured. Compared to controls, the mean levels of PG1 and gastrin were significantly higher in the patients; 12 children (80%) had high levels of PG1 and the remaining 3 (20%) had normal levels. The blood group O was the most prevalent: 64% of the cases.

Topics: ABO Blood-Group System; Adolescent; Child; Child, Preschool; Disease Susceptibility; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastroscopy; Humans; Male; Pentagastrin; Pepsinogens

A total of 61 patients with frequently relapsing duodenal ulcer were examined. Of these, 18 patients were in the acute phase and 43 experienced remission. Using 1 mm2 of the mucosa, measurements were made of the counts of duodenal and pyloric G-cells (by immunomorphologic assay), of the absolute and relative counts of T and B lymphocytes, the content of IgA, IgM and IgG, histamine and serotonin (by fluorometry) in the blood, and of the concentration of uropepsin in the urine. In the stages of exacerbation and remission, the patients suffering from duodenal ulcer with hyperplasia of G-cells manifested, as compared with the analogous patients without hyperplasia, a decrease of the absolute and relative counts of T cells, especially of those of B cells, combined with a rise of the content of IgM and IgG during exacerbation, followed by its returning to normal in the phase of remission. Over one year part of the duodenal ulcer patients with hyperplasia of G-cells received preventive treatment with ranitidine, which resulted in a tendency towards the lowering of the count of pyloric G-cells and the rise of the absolute and relative counts of T cells.

Topics: Adolescent; Adult; Antibody Formation; Chromaffin System; Duodenal Ulcer; Enterochromaffin Cells; Gastrins; Humans; Hyperplasia; Immunity, Cellular; Immunoglobulins; Leukocyte Count; Middle Aged; Pylorus; Recurrence

Topics: Campylobacter Infections; Duodenal Ulcer; Food; Gastrins; Humans

Complex examination of 73 patients with ulcer disease (bulbus duodeni location) revealed regularities of evacuation of a test breakfast from the stomach depending on the phase of the disease. Significant disorders of the motor-emptying gastric and duodenal function were found that are to be considered in the treatment of this category of patients.

Topics: Adult; Biopsy; Duodenal Ulcer; Duodenoscopy; Duodenum; Female; Gastric Acidity Determination; Gastric Emptying; Gastrins; Gastrointestinal Motility; Gastroscopy; Humans; Male; Stomach; Stomach Ulcer

The endocrine system of the antrum of the resected stomachs in 19 patients with chronic duodenal ulcer was studied. It is established that a clear view of the hormonal system of the stomach can be formed on the basis of studying the histotopograms, or a large number of biopsy specimens of the gastric mucosa. The hormonal cells can be found in the deep portions of the mucosa, as a rule, in the region of the fundus and body of the glands. The ulcer recurrence after vagotomy not always can be related to hyperplasia of the endocrine cells of the gastric antrum.

Topics: APUD Cells; Cell Count; Duodenal Ulcer; Gastrins; Histamine Release; Humans; Pyloric Antrum; Serotonin

Topics: Adult; Antacids; Anti-Ulcer Agents; Campylobacter Infections; Duodenal Ulcer; Gastrins; Humans; Male; Metronidazole; Organometallic Compounds; Pyloric Antrum

Topics: Antacids; Campylobacter; Campylobacter Infections; Duodenal Ulcer; Gastrins; Gastritis; Humans; Metronidazole; Organometallic Compounds; Pyloric Antrum

Topics: Actihaemyl; Adult; Cyclic AMP; Cyclic GMP; Drug Evaluation; Duodenal Ulcer; Female; Gastrins; Humans; Insulin; Male; Middle Aged; Stomach Ulcer; Tissue Extracts

Radioimmunoassay was employed to measure blood levels of LH, FSH, testosterone, estradiol, progesterone, estriol, gastrin and cAMP in 184 duodenal ulcer patients (141 males and 43 females) and 81 controls (40 males and 41 females). For duodenal ulcer patients hypophyseal gonadotropic function was activated while the blood picture of sex hormones is sex-related. Functional balance between the study hormones typical for healthy subjects in duodenal ulcer was found impaired. Derangement of hormonal homeostasis of hypophyseal-gonadal system of the blood and its functional relations with gastroduodenal system may be a contributing factor in pathogenesis of peptic ulcer.

Topics: Adult; Cyclic AMP; Duodenal Ulcer; Estradiol; Estriol; Female; Follicle Stimulating Hormone; Gastrins; Gonadal Steroid Hormones; Gonadotropins, Pituitary; Homeostasis; Humans; Luteinizing Hormone; Male; Middle Aged; Progesterone; Radioimmunoassay; Testosterone

The possibility that Campylobacter pylori (CP) in the gastric antrum stimulates gastrin release in duodenal ulcer (DU) disease was examined in 31 patients. The 25 patients with antral colonisation with CP had higher basal and meal-stimulated plasma gastrin concentrations, and higher peak acid output (PAO), than did the 6 without CP in the autumn.

Topics: Adult; Aged; Campylobacter Infections; Duodenal Ulcer; Eating; Evaluation Studies as Topic; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Pyloric Antrum

Topics: Campylobacter; Campylobacter Infections; Duodenal Ulcer; Gastrins; Humans; Pyloric Antrum

Topics: Adult; Aged; Campylobacter; Campylobacter Infections; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged

Topics: Adult; Campylobacter Infections; Duodenal Ulcer; Evaluation Studies as Topic; Gastric Acidity Determination; Gastrins; Gastritis; Humans; Middle Aged

Topics: Campylobacter Infections; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Humans; Pyloric Antrum

Topics: Duodenal Ulcer; Gastrins; Humans; Liver Cirrhosis; Postoperative Period; Prognosis; Stomach Neoplasms

A 14-year-old case was reported with a primary postbulbar duodenal ulcer, which was confirmed by barium meal study and duodenoscopy. In the preoperative study, the patient showed marked gastric hyperacidity: maximal and peak acid output were 0.980 and 1.434 mEq/kg/hr, respectively. As previously described, hyperacidity appears to be a main factor in the pathogenesis of postbulbar duodenal ulcer. Fasting and postprandial serum gastrin secretion was not thought to be responsible for gastric hyperacidity in the present case. Upon histological investigation, the operatively resected stomach did not suggest a possible relationship between hyperacidity and an enlarged parietal cell mass.

Topics: Adolescent; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Radiography

Gastric acid secretion, gastrinemia, the type of gastritis of the fundic mucosa and the parietal cell mass, expressed by means of a 'parietal index', were considered in 70 patients with active duodenal ulcer. Hypersecretion was found in 60% of cases, normosecretion in 35.7% and hyposecretion in 4.3%, while achlorhydria was absent. Chronic fundic gastritis of the superficial or follicular type occurred at a similar rate in normosecretors (22%) and in hypersecretors (26%), being constantly of the preatrophic type in the 3 cases of hyposecretion. The parietal index was strictly correlated with maximal acid output but there was no correlation between gastrinemia and the secretory state or with the histological picture of the fundic mucosa. The results outline the prevalence of hypersecretion-hyperparietalism in duodenal ulcer but indicate also the frequent occurrence of normosecretion and normoparietalism and the rare finding of hypersecretion and hypoparietalism.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric

A different pathophysiological mechanism is widely accepted for gastric and duodenal ulcer. In particular, the exact role of gastrin in the determinism of nonhormone-dependent peptic ulcer disease has been completely clarified. The aim of the present study was to analyse fasting and postprandial serum gastrin levels in 99 duodenal ulcer patients, 17 gastric ulcer patients and 11 subjects presenting an association of gastric and duodenal ulcer. The possible correlation between postprandial gastrin concentrations and basal and maximal acid output in the 3 groups of patients has also been investigated. Fasting serum gastrin levels do not appear different among the 3 classes of patients, while postprandial gastrin concentrations are statistically higher at 15 minutes in duodenal ulcer patients and in subjects with the association of gastric and duodenal ulcer as compared to gastric ulcer patients. Mean fasting and stimulated gastrin levels are higher in gastric ulcer females than in males during the entire test and with a statistically significant difference at 30 minutes. The concentrations of the hormone are not different in males of the 3 groups of patients at basal time, while they are statistically lower at 15 and 30 minutes in gastric ulcer males compared to those with duodenal ulcer and the association of the localization. Finally, positive correlation has been observed between B.A.O. and M.A.O. and postprandial gastrin concentration in the 3 groups of patients, while there is an inverse correlation between the previous parameters as regards sex, both in gastric and duodenal ulcer.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Feeding Behavior; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Sex Characteristics; Stomach Ulcer; Time Factors

Examinations of different patients with duodenal ulcer performed during one year revealed seasonal changes in the function of the regulatory systems. Secretion of histamine, serotonin, insulin, and hydrocortisone was increased in spring and reduced in autumn. Secretion of adrenalin, noradrenalin and acetylcholinesterase activity were high in summer and low in autumn. The acid-producing function of the stomach did not depend on the season. It is suggested that deviations in the activity of the regulatory systems in spring and autumn may cause seasonal exacerbations of duodenal ulcer.

Topics: Acetylcholinesterase; Duodenal Ulcer; Gastrins; Histamine; Hormones; Humans; Hydrocortisone; Insulin; Seasons; Serotonin

Cholecystokinin (CCK) is a polypeptid released postprandially by the upper intestinal mucosa. There are several biological active forms of CCK. Radioimmunological measurements of CCK may not detect all biological active forms or may have the disadvantage of crossreacting with gastrin. In the following we describe a modification of a bioassay for CCK which was first developed by Liddle et al. (J Clin Invest 1985). By means of this bioassay pre- and postprandial plasma CCK-levels of healthy male volunteers are compared with CCK-levels of patients with partial gastric resections and excluded duodenum. Both groups showed similar basal CCK-values (about 1 pM) and a food induced increase of this hormone by reaching maximal values after 15 to 30 min (control: 4.30 +/- 0.65 vs. operated: 13.37 +/- 2.83 pM). Patients with gastric resections, however, had about three times more CCK released over the 60 min time period studied as compared to controls. Thus exclusion of the duodenum, the supposed main place of CCK production, does not cause a lower but rather higher increase of postprandial CCK release.

Topics: Adult; Aged; Anastomosis, Roux-en-Y; Cholecystokinin; Duodenal Ulcer; Gastrectomy; Gastric Emptying; Gastrins; Humans; Intestinal Absorption; Middle Aged; Peptic Ulcer Hemorrhage; Postoperative Complications; Radioimmunoassay; Stomach Ulcer

Conflicting data are present in the literature on pathophysiological role of serum gastrin and peptic ulcer disease. The aim of this study was to evaluate, in duodenal ulcer patients, the possible correlation between post-prandial serum gastrin concentrations and some epidemiological (sex, family history, onset of the disease, blood group status, smoking habit, alcohol consumption) and clinical (effectiveness of therapy, bleeding episodes) factors. The gastrin levels were expressed in absolute values and as per cent increase of fasting serum gastrin concentrations. As regards sex, the per cent increase of fasting serum gastrin concentration was significantly higher in females (No. 16) than in males (No. 60) at 30 and 60 minutes (192.25% vs 116.52% and 105.42% vs 40.96% respectively; p less than 0.05 and p less than 0.005). Post-prandial serum gastrin concentrations, expressed as per cent increase, were higher in heavy drinkers (No. 14) and statistically significant at 120 minutes (40.57% vs 9.58%, p less than 0.025); as well as in smoker patients (No. 31), at 15, 30 and 60 minutes (227.59% vs 123.52%, 177.23% vs 101.62%, 0.025 and p less than 0.05). Post-prandial gastrin was unrelated to blood group status, onset of the disease, family history, effectiveness of medical treatment and bleeding episodes.

Topics: Adult; Alcohol Drinking; Dietary Proteins; Duodenal Ulcer; Eating; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Sex Factors; Smoking; Time Factors

A computer simulation model is presented of the gastric phase regulation of gastric acid secretion in humans. The model is based on experimental data from the literature and includes terms representing gastric pH and gastric volume-dependent gastrin secretion, gastrin-dependent acid secretion, food storage in the stomach, and gastric emptying. We have explored the predictive value of the model in assessing the relative importance of gastric pH-dependent and gastric volume-dependent acid secretion mechanisms under various conditions. Similarly we have studied the role of gastric acid deregulation in achlorhydria, the Zollinger-Ellison syndrome, and duodenal ulcer, and the influence of the antacid drugs cimetidine and ranitidine under duodenal ulcer conditions. Model analysis of normal gastric acid regulation suggests that gastric volume-controlled acid secretion is of major importance during eating and predicts that pH-dependent gastrin secretion is of major importance in preventing excessively low pH levels between meals and during the night.

Topics: Achlorhydria; Cimetidine; Computer Simulation; Duodenal Ulcer; Food; Gastric Acid; Gastric Emptying; Gastrins; Humans; Hydrogen-Ion Concentration; Mathematics; Models, Biological; Ranitidine; Stomach; Zollinger-Ellison Syndrome

This report describes the clinicopathologic features of a 55-yr-old man found to have a bleeding, postbulbar duodenal ulcer and fasting hypergastrinemia. Gastric analysis revealed pentagastrin-fast achlorhydria. Healing of the ulcer was documented 8 wk after vagotomy, antrectomy, gastrojejunostomy, and a course of sucralfate therapy. The etiology of the postbulbar ulcer was uncertain. This is the first documented case of a duodenal ulcer with pentagastrin-fast achlorhydria.

Topics: Achlorhydria; Combined Modality Therapy; Duodenal Ulcer; Fasting; Gastrins; Humans; Male; Middle Aged; Wound Healing

The etiology of peptic ulcer disease is completely unknown. However, gastric acid secretion plays an important role in the pathogenesis of the disease. Acetylcholine, gastrin and histamine are recognized as the main stimulators of the acid secretion. Extensive studies on blood gastrin have not incriminated this hormone in the pathogenesis of the disease. The present study was done to evaluate the role of circulating histamine in peptic ulcer disease using a sensitive and specific radioimmunoassay method. Since gastrin at least in some species seems to exert its stimulatory effect by releasing histamine, serum gastrin was also determined. There was no significant difference in plasma histamine between patients with duodenal or gastric ulcer, nonulcer dyspepsia or ulcer patients after proximal gastric vagotomy. However, patients taking a histamine-2 blocker (cimetidine or ranitidine) had significantly higher plasma histamine than those not taking these drugs. This effect was not due to interference in the histamine assay. There was no correlation between plasma histamine and plasma gastrin. Plasma gastrin was significantly increased in patients having been operated on with a proximal gastric vagotomy. In conclusion, plasma histamine is similar in patients with different upper gastrointestinal disorders. However, histamine-2 blockers may increase plasma histamine.

Topics: Blood Specimen Collection; Duodenal Ulcer; Gastrins; Gastrointestinal Diseases; Histamine; Histamine Antagonists; Humans; Radioimmunoassay; Vagotomy, Proximal Gastric

We compared plasma gastrin concentrations in male and female patients with duodenal ulcers because a group in Denmark reported a difference, but two groups in the Far East did not. Median basal gastrin was 23 pmol/l in males compared with 43 pmol/l in females. Median peak postprandial gastrin was 71 pmol/l in males, compared with 142 pmol/l in females (p less than 0.03). Elevated gastrin may reflect diminished sensitivity of parietal cells to gastrin in females.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Osmolar Concentration; Sex Characteristics

To improve surgical results of duodenal ulcer, transgastric myotomy (TGM) was added to the traditional selective proximal vagotomy (SPV) and its efficacy was evaluated clinically in 40 patients. 35 men and 5 women were involved, with a mean age of 33.07 +/- 14.25 years. Pyloroplasty was added in 12 operations for stenosis and perforation. 28 patients in this series underwent TGM with SPV without drainage. In the 36 patients, basal and maximal acid output (BAO and MAO) was compared preoperatively and at 6 months postoperatively. A satisfactory reduction of acid output was achieved, with a mean reduction rate of 71.4% in BAO and of 79.9% in MAO. All 40 patients were negative in Hollander's insulin stimulation test at 6 months postoperatively. The gastric mucosa was injured during myotomy in 2 of the patients (5.0%), and was simply sutured using 3-0 Dexon, without causing any problems. No other early or late postoperative complication was present. In addition, no peptic ulcer recurrence has been noted over a maximal follow-up of 8 years. The present results suggest the completeness of gastric denervation by TGM+SPV, and establish the efficacy of TGM with SPV, and therefore this method is recommended in the surgical treatment of duodenal ulcer.

Topics: Adolescent; Adult; Duodenal Ulcer; Esophagogastric Junction; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Vagotomy; Vagotomy, Proximal Gastric

A series of 31 infants and children with acute duodenal ulcer verified by endoscopy was studied over an eight year period. Eighteen (58%) of them were under 2 years of age. The most common symptom was upper gastrointestinal bleeding (n = 27, 87%). Twenty nine patients (94%) had a preceding illness characterised by diarrhoea, upper respiratory tract infection, or fever, which was not necessarily treated with antipyretic drugs. Initial endoscopy showed that ulcer lesions were solitary in 14 patients and present on the anterior wall (n = 11), posterior wall (n = 2), or both (n = 1). Multiple ulcers were found in 17 patients, and present in the bulb with (n = 6) or without (n = 11) extension into the second part of duodenum. The most conspicuous finding was the irregularly shaped ulcers seen in eight young children with similar clinical and endoscopic features. Sixteen patients were re-endoscoped one to two weeks after the initial examination; the ulcers had entirely disappeared in 13, and there were only small residual ulcers in three. Thirty patients were treated medically and only one (with uncontrollable haemorrhage) required operation. Most patients were symptom free two to six years after the initial diagnosis. Our results suggest that young children may develop acute duodenal ulcers after viral illnesses whether or not they are treated with drugs, mainly antipyretics. This kind of acute duodenal ulcer usually heals quickly irrespective of the morphology, site, and number of ulcers.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Duodenal Ulcer; Duodenoscopy; Duodenum; Female; Follow-Up Studies; Gastrins; Humans; Infant; Male

Antral G and D cells were microscopically counted by the immunoperoxidase method in the resected stomachs of 18 patients with duodenal ulcer (DU group), 4 with recurrent duodenal ulcer after selective proximal vagotomy (SPV-REC group) and 6 with early gastric cancer in the corpus (control group). In DU and SPV-REC groups, preoperative acid secretion stimulated by the tetragastrin (Tg-MAO, Tg-PAO) was examined. In 9 patients of DU and SPV-REC groups, adrenalin stimulated acid secretion (Adr-PAO) and integrated gastrin response (Adr-PGO) were also examined. The G cell count in DU group (Tg-MAO greater than or equal to 20) and SPV-REC group were significantly more than in DU group (Tg-MAO less than 20) and control group. In DU and SPV-REC groups, a significant correlation was observed between Tg-PAO and total G cell count. In 9 DU patients, a significant correlation was observed between the total G cell count and Adr-PGO or Adr-PAO, between Adr-PGO and Adr-PAO or Tg-PAO and between Tg-PAO and Adr-PAO. The above results suggested that increase of antral G cell counts is one of the great cause of duodenal ulcer and recurrent ulcer after SPV, greatly affecting on increase of acid secretion intermediating serum gastrin. Both Tg-PAO and Adr-PAO were regarded as good index of functional G cell mass of the antrum.

Topics: Adolescent; Adult; Aged; Cell Count; Duodenal Ulcer; Epinephrine; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pyloric Antrum; Recurrence; Tetragastrin; Vagotomy, Proximal Gastric

Morphofunctional state of the gastrin-producing cells in the antral gastric mucosa depending upon the gastric secretion and serum gastrin was investigated in patients with duodenal ulcer before and after the selective proximal vagotomy (SPV). Morphometric analysis of the hormone containing granules in G-cells showed the increase of their functional activity after SPV. It was demonstrated that serum basal gastrin reflects morphofunctional state of the gastrin-producing cells. Functional capabilities of the gastrin regulation of the gastric secretion after the vagus denervation of the acid-producing part of the stomach must be taken into consideration in duodenal ulcer surgery.

Topics: Adolescent; Adult; Cytoplasmic Granules; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Vagotomy, Proximal Gastric

Some patients with hypergastrinemic achlorhydria may have false-positive secretin provocation as an exaggeration of the normal gastrin response to secretin, presumably related to an increased, or more responsive, antral G-cell mass. To test this hypothesis, we reviewed our experience with secretin provocation in normogastrinemic subjects with presumed normal antral G-cell mass (normal--17, duodenal ulcer--13) and in patients with hypergastrinemia related to changes in antral G-cells (vagotomy--5, hypochlorhydria--7, achlorhydria--10). Basal serum gastrin (mean +/- SEM) was progressively higher for each group; normal (42 +/- 3 pg/ml), duodenal ulcer (53 +/- 4 pg/ml), vagotomy (226 +/- 54 pg/ml), hypochlorhydria (346 +/- 92 pg/ml), achlorhydria (844 +/- 100 pg/ml). On selective analysis of only those with gastrin rises, significant differences (p less than 0.05) in peak gastrin change were found between achlorhydria (93 +/- 21 pg/ml) compared with all other groups and between hypochlorhydria (40 +/- 12 pg/ml) versus normal (6 +/- 1 pg/ml). Linear regression in these responders showed a significant correlation (p less than 0.001) between basal gastrin and peak gastrin change after secretin. There were no false-positive secretin provocation tests, but four achlorhydric patients had gastrin rises greater than 100 pg/ml, whereas no patient in the other categories had rises above 90 pg/ml. Our results support the concept that patients with hypergastrinemic achlorhydria tend to have greater G-cell responsiveness to secretin provocation, which may account for the false-positive results in some such patients.

Topics: Achlorhydria; Adult; Aged; Cell Count; Chromaffin System; Duodenal Ulcer; Enterochromaffin Cells; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Secretin

The roles of plasma gastrin and duodenal acidity in duodenal ulcer disease remain unclear. In this pathophysiologic study, plasma gastrin and dual gastro-duodenal pH were measured before, during, and after cephalic stimulation (modified sham feeding) and the ingestion of a meal in 16 duodenal ulcer (DU) patients and twelve healthy subjects. Gastrin levels were significantly higher in DU patients both in the fasting state (42.5 ng/l vs. 22.5 ng/l, p less than 0.001) and after the meal (130 vs. 60, p less than 0.02). Two separate patient subsets were identified: a "hypergastrinemic" (HRG) group exhibiting exaggerated gastrin responses and a "Normogastrinemic" (NOG) group comprised of patients with gastrin levels similar to those of controls. Only the HRG group exhibited a significant gastrin response to sham feeding. Both patient groups exhibited a delayed onset of duodenal acidity and delayed peak acid response after feeding indicative of delayed gastric emptying of the acid load. The HRG group exhibited a longer duodenal acid exposure and a prolonged return to premeal pH levels, suggesting a defective switch-off mechanism of acid secretion after duodenal acidification.

Topics: Adult; Aged; Duodenal Ulcer; Duodenum; Eating; Female; Food; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with biochemical indices of growth in gastric and duodenal mucosa in rats with intact or removed salivary glands after treatment with epidermal growth factor (EGF) or somatostatin, or both. After the extirpation of salivary glands, the healing rate of gastric and duodenal ulcerations was delayed and gastric content of immunoreactive EGF was reduced. This was accompanied by a significant decrease in the contents of deoxyribonucleic acid and ribonucleic acid in the gastric and duodenal mucosa. Repeated administration of EGF either subcutaneously or orally accelerated the healing of gastroduodenal ulcers in rats with intact salivary glands and completely reversed the delay in ulcer healing in sialoadenectomized animals. These effects were also accompanied by a significant increase in the growth parameters of gastric and duodenal mucosa. Administration of somatostatin, which prevented the growth-promoting action of subcutaneous EGF, resulted in a significant decrease in the EGF-stimulated healing of gastric and duodenal ulcerations in both intact and sialoadenectomized rats. Our findings suggest that cell proliferation is an important factor in healing of gastric and duodenal ulcerations and that EGF plays an important role in ulcer healing due to its mitogenic action.

Topics: Administration, Oral; Animals; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastrins; Infusions, Parenteral; Intestinal Mucosa; Male; Nucleic Acids; Rats; Rats, Inbred Strains; Somatostatin; Stomach Ulcer; Wound Healing

Topics: Animals; Cats; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastrins; Hexosamines; Male; Pepsin A; Pirenzepine; Rats; Rats, Inbred Strains; Stomach Ulcer

To clarify the contributive factors in the recurrence of duodenal ulcer, the present study was carried out on 65 male patients with active duodenal ulcers and 20 healthy male subjects. After having verified that the ulcer had healed, gastric acid secretory responses to graded doses of tetragastrin from 62.5 to 16,000 ng/kg/hr were investigated using a logarithmic transformation model. Several clinical features were also investigated. The patients were divided into three groups based on the later endoscopic follow-up study for two years. The early-recurrent group included 16 patients with recurrence occurring within three months. The late-recurrent group included 25 with recurrence occurring after three months. The nonrecurrent group included 24 patients without recurrences during the follow-up period. The 20 healthy male subjects were defined as a control group. The results were as follows: (1) Significant differences were not discerned either in basal and peak acid outputs between the three patients groups. (2) The ED50 value for tetragastrin was lower in the early-recurrent group than in the other three groups. (3) The early-recurrent group showed a higher percentage of smokers than the other patient groups. These results suggest that smoking and increased parietal cell responsiveness correlates strongly with duodenal ulcer recurrence.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Parietal Cells, Gastric; Recurrence; Smoking; Tetragastrin; Time Factors

Serum pepsinogen 1, serum gastrin, ABO blood groups, secretor status of ABH blood group substances and behavioral factors were studied in 15 patients with duodenal ulcer and 61 their relatives affected and unaffected to duodenal ulcer. Duodenal ulcer patients had hyperpepsinogenemia 1 either with or without a positive family history of duodenal ulcer. Serum gastrin level was higher in duodenal ulcer patients and unaffected relatives with a positive family history of duodenal ulcer than those with a negative family history. Non secretor status was frequently observed in duodenal ulcer patients with a positive family history. There was no difference in behavioral factors between duodenal ulcer patients and unaffected relatives with a positive family history. It is concluded that genetically determined variables such as hyperpepsinogenemia 1 and non secretor status play an important role on the susceptibility to duodenal ulcer in subjects with a positive family history, and hypergastrinemia may be subclinical marker of familial aggregation of duodenal ulcer.

Topics: ABO Blood-Group System; Adult; Duodenal Ulcer; Female; Gastrins; Humans; Male; Pedigree; Pepsinogens; Smoking; Stress, Psychological

The effect of intermittent dosage with omeprazole on basal and pentagastrin stimulated gastric acid secretion and fasting plasma gastrin was assessed in eight duodenal ulcer subjects who were in remission. Omeprazole (20 mg daily) was given for a three day 'weekend' each week for two months. Twenty four hours after the first and eighth weekend, basal and peak acid output were still markedly suppressed (greater than 50%) compared with pretreatment. After the treatment free four days, however (just before the eighth weekend), peak acid output had returned to pretreatment values; basal acid output was still somewhat reduced (mean 3.6 mmol/l) but the difference from baseline was not statistically significant. Fasting plasma gastrin concentration increased slightly but significantly, from a baseline median of 17 pmol/l to 25 and 31 pmol/l respectively, 24 hours after the first and eighth weekends. All but two values (of 16) remained within the reference range. Before the fourth and eighth weekends, and again at 12 days and three months after treatment, gastrin values were not significantly different from baseline. Thus a 'weekend therapy' regimen with this long acting antisecretory compound produces substantial acid suppression, but for only part of the week, with modest and reversible changes in fasting plasma gastrin. It should therefore be suitable for efficacy testing for prevention of recurrence of peptic ulcer or reflux oesophagitis.

Topics: Adult; Drug Administration Schedule; Duodenal Ulcer; Fasting; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Omeprazole

Topics: Adolescent; Child; Child, Preschool; Duodenal Ulcer; Eating; Gastric Mucosa; Gastrins; Gastritis; Humans

Topics: Adolescent; Adult; Drugs, Chinese Herbal; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Nucleotides, Cyclic; Stomach Ulcer

Duodenal acidification was studied in 53 peptic ulcer patients. Gastric and duodenal pH was studied using an electric probe with silver chloride and antimony electrodes. For a study of the mechanisms of changes of duodenal acidification gastrin was investigated using various exercise tests. Two types of disorders of duodenal acidification were established in the patients: related and unrelated to the vagus nerve. Characterization of the mechanism of disorders of duodenal acidification was provided. A study of duodenal acidification in peptic ulcer gave an opportunity for the development of effective pathogenetically substantiated therapeutic measures.

Topics: Adolescent; Adult; Atropine; Chronic Disease; Duodenal Ulcer; Duodenum; Fasting; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Insulin; Male; Middle Aged; Stomach; Time Factors

Our previous secretin provocation studies in normal volunteers and unoperated duodenal ulcer patients suggested that the gastrin rise in gastrinoma may be an exaggeration of the normal response rather than paradoxical. We report further studies in various clinical settings having normogastrinemia (normal, n = 17; unoperated duodenal ulcer, n = 13; primary hyperparathyroidism, n = 7) and hypergastrinemia (postvagotomy, n = 5; hypochlorhydria, n = 7; achlorhydria, n = 10; chronic renal failure, n = 10; gastrinoma, n = 5). Under all nongastrinoma conditions, there were similar gastrin rises of 9-19% between 2 and 5 min after bolus intravenous GIH secretin (2 CU/kg), which fell to baseline by 8 min, except for chronic renal failure. In chronic renal failure, gastrin remained elevated from 7 to 30 min and was significantly different (p less than 0.05) at 10-30 min compared to all other nongastrinoma conditions except hyperparathyroidism. Peak rises occurred within 5 min in all entities, but only three gastrinoma patients had positive secretin provocation tests by the predefined criterion of a gastrin rise greater than 200 pg/ml. The results of secretin provocation in various clinical entities with and without hypergastrinemia further support the hypothesis that the gastrin rise in gastrinoma is an exaggeration of the normal response. The prolonged gastrin rise seen in chronic renal failure may be due to altered renal clearance, inasmuch as other hypergastrinemic states had responses similar to normal and duodenal ulcer.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Male; Middle Aged; Secretin; Vagotomy

Campylobacter pylori may cause gastritis and has been proposed as an etiologic factor in the development of peptic ulcer. However, it may be an acid-sensitive microbe and before it can be implicated in the pathogenesis of peptic ulcer, it should be consistently found in ulcer patients with normal acid secretion. Thirty-six patients with C. pylori by Warthin-Starry stain underwent gastric analysis; 25 were normochlorhydric and 11 hypochlorhydric. Ulcers were present in 19 normochlorhydric patients (10, gastric; 9, duodenal) and 2 hypochlorhydric patients (gastric). Median basal acid output was higher for those with duodenal ulcer (38 mmol/h) than gastric ulcer (28 mmol/h) or miscellaneous endoscopic features (33 mmol/h). The hypergastrinemia seen in 12 patients with negative secretin provocation tests was believed to be due to various nongastrinoma conditions. Campylobacter pylori was found in 6 normogastrinemic patients with elevated acid output and in 1 gastrinoma patient with marked acid hypersecretion. Histologic chronic gastritis was present in all subjects and 29 had active chronic gastritis. Twenty-three patients were taking H2-receptor antagonists at the time of diagnosis which did not seem to interfere with culture results. Using standard acid secretory tests, we conclude that C. pylori can survive in a wide range of acid conditions.

Topics: Adult; Campylobacter; Campylobacter Infections; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Humans; Male; Stomach Ulcer

We have studied the effect on serum gastrin concentrations of weekly 3-day courses of 20 mg/day omeprazole followed by a 4-day period without medication (weekend therapy) for 4 weeks in 10 patients with duodenal ulcer. Basal and postprandial serum gastrin concentrations were measured in week 1, before (day 1) and immediately after the 3-day omeprazole course (day 4), and further on day 6 and day 8, immediately before the next course, and at similar intervals in week 4 (days 22, 25, 27, and 29). Basal serum gastrin concentrations were not significantly different from day 1, but postprandial peak gastrin concentrations on days 6, 8, 22, 25, 27, and 29 and integrated postprandial gastrin secretion on days 25 and 27 were significantly increased (p less than 0.01 to p less than 0.05). However, the increases in serum gastrin concentration were modest and clinically irrelevant. It is concluded that this intermittent weekend schedule of omeprazole therapy does not induce marked hypergastrinemia and may therefore be suitable for long-term therapy with this drug.

Topics: Adult; Aged; Drug Administration Schedule; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole

Serum gastrin concentrations were determined in 25 children with duodenal ulcer (DU) and 25 normal children. Fasting values were significantly higher in DU children (mean +/- SE = 60.4 +/- 9.7 pg/mL) than in controls (mean +/- SE = 38.0 +/- 4.2 pg/mL; P less than .05). Integrated gastrin response to meal stimulation was also significantly higher in DU children (mean +/- SE = 140.5 +/- 32.4%) than in controls (mean +/- SE = 62.3 +/- 12.2%; P less than .05). Excessive gastrin activity (greater than normal mean + 2 SD), either fasting or meal-stimulated, occurred in 11 of 17 normal acid secretors and in two of eight hypersecretors in the DU group. The present findings suggest that excessive gastrin activity is a major factor in the pathogenesis of childhood DU. Unlike adult DU, which is associated with normal fasting gastrin concentrations, childhood DU manifests exaggerated gastrin activity both in the fasting and postprandial states.

Topics: Adolescent; Child; Child, Preschool; Duodenal Ulcer; Fasting; Female; Food; Gastric Acid; Gastrins; Humans; Male

Topics: Adult; Age Factors; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Sex Factors; Stomach Ulcer

94 patients with peptic ulcerations of duodenum, stomach, and esophagus, who did not respond to 3 or more months high-dose (450 or 600 mg) treatment with ranitidine, were treated orally with 40 mg omeprazole daily. After healing all patients were offered long-term maintenance therapy with the same dose for 5 years. In 75 patients the peptic ulcerations healed within 4 weeks, in 13 patients within 8 weeks, and in 3 patients only after an increase to 60 mg omeprazole daily. In 3 patients the ulcers did not heal. So far 83 patients have entered long-term maintenance therapy. 59 of these patients are on the drug between 1 and 4 years. During maintenance therapy with 40 mg omeprazole no relapses have occurred up to now as demonstrated by endoscopy and no drug-related adverse effects were observed. Routine laboratory tests remained without significant changes in all patients including 18 patients with concomitant liver cirrhosis. Serum gastrin levels were already elevated during the initial high-dose ranitidine treatment (106 +/- 15.4 pg/ml). 4 weeks after the start of omeprazole treatment serum gastrin levels rose to 4 times normal levels (195 +/- 28 pg/ml). Thereafter, no further increase in serum gastrin was observed even up to 4 years of continuous observation. It is therefore concluded that omeprazole is highly effective in healing ranitidine-resistant peptic ulcerations and that omeprazole maintenance therapy with 40 mg omeprazole is safe during the time observed and highly effective in the prevention of ulcer recurrence.

Topics: Adult; Aged; Duodenal Ulcer; Esophagitis, Peptic; Female; Gastrins; Humans; Male; Middle Aged; Omeprazole; Ranitidine; Stomach Ulcer; Time Factors

The basal and postprandial serum gastrin concentrations (SGC) were compared between 151 duodenal ulcer (DU) patients and 41 non-dyspeptic volunteers. All DU patients had an eventful history and were submitted to us for surgery. The basal SGC was significantly higher in DU patients (40 +/- 30 vs 17 +/- 8 pg/ml). The peak post-prandial SGC was also significantly higher (123 +/- 83 vs 52 +/- 28 pg/ml) and the integrated gastrin output twice as high as in healthy subjects (5311 +/- 3879 vs 2554 +/- 1995 pg/ml x min; P less than 0.01). A statistically significant linear correlation for fasting and maximal postprandial SGC was found. No statistically significant interrelation between gastrin and acid parameters existed. In the DU patients no differences in SGC were found according to age. Fifteen patients complained of nonalimentary vomiting as part of their ulcer symptoms. They had significantly higher SGC although no differences in acid secretion were found. No significant differences in gastrin or acids were related to ulcer complications.

Topics: Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Fasting; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged

The distribution of gastrin-, gamma-endorphin and somatostatin-producing cells in antral and duodenal mucosa was studied in biopsies from 26 patients with duodenal ulcer and from 13 controls by the immunohistochemical (PAP) method. The number of antral somatostatin-producing cells after dalargin treatment was significantly higher in comparison with controls and patients treated with antacids plus atropine. These changes may be connected with the antiulcer activity of dalargin, a new opioid peptide drug.

Topics: Adult; Chromaffin System; Duodenal Ulcer; Duodenum; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enterochromaffin Cells; gamma-Endorphin; Gastrins; Gastrointestinal Hormones; Humans; Male; Pyloric Antrum; Somatostatin

The synchronous change in the antral release of gastrin and somatostatin into a vein draining the stomach was studied during acidic and alkaline intragastric pH in six anaesthetised duodenal ulcer patients and six controls after atropinisation. No differences in the basal secretion of gastrin and somatostatin were observed among the two groups. Alkaline as well as acidic intragastric pH had no effect on the antral release of somatostatin in duodenal ulcer patients and controls. In contrast, alkaline intragastric pH was associated with a significantly higher antral gastrin release in duodenal ulcer patients than in controls. Acidic intragastric pH was associated with a significantly smaller inhibition of antral gastrin release in duodenal ulcer patients than in controls. These results suggest that atropinised anaesthetised duodenal patients release gastrin abnormally in the presence of acidic or alkaline intragastric pH and that any inverse relationship between antral gastrin and somatostatin release is uncoupled under these conditions.

Topics: Adult; Anesthesia, General; Atropine; Bicarbonates; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hydrochloric Acid; Hydrogen-Ion Concentration; Male; Middle Aged; Pyloric Antrum; Sodium; Sodium Bicarbonate; Somatostatin

To further investigate differences in the responses of normals and patients with duodenal ulcer with respect to gastrin release and acid and pepsin secretion, we infused bombesin (1 microgram/kg X h) or bethanechol (40 micrograms/kg X h) during the middle hour of a 3-h infusion of pentagastrin and compared the results with a pentagastrin infusion without added drug. Pentagastrin dosage (0.1 microgram/kg X h) was set to give about half-maximal response, to detect either inhibition or further stimulation of gastric secretion, whereas the dose of bombesin was chosen to give maximal gastrin but less than maximal acid secretion. Serum gastrin and somatostatin were also measured. In all subjects tested, bethanechol produced no effects on acid, gastrin, or somatostatin release but increased pepsin output. By contrast, bombesin inhibited pentagastrin-stimulated acid output in all 6 normal men by an average of 55%, whereas it inhibited acid output in only 2 of the 9 men with duodenal ulcer. Serum gastrin increases after bombesin in duodenal ulcer were three to four times greater than in normals. Although bombesin stimulates acid only by releasing gastrin, we postulate that bombesin may also simultaneously limit acid and pepsin secretion and speculate that this effect could be mediated by bombesin-induced somatostatin release. The cause for differences between duodenal ulcer and normal remain speculative.

Topics: Adult; Bethanechol; Bethanechol Compounds; Bombesin; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Pepsin A; Somatostatin

A single duodenal ulcerogenic dose of cysteamine administered into rats induced time-dependent depletion of immunoreactive somatostatin in the gastric corporeal, antral, and duodenal mucosa with a parallel increase (up-regulation) of somatostatin binding sites. The concentration of somatostatin binding sites returned to the control level in the corporeal mucosa when measured at 24 hrs; however, in the duodenal mucosa there was only a partial return to the control level. Somatostatin binding sites in the antral mucosa did not return to control level even after 24 hrs. Except for the duodenum mucosal immunoreactive gastrin level was unaffected by cysteamine administration, but corporeal mucosal gastrin I binding sites were diminished (down-regulation) after 24 hrs.

Topics: Animals; Cysteamine; Duodenal Ulcer; Gastric Mucosa; Gastrins; Intestinal Mucosa; Male; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; Receptors, Neurotransmitter; Receptors, Somatostatin; Somatostatin

The concentrations of gastrin-releasing polypeptide, somatostatin (SS), and gastrin in extracts of endoscopically obtained biopsies from the fundus, antrum, and duodenum of patients with uncomplicated bile stones (controls) or duodenal ulcer disease were measured with specific radioimmunoassays. The validity of the tissue sampling was confirmed by characteristic and significant differences between gastrin concentrations at the different biopsy sites. Gastrin-releasing polypeptide levels were at their highest in the fundic and duodenal bulb compared to the antrum in controls (p less than 0.01), whereas no differences in gastrin-releasing polypeptide content of the different parts of the stomach were found in duodenal ulcer patients. Compared to controls gastrin-releasing polypeptide in duodenal ulcer patients was reduced in fundic and duodenal bulb mucosa (p less than 0.01). SS levels were highest (p less than 0.05) in the first part of duodenum in controls. Compared to controls duodenal ulcer patients had lower SS concentrations present in fundic (p less than 0.01) and highest SS concentrations present in duodenal bulb mucosa (p less than 0.01). There was no correlation between acid secretion and mucosal gastrin-releasing polypeptide or SS concentrations in any part of the stomach and duodenum.

Topics: Adult; Cholelithiasis; Duodenal Ulcer; Duodenum; Female; Gastric Acid; Gastric Fundus; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Peptides; Pyloric Antrum; Somatostatin

We defined duodenal ulcers (DUs) not healed within 3 months with H2-antagonists as "intractable", because the recurrence rate of these DUs is higher than that of DUs healed within the same periods, and etiological differences are suggested to exist among these two groups. To verify the pathophysiological differences, gastric analysis including modified sham-feeding (MSF) were performed in 12 intractable, 10 tractable DUs and 5 healthy controls. By MSF stimulation, acid output increased in all subjects and the mean acid output of MSF amounted to about 60% of the tetragastrin maximum. Mean acid output of intractable DU cases was significantly higher than the controls in any stimulatory state and was different only in MSF with tractable DU. No significant changes of serum gastrin were recognized during MSF and both serum pepsinogen I and II are higher in DU cases than the control in basal state, but the two DU groups show no significant difference or increase by MSF or gastrin stimulation. These data suggest that vagal activity of intractable DUs is higher than not only healthy subjects, but tractable DUs and participation of gastrin in the increase of acid output by MSF might be denied.

Topics: Adult; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Middle Aged; Pepsinogens; Tetragastrin; Vagus Nerve

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Male; Time Factors

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.

Topics: Adult; Aged; Anemia, Pernicious; Circadian Rhythm; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Stomach Ulcer

Simultaneous 24-hour intragastric acidity and plasma gastrin concentrations were measured in 12 duodenal ulcer patients before and on the twenty-eighth day of treatment with either ranitidine 150 mg b.d. or omeprazole 20 mg o.m. Median integrated 24-hour intragastric acidity was decreased significantly from 1148 to 490 and 36 mmol.hour litre-1 during treatment with ranitidine and omeprazole, respectively, whilst median intragastric 24-hour plasma gastrin was raised significantly from 328 to 799 and 1519 pmol.hour litre-1 respectively. When the results of all 48 experiments were considered together, there was a significant inverse correlation between the 24-hour integrated values for intragastric acidity and plasma gastrin concentration. Both drugs caused a significant elevation of plasma gastrin throughout the 24 hours, although ranitidine had no effect on intragastric acidity from 1900 to 2200 hours. When compared with similar profiles of acidity and gastrin in pernicious-anaemia patients, the modest elevations of plasma gastrin observed in this study suggest that neither drug will be associated with clinically relevant enterochromaffin-like cell proliferation in duodenal ulcer patients.

Topics: Adult; Circadian Rhythm; Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Omeprazole; Ranitidine

The antral mucosa has been examined in four duodenal ulcer patients before and during long-term, low dose treatment with cimetidine (given a total dose of between 472 g and 894 g). No convincing changes were found in the number or the volume of G cells. Signs of inactivity were demonstrated ultrastructurally, with small granules of intermediate type, a reduced amount of granular endoplasmatic reticulum and Golgi complex, mostly showing no signs of granulogenesis. The occurrence of bundles of cytoplasmic microfilaments, not observed before treatment and the reduced number of D cells may also be signs of inactivity. Hyperplasia and/or neoplasia were not seen in other antral endocrine cells.

Topics: Aged; Aged, 80 and over; Cimetidine; Cytoplasm; Cytoplasmic Granules; Duodenal Ulcer; Endoplasmic Reticulum; Gastric Mucosa; Gastrins; Golgi Apparatus; Humans; Male; Microscopy, Electron; Middle Aged; Pyloric Antrum

A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24-hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G-17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin-containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia.

Topics: Adult; Cimetidine; Duodenal Ulcer; Enprostil; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Hyperplasia; Male; Pirenzepine; Prostaglandins E, Synthetic; Pyloric Antrum

It has not been established whether multiple duodenal ulcer is associated with a different natural history, pathophysiology, and therapeutic response than a single duodenal ulcer. A consecutive series of 96 patients with two or more duodenal ulcers at endoscopy, representing 9.6% of the total number of new patients with duodenal ulcer seen during the period 1980-1985, were compared with a random series of 200 patients with single duodenal ulcer seen in the middle years of this period. Multiple duodenal ulcer was associated with higher (p less than 0.02) male to female ratio, more (p less than 0.05) late onset patients (those with ulcer symptoms starting after age 30 years, more (p less than 0.05) chronic cigarette smokers, and more frequent (p less than 0.05) moderate to severe deformity of the duodenal bulb. More (p less than 0.05) patients with multiple duodenal ulcer had abnormally low D50 derived from pentagastrin dose response tests, indicating that they were more sensitive to gastrin stimulation. Furthermore, their mean fasting and meal stimulated serum gastrin concentrations were significantly higher than those of patients with single ulcer (p less than 0.005), or of controls (p less than 0.05). Compared with single duodenal ulcer, multiple ulcer had significantly lower placebo healing rate, and required a higher dose of misoprostol (1200 v 800 micrograms/day) to achieve a similar healing efficacy at four weeks. We conclude that multiple duodenal ulcer is associated with different clinical features, pathophysiology, and possibly therapeutic response from single duodenal ulcer, and appears to represent the more aggressive side of the ulcer spectrum.

Topics: Adult; Alprostadil; Anti-Ulcer Agents; Duodenal Ulcer; Duodenoscopy; Female; Gastric Acid; Gastrins; Humans; Male; Misoprostol; Pentagastrin; Retrospective Studies

Topics: Adolescent; Child; Child, Preschool; Duodenal Ulcer; Duodenum; Eating; Gastric Mucosa; Gastrins; Gastritis; Humans; Intestinal Mucosa

The heterogeneity of gastrin-containing G cells present in human gastric mucosa has been examined immunohistochemically. Calcitonin gene-related peptide (CGRP), calcitonin and human chorionic gonadotropin (hCG)-immunoreactivity were detected in about 500, 20 and 10 cells pro 1,000 G cells, respectively, these findings supporting the "one cell, multi-hormone theory". Gastrin, calcitonin immunoreactive tumor cells were demonstrated in 13%, 3% of the antral adenocarcinomas and 17% and 10% of antral endocrine tumors, but they were not found in fundic adenocarcinomas and endocrine tumors. Cell hybridization between the tumor cell and the G-cell might be a possible mechanism for the occurrence of gastric and calcitonin in the gastric tumors. HCG-immunoreactive tumor cells were detected in 27% of antral adenocarcinomas, and in 24% of the fundic adenocarcinomas, and the production of hCG by gastric tumor cells might be based on the gene expression during carcinogenesis, regardless of the tumor localization.

Topics: Adenocarcinoma; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma; Chorionic Gonadotropin; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Immunochemistry; Neuropeptides; Pyloric Antrum; Stomach Neoplasms

The effects of the anticholinergic drug benzilonium bromide and the opiate receptor blocker naloxone, given alone or in combination, on the acid secretory response and on plasma gastrin releasing peptide (GRP) response to sham feeding was tested in eight duodenal ulcer (DU) patients. Naloxone alone had no effect on the acid secretion after sham feeding. Benzilonium reduced basal acid secretion and the acid response to sham feeding but did not abolish the response. The combination of benzilonium and naloxone was not more effective than benzilonium alone. Neither drug, nor the combination had any effect on plasma GRP following sham feeding. It is concluded that enkephalins are unlikely to participate in the acid response to sham feeding in patients with DU.

Topics: Adult; Duodenal Ulcer; Enkephalins; Gastric Juice; Gastrin-Releasing Peptide; Gastrins; Humans; Male; Middle Aged; Naloxone; Peptides; Pyrrolidines; Stomach; Vagus Nerve

Antral gastrin-producing cell densities, as well as serum gastrin and gastric acid secretion were obtained prior to parietal cell vagotomy from 60 patients suffering from chronic duodenal ulcer disease. Acid secretion was also measured postoperatively. The patients were followed for five years. The ulcer recurrence rate was 20%. No differences were found in the G-cell densities, fasting serum-gastrin or gastric acid secretion preoperatively between the two groups: recurrence and non-recurrence. The acid secretion was higher postoperatively in patients with recurrent ulcer as compared to those without recurrence of the ulcer, suggesting that incomplete vagotomy is a reasonable explanation of the recurrence, even though post-operative G-cell abnormality cannot definitely be ruled out.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pyloric Antrum; Vagotomy

The effects of truncal vagotomy and parietal cell vagotomy on gastric acid secretion and plasma gastrin and pancreatic polypeptide release were studied in 28 duodenal ulcer patients under basal conditions and after modified sham feeding and infusion of pentagastrin (2 micrograms/kg/h). Before vagotomy gastric acid output in response to modified sham feeding was significantly higher than basal acid secretion in all subjects tested and reached about 45% of the pentagastrin maximum. No difference in the increase in acid response, or in the pancreatic polypeptide response to modified sham feeding was found between patients with high and low basal secretion. Plasma gastrin concentration was unaltered by modified sham feeding before and after truncal vagotomy or parietal cell vagotomy, although after vagotomy it tended to reach higher values than before this procedure. After truncal vagotomy, basal pancreatic polypeptide concentration was decreased and modified sham feeding-induced pancreatic polypeptide increment was completely eliminated. Four weeks after parietal cell vagotomy, the modified sham feeding-induced increment in plasma pancreatic polypeptide was significantly decreased and observed only in seven of 12 patients. Four to five years after parietal cell vagotomy all subjects responded to modified sham feeding with pancreatic polypeptide increment similar to that before vagotomy and in three of 12 patients acid response to modified sham feeding was seen. This study indicates that truncal vagotomy eliminates gastric acid and plasma pancreatic polypeptide responses to vagal excitation while parietal cell vagotomy abolishes gastric acid response and reduces temporarily the pancreatic polypeptide response to modified sham feeding (possibly because of transient impairment of the vagal innervation of the pancreas). (2) A high ratio of basal to maximal acid output in non-operated duodenal ulcer patients is not associated with a low acid response to modified sham feeding, nor with a high pancreatic polypeptide concentration, and (3) Restitution of the pancreatic polypeptide response to modified sham feeding five years after parietal cell vagotomy does not indication ineffective denervation of the parietal cells.

Topics: Adolescent; Adult; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreatic Polypeptide; Pentagastrin; Stomach; Vagotomy; Vagotomy, Proximal Gastric; Vagus Nerve

We calculated gastric HCO3- and H+ secretion, as well as nonparietal and parietal volume secretion, in 15 duodenal ulcer patients who had previously undergone successful proximal gastric vagotomy, 15 unoperated duodenal ulcer patients, and 15 normal control subjects. Basal HCO3- secretion was not significantly altered after vagotomy, while basal H+ secretion, parietal volume and nonparietal volume secretion were reduced significantly. Intravenous gastrin-17 infusion reduced gastric HCO3- secretion by approximately 50% in both unoperated ulcer patients and normal subjects (P less than 0.05). Gastrin-17 infusion did not inhibit gastric HCO3- secretion after vagotomy. In fact, mean gastric HCO3- secretion increased to a nearly significant extent in response to gastrin (P = 0.06). These findings indicate that gastrin inhibits gastric HCO3- secretion in humans and that the gastrin-induced reduction in gastric HCO3- secretion is dependent upon intact vagal innervation to the oxyntic mucosa.

Topics: Bicarbonates; Depression, Chemical; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Secretory Rate; Vagotomy, Proximal Gastric

Topics: Circadian Rhythm; Duodenal Ulcer; Gastrins; Humans; Pepsinogens; Peptic Ulcer; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Vagotomy

The present study explored the 24-hr variations in serum gastrin and pepsinogen in clinically healthy subjects and in patients with gastric ulcer, duodenal ulcer, and erosive gastroduodenopathy. Time-qualified data were analyzed by means of cosinor procedures. Significant changes in rhythmometric properties were documented in patients with peptic disease when compared to clinically healthy subjects. In essence, it was discovered that gastric ulcer patients exhibit a higher mesor and amplitude for both gastrin and pepsinogen, whereas duodenal ulcer patients and those with erosive gastroduodenopathy show only a significant increase in the pepsinogen mesor. These characteristics are so specific in the groups investigated that one can hypothesize that the disorders in the circadian rhythmicity of gastrin and pepsinogen have a role in determining the clinical manifestations of peptic disease.

Topics: Circadian Rhythm; Duodenal Ulcer; Female; Gastrins; Humans; Male; Pepsinogens; Stomach Ulcer

Antrectomy is accepted as the most effective surgical treatment of recurrent duodenal ulcer after complete vagotomy. Although antrectomy is aimed at reducing serum gastrin levels, both human and experimental reports seem to indicate that gastrin concentrations may be unchanged following this operation. The probable source of gastrin has been considered to be the proximal third of the duodenum, since at this level increased tissue gastrin concentrations were found after antrectomy. The present study was carried out in order to gain insight into the mechanism by which the duodenum may compensate for the removal of the antrum. Forty white rats were randomly divided into two equal groups and underwent antrectomy with gastroduodenostomy or simple laparotomy. Three to four months after surgery, serum gastrin determinations were carried out by radioimmunoassay both in fasted and freely fed rats. The duodenum was then removed and its proximal third was used for G cell counts (immunoperoxidase method) and for assessment of G cell cytoplasmic granule distribution (electron-microscopic examination). Antrectomy significantly increased fasting serum gastrin levels (p less than 0.01), while it completely abolished the gastrin response to food ingestion (p less than 0.001). In antrectomized rats, the duodenal G cell number was significantly higher than in control rats (p less than 0.001), whilst the G cell cytoplasmic granule number remained unchanged. In conclusion, the present study indicates that in the rat the proximal duodenum increases its content of tissue gastrin following antrectomy mainly by enhancing the regional G cell density.

Topics: Animals; Duodenal Ulcer; Duodenum; Gastrins; Male; Microscopy, Electron; Pyloric Antrum; Rats; Vagotomy

Serum gastrin concentrations were measured using antisera with specificity for the carboxyl and amino terminus of gastrin-17 in 50 healthy subjects and 18 patients with active duodenal ulcer disease (DU). The amino terminal of gastrin-17 immunoreactivity was significantly higher in DU patients than in healthy subjects. NH2-terminus of gastrin-17 immunopurified material from serum of DU patients was subjected to Sephadex G50 column chromatography and eluates were monitored by an additional antiserum EG10 that recognizes COOH-terminally extended gastrin. Besides the NH2 terminal tridecapeptide of gastrin-17, COOH-terminally extended progastrin was found. This may reflect abnormal processing of gastrin in patients with active duodenal ulcer disease.

Topics: Adolescent; Adult; Aged; Amino Acid Sequence; Duodenal Ulcer; Female; Gastrins; Humans; Immune Sera; Male; Middle Aged; Protein Precursors

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p less than 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p = 0.034) circadian rhythm in unstimulated acid secretion in a group (N = 14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N = 17) of postvagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.

Topics: Adult; Circadian Rhythm; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pylorus; Vagotomy

Although meal-stimulated neurotensin release from the small intestine is inhibited by cholinergic blockade, it is uncertain whether this cholinergic mechanism involves the vagus. This study examines the role of the vagus in neurotensin release by first determining the effect of vagotomy on meal-stimulated plasma neurotensin in man and second, the effect on plasma neurotensin of electrical stimulation of the vagus in sheep. Six volunteers were studied 6-8 weeks after truncal vagotomy and pyloroplasty. Basal plasma neurotensin at 32(15-67) pmol/l (median, range) was greater than in normal controls at 17 (9-52) pmol/l (P less than 0.05). Following a standard meal, plasma neurotensin rose significantly (P less than 0.05), but similarly in both post-vagotomy and control groups to maxima of 74 (43-76) pmol/l and 52 (35-65) pmol/l, respectively. Basal plasma neurotensin in the six sheep was below the detection limit of the assay and remained undetectable during electrical stimulation of the vagus. Significant rises in plasma pancreatic polypeptide and gastrin confirmed the efficacy of the electrical stimulation. It is concluded that although the vagus might have a tonic inhibitory effect on basal plasma neurotensin, meal-stimulated neurotensin release is vagally independent. The inhibitory cholinergic influence on meal-stimulated release is most likely therefore to be mediated by cholinergic nerves of the enteric nervous system.

Topics: Adolescent; Adult; Aged; Animals; Duodenal Ulcer; Electric Stimulation; Food; Gastrins; Humans; Middle Aged; Neurotensin; Pancreatic Polypeptide; Sheep; Vagotomy; Vagus Nerve

We measured basal and peak acid outputs, food-stimulated acid secretion, and basal and food-stimulated serum gastrin concentrations in a large group of duodenal ulcer patients and normal subjects. Basal and peak acid outputs were significantly higher in ulcer patients. In contrast, acid secretion was similar in the groups when food was infused into the stomach and when sham feeding was combined with meal infusion to simulate normal eating. Meal-stimulated acid secretion, expressed as a percentage of peak acid output to correct for differences in secretory capacity, was lower in ulcer patients (P less than 0.002). Basal serum gastrin concentrations were higher in ulcer patients, which may have contributed to higher basal acid output. However, increases in serum gastrin after food were similar in the groups. Duodenal ulcer patients, as a group, have increased basal and maximal acid secretion, but the amount of acid secreted and gastrin released after eating is normal.

Topics: Adult; Aged; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Kinetics; Male; Middle Aged; Reference Values; Time Factors

The secretin provocation test for gastrinoma is based on the premise that secretin decreases or has no effect on serum gastrin in normal and duodenal ulcer subjects while inducing a paradoxical rise in gastrinoma. We reexamined the serum gastrin response to pharmacologic amounts of secretin in normal volunteers (N = 17) and unoperated duodenal ulcer patients (N = 10). GIH secretin caused significant early gastrin rises from baseline in both groups (P less than 0.05). The gastrin response curves after secretin were not significantly different between normal and ulcer subjects. Similar gastrin rises were seen when synthetic secretin was administered to normal subjects (N = 6). In normal volunteers, intravenous bolus saline (N = 10) or amino acid (L-cysteine, N = 8) caused no change in serum gastrin from baseline. The gastrin response curves to GIH secretin and saline were significantly different (P less than 0.05). Our findings suggest that the gastrin rise in gastrinoma patients after secretin is an exaggeration of the normal response and not paradoxical.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Secretin; Time Factors; Zollinger-Ellison Syndrome

Serum gastrin concentrations were measured in 26 patients (Group A) who underwent partial gastrectomy for duodenal ulcer disease at least 25 years previously. The basal serum gastrin level was 31.6 +/- 1.5 pg/ml, increasing significantly after food stimulation to 36.8 +/- 2.4 pg/ml (p less than 0.05). In 16 of these patients (Group B), endoscopic biopsy specimens were taken from the minor and major curvatures of the stomach, from the jejunal part of the gastrojejunostomy, and from the duodenum. Mucosal gastrin concentrations measured were 0, 20.4 +/- 3 ng/g, and 30 +/- 7.1 ng/g, respectively. Ten of these patients (Group C) had a repeated gastroscopy with food stimulation of the duodenal pouch, using a balloon catheter in the lower duodenum. Serum gastrin concentrations after pouch stimulation did not differ significantly compared with basal values. No changes in the mucosal gastrin concentrations during pouch stimulation were seen. In conclusion, since no gastrin could be detected in the gastric mucosa and the mucosal gastrin concentration in the duodenum was 50 times lower than reported in other studies, the gastrin release measured after food stimulation could have been of extragastric or extraduodenal origin.

Topics: Aged; Duodenal Ulcer; Female; Follow-Up Studies; Food; Gastrectomy; Gastrins; Humans; Intestinal Mucosa; Jejunum; Male; Middle Aged; Time Factors

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with the biochemical indices of growth in gastric and duodenal mucosa in the following three groups of rats: (a) chow-fed, (b) fed an isocaloric liquid diet, (c) fed the liquid diet plus pentagastrin injections (250 micrograms/kg, 3 times/day). Animals received the diet regimen for 10 days from 1 day after induction of ulcer (day 0). Following the feeding regimens, serum gastrin levels, oxyntic gland mucosal DNA synthesis, and gastric secretory function were significantly lowered in the rats fed liquid diets. DNA synthesis in the duodenal mucosa was not different from the pre-ulcer levels. Pentagastrin significantly restored the DNA synthetic and gastric secretory activity of the liquid diet-fed rats toward the levels in the chow-fed group. In the latter group, a significant increase in DNA synthesis and levels of serum gastrin was found at day 6 (after 5 days feeding), which corresponded with a rapid, spontaneous healing of ulcers. Feeding rats liquid diet significantly delayed the healing of gastric, but not duodenal ulcers. Repeated administration of pentagastrin accelerated gastric ulcer healing in the liquid diet group toward the rate observed in the chow-fed group, but had no effect on the healing of duodenal ulcers. These results indicate that cell proliferation is an important factor in the healing of gastric ulcers.

Topics: Animals; Cell Division; DNA; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Intestinal Mucosa; Male; Pentagastrin; Rats; Rats, Inbred Strains; RNA; Stomach Ulcer; Wound Healing

Topics: Adult; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Middle Aged

Grimelius reaction and immunohistochemical PAP method were used to study endocrine cells producing gastrin (G-cells), somatostatin (D-cells) and gamma-endorphin (GER-cells) in gastric and duodenal mucosa of 95 males with atrophic gastritis with intestinal and pyloric metaplasia. The number of cells was counted per 1 mm2 of the mucosa. In the cases of marked intestinal metaplasia the number of G-, GER- and especially D-cells in the pyloric region non-metaplastic epithelium decreases and is approaching to its number in the duodenum of the control group. In the foci of marked pyloric metaplasia of gastric corpus the number of G- and GER-cells is almost the same as in the zones of gastric metaplasia of duodenum, and is approximating their number in the pyloric region of controls, thus allowing the designation of pyloric metaplasia as a complete one.

Topics: Adolescent; Adult; Aged; APUD Cells; Biopsy; Duodenal Ulcer; Duodenum; Endorphins; gamma-Endorphin; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Histocytochemistry; Humans; Immunoenzyme Techniques; Metaplasia; Middle Aged; Pylorus; Somatostatin; Stomach Ulcer

The behaviour of gastrin (G) cells and somatostatin (D) cells in endoscopic antral biopsies and that of intraluminal gastrin (ILG) and somatostatin (ILS) release in the gastric juice were investigated in three groups of patients: control subjects, duodenal ulcer (DU) patients and DU patients treated by a superselective vagotomy (SSV). G and D cell densities were correlated in the three groups of subjects. The G/D cell ratio was significantly increased in SSV patients (P less than 0.001) as compared to control and DU patients. No correlation was found between gastrin or somatostatin cell densities and basal intraluminal levels of the two peptides. ILG output was significantly higher in DU patients than in control or SSV patients (P less than 0.001). ILS output was also higher in DU patients than in controls (P less than 0.001) and in SSV patients (P less than 0.05). It was also significantly augmented in SSV (P less than 0.001) as compared to control patients. ILG and ILS concentrations were only correlated in controls. Within each of the three groups of subjects, ILG and ILS release varied in function of the gastric juice pH. Our results emphasize the necessity to consider the intragastric pH as well as the physiological or pathological state to study intraluminal peptides in man.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Cell Count; Chromatography, Gel; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Vagotomy, Proximal Gastric

Organ culture was used to compare gastrin and somatostatin release from cultured antral mucosa obtained from duodenal ulcer and non-ulcer (control) subjects. In response to dibutyryl cyclic AMP (DBCAMP) cultured antral mucosal explants from patients with a history of duodenal ulcer released a greater proportion of antral gastrin into the medium than did antral mucosal explants from non-ulcer subjects. Somatostatin release from antral mucosa from duodenal ulcer patients was substantially less than somatostatin released by antral explants from non-ulcer subjects. In the non-ulcer subjects there was a direct positive correlation between the amounts of antral somatostatin and gastrin released into the culture medium (r = 0.64, less than p 0.01). In the duodenal ulcer patients, however, there was no correlation between gastrin release and somatostatin release from antral mucosa ( r = 0.09; p greater than 0.2). Results of these studies identify enhanced gastrin release in response to stimulation and decreased release of somatostatin from antral mucosa of duodenal ulcer patients. These alterations in paracrine relationships of antral somatostatin and gastrin in duodenal ulcer subjects may contribute, at least in part, to the pathogenesis of duodenal ulcer disease.

Topics: Adult; Bucladesine; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Organ Culture Techniques; Pyloric Antrum; Somatostatin

Serotonin-containing EC cells in human fetal, infantile and adult stomachs both normal and affected by gastritis, were studied by immunohistochemical, electron microscopic and autoradiographic methods. EC cells were sparse in fetal and infantile stomachs, while they occurred in the lower half of the gastric mucosa in adult stomachs showing no atrophic changes and their distribution density was higher than that of D cells. With the progress of chronic gastritis, the number of EC cells gradually decreased, but intestinal type of EC cells appeared in intestinalized gastric mucosa, often showing hyperplasia. Most of EC cells showed argyrophil reaction, but only about 10-20% of them were positive with argentaffin. Epithelial cells with 3H-TdR labeled nuclei were frequently detected in the gastric mucosa where EC cells were sparse or almost absent. Electron microscopically, EC cells had typical electron dense granules in both the normal gastric mucosa and in the intestinal metaplastic glands, but the number of secretory granules was greater in the latter than in the former. These findings suggested that EC cells are preferentially present in the gastric mucosa with a small number of labeled nuclei and have morphological heterogeneity.

Topics: Adult; Aged; Autoradiography; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Histocytochemistry; Humans; Infant; Microscopy, Electron; Pregnancy; Serotonin; Somatostatin; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Male; Pyloric Antrum; Somatostatin; Stomach Ulcer

Topics: Adult; Duodenal Ulcer; Endorphins; Gastric Mucosa; Gastrins; Gastritis; Humans; Intestinal Mucosa; Male; Middle Aged; Somatostatin

The number of G cells and D cells per area unit and the G cell/D cell ratio was studied in control subjects and patients with duodenal or gastric ulcer. A great inter-individual variation in the population density of both types of cells was observed in the three groups studied. G cell density was significantly decreased in both duodenal and gastric ulcer patients, when compared with controls; whereas no difference in G cell density was seen between duodenal ulcer patients and gastric ulcer patients. However, D cell density was significantly decreased in duodenal ulcer patients when compared with control subjects and gastric ulcer patients. In this latter group, D cell density was also lower than in control subjects. A significant positive linear correlation between G cell number and D cell number was found in the three groups studied. The G cell/D cell ratio was significantly increased in duodenal and gastric ulcer patients when compared with controls. This was mainly due to a decrease in D cell numbers. It is concluded that a local deficit in antral D cells in patients with peptic ulcer may favor the pathogenesis of ulcer disease.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Fifty-eight subjects including controls, patients with duodenal ulcer, non-operated or treated with a superselective vagotomy underwent endoscopic fundic and antral biopsies. Histologic classification of the two mucosae was performed. We examined the relationship between the histologic grade of gastritis in the two mucosae, then between the histologic aspect of the antral mucosa and antral gastrin-and somatostatin-cell densities, the basal intraluminal secretion of gastrin and somatostatin. There was a significant correlation between the histologic aspect of fundic or antral mucosa and the age of patients, except in the case of vagotomized patients. Fundic and antral histologic patterns were also correlated in each patient, except for vagotomized. Gastrin and somatostatin cell densities showed no variation in function of the degree of inflammation of non atrophic gastritis. These cell densities showed a tendency to decrease in atrophic gastritis, especially when intestinal metaplasia was present. Intraluminal gastrin secretion was increased in patients with mild atrophic gastritis (p less than 0.05 to p less than 0.02) in comparison with those whose histology was roughly normal. It was also increased in severe atrophic gastritis. The highest intraluminal secretion of somatostatin was observed in patients with mild atrophic gastritis while this secretion fell noticeably in those showing severe atrophic gastritis, as compared to the other groups. This work seems to suggest a relationship between intraluminal peptides and the evolution of gastritis. While results are still preliminary, they do not indicate that these peptides, thus released, play any pathophysiologic role.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Prospective Studies; Somatostatin; Vagotomy, Proximal Gastric

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin

The effects of proximal gastric vagotomy on the gastric secretion of acid and pepsin, and on the release of gastrin and pancreatic polypeptide in response to sham feeding were assessed comparatively within 1-4 months after surgery in 32 male duodenal ulcer patients. Each test comprised three successive periods: basal, modified sham feeding (MSF) and pentagastrin stimulation. In each test period the acid output was strongly correlated with the corresponding pepsin output, both parameters being reduced to similar extents after vagotomy. The percentage of postoperative reduction of MSF-induced acid and pepsin outputs was positively correlated with the preoperative values. MSF resulted in a limited but significant release of gastrin, the response being significantly greater after surgery. The MSF-induced release of pancreatic polypeptide was significantly reduced by proximal gastric vagotomy, the reduction percentage being negatively correlated with the time elapsed since surgery. Neither pre- nor post-operatively did the gastrin and pancreatic polypeptide responses bear any relationship to the other parameters tested. We conclude that the study of sham feeding responses of pepsin, gastrin and pancreatic polypeptide provides no further information than does the measurement of acid secretion for the segregation of duodenal ulcer patients, especially with respect to follow-ups for ulcer recurrence.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pancreatic Polypeptide; Pentagastrin; Pepsin A; Recurrence; Time Factors; Vagotomy, Proximal Gastric

In a series of 59 experiments on nine duodenal ulcer patients, 24-hour intragastric acidity was measured before, during and after treatment with daily oral omeprazole. Omeprazole, 10, 20, ro 30 mg/day for 1 week, caused a 37%, 90%, and 97% decrease respectively of 24-hour intragastric acidity. No further decrease of acidity was observed when the dose of omeprazole was doubled to 60 mg/day, or after a second week of treatment with 30 mg/day. One week after stopping treatment with omeprazole (14 doses), there was still a significant 26% decrease of 24-hour intragastric acidity, with full recovery 7 weeks later. Fasting plasma gastrin concentration was significantly elevated during treatment with all doses of omeprazole. The optimal dose of omeprazole is 30 mg/day for a maximal decrease of 24-hour intragastric acidity in duodenal ulcer patients.

Topics: Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Dose-Response Relationship, Drug; Duodenal Ulcer; Fasting; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Kinetics; Male; Middle Aged; Omeprazole; Time Factors

Post-prandial serum levels of gastrin, the main hormonal stimulator of acid secretion, have been shown to be significantly elevated after HSV compared with controls. The mechanism for this elevation is not known but could be secondary to an increased antral gastrin concentration (AGC). In this study AGCs were measured in endoscopic biopsies before and at intervals of 6 and 32 weeks after HSV in 12 patients with duodenal ulcer. Results were compared with 13 normal controls and 12 duodenal ulcer patients treated with cimetidine for 6 weeks. Blood was taken for fasting serum gastrin concentration at each endoscopy. In the HSV group AGC significantly increased on both postoperative occasions when compared with pre-operative values (P less than 0.01). AGC also showed a significant correlation with time after HSV (r = 0.71; P less than 0.01). Only one patient, who had a persistent duodenal ulcer, failed to show an increase in AGC. Cimetidine failed to increase AGCs in duodenal ulcer patients after 6 weeks of treatment. However, a subgroup (n = 7) of cimetidine-treated patients with low pretreatment AGCs, below 10 ng/mg, did show a significant rise at 6 weeks (P less than 0.05). Fasting serum gastrin levels did not change significantly in any of the three groups. It is concluded that HSV causes a significant increase in AGC with time.

Topics: Adult; Aged; Cimetidine; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Postoperative Period; Pyloric Antrum; Vagotomy

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Secretion; Male; Pancreatic Diseases; Vagotomy

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Immunoenzyme Techniques; Male; Middle Aged; Stomach Ulcer

In patients with hyperacidic duodenal ulcer the hyperproduction of hydrochloric acid was shown to occur both during the nervous-reflectory and humoral phases of secretion. Vagotomy with antrumectomy is considered to be the most effective method in such patients, since it inhibits both the I and II phases of the acid gastric secretion.

Topics: Duodenal Ulcer; Follow-Up Studies; Gastric Acid; Gastrins; Humans; Pyloric Antrum; Vagotomy

Topics: Adult; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Pylorus; Vagotomy

Topics: Adult; Atropine; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pyloric Antrum

Topics: Adolescent; Adult; Aged; Dietary Proteins; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Male; Middle Aged; Reagent Kits, Diagnostic

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.

Topics: Adult; Duodenal Ulcer; Dyspepsia; Female; Food; Gastrins; Humans; Male; Pancreatic Polypeptide

The purpose of this work was to compare the effects of a long acting antisecretory drug on 24-h gastric acidity after acute and chronic administration and to correlate the results observed with modifications of pharmacokinetic parameters. 40749 RP is a carbothioamide derivative antisecretory drug with a non anti H2, non anticholinergic mechanism of action. Eleven patients with an endoscopically proven duodenal ulcer received 100 mg of 40749 RP at 8 PM for 3 wk and thereafter a placebo for an additional 3 wk study period. At the end of the active drug treatment period all patients but one had healed. Continuous 24-h gastric pH recordings performed after the first and the last dose of 40749 RP showed a strong and yet still increasing acid inhibition, nine patients being nearly achlorhydric (i. e. pH greater than 3) during night at the end of treatment. Variations of acid inhibition between the start and the end of treatment were significantly correlated with modifications of pharmacokinetic parameters. Eight days after discontinuation of 40749 RP, basal acid secretion remained strongly inhibited. However at the end of the placebo period, endoscopy showed ulcer relapse in 4 patients (previously resistant to H2-blockers). These results confirmed that 40749 RP is a powerful and very long-acting antisecretory drug. They showed that the antisecretory effects of a long-acting drug should be assessed in conditions of chronic administration when therapeutic dose and regimen are to be determined.

Topics: Adult; Aged; Anti-Ulcer Agents; Drug Evaluation; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Kinetics; Male; Middle Aged; Thiophenes; Time Factors

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Male; Microscopy, Electron; Middle Aged; Pancreas; Pancreatic Neoplasms; Postoperative Complications; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Duodenoscopy; Gastrectomy; Gastrins; Humans; Postoperative Complications; Recurrence; Reoperation; Vagotomy, Proximal Gastric

Serum gastrin concentrations and gastric acid secretion were measured during intravenous infusion of gastrin heptadecapeptide (G-17) (0, 7, 22.1, 70, 221, and 700 pmol/kg X h) in 15 duodenal ulcer patients and 15 healthy controls. Ulcer patients developed higher serum gastrin concentrations during G-17 infusion due to nearly twofold slower clearance of gastrin (8.8 vs. 15.7 ml/kg X min; P less than 0.01). Despite slower clearance of G-17, ulcer patients had plasma elimination half-times for G-17 similar to controls (6.0 vs. 6.1 min, respectively). Thus, calculated volume of distribution for G-17 was lower in ulcer patients than controls (78.5 vs. 140.7 ml/kg; P less than 0.025). For any serum gastrin during gastrin-17 infusion, acid secretion (millimoles per hour) was higher in ulcer patients than in controls. However, when acid secretion was expressed as a percentage of peak acid output to G-17 (to correct for differences in parietal cell mass), curves relating acid secretion to serum gastrin were identical in ulcer patients and controls.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Half-Life; Humans; Kinetics; Male; Metabolic Clearance Rate; Middle Aged

Topics: Duodenal Ulcer; Gastrins; Gastritis; Humans; Radioimmunoassay; Vagotomy

The principal sites of gastrin production in man are localized at the level of the gastric antrum; both the oral glucose load and the protein meal stimulate the gastrin secretion. The aim of this study was to verify the gastrin response in patients with gastric resections presented with various stimuli. In the operated patients, the behavior of serum gastrin after a protein meal was different with respect to that observed in control subjects. After glucose, on the contrary, a very similar result was seen when compared to controls. The increase in serum gastrin of patients with Billroth II provides a further confirmation of an extragastric origin of gastrin.

Topics: Dietary Proteins; Duodenal Ulcer; Duodenum; Gastrins; Gastrostomy; Glucose; Humans; Jejunum; Middle Aged

Twenty-one men with active duodenal ulcer underwent hourly gastric acid and 4-hourly plasma collections under fasting conditions. A statistically significant circadian rhythm was demonstrated for the group by population-mean cosinor analysis, a statistical technique designed for time-dependent measurements, for the 24-hr acid secretory output but not for plasma gastrin concentration. These findings are compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, here observed in most patients of the active ulcer group and previously reported for a group of healthy subjects, does not depend critically upon a circadian-rhythm change in plasma gastrin. Chronobiologic statistical techniques add an important quantitative element to the time-dependent measurement of gastrointestinal function of which one example is gastric acidity, with high rates occurring during the evening and low ones in early morning.

Topics: Adult; Circadian Rhythm; Duodenal Ulcer; Fasting; Gastric Acid; Gastrins; Humans; Male; Middle Aged

Duodenal gastrin concentration was measured in endoscopic forceps biopsy specimens of the juxta-pyloric duodenal mucosa in patients with various gastrointestinal disorders. Duodenal gastrin concentration was 5.9 +/- 1.2 ng/mg (mean +/- 1 SEM) in control patients. Duodenal gastrin concentration was similar to control values in patients with duodenal ulcer, pyloric channel ulcer, vagotomy and pyloroplasty, and gastric atrophy and hypergastrinemia. In gastric ulcer patients, duodenal gastrin concentration, 2.8 +/- 0.6 ng/mg, was significantly less than the control value (P less than 0.05). Duodenal gastrin concentration was approximately one third of antral gastrin concentration in control, duodenal ulcer, and gastric ulcer patients and was approximately one fifth of antral gastrin concentration in vagotomy and pyloroplasty patients and gastric atrophy patients. Duodenal and antral gastrin concentrations were significantly correlated in normal controls and in gastric ulcer patients. The finding of normal duodenal gastrin concentration in patients with vagotomy and pyloroplasty and patients with gastric atrophy suggests that, unlike antral gastrin concentration, duodenal gastrin concentration is unaffected by a decrease in acid secretion rate. The low duodenal gastrin concentration in gastric ulcer patients indicates that the duodenum may be involved in the pathophysiology of gastric ulcer disease.

Topics: Biopsy; Duodenal Ulcer; Duodenum; Gastrins; Gastritis, Atrophic; Gastrointestinal Diseases; Humans; Intestinal Mucosa; Pyloric Antrum; Stomach Ulcer

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.

Topics: Duodenal Ulcer; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Reference Values; Sex Factors

Topics: Adult; Disease Susceptibility; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Middle Aged

The effects on fasting serum gastrin concentrations of hourly doses of magnesium and aluminum hydroxide antacid, with and without intravenous cimetidine, were determined in 8 patients with duodenal ulcer disease. Gastrin levels rose significantly over 10 h when antacid was given either as a bolus of 30 ml every hour or as a constant infusion of 0.5 ml/min (36 +/- 5 pg/ml and 33 +/- 6 pg/ml to 108 +/- 32 pg/ml and 109 +/- 22 pg/ml, respectively, p less than 0.05). This effect was specific for some component of the antacid and not for neutralization of acid per se, inasmuch as sodium bicarbonate, infused to keep gastric pH at levels at or above those of antacid, produced no significant rise in serum gastrin concentration. When intravenous cimetidine was administered simultaneously with intragastric antacid, gastrin levels did not rise. This occurred even though intragastric pH levels were actually higher with cimetidine plus antacid than with antacid alone. The ability of intravenous cimetidine to block antacid-induced hypergastrinemia was counteracted by infusing simultaneously both hydrochloric acid and antacid into the stomach. Since hydrochloric acid reacts with magnesium and aluminum hydroxide to form ionic magnesium and aluminum chloride, cimetidine most likely blocks antacid-induced hypergastrinemia by reducing acid secretion from the stomach and thereby limiting the generation of ionic magnesium and aluminum.

Topics: Adult; Aged; Aluminum Hydroxide; Antacids; Cimetidine; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Magnesium Hydroxide; Male; Middle Aged

To study the relationship between gastric acid secretion and serum gastrin concentration after vagotomy, gastric acid output and serum gastrin concentration were measured simultaneously during intravenous infusion of graded doses of human gastrin heptadecapeptide (G-17) in duodenal ulcer patients with parietal cell vagotomy and in unoperated patients with duodenal ulcer disease (controls). The curve relating serum gastrin concentration to gastric acid output was shifted downward and to the right after vagotomy; the peak acid output to G-17 was reduced by 50% (p less than 0.001). The serum gastrin concentration that produced half of peak acid output (EC50%) averaged 185.5 pg/ml after vagotomy and 74.1 pg/ml in controls (p less than 0.01). Mean basal and postprandial serum gastrin concentrations were twofold to threefold higher in vagotomy patients than in controls (p less than 0.005). However, when peak postprandial serum gastrin concentrations were used to predict acid secretion from curves relating serum gastrin to acid output, predicted acid secretion was only 12.6 mmol/h in vagotomy patients compared to 24.4 mmol/h in controls. Parietal cell vagotomy decreases "functional" parietal cell mass, as reflected by a 50% decrease in peak acid output, and also reduces the responsiveness of "functional" parietal cells to gastrin to such an extent that acid secretion is reduced after vagotomy despite basal and postprandial hypergastrinemia.

Topics: Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Parietal Cells, Gastric

40749 RP is a pyridil-2-tetrahydrothiophene derivative, belonging to a new class of gastric antisecretory drugs. We compared its effects on gastric secretion with cimetidine. Intragastric acidity, nocturnal acid output, gastrin and pepsinogen-I profiles were measured in patients with duodenal ulcer in clinical remission. A single dose of 100 mg 40749 RP reduced median 24 h gastric acidity as effectively as cimetidine 1000 mg given as four divided doses, 0.63 vs 1.6 mmol/l. Continued treatment with 40749 RP for 10 days reduced the median 24 h gastric acidity even further, to 0.006 mmol/l (p less than 0.001) and significantly increased fasting concentrations of gastrin and pepsinogen-I (p = 0.02). The incremental gastrin secretion to a standard meal was significantly increased after 10 days treatment with 40749 RP when compared with the first day of 40749 RP, or with cimetidine. These results show that 40749 RP exerts a powerful inhibitory effect on gastric acid secretion after a single 100 mg dose, and that this inhibitory effect increases with continued administration.

Topics: Adult; Anti-Ulcer Agents; Cimetidine; Depression, Chemical; Drug Evaluation; Duodenal Ulcer; Gastric Acid; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Pepsinogens; Thiophenes; Time Factors

The effects of eight-week ranitidine treatment on changes in plasma gastrin, histamine and serotonin levels, and in intragastric pH and urinary 5-hydroxyindoleacetic acid in duodenal ulcer patients were studied. Elevated plasma gastrin and histamine levels, as well as intragastric pH were found after four weeks of ranitidine treatment, only in patients whose ulcers had healed. Plasma serotonin and urinary 5-hydroxyindoleacetic acid levels decreased as drug treatment continued, and the falls were similar in patients whose ulcers healed or did not. It is suggested that the increases in plasma gastrin, histamine and serotonin levels could be due to gastric and duodenal acid reductions by ranitidine. However, the possibility of a direct action of the drug on their release is yet to be excluded.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Histamine; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Ranitidine; Serotonin

The effect of diverting bile from the duodenum in four dogs with cholecystojejunostomy was studied using a double-marker perfusion technique. After the diversion procedure, a liquid meal increased acid secretion from 0.8 mmol H+/min to 1.48 mmol H+/min (P less than 0.05, paired t test); there was an associated rise in serum levels of gastrin 120 min after feeding (P less than 0.001, paired t test). Pancreatic secretion of trypsin decreased from 3.91 IU/min to 2.66 IU/min after bile diversion (P less than 0.01, paired t test), and the level of CCK was significantly lower 60 min after feeding (P less than 0.05, paired t test). There was no significant change in the rate of gastric emptying after bile diversion, but the pH of duodenal contents was lower in the later stages of digestion. These changes may explain the reported increase of peptic ulcer after diverting bile from the duodenum, and the procedure should not be considered unless the consequences of acid hypersecretion and pancreatic inhibition have been anticipated.

Topics: Amylases; Animals; Bile; Cholecystectomy; Cholecystokinin; Dogs; Duodenal Ulcer; Duodenum; Fasting; Gastric Emptying; Gastric Juice; Gastrins; Hydrogen-Ion Concentration; Jejunum; Pancreas; Stomach; Trypsin

To further elucidate the pathophysiological role of peptide hormones in duodenal ulcer (DU) disease, several endocrine, paracrine and neurocrine peptides were determined radioimmunologically in biopsies of gastroduodenal mucosa obtained endoscopically in 8 subjects without upper gastrointestinal disease, and in 8 duodenal ulcer patients. The DU patients had a BAO of 6.6 +/- 1.9 and a PAO of 41.8 +/- 6.1 mEq/h. In DU patients, a lack of the acid and gastrin-release inhibiting agent somatostatin was found neither in antral nor in fundic mucosa (185 +/- 60 vs 83 +/- 19 pmol/g tissue wet weight in controls). Basal and peak acid outputs of DU patients were positively correlated with fundic somatostatin concentrations (p less than 0.01). While gastrin levels were not significantly elevated in the antrum of DU patients, the mucosal content of potentially releasable gastrin of the duodenal bulb and the descending duodenum was higher than in controls (p less than 0.01). In the whole duodenum, CCK-like immunoreactivity was also more abundant in DU patients than in controls, whereas GIP and motilin did not exhibit characteristic profiles. Presumably as a reactive phenomenon, the mucosal levels of the peptidergic neurotransmitters VIP and substance P were markedly increased in the proximal duodenum of DU patients.

Topics: Adult; Cholecystokinin; Duodenal Ulcer; Duodenum; Female; Gastric Inhibitory Polypeptide; Gastrins; Hormones; Humans; Intestinal Mucosa; Male; Middle Aged; Motilin; Somatostatin; Stomach; Substance P; Tissue Distribution; Vasoactive Intestinal Peptide

Antral somatostatin-immunoreactive cells (D cells) were counted pre- and postoperatively in 20 patients with duodenal ulcer and in 8 patients with gastric ulcer. Counts were obtained either over a 2-yr postoperative period (duodenal ulcer patients) at intervals of 0.5, 1, and 2 yr or over a greater than or equal to 4-yr postoperative period (gastric ulcer patients) at intervals of 1-2 yr. In patients with a normal population of gastrin-immunoreactive cells (G cells), the D cells were within the normal range (mean value 0.53% in duodenal ulcer patients and 0.67% in gastric ulcer patients). High G-cell values were accompanied by high D-cell values (e.g., in gastrin-cell hyperplasia) and low G-cell values were accompanied by low D-cell values. The G-cell to D-cell ratio was 8:1 and 6.6:1 in duodenal and gastric ulcer patients, respectively. After selective proximal vagotomy and pyloroplasty, the following observations were made: the relation of number of G cells to number of D cells remained unchanged; the postoperative rise in G-cell population was accompanied by a rise in D-cell population; hypertrophy of the D cells was apparent as was postoperative hyperplasia, with a postoperative increase in D-cell size. Morphologic coupling of the gastrin-somatostatin system in the antrum is assumed. This is constant in ulcer disease both before and after vagotomy.

Topics: Adult; Cell Count; Duodenal Ulcer; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Hyperplasia; Hypertrophy; Immunoenzyme Techniques; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer; Vagotomy

Topics: Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Somatostatin

Topics: Adult; Cyclic AMP; Cyclic GMP; Deoxyglucose; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Stimulation, Chemical

Topics: Adult; Common Bile Duct; Duodenal Ulcer; Duodenoscopy; Esophagogastric Junction; Female; Gastric Acid; Gastrins; Humans; Jejunum; Male; Manometry; Middle Aged; Postoperative Complications

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged

Topics: Adult; Alcohol Drinking; Dietary Proteins; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Genetic Markers; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pepsinogens; Salicylates; Secretory Rate

Topics: Adaptation, Physiological; Age Factors; Aged; Duodenal Ulcer; Female; Gastrins; Hormones; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Pituitary Hormones, Anterior; Thyroid Hormones

Topics: Adolescent; Adult; Duodenal Ulcer; Duodenitis; Female; Gastrins; Gastroenteritis; Hormones; Humans; Insulin; Male; Middle Aged; Pituitary Hormones, Anterior; Thyroxine

Topics: Adult; Duodenal Ulcer; Electrophysiology; Female; Gastrins; Heart; Hormones; Humans; Insulin; Male; Myocardial Contraction; Thyrotropin; Thyroxine

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Stomach Ulcer

Ultrastructural examination of the antral G cells has been carried out on 11 patients with chronic duodenal ulcer, before and after treatment with a histamine H-2 - receptor antagonist (cimetidine 1 g/day) for 8 weeks. The study demonstrated an increased area of the Golgi complex, rough endoplasmic reticulum and electron-dense granules, indicating increased G cell activity during treatment. An increased number of lysosomes was a constant feature during treatment. As an hypothesis we suggest that these lysosomes may participate in the secretory mechanism of human G cells, by destroying superfluous (Gastrin) components produced during hyperactivity.

Topics: Adult; Cimetidine; Duodenal Ulcer; Endocrine Glands; Female; Gastrins; Golgi Apparatus; Humans; Male; Middle Aged; Pyloric Antrum

Gastric acid and pepsin secretion and serum gastrin concentrations were measured in nine patients with uncomplicated duodenal ulcer (DU) and 10 normal controls in the fasting state and in response to graded doses of bombesin, a tetradecapeptide gastrin releaser, and, for reference, synthetic gastrin G-17. Serum gastrin with bombesin stimulation was significantly greater in duodenal ulcer (maximum 467 pg/ml) than in controls (153 pg/ml), while in seven of the DU group tested gastrin levels after a meal were not different from that seen in five of the normal controls. Gastric acid concentrations and outputs were greater in duodenal ulcer with both stimuli. Secretory responses were then related to serum gastrin levels; despite increasing gastrin levels with bombesin stimulation, peak outputs achieved with bombesin were only 50% of G-17 maximum in normals and up to 90% of maximum in duodenal ulcer. Up to the point of peak response to bombesin, acid and pepsin outputs were the same with exogenous and endogenous gastrin, ie, bombesin acted only via G-17. Furthermore, in direct comparison of duodenal ulcer and normals with G-17 infusion, acid and pepsin outputs related to serum gastrin were congruent up to 75% of duodenal ulcer maximum, at which point normals reached their maximum level. These data have shown that duodenal ulcer patients are not more sensitive to either exogenous or endogenous gastrin; we have also shown regulatory defects in duodenal ulcer patients not previously described: an exaggerated release of gastrin with bombesin stimulation, and a defective inhibition of acid and pepsin secretion with higher doses of bombesin.

Topics: Adult; Bombesin; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Hormones; Humans; Male; Pepsin A; Stimulation, Chemical

Misoprostol, a synthetic derivative of prostaglandin E1, was tested and shown to be an effective gastric antisecretory agent against histamine-, pentagastrin-, and meal-stimulated acid secretion in dogs. Misoprostol reduced the volume of acid secretion as well as the hydrogen ion concentration. Misoprostol did not reduce gastric mucosal blood flow, nor did it alter meal-stimulated serum gastrin levels. Misoprostol inhibited acid secretion in histamine-stimulated isolated gastric glands indicating a direct antisecretory effect on parietal cells. The potency of misoprostol was greatest when administered in direct contact with the gastric mucosa indicating local absorption and action. Misoprostol strengthened the gastric mucosal barrier as shown by the attenuation of aspirin-induced lowering of transmucosal electrical potential differences. Misoprostol protected the gastric mucosa of rats subjected to ethanol-, taurocholate-, pyloric ligation-, stress- and indomethacin-induced damage. Misoprostol also protected against indomethacin-induced intestinal lesions in rats and reduced duodenal ulcer formation in guinea-pigs and cats. The doses of misoprostol required to protect against gastric damage were about one-tenth of those required to inhibit acid secretion. The results of these and other studies indicate that misoprostol is a safe agent with unique properties that should provide a new approach for treatment of ulcer diseases of the gastrointestinal tract.

Topics: Airway Resistance; Alprostadil; Animals; Anti-Ulcer Agents; Diarrhea; Drug Contamination; Drug Evaluation, Preclinical; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Hemodynamics; Isomerism; Membrane Potentials; Misoprostol; Regional Blood Flow; Stomach Ulcer

Topics: Adolescent; Diagnosis, Differential; Duodenal Diseases; Duodenal Ulcer; False Positive Reactions; Female; Gastrins; Gastroesophageal Reflux; Humans; Pain; Stomach Diseases; Zollinger-Ellison Syndrome

Cigarette smoking has been linked with duodenal ulcer disease although the mechanism of this association is unclear. This study assessed basal gastric secretory response to acute smoking of smokers with an active duodenal ulcer; in addition the possible effects of chronic smoking on gastric secretory capacity, as expressed by pentagastrin stimulated gastric acid secretion and fasting serum pepsinogen I (PG I) concentrations, were investigated in patients with active duodenal ulcer, or non-ulcer dyspepsia. In 10 smokers with duodenal ulcer smoking four cigarettes during 40 minutes did not influence basal gastric secretion of acid and pepsin, or serum PG I and gastrin concentrations. In 136 patients with duodenal ulcer and 90 controls with non-ulcer dyspepsia, pentagastrin stimulated acid secretion and fasting serum PG I concentrations were significantly higher among habitual heavy smokers than among non-smokers. These findings suggest that in heavy smokers with duodenal ulcer acid- and pepsin-secreting cell function is not affected by acute cigarette smoking. By contrast, chronic cigarette smoking seems to be associated either with an increase of parietal- and chief-cell mass, or with an enhancement of their secretory capacity.

Topics: Adult; Duodenal Ulcer; Dyspepsia; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pepsin A; Pepsinogens; Smoking

Amino acid induced acid and gastrin responses during intragastric titration at pH 2.5 and 5.5 were compared in normal subjects and duodenal ulcer patients with G-cell hyperfunction. The latter were identified on the basis of raised basal or maximal acid outputs and increased gastrin responses to feeding. In normal subjects the mixed amino acid meal stimulated only modest increases in serum gastrin, and the highest observed increase was about 30% that after a standard meal. In contrast, in the G-cell hyperfunction group the highest gastrin concentrations were similar to those after a standard meal. In the G-cell hyperfunction group the increment in serum gastrin at pH 2.5 expressed as a proportion of that at pH 5.5 was 0.29 indicating that the capacity of acid to inhibit gastrin release was well established in these patients. Acid secretory rates were close to maximal at both pH 2.5 and 5.5 during intragastric titration in the ulcer patients, but in normal subjects acid output was about 50% maximal at 2.5 and close to maximal at 5.5. The results suggest that the enhanced gastrin response to feeding in G-cell hyperfunction patients is because of increased sensitivity to amino acid stimulation rather than to diminished acid-inhibitory mechanisms.

Topics: Adult; Amino Acids; Chromaffin System; Duodenal Ulcer; Enterochromaffin Cells; Female; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Radioimmunoassay; Stomach

A marked increase in the number and size of the antral gastrin cells and parietal cells could be shown in long term examinations of the antrum mucosa after SPV and pyloroplasty. Twenty-five patients with UD, 12 with UV and five with Dragstedt combination (UV and UD) were examined over a period of five to seven years. A significant correlation of parietal cell increase and a positive reaction to insulin was found. The findings were compared with the changes in the fundic mucosa, where a marked decrease of parietal cells occur after SPV.

Topics: Cell Count; Cell Division; Duodenal Ulcer; Follow-Up Studies; Gastric Fundus; Gastrins; Humans; Parietal Cells, Gastric; Pyloric Antrum; Stomach Ulcer; Vagotomy; Vagotomy, Proximal Gastric

The sulfation of gastrin in serum, antrum and duodenum was studied in 22 normo- and 20 hypergastrinemic patients. The ratio between gastrin-17 and gastrin-34 was measured in antrum and duodenum. The degree of sulfation was reduced in the antrum of hypergastrinemic patients (35.3 +/- 1.3%, mean +/- SEM) compared with 48.0 +/- 2.1% in normo-gastrinemic patients (p less than 0.001). The degree of sulfation in serum and duodenum was similar to that of the antral gastrins in all patients. The percentage of gastrin-34 in antrum was increased (7.3 +/- 0.7%) in hypergastrinemic compared with 4.9 +/- 0.3% in normogastrinemic patients (p less than 0.01). In the duodenum the percentage of gastrin-34 was similar in normo- and hypergastrinemia. When classified according to clinical diagnosis, sulfation of antral gastrin was normal in duodenal ulcer (47.6 +/- 4.5%) but decreased in gastric ulcer (36.7 +/- 1.6%, p less than 0.01) and pernicious anemia (31.3 +/- 1.9%, p less than 0.001) compared with 48.2 +/- 2.2% in control patients. In pernicious anemia a larger proportion of antral gastrins occurred as gastrin-34 (8.2 +/- 0.9%) compared with 4.8 +/- 0.4% in control patients (p less than 0.01). Our study suggests that both sulfation and proteolytic processing of the gastrin precursor is diminished in hypergastrinemia of antral origin.

Topics: Anemia, Pernicious; Duodenal Ulcer; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Stomach Ulcer; Sulfuric Acids

Topics: Calcium; Duodenal Ulcer; Fasting; Gastrins; Glucagon; Humans; Secretin; Zollinger-Ellison Syndrome

The authors describe the results of studying basal gastrin secretion in patients with peptic ulcer of the duodenum at different phases of disease treated in 3 stages. It was revealed that basal secretion of gastrin experienced substantial changes in the course of transition from the phase of exacerbation to the phase of disease remission. It was noted that the onset of the clinico-endoscopic remission of peptic ulcer did not correlate in all the cases with normalization of basal gastrin level. Patients who did not show normalization of basal gastrin level during treatment were more prone to the development of repeated exacerbations. Based on the data obtained the authors determined the prognostic importance of radioimmunoassay of gastrin basal concentration over time. The increment of gastrin concentration by more than 35 pg/ml of the level seen during peptic ulcer exacerbation is a prognostically unfavourable sign, for the probability of relapses rises up to 79% during a year.

Topics: Adult; Aged; Chronic Disease; Duodenal Ulcer; Duodenoscopy; Gastrins; Humans; Male; Middle Aged; Prognosis; Radioimmunoassay; Recurrence; Time Factors

Topics: Adult; Chlorides; Diagnostic Errors; Duodenal Ulcer; Female; Gastrins; Humans; Water-Electrolyte Imbalance; Zollinger-Ellison Syndrome

Proximal gastric vagotomy-mucosal antrectomy (PGV-MA) was devised in an attempt to reduce the cephalic and hormonal phases of acid secretion without disturbing gastric emptying. The current study determines the effects of proximal gastric vagotomy (PGV), or PGV-MA on acid secretion, gastrin, and gastric emptying. Twelve dogs underwent measurement of gastric emptying, fasting and postcibal acid production, and fasting and postprandial gastrin levels. The animals then underwent either PGV or PGV-MA and the studies were repeated. PGV markedly decreased basal acid (P less than 0.001); however, there was still a large postprandial acid increase. In contrast, PGV-MA nearly abolished both fasting and postprandial acid secretion (difference from control and PGV significant at P less than 0.001). Gastric emptying was not significantly altered by either procedure. PGV was associated with increased fasting and postprandial gastrin levels, while PGV-MA produced lower gastrin levels at all intervals than either controls or PGV-MA. PGV-MA emulates the effects of truncal vagotomy and antrectomy on acid secretion, without affecting gastric emptying and deserves further investigation as a possible surgical alternative in the treatment of duodenal ulcer disease.

Topics: Animals; Dogs; Duodenal Ulcer; Fasting; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Pyloric Antrum; Vagotomy; Vagotomy, Proximal Gastric

The basal and food-stimulated gastrin secretion after selective proximal vagotomy, selective gastric vagotomy and truncular vagotomy was found to be elevated. Hypergastrinemia increased as gastric secretion was inhibited, thus attesting to the role of acid formation inhibition in the origin of the postvagotomy increase in the hormonal secretion. However the values of the intragastral pH being equal, the blood gastrin level was higher after vagotomy as compared to that seen in unoperated peptic ulcer patients. After vagotomy coupled with antrumectomy gastrin secretion remained at the level seen in the unoperated patients, indirect evidence for increased function of extraantral G cells. Inhibition of gastric secretion is no single cause of the postvagotomy hypergastrinemia, since the latter was essentially increased in the early postoperative times and in the presence of the vagotomy-induced disorders. It is concluded that increased secretion of gastrin after vagotomy secures trophic and compensatory-adaptation processes.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Male; Middle Aged; Postoperative Period; Pyloric Antrum; Time Factors; Vagotomy; Vagotomy, Proximal Gastric

An x-ray method modified by the authors was employed in 40 patients with peptic ulcer of the duodenum to examine the effect of pentagastrin and histamine on the rate of gastric evacuation of x-ray capsules 3, 5 and 10 mm in diameter taken with the trial breakfast. It was established that pentagastrin inhibits gastric evacuation (P less than 0.05) mainly at the expense of retention of the egress from it of the capsules 10 mm in diameter (P less than 0.05). Administration of histamine does not exert any essential effect on the rate of gastric evacuation. Administration of gastrin following cimetidine also brings about an inhibition of gastric evacuation (P less than 0.05) largely at the expense of retention of evacuation of the capsules larger in diameter. It is concluded that inhibition of gastric evacuation after gastrin administration occurs at the expense of an elevation of the tone of the pyloric sphincter. It is suggested that in the mechanism of the inhibitory action of pentagastrin, the level of hydrochloric acid secretion and H2 receptors of histamine do not play any important role. The inhibitory effect of pentagastrin is likely to be caused by an elevation of the somatostatin level.

Topics: Adult; Depression, Chemical; Duodenal Ulcer; Female; Gastric Emptying; Gastrins; Histamine; Hormones; Humans; Male; Middle Aged; Muscle Tonus; Muscle, Smooth; Pentagastrin; Pyloric Antrum; Time Factors

Eighteen patients with active duodenal ulcer were treated with a novel antisecretory drug, RP 40749, either 100 mg or 150 mg as a daily nocturnal dose for 28 days. In these patients we evaluated the clinical course, endoscopic healing rates after 28 days, routine laboratory parameters, basal serum gastrin and pepsinogen I levels, meal-stimulated serum gastrin concentration, and the gastrin content of the antral mucosa. All nine patients receiving 150 mg RP 40749 and eight of nine patients receiving 100 mg RP 40749 healed their ulcers completely within 28 days, becoming rapidly symptom-free after an average of three days. The basal (53.8 +/- 5.2 vs 99.8 +/- 11.4 pg/ml) and meal-stimulated serum gastrin levels (109.2 +/- 12.1 vs 189.2 +/- 16.7 pg/ml) rose significantly after treatment with RP 40749, as did the gastrin content of the antral mucosa (11.3 +/- 2.1 vs 26.0 +/- 5.1 micrograms/g), suggesting increased synthesis and secretion of gastrin. Between the 100 mg and 150 mg groups, no significant differences in response were observed. Serum pepsinogen I levels (64.9 +/- 7.3 vs 147.9 +/- 17.9 ng/ml) increased after treatment; the increase after 150 mg RP 40749 was significantly greater than that after 100 mg RP 40749. The increase of serum pepsinogen levels are probably due to a spillover effect resulting from a blockade in exocrine secretion into the lumen. There were no relevant changes in routine laboratory parameters.

Topics: Adult; Aged; Anti-Ulcer Agents; Creatinine; Dose-Response Relationship, Drug; Duodenal Ulcer; Duodenoscopy; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pepsinogens; Pyloric Antrum; Thiophenes

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.

Topics: Adult; Aged; Cimetidine; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Stomach Ulcer; Time Factors

Addition of guar gum to a meal increases its viscosity. Two test meals of differing viscosities were eaten by 15 duodenal ulcer patients. Gastric emptying rates were measured over 120 minute periods after ingestion of the meals by determining the intragastric content of the polyethylene glycol which had been included in the meals. Serum gastrin levels were determined over the same period by radioimmunoassay. The gastric emptying rate was significantly (p less than 0.05) lower after the meal of higher viscosity, but there were no significant differences in serum gastrin levels at any time of measurement after the two meals.

Topics: Adult; Aged; Duodenal Ulcer; Female; Food; Gastric Emptying; Gastrins; Humans; Male; Middle Aged; Viscosity

The role of gastrin in the pathogenesis of recurrent peptic ulceration is not established although it is known that plasma gastrin levels are frequently elevated after vagotomy. This study aims to determine whether there is a relationship between gastrin and gastric secretion in patients with and without recurrent ulceration after surgery for duodenal ulceration (DU). The basal acid output (BAO) in 23 and the peak acid output to pentagastrin (PAOPg) in 10 patients with symptomatic recurrent ulcers after DU surgery were determined along with the BAO and PAOPg in 10 control patients who were asymptomatic following DU surgery. The fasting plasma gastrin was determined in all patients and correlated with the acid output. An inverse correlation was demonstrated between the BAO and plasma gastrin in the asymptomatic patients (p less than 0.05) and the patients with proven recurrent ulcers (p less than 0.01) and there was a direct correlation between the PAOPg and plasma gastrin in the recurrent ulcer group (p less than 0.05) which was not observed in the control group. It is suggested that in a subgroup of recurrent ulcer patients 'G cell hyperfunction' may occur and this may have a role in the aetiology of this condition.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Recurrence

The effect of sham feeding upon gastric acid secretion and pancreatic polypeptide release was investigated in 28 patients with duodenal ulcer in order to evaluate whether high basal vagal activity is the cause of basal acid hypersecretion in patients with duodenal ulcer and basal secretion higher than 30% of their peak acid output. The patients were divided into two groups based on the ratio of basal/pentagastrin stimulated peak acid output (BAO/PAO) was higher or lower than 0.30: group A n = 19 (BAO/PAO less than or equal to 0.30) and group B n = 9 (BAO/PAO greater than 0.30). Gastric acid response to sham feeding (SAO) was significantly higher than basal level in group A (SAO: 11.4 mEq/h (2.5-20.1) vs BAO: 5.2 mEq/h (0.8-22.9), p less than 0.01, median (range)) while in group B the acid secretion did not increase with sham feeding (SAO: 9.6 mEq/h (4.5-13.6) vs BAO: 8.8 mEq/h (6.3-13.8) ns, median (range)). A negative correlation (r= -0.6118226, p less than 0.01) was found between acid increase expressed as basal subtracted sham feeding response (SAO-BAO) and BAO/PAO ratio of the entire group of duodenal ulcer patients (n = 28) suggesting that the greater is basal acid secretory capacity the smaller is acid increase in response to residual vagal activation. Pancreatic polypeptide response to sham feeding was higher in group A than in group B but no correlation (r = 0.20, n = 28) nor individual covariation was found between acid and pancreatic polypeptide secretions during vagal stimulation. sham feeding did not change serum gastrin. It is concluded that an increased vagal stimulation seems to be the cause of basal hypersecretion in a subgroup of patients with duodenal ulcer. The lact of correlation between the pancreatic polypeptide and acid responses to vagal stimulation interferes with the reliability of pancreatic polypeptide as indicator of vagal tone on gastric parietal cells.

Topics: Adult; Aged; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreatic Polypeptide; Pentagastrin; Vagus Nerve

Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Monoamine Oxidase; Rats

Topics: Duodenal Ulcer; Evaluation Studies as Topic; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum; Vagotomy, Proximal Gastric

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Monoamine Oxidase; Prospective Studies

Heterogeneity is the most important consideration in the pathophysiology of peptic ulcer disease. Acute ulcers and erosions present clinically with gastrointestinal bleeding or perforation. If they heal there is no predictable recurrence. Factors concerned with mucosal defense are relatively more important than aggressive factors such as acid and pepsin. Local ischemia is the earliest recognizable gross lesion. The gastric mucosa is at least as vulnerable as the duodenal mucosa and probably more so. Most drug-induced ulcers occur in the stomach. Chronic or recurrent true peptic ulcers (penetrating the muscularis mucosae) usually present with abdominal pain. Many duodenal ulcer patients report that the pain occurs when the stomach is empty or is relieved by food, and follows a pattern of relatively long periods of freedom from symptoms between recurrences. Approximately 50% of patients experience a recurrence within a year if anti-ulcer medication is stopped. In most western countries recurrent duodenal ulcer is more common than gastric ulcer. Peptic ulcer disease is also more common in men. Recent evidence indicates genetic and familial factors in duodenal ulcer and increased acid-pepsin secretion in response to a variety of stimuli. However, it is also becoming clear that of all the abnormal functions noted, few are present in all subjects and many are clustered in subgroups. In chronic gastric ulcer of the corpus, defective defense mechanisms, such as duodenogastric reflux and atrophic gastritis, seem to be more important than aggressive factors. Nevertheless, antisecretory medications accelerate the healing of such ulcers. It remains to be seen whether prostaglandins, mucus secretion, or gastric mucosal blood flow are impaired in chronic ulcer disease.

Topics: Acute Disease; Animals; Burns; Chronic Disease; Duodenal Ulcer; Gastric Acid; Gastric Emptying; Gastrins; Humans; Intestinal Mucosa; Peptic Ulcer; Recurrence; Spinal Cord Injuries; Stomach Ulcer; Stress, Physiological

The secretin injection test is considered a useful adjunct to the diagnosis of gastrinoma, although it may lack specificity. This study determined whether the release of gastrin in response to secretin was different in duodenal ulcer and control patients. Tests were performed on 10 duodenal ulcer patients, 10 normal control subjects, 20 patients asymptomatic after ulcer surgery, of whom 13 had a vagotomy and drainage, 4 a highly selective vagotomy and 3 a vagotomy and antrectomy. The secretin test was also performed in 49 patients with endoscopically proven recurrent ulcers. The surgery performed in this latter had consisted of a vagotomy and drainage in 36, a highly selective vagotomy in 7 and a vagotomy and antrectomy in 6 patients. The basal plasma gastrin level was similar in normal controls, duodenal ulcer patients and patients with vagotomy and antrectomy, both with and without recurrent ulcers. The level was elevated in all the other groups of patients with vagotomy both with and without recurrent ulcer. The plasma gastrin did not change significantly after secretin injection in the normal control or asymptomatic ulcer surgery patients, but rose in the duodenal ulcer patients and all the groups of patients with recurrent ulcer. Most of these increases were validated statistically as were the differences in response between the ulcer and control patients. These results indicate that there are differences in the plasma gastrin response to intravenous secretin between active duodenal ulcer and control patients. This findings may aid our understanding of the pathophysiology of peptic ulcer disease and explains the lack of specificity of the secretin test.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Humans; Kinetics; Male; Middle Aged; Recurrence; Secretin; Vagotomy

The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.

Topics: Cimetidine; Duodenal Ulcer; Eating; Gastrins; Humans; Protein Precursors; Stomach Ulcer; Time Factors

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Humans

Serum gastrin changes before and after selective proximal vagotomy (SPV) were studied in relation to the gastric motility and the acid secretion clinically and experimentally and the effects of pyloroplasty were investigated.. Experimental studies revealed that test meals provoked gastrin secretion to stimulate gastric motility. Periodical gastric acid secretions were observed during hunger period, along with elevated serum gastrin levels. After SPV, gastrin responses to the test meals were significantly increased so that the pyloric ring motility was disturbed. Clinical studies revealed that adrenaline infusion test provoked significant gastrin responses to secrete acid secretions in duodenal ulcer patients. After SPV, increased gastrin responses to adrenaline restored acid secretions as much as preoperative acid secretions responded to the adrenaline test. Pyloroplasty for the SPV inhibited the gastrin and acid secretions responded to the adrenaline test.

Topics: Animals; Dogs; Duodenal Ulcer; Gastrins; Gastrointestinal Motility; Humans; Pyloric Antrum; Vagotomy, Proximal Gastric

The function of residual G cells after selective vagotomy with pyloroplasty (SV + P) in 24 duodenal ulcer patients was assessed by physiological and electron microscopical studies. We studied the mechanism of gastrin release following insulin-induced hypoglycemia with respect to plasma catecholamines in mongrel dogs. Basal serum gastrin was significantly increased one month after surgery. Integrated gastrin response to meat extract and insulin hypoglycemia stimulation was also increased significantly six months postoperatively. The G cells were still increasing in number six months after SV-P, and G cell hyperplasia became more remarkable after one year. Emiocytotic figures were observed in denervated G cells which were stimulated by meat extract or insulin hypoglycemia. Both serum gastrin and plasma epinephrine began to increase 15 minutes after administration of insulin, peaked at the 45th minute, and decreased thereafter in control dogs and vagotomized dogs. In bilaterally adrenalectomized dogs, both responses were significantly inhibited. In control dogs, the gastrin response was seen under continuous infusion of epinephrine (0.5 micrograms/kg/min). Therefore, our results suggest that regardless of the presence or absence of vagal innervation, gastrin is released from G cells mainly due to epinephrine secreted from the adrenal medulla under insulin-induced hypoglycemia.

Topics: Animals; Chromaffin System; Dogs; Duodenal Ulcer; Enterochromaffin Cells; Female; Follow-Up Studies; Gastrins; Male; Pyloric Antrum; Vagotomy, Proximal Gastric

Topics: Duodenal Ulcer; Gastrins; Humans; Radioimmunoassay

Cysteamine (beta-mercaptoethylamine HCl) administration to rats induces a hypergastrinemia and a reduction in gastric tissue somatostatin content. The possibility that this reduction may contribute to the elevated gastrin levels has been investigated in the isolated perfused rat stomach. Cysteamine (1 mM) rapidly increased immunoreactive gastrin release to levels ranging between 41% and 125% above basal. Increasing the dose to 10 mM caused a 1148% increase in immunoreactive gastrin. Secretion of somatostatinlike immunoreactivity did not change. Perfusion of gastric inhibitory polypeptide (1 nM) induced a sustained increase in somatostatinlike immunoreactivity secretion and a transient rise in gastrin. Addition of 10 mM cysteamine during gastric inhibitory polypeptide perfusion caused a 300% increase in immunoreactive gastrin. These levels were lower than in response to cysteamine alone. The results demonstrate that cysteamine can stimulate immunoreactive gastrin secretion without any change in somatostatinlike immunoreactivity release. When somatostatinlike immunoreactivity secretion is stimulated by an agent such as gastric inhibitory polypeptide, the cysteamine-induced release of immunoreactive gastrin is attenuated, suggesting the presence of a functional linkage between somatostatin and gastrin under these conditions.

Topics: Animals; Cysteamine; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Male; Rats; Rats, Inbred Strains; Somatostatin

Changes in gastric acid secretion and plasma levels of CCK, gastrin, motilin, neurotensin and somatostatin in response to modified sham feeding (MSF) were investigated in 8 asymptomatic duodenal ulcer patients. MSF caused a significant increase in gastric acid secretion whereas the peripheral plasma concentrations of the various polypeptides remained unchanged. The study gives further support for the notion that MSF activates the vagal innervation to the parietal cells more selectively than insulin hypoglycaemia.

Topics: Adult; Aged; Cholecystokinin; Duodenal Ulcer; Food; Gastric Acid; Gastrins; Gastrointestinal Hormones; Humans; Middle Aged; Motilin; Neurotensin; Somatostatin

The relation between gastric acid secretion and plasma concentrations of adrenaline, noradrenaline, dopamine and gastrin was investigated in normal volunteers, adrenalectomized subjects and patients with duodenal ulcer (DU) during digestion and in response to insulin and modified sham feeding (MSF). Basal plasma noradrenaline concentrations were significantly higher in DU patients than in normals whereas basal plasma adrenaline and dopamine concentrations were low in both groups. Basal acid output was similar in the two groups. Insulin markedly increased plasma adrenaline in controls but had no discernible effect in adrenalectomized subjects. Still, there was no difference between acid secretion in the two groups. Insulin, but not MSF, caused a marked increase in plasma catecholamine concentrations in DU patients whereas the acid responses were the same. The significantly increased plasma noradrenaline concentration in DU patients was normalized 6 weeks after highly selective vagotomy but tended to return to the preoperative value 1 year postoperatively. Our results suggest that endogenously released adrenaline might affect gastric function only when present in extremely high plasma concentrations. The pathophysiological role of noradrenaline in DU disease remains obscure.

Topics: Catecholamines; Chronic Disease; Duodenal Ulcer; Eating; Gastric Acid; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Hypoglycemia; Insulin; Vagotomy

Studies were designed (a) to determine whether somatostatin is released into the circulation after meals in sufficient amounts to regulate gastric or pancreatic islet function in humans and (b) to investigate the possible role of somatostatin in the pathogenesis of duodenal ulcer disease. Mean plasma somatostatin-like immunoreactivity (SLI) increased from 6.2 +/- 1.5 pg/ml to a peak level of 13.8 +/- 1.3 pg/ml in eight healthy subjects after a 1,440-cal steak meal (P less than 0.005). When somatostatin-14 was infused intravenously, basal and food-stimulated gastric acid secretion and also basal and food-simulated plasma insulin and glucagon concentrations were reduced significantly at mean plasma SLI concentrations within the range seen after a meal. Thus, the amount of somatostatin reaching the systemic circulation after a steak meal was sufficient to inhibit gastric acid secretion and islet cell function. On the other hand, basal and food-stimulated plasma gastrin concentrations were reduced by intravenous somatostatin only at plasma SLI concentrations that were several-fold greater than post-prandial SLI concentrations. Although duodenal ulcer patients had significantly higher basal, food-stimulated, and peak pentagastrin-stimulated gastric acid secretion rates than healthy controls, duodenal ulcer patients and controls had nearly identical basal and food-stimulated SLI concentrations. Moreover, food-stimulated gastric acid secretion and gastrin release were inhibited by intravenous somatostatin to the same extent in ulcer patients and controls. These studies suggest that duodenal ulcer patients release normal amounts of somatostatin into the circulation and that target cells controlling acid secretion and gastrin release are normally sensitive to somatostatin in these patients.

Topics: Adult; Animals; Cattle; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Islets of Langerhans; Kinetics; Male; Meat; Middle Aged; Reference Values; Somatostatin; Time Factors

Topics: Adult; Duodenal Ulcer; Famotidine; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Secretin; Thiazoles

Topics: Adolescent; Adult; Cyclic AMP; Cyclic GMP; Duodenal Ulcer; Duodenum; Female; Gastrins; Hormones, Ectopic; Humans; Intestinal Mucosa; Male; Middle Aged; Somatostatin

Three types of endocrine cells (G cells producing gastrin-17, D cells producing somatostatin, and GER cells containing endorphine) in the mucous membrane of the stomach antrum from 14 patients with duodenal ulcer and 10 healthy persons were studied. Biopsies were fixed in a modified Bowen solution and imbedded into paraffin. The slides were stained by Grimelins' method and immunohistochemically with the use of the peroxidase-antiperoxidase method. The number of cells per 1 mm2 of the mucous membrane was counted. Patients with ulcer have shown the increased number of G and GER cells and decreased number of D cells. Besides, pronounced G cell hyperplasia with a relative decrease of GER cells and a marked decrease of Grimelins-positive cells (as compared to other patients with duodenal ulcer) were observed in 3 out of 14 ulcer patients. The authors conclude that the alteration of the balance between antagonistic hormone effects results in the hypersecretory syndrome that plays the main role in the pathogenesis of duodenal ulcer.

Topics: Adult; Cell Count; Duodenal Ulcer; Endocrine Glands; Endorphins; Gastrins; Hormones, Ectopic; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Somatostatin

Topics: Aluminum; Antacids; Anti-Ulcer Agents; Cimetidine; Duodenal Ulcer; Gastrectomy; Gastric Acid; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Histamine H2 Antagonists; Humans; Intestinal Absorption; Metoclopramide; Mucus; Parasympatholytics; Ranitidine; Smoking; Stomach Ulcer; Sucralfate; Vagotomy

Topics: Adult; Cell Count; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

The effect of pirenzepine--a selective antimuscarinic compound--on plasma catecholamine, serum gastrin and somatostatin concentrations was studied in duodenal ulcer patients. Plasma concentration of noradrenaline decreased significantly after injection of pirenzepine (10 mg intravenously), whereas the circulating levels of adrenaline, dopamine, gastrin and somatostatin remained unchanged. The results may be explained by a decreased activity in postganglionic sympathetic ganglia. This is in line with the recent observation in vitro that pirenzepine effectively blocks muscarinic receptors in some sympathetic ganglia.

Topics: Adult; Aged; Anti-Ulcer Agents; Benzodiazepinones; Dopamine; Duodenal Ulcer; Epinephrine; Female; Gastrins; Humans; Male; Middle Aged; Norepinephrine; Pirenzepine; Somatostatin

It has been previously suggested that antral pH governs the density of antral G- and D-cells. Therefore, we investigated the effect of acid neutralization by an antacid (magaldrat; in vivo neutralization capacity of 144 mval/day) and the effect of suppression of gastric acid secretion by an H2-receptor blocker (oxmetidine, 400 mg/day) on the density of both cell types in healthy volunteers and duodenal ulcer patients. Four weeks after antacid treatment antral G-cell density decreased significantly in both groups, while antral D-cells decreased only in volunteers. Basal serum gastrin was not altered, whereas the integrated postprandial serum gastrin response and antral gastrin concentration was significantly reduced in volunteers but not in ulcer patients. None of the parameters investigated was changed by oxmetidine treatment. Considering the short-lasting effect on acid neutralization induced by the antacid dosage used in this study and the inability of oxmetidine treatment to influence volume densities and secretory activities of antral G- and D-cells it is concluded that mechanisms other than a change of antral pH may account for the results obtained during antacid treatment.

Topics: Adult; Aluminum Hydroxide; Antacids; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histamine H1 Antagonists; Humans; Imidazoles; Magnesium; Magnesium Hydroxide; Male; Middle Aged; Pyloric Antrum

Immunohistochemistry was used to study the changes in the number of G cells in the antral part of the stomach of rats (40 animals) with cystamine-induced duodenal ulcer treated with beta-endorphine. In the stomach of rats with cystamine-induced ulcer the number of G cells was discovered to be significantly increased, which was removed by an opioid peptide. Naloxone did not block the action of beta-endorphine. Thus, beta-endorphine changes the number of G cells, the drug action being not associated with opiate receptors.

Topics: Animals; beta-Endorphin; Cysteamine; Duodenal Ulcer; Endorphins; Gastric Mucosa; Gastrins; Male; Rats; Rats, Inbred Strains; Stomach

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Insulin; Peptic Ulcer Perforation

The effects of omeprazole, a benzimidazole derivative, have been determined on the secretory responses to modified sham feeding and pentagastrin, and upon serum gastrin and pancreatic polypeptide concentrations in duodenal ulcer patients. Intragastric administration of omeprazole in doses of 2 and 6 mumol/kg produced, respectively, about 50% and 90% reduction in acid outputs in responses to modified sham feeding and pentagastrin without affecting serum gastrin and pancreatic polypeptide response to modified sham feeding.

Topics: Adult; Benzimidazoles; Dose-Response Relationship, Drug; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Humans; Intestinal Secretions; Male; Omeprazole; Pancreatic Polypeptide; Pentagastrin; Pepsin A; Stomach

This review concerns itself with the current understanding of the control of gastric secretion and the application of this knowledge to the design of treatment for duodenal ulcer through the reduction of acid and pepsin load on the duodenal bulb. The control of gastric secretion is described under the headings: (i) neurohormonal; (ii) endocrine; (iii) paracrine; (iv) luminal; and (v) cellular. This discussion is followed by a description of the pathophysiology of gastric secretion in duodenal ulceration. The strategies of treatment are discussed under four headings: (i) postsecretory treatments; (ii) destruction of the gastric mucosa; (iii) alteration of neurohormonal controls; and (iv) modification or inhibition of the cellular mechanisms of acid and pepsin secretion. Several currently useful and potentially important new lines of treatment are described.

Topics: Benzimidazoles; Carbenoxolone; Dinoprostone; Duodenal Ulcer; Food; Gastrectomy; Gastric Acid; Gastric Fundus; Gastric Mucosa; Gastrins; Glucose; Humans; Pepsin A; Prostaglandins E; Pyloric Antrum; Vagotomy, Proximal Gastric; Vagus Nerve

Muscarinic mechanisms in basal acid and pepsin secretion in man were quantitated by graded intravenous doses of atropine (1-16 micrograms/kg). Secretion was dose-responsively inhibited in six healthy controls. For the mean dose response, maximum inhibition (Imax) was 100%, and D50 (dose inhibiting 50%) was 0.31 +/- 0.06 and 0.93 +/- 0.13 micrograms/kg, respectively, for acid and pepsin. In 24 patients with duodenal ulcer (DU), calculated Imax was also 100%, and D50S were 1.2 +/- 0.27 and 1.7 +/- 0.3 micrograms/kg, respectively. The low D50 values and the 100% calculated maximum inhibition indicated that in both groups basal secretion was largely or completely cholinergic dependent. We also found that atropine raised heart rate in controls by 44 +/- 1 beats per min (bpm) (D50 = 6 +/- 1.1 micrograms/kg), while the mean maximum increase in DU was only 23 +/- 2 bpm (P less than 0.01) with (D50 = 5.3 +/- 1.0 micrograms/kg (NS)). In DU atropine increased fasting serum gastrin from 62 to 82 pg/ml (P less than 0.05); the increase in normals from 32 to 38 pg/ml was not significant. Thus, while both normals and DU exhibited the same qualitative responses to muscarinic receptor antagonism by atropine with respect to gastric secretion, gastrin levels, and heart rate, there were quantitative differences in all three parameters.

Topics: Acetylcholine; Adult; Atropine; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Heart Rate; Humans; Male; Pepsin A

The concentrations of gastrins containing the active C-terminal tetrapeptide amide (mainly gastrin-34 and gastrin-17) and the N-terminal tridecapeptide fragment of gastrin-17 were measured in antral and duodenal biopsy specimens. The antral concentration of the N-terminal gastrin fragment was much higher in patients with active duodenal ulcer (33.4 +/- 6.8 nmol g-1, mean +/- SEM, n = 15) than in controls (5.6 +/- 2.9 nmol g-1, n = 10), patients with gastric ulcer (5.6 +/- 1.8 nmol g-1, n = 10) or patients with pernicious anaemia (7.7 +/- 2.5 nmol g-1, n = 6). No differences were found between the groups regarding gastrin-34 and gastrin-17 concentrations. In duodenal extracts, the N- and C-terminal gastrin concentrations were similar in all groups of patients. These data suggest that the posttranslational processing of antral gastrin is abnormal in patients with active duodenal ulcer disease.

Topics: Adult; Aged; Anemia, Pernicious; Chromatography, Gel; Duodenal Ulcer; Female; Gastrins; Hormones; Humans; Male; Middle Aged; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Stomach Ulcer

Topics: Adult; Animals; Cats; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Vagotomy; Vagus Nerve

Duodenal ulcer has not been observed in full-heritage Pima Indians, while gastric cancer is relatively frequent. To investigate possible underlying factors for this phenomenon, we determined gastric acid output, gastric emptying rate, and plasma levels of gastrin, pepsinogen I, and pepsinogen II in apparently healthy Pima Indians and in Caucasian controls. The Pimas had significantly lower basal and stimulated outputs of gastric acid and higher fasting and postprandial plasma gastrin concentrations than the Caucasians. Plasma pepsinogen I levels were similar in the two groups, but plasma pepsinogen II was significantly higher and the ratio of pepsinogen I to pepsinogen II was significantly lower in the Pima Indians. In addition, gastric emptying of acaloric liquid meal was significantly delayed in the Pimas. The results suggest that the absence of duodenal ulcer in Pima Indians may be related to low gastric acid production and a slow rate of gastric emptying in this population. The associated findings of hypergastrinemia, hyperpepsinogenemia II, and a low ratio of pepsinogen I to pepsinogen II suggest that the hypochlorhydria may reflect an increased prevalence of chronic gastritis in full-heritage Pima Indians. This, in turn, could represent a risk factor for the development of gastric cancer in this population.

Topics: Achlorhydria; Adolescent; Adult; Arizona; Betazole; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastrins; Humans; Indians, North American; Male; Pepsinogens

In a series of 59 experiments in nine duodenal ulcer patients, 24 hour intragastric acidity was measured before, during, and after treatment with daily oral omeprazole. Omeprazole 10, 20, and 30 mg/day for one week caused a 37, 90, and 97% decrease of 24 hour intragastric acidity, respectively. No further decrease of acidity was observed when the dose of omeprazole was doubled to 60 mg/day, or after a second week of treatment with 30 mg/day. One week after stopping treatment with omeprazole (14 doses) there was a significant 26% decrease of 24 hour intragastric acidity, with full recovery seven weeks later. Fasting plasma gastrin concentration was significantly raised during treatment with all doses of omeprazole. Omeprazole 30 mg/day is the optimal dose for a maximal decrease of 24 hour intragastric acidity in duodenal ulcer patients.

Topics: Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Omeprazole; Time Factors

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

The relationship between gastric acid secretion and the release of pancreatic polypeptide (PP) during modified sham feeding was studied in 29 duodenal ulcer patients and 10 healthy controls. Ulcer patients showed higher basal plasma PP levels than age-matched controls (p less than 0.01). Acid secretion and PP levels were stimulated in the majority of patients and controls during sham feeding; however, no correlation was found between basal and vagally stimulated acid secretion and basal PP levels. Gastrin levels did not change in both groups. It is concluded from the present study that changes in plasma PP levels do not reflect sham feeding induced stimulation of the parietal cells.

Topics: Adult; Aged; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Humans; Middle Aged; Pancreatic Polypeptide; Vagus Nerve

It has been demonstrated that the basal gastrin level in the blood of patients with peptic ulcer of the duodenum is similar to that in normal subjects. Food stimulation raises blood gastrin in normal subjects and patients. However, in patients, the peak of the blood hormone rise is higher, with this rise lasting for a longer time. Besides, the total output of the hormone is greater. These changes are most marked during an incomplete disease remission, being less remarkable when exacerbation gets attenuated and during a complete remission. A correlation has been noticed between the acid-forming function of the stomach and basal blood gastrin level that increases as the acid content in gastric juice descends. In patients experiencing a complete remission and in those in the stage of an incomplete remission and attenuated exacerbation, a direct correlation was ascertained between the stimulated hypergastrinemia and duration of the intragastral pH elevation in response to food intake. It is suggested that in peptic ulcer of the duodenum, hypergastrinemia occurs as a defence reaction aimed at the activation of trophic processes in the mucous membrane of the gastroduodenal zone.

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Time Factors

An 8-year-old boy with persistent duodenal ulceration was found to have hypergastrinaemia due to a solitary hepatic gastrinoma. Surgical resection has been followed by total clinical remission for a period exceeding 2 years.

Topics: Child; Duodenal Ulcer; Gastrins; Humans; Liver Neoplasms; Male; Zollinger-Ellison Syndrome

A method for measurement of gastrin in human antral mucosa or in extragastric tissue has been developed and validated. Tissue gastrin was extracted by boiling followed by homogenization at neutral pH. Extractable gastrin immunoreactivity was measured by radioimmunoassay using an antiserum with equal affinity towards G-17 I, G-17 II, G-34 I and G-34 II molecular forms. Almost all extractable gastrin immunoreactivity was recovered after a single extraction and no significant interference by other peptides and/or substances present in tissue was found. The mean gastrin concentration in antral mucosa of healthy subjects was similar to that observed in duodenal ulcer patients, while patients with type A chronic atrophic gastritis or with antral gastrin cell hyperplasia had mean values significantly higher. Gastrin concentration in all specimens from gastrinoma or its metastases was above the upper limit of the range of control tissue. Measurement of tissue gastrin seems to be a valuable tool in the diagnosis of antral gastrin cell hyperplasia and Zollinger-Ellison syndrome.

Topics: Adolescent; Adult; Aged; Cholecystitis; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Male; Middle Aged; Pancreatic Neoplasms; Pyloric Antrum; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastrins; Humans; Stomach Ulcer

The effects of proximal selective vagotomy (PSV) on parietal cell morphology and the degree of gastric inflammation were investigated and correlated with changes in gastric acid secretion and serum gastrin concentrations in 17 duodenal ulcer patients. Endoscopy, acid secretion tests, and blood sampling were performed preoperatively and 2 months, 1 year, and 3 years postoperatively. The mucosal biopsy specimens obtained at endoscopy were analyzed both light- and electron-microscopically. Five healthy persons also underwent gastroscopy and biopsy for comparison. Preoperatively, the duodenal ulcer patients differed significantly from this control group, 33% of whose parietal cells appeared 'secretory'; the corresponding figure for the duodenal ulcer patients was 47%. Two months after the operation the number of secretory parietal cells had fallen to 30%, after which the percentage increased slightly again to 35% 3 years after PSV. A similar phenomenon was observed in the acid secretion capacities, which were maximally depressed 2 months postoperatively and recovered slightly but significantly during the 3-year follow-up period. There was a significant increase in the degree of gastric inflammation after the operation.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Parietal Cells, Gastric; Vagotomy; Vagotomy, Proximal Gastric

The serum values of PG I and gastrin have been established in a normal population and in several clinical diseases. The PG I is raised in duodenal, gastric, and pyloric ulcer even though the gastrin is normal. Both PG I and gastrin values are raised in renal insufficiency and the Zollinger-Ellison syndrome. The PG I is lowered in atrophic gastritis and alcoholic cirrhosis, and is at the limit of detection in Biermer anemia and total gastrectomy. Insulin and sham-feeding are stimulants for PG I release by patients with duodenal ulcer, but no correlation is observed between PG I output and PAO in the studied group. The results show that PG I is able to distinguish between associated hypergastrinemia and hypoacidity (Biermer anemia type) or a hyperacidity (Zollinger-Ellison syndrome type), and that PG I is a good indicator for gastric hypoacidity. Overlapping between normal and ulcer subjects is comparable to those obtained in acid output determinations.

Topics: Adolescent; Adult; Aged; Anemia, Pernicious; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Gastritis, Atrophic; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Pepsinogens; Reference Values; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Combined Modality Therapy; Duodenal Ulcer; Female; Gastrins; Health Resorts; Humans; Male; Middle Aged

The most important purposes of morphometry in endocrine pathology are described. With the introduction of immunocytochemical techniques by Sternberger in 1969 a new field for detailed morphometric analysis in endocrine pathology was opened. The application of morphometry in combination with the immunocytochemical staining of cells is illustrated by studies of the role of gastrin and gastric secretion in the etiology of duodenal ulcer. For such studies morphologic alterations have to be quantified. Morphometry as an instrument for characterizing diseases has been used in various fields, e.g. to analyse nesidioblastosis, diabetes mellitus or papillary carcinomas of the thyroid gland.

Topics: Duodenal Ulcer; Endocrine Glands; Female; Gastric Acid; Gastrins; Humans; Infant, Newborn; Male; Pancreas; Pregnancy; Pregnancy in Diabetics

Topics: Adult; Duodenal Ulcer; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Methods; Middle Aged; Stomach Ulcer

The effects of 9-hydroxy-19,20-bis norprostanoic acid (rosaprostol, IBI), a new prostaglandin analogue, on gastric secretion and gastrin release were studied in 15 patients with duodenal ulcer. In acute experiments, rosaprostol lowered pentagastrin-stimulated acid secretion by 27-36%, whereas after chronic administration there were no changes in acid secretion or gastrin release (fasting and oxo-stimulated) but N-acetylneuraminic acid (NANA)-glycoproteins increased significantly. Our results indicate that the antisecretory and mucopoietic activities of 9-hydroxy-19,20-bis-norprostanoic acid are the basis of its healing effect in duodenal ulcer patients.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Duodenal Ulcer; Fatty Acids; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Prostanoic Acids

Gastroduodenal rugal enlargement is associated with gastric acid hypersecretion. This study investigates the effects on the upper gastrointestinal (GI) examination of gastric acid suppression by cimetidine. Radiographs were evaluated for gastric and small-bowel fold size, small-bowel dilatation, and the presence of fluid in the stomach and small bowel. Six patients with basal gastric-acid hypersecretion (three with ordinary duodenal ulcer disease and three with Zollinger-Ellison syndrome) were studied. Results revealed that hypersecretors with ordinary duodenal ulcer disease could not be distinguished from those with Zollinger-Ellison syndrome by means of the upper GI study. The effects on the GI examination of the acid suppression by cimetidine were apparent in four of the six patients. Relations between observed radiographic effects and basal acid output and cimetidine dose were suggested only among the duodenal ulcer disease patients.

Topics: Adolescent; Adult; Cimetidine; Digestive System; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Radiography; Zollinger-Ellison Syndrome

Cholecystokinin (CCK) is structurally similar to gastrin and is known to competitively inhibit the action of gastrin on the parietal cell, but little information has been accumulated about circulating levels of CCK in patients with duodenal ulcer (DU). In a group of 18 healthy volunteers (controls) and 22 DU patients (13 with active DU, nine with inactive DU), we stimulated endogenous release of CCK with oral administration of Lipomul corn oil. Plasma concentrations of CCK were measured by radioimmunoassay; ultrasonographic measurements of gallbladder volume were used as a biologic correlate for CCK in control patients and in patients with active DU. No significant difference was found in fasting plasma concentrations of CCK between controls (107 +/- 8 pg/ml) and DU patients (123 +/- 15 pg/ml), or in their total integrated release of CCK during the first hour after Lipomul ingestion (3.7 +/- 0.7 ng-min/ml in controls, 2.8 +/- 0.4 ng-min/ml in DU patients). Furthermore, no significant difference was found in integrated release of CCK between patients with active DU (2.9 +/- 0.6 ng-min/ml) and those with inactive DU (2.8 +/- 0.6 ng-min/ml). Gallbladder volume was highly correlated with plasma concentrations of CCK in controls (r = -0.91) and in active DU patients (r = -0.98). Patients with active DU had significantly smaller volumes of their resting gallbladders, they emptied less of their resting gallbladder contents in response to fat, and they showed diminished sensitivity to endogenously released CCK compared to controls. In six patients with active DU who underwent truncal vagotomy and drainage, integrated release of CCK increased significantly, from 1.9 +/- 0.6 ng-min/ml before vagotomy to 9.3 +/- 3.0 ng-min/ml after vagotomy. We found no evidence to suggest that abnormalities in release of CCK contributes to the development of duodenal ulcers. We speculate, however, that the increased release of endogenous CCK after truncal vagotomy may possibly play an etiologic role in the syndrome of postvagotomy diarrhea.

Topics: Adult; Aged; Cholecystokinin; Duodenal Ulcer; Female; Gallbladder; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Ultrasonography; Vagotomy

A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 in doses of 50,200, and 500 ng/kg/h was performed in eight healthy volunteers and in eight patients with duodenal ulcer. The study was repeated on a separate day during intravenous infusion of calcium gluconate (0.1 mmol Ca2+/kg/h). In healthy subjects the acid response to the combined infusion of synthetic human gastrin and calcium did not significantly exceed the response to synthetic human gastrin alone, in contrast with patients with duodenal ulcer in whom the combined infusion did significantly improve acid output compared with infusion of synthetic human gastrin alone. The dose of synthetic human gastrin required for half maximal acid response (D50) was reduced in both groups but significantly more in patients with duodenal ulcer. No difference in serum gastrin concentrations or in serum calcium concentrations were found. It is hypothesised that extracellular calcium plays a role in gastrin stimulated acid secretion in man and that patients with duodenal ulcer are more sensitive to this calcium dependent mechanism than non-duodenal ulcer subjects.

Topics: Adult; Calcium Gluconate; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gluconates; Hormones; Humans; Male; Middle Aged

A comparison was made between use of isotonic 0.15 M sodium chloride and 5.8 g/100 ml glucose solutions for measurement of gastric acid secretion by intragastric titration in normal and ulcer subjects. Glucose distention did not cause significantly different acid secretion than saline distention in either group. The total amounts of glucose entering the duodenum over the 3.5-hr study period were 99 g in normal subjects and 122 g in ulcer subjects. In normal subjects, circulating gastrin-related acid secretion curves were not significantly different during endogenous peptone and exogenous G-17 stimulation using either the glucose or the saline meals. This finding provides evidence that glucose meals of this size do not alter sensitivity to gastrin. With glucose meals, inhibition of gastric emptying caused retention of a sufficient volume in the stomach to permit accurate continuous intragastric titration. Saline meals caused pronounced diarrhea which was not seen after glucose meals. Glucose distention intragastric titration allows reliable comparisons of endogenously and exogenously stimulated gastric acid secretion without serious side effects and is especially suitable for studying acid secretion in duodenal ulcer subjects.

Topics: Adult; Aged; Duodenal Ulcer; Evaluation Studies as Topic; Food; Gastric Acid; Gastric Acidity Determination; Gastric Emptying; Gastrins; Glucose; Humans; Infusions, Parenteral; Male; Middle Aged; Peptones; Sodium Chloride; Time Factors

Maximal acid outputs were determined during intravenous pentagastrin tests (6 micrograms/kg/h) in 119 male subjects: 17 controls, 74 patients with duodenal ulcer and 28 with atrophic gastritis. Basal and postprandial serum gastrin levels were also determined in order to estimate the integrated gastrin response to the meal. In patients with atrophic gastritis the maximal acid output was decreased (p less than 0.01) and the integrated gastric response was increased (p less than 0.01) but the basal gastrin levels in these patients did not differ from that of controls. An integrated gastrin response greater than 2.5 ng/ml/100 min was observed in 89 p. 100 of patients with atrophic gastritis. An integrated gastrin response smaller than 2.5 ng/ml/100 min was observed in 76 p. 100 of controls. The maximal acid output was smaller than 20 mmol/l in all patients with atrophic gastritis but was greater than this value in all controls. In duodenal ulcer patients, the measured parameters were not significantly different from control values. The measure of the integrated gastrin response which reflects the presence of an antral endocrine hyperactivity may be useful to detect patients with atrophic gastritis, but this test is less sensitive and less specific than the determination of the maximal acid output.

Topics: Duodenal Ulcer; Eating; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Humans; Male; Pentagastrin

A newly synthesized human big gastrin (G34) that was prepared according to the revised structure and that contained less than 3% oxidized methionine residues was compared with synthetic human little gastrin (G17) for acid-stimulating activity and clearance in human subjects. Prolonged infusions of each type of gastrin revealed that the time required to approach stable plasma concentrations was much longer for G34 than for G17. The time course of plasma gastrin concentration could be described by one-compartment models with half-lives of 44 min for G34 and 8 min for G17. After rapid intravenous infusion, G34 produced a much larger total acid response than did an equimolar dose of G17, and the responses were directly proportional to the integrated plasma gastrin increments. During the third hour of prolonged intravenous infusions of G34 and G17, the exogenous dosage of G34 required to produce the same blood concentration of gastrin was only one-fourth that of G17. Equivalent blood concentrations of G34 and G17 were associated with similar rates of acid secretion. These results suggest that G34 is more potent than has been thought, that it has an activity similar to that of G17 and that it must not be ignored in estimating total acid-stimulating activity of circulating gastrins. The measurement of total carboxyl-terminal immunoreactive gastrin can produce a good estimate of total acid-stimulating activity.

Topics: Adult; Aged; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Protein Precursors; Radioimmunoassay

Topics: Duodenal Ulcer; Epinephrine; Gastric Acid; Gastrins; Humans; Pyloric Antrum; Zollinger-Ellison Syndrome

Twenty-six patients were treated for duodenal or recurrent ulcer with selective gastric vagotomy plus precise antrectomy--that is, complete removal of the entire antrum. Sixteen had a gastroduodenal anastomosis and 10 a gastrojejunal anastomosis. Fasting and protein meal-stimulated serum gastrin concentration was measured in 10 patients before antrectomy and in all after the operation. Fasting serum gastrin concentration was reduced and food-stimulated gastrin response abolished irrespective of the type of the anastomosis. It is concluded that a postprandial gastrin rise means retained antral tissue in the gastric remnant and that neither protein nor mechanical stimulation of the passage of food through the duodenum stimulates the duodenal G-cells to gastrin release.

Topics: Adult; Aged; Duodenal Ulcer; Duodenum; Fasting; Female; Gastrins; Humans; Jejunum; Male; Middle Aged; Pyloric Antrum; Recurrence; Vagotomy; Vagotomy, Proximal Gastric

A secretin provocative test was performed in 16 patients with chronic duodenal ulcer and in five patients with the Zollinger-Ellison syndrome. In four chronic duodenal ulcer patients a second secretin test was done during acute iv cimetidine administration. There were only slight variations of gastrin compared with the first test. A third test was done on the same four chronic duodenal ulcer patients after 1 month's po cimetidine treatment (1 g/day); gastrin at 0 time was significantly higher than in the previous two tests (p less than 0.01). Integrated gastrin response after secretin was significantly lower in the third test than in the first (p less than 0.05). In two Zollinger-Ellison syndrome patients treated with 1.0 and 1.4 g/day cimetidine for 3 months, gastrin at 0 time was not markedly increased, whereas compared with the first test gastrin levels were higher at each time after secretin. These data suggest that previous cimetidine treatment does not alter, and may even increase, the diagnostic sensitivity of the secretin test.

Topics: Adolescent; Adult; Chronic Disease; Cimetidine; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastrins; Humans; Pancreatic Function Tests; Pancreatitis; Peptic Ulcer Hemorrhage; Secretin; Stomach Ulcer

The mechanisms by which the potent antiinflammatory agent, mepirizole, causes duodenal ulceration were investigated in the rat. After subcutaneous administration of 200 mg/kg of mepirizole, basal gastric acid secretion remained unchanged for 5 h but duodenal alkaline output, reliably measured, decreased significantly (p less than 0.05) within 2 h. The decrease was maximal (-45%) at 3 h and persisted for a total of 6 h. The duodenal alkaline secretion returned to near normal by 24 h. A dose-response study showed that the threshold ulcerogenic dose of mepirizole (30 mg/kg) did not significantly reduce alkaline secretion, whereas higher doses did. Plasma levels of immunoreactivity of gastrin, pancreatic polypeptide, vasoactive intestinal polypeptide, and secretin were not changed at either 6 or 24 h after oral mepirizole. Vasoactive intestinal peptide levels in the duodenal mucosa were increased by 158% at 24 h after administration. Secretin levels in the duodenal mucosa were decreased by greater than 60% at both 6 and 24 h after drug treatment. Intravenous secretin (1 CU/kg X h) had no effect on duodenal alkaline secretion in either saline- (154 mM NaCl) or mepirizole-treated animals. Exogenous 16,16-dimethyl prostaglandin E2 (10 micrograms/kg X h, i.v.) reversed the action of mepirizole on duodenal alkaline secretion. These findings suggest that mepirizole causes a reduction in duodenal alkaline secretion that can be reversed by administration of an exogenous prostaglandin.

Topics: 16,16-Dimethylprostaglandin E2; Alkalies; Animals; Dose-Response Relationship, Drug; Duodenal Ulcer; Duodenum; Epirizole; Gastric Acid; Gastrins; Injections, Subcutaneous; Male; Pyrazoles; Radioimmunoassay; Rats; Rats, Inbred Strains; Secretin; Time Factors; Vasoactive Intestinal Peptide

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Postoperative Period; Stomach; Vagotomy

In 28 patients with the Zollinger-Ellison syndrome (ZES), 26 studied before and two after tumor excision, and in 26 age-matched control patients with duodenal ulcer (DU), plasma pancreatic polypeptide and serum gastrin concentrations were studied before, during, and after infusion of pure secretin (3 CU/kg/hr). In 21 ZES patients, gastric acid output was simultaneously studied. Fasting pancreatic polypeptide concentrations were over 300 pmol/liter in five of 26 gastrinomas. In DU, secretin caused a nonsignificant increase in plasma pancreatic polypeptide concentration and markedly decreased gastric acid output. In ZES, however, it resulted in a marked increase of both plasma pancreatic polypeptide concentration and gastric acid output. Basal and post secretin pancreatic polypeptide concentrations showed no correlation with gastric acid output, serum gastrin levels, or the age of the subjects, in DU patients as well as in ZES. These concentrations were not different in ZES patients who had a vagotomy compared to nonvagotomized ZES patients. Furthermore, the pancreatic polypeptide response to intravenous secretin was abolished by gastrinoma excision.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreatic Polypeptide; Secretin; Zollinger-Ellison Syndrome

Gastric acid secretion, pepsin secretion, and fasting serum gastrin levels were measured in 23 patients with duodenal ulcer disease, divided into three groups which received either cimetidine 800 mg daily, cimetidine 1600 mg daily, or ranitidine hydrochloride 300 mg daily for eight weeks. Pentagastrin tests were carried out at intervals both before and after treatment. Each dose of cimetidine reduced acid secretion to 42% of control one week after starting therapy. Ranitidine reduced acid secretion to 33% of the pretreatment value. Acid secretion remained suppressed to these levels throughout treatment with each drug. Acid secretion returned to pretreatment levels in all patients one week after treatment and remained normal until the end of the study. Both drugs reduced pepsin, which fell to 64% and 61% (p less than 0.01) after 800 mg and 1600 mg cimetidine respectively and to 65% (p less than 0.005) with ranitidine after one week's treatment. Pepsin secretion remained at this reduced level in both cimetidine groups till the end of treatment. Pepsin levels fell to 50% at two weeks of therapy with ranitidine but stabilised at this level till the end of therapy. Cimetidine withdrawal was followed by a return towards pretreatment levels of pepsin secretion; but secretion remained significantly depressed (p less than 0.05) to the end of the study period. In the ranitidine-treated patients pepsin output returned to normal after drug withdrawal. Fasting gastrin levels rose during treatment with both drugs but failed to reach significant levels. After withdrawal of treatment fasting serum gastrin levels returned to normal in all three groups of patients.

Topics: Anti-Ulcer Agents; Cimetidine; Duodenal Ulcer; Furans; Gastric Acid; Gastrins; Guanidines; Histamine H2 Antagonists; Humans; Pentagastrin; Pepsin A; Ranitidine; Secretory Rate

Topics: Adult; Cimetidine; Diagnosis, Differential; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Humans; Male; Multiple Endocrine Neoplasia; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

This paper reports a personal experience in the management of 45 patients with recurrent ulcer after gastric surgery. Inadequate acid reduction was the major cause of ulcer recurrence and treatment was by further acid reduction. Revisional surgery was performed in 23 patients (including a patient with a gastro-jejuno-colic fistula) with one mortality. Preliminary results of therapy with histamine H2-receptor antagonists have been encouraging and there appears to be a reduced need for re-operation in these patients in recent years. Less common causes of ulcer recurrence include retained suture material (2 cases) and the Zollinger-Ellison syndrome (2 cases). The incidence of post-surgical ulcer recurrence may be reduced by: improved surgical techniques, particularly in the performance of vagotomy, and avoidance of operations without acid reducing procedures e.g., gastro-jejunostomy without vagotomy; wider use of emergency ulcer curative surgery for perforated peptic ulcer. Experience at two local centres has been that this is a safe procedure in selected patients, there being no mortality in 58 cases. Routine screening of peptic ulcer patients for the Zollinger-Ellison Syndrome by measuring the serum gastrin level facilitates early diagnosis of the condition, thus forestalling gastric surgery and the inevitable recurrent ulceration.

Topics: Combined Modality Therapy; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Pentagastrin; Peptic Ulcer; Peptic Ulcer Perforation; Recurrence; Vagotomy; Zollinger-Ellison Syndrome

Previous studies have shown that alkalinizing the stomach with sodium bicarbonate for periods up to 3 h does not cause an increase in serum gastrin concentration. We evaluated the effect of a 5-h period of continuous intragastric alkalinization on serum gastrin concentration in 12 healthy humans and 12 asymptomatic duodenal ulcer patients. On the first day, intragastric pH was maintained between 6.0 and 7.0 for 5 h by infusing 0.3 N sodium bicarbonate into the stomach. On the second day, an identical amount of sodium bicarbonate was infused intravenously while intragastric pH was permitted to remain at its natural level for 5 h. Serum gastrin concentration was also measured in each subject and patient after infusion of a homogenized steak meal. In both healthy subjects and duodenal ulcer patients, mean serum gastrin concentrations were significantly (p less than 0.05) higher after 5 h of intragastric bicarbonate infusion than after 5 h of intravenous bicarbonate infusion during which intragastric pH remained at its natural level. Increases in serum gastrin concentration with alkalinization averaged 23% and 30% of the increases in serum gastrin after a homogenized steak meal in the same subjects and patients, respectively. We conclude that continuous gastric alkalinization for 5 h increases serum gastrin concentrations in humans.

Topics: Bicarbonates; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Sodium Bicarbonate; Time Factors

Topics: Adult; Aldosterone; Carbenoxolone; Duodenal Ulcer; Gastrins; Glycyrrhetinic Acid; Growth Hormone; Humans; Hydrocortisone; Insulin; Male; Metoclopramide; Middle Aged; Parasympatholytics; Prolactin; Stimulation, Chemical

Topics: Adult; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Digestion; Duodenal Ulcer; Female; Gastrins; Growth Hormone; Humans; Insulin; Intestinal Absorption; Malabsorption Syndromes; Male; Middle Aged

Two in vivo methods that permit quantitation of gastric acid secretion immediately after the meal are currently in use: intragastric titration and the serial dilution indicator method. During intragastric titration, intragastric pH is artificially maintained at 5.5 to 7 by the continuous addition of alkali to the gastric contents, while during serial dilution the intragastric pH is permitted to seek its natural pH. This study compared gastric acid secretion and serum gastrin in response to a liquid protein meal measured by both techniques in 10 subjects. Mean (+/- SE) 3-hr acid outputs were almost identical (53.6 +/- 6.0 mmol/3 hr with intragastric titration and 52.0 +/- 8.5 mmol/3 hr with serial dilution indicator). Furthermore, 30 min secretory responses in individual subjects were highly correlated (r = 0.98 +/- 0.01, P less than 0.001). Also, in spite of intragastric pH being less than 1.5 by 90 min after the meal during the serial dilution method, total integrated serum gastrin concentrations after the meal were similar (intragastric titration = 20.6 +/- 7.3 ng min/ml versus serial dilution indicator = 23.5 +/- 9.8 ng min/ml) and individual 30-min gastrins during the two separate tests were highly correlated (r = 0.80 +/- 0.06, P less than 0.01). It is concluded that both meal-stimulated gastric acid secretion and serum gastrin concentrations as measured by intragastric titration and by the serial dilution indicator method produced similar results.

Topics: Dietary Proteins; Duodenal Ulcer; Food; Gastric Acid; Gastric Emptying; Gastrins; Humans; Hydrogen-Ion Concentration; Indicator Dilution Techniques; Male; Methods; Middle Aged; Time Factors

Experimental studies were carried out to investigate the effect of various biliary tract reconstructions upon the secretion of gastric acid and gastrointestinal hormones. Jejunal interposition cholecystoduodenostomy with a short jejunal segment (Group-I), jejunal interposition cholecystoduodenostomy with a long jejunal segment (Group-II), and Roux-en-Y cholecystojejunostomy (Group-III) were constructed in seventeen Heidenhain pouch dogs. Peptic ulcer was only observed in 2 out of 7 dogs of Group-III. Although food-stimulated gastric acid output did not differ significantly in all the groups, the amount of gastric acid reached a peak much later and remained elevated in Group-III compared with that in other groups. The changes in plasma gastrin, gastric inhibitory polypeptide and total glucagon are regarded to be affected by the length of the jejunum excluded from the stream of chyme and the direct contact of the jejunum with bile. It is concluded that the pattern of acid secretion is more important than its volume for the mechanism of peptic ulceration in Roux-en-Y cholecystojejunostomy.

Topics: Animals; Biliary Tract Surgical Procedures; Cholecystectomy; Dogs; Duodenal Ulcer; Duodenum; Gastric Acid; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Jejunum; Secretin

The effects of a stable prostaglandin (PG) E2 analog (15-R-15 methyl PGE2) and aspirin, a potent inhibitor of cyclooxygenase, on modified sham-feeding (MSF)-stimulated gastric secretion and serum gastrin and pancreatic polypeptide (PP) levels were measured in patients with duodenal ulcer. PGE2 analog given orally significantly reduced gastric acid and pepsin secretion and suppressed serum PP but not gastrin responses to MSF. Suppression of PG generation in the gastric mucosa did not influence the secretory or hormonal responses to MSF. This study shows that endogenous PGs are not involved in the control of vagally stimulated gastric secretion, but exogenous PGE2 analog is an effective inhibitor of such secretion and merits clinical evaluation in the treatment of duodenal ulcer.

Topics: Adult; Arbaprostil; Aspirin; Duodenal Ulcer; Gastric Acid; Gastric Juice; Gastrins; Humans; Pepsin A; Prostaglandins E, Synthetic; Vagus Nerve

Interdigestive contractile activity in the gastrointestinal tract was measured in dogs and humans. During the interdigestive state, it was found that in healthy dogs and humans, cyclically-recurring strong contractions occurred in the stomach at approximately 100 min intervals and migrated through the small bowel in a caudal direction. The interdigestive contractions consist of three phases, phase I being quiescent while phases II and III are contractile. Phase II contractions resemble those in the digestive state and therefore mix the contents, and phase III contractions are strong in contractile force and consequently squeeze and expel the contents in a caudal direction. Intraduodenal pH changes were studied together with motor activity and it was found that intraduodenal pH remained at a slightly alkaline level during the interdigestive state in the dog; however, in human studies, it was revealed that intraduodenal pH drops below pH 7.0 only during the phase II period. These characteristic contractile changes in the interdigestive state are controlled at least in part by the cyclic increase in motilin concentration in the plasma, but it is not known what regulates the cyclic release of motilin during the interdigestive state. Feeding promptly eliminates changes in the plasma motilin concentration. It is not known whether other gut hormones are involved in the regulation of these specific motor changes in the interdigestive state. One of the typical disorders in motor activity was found in duodenal ulcer. In duodenal ulcer patients, the most characteristic difference from normal subjects was that the duration of phase II activity was significantly prolonged and intraduodenal pH fluctuated widely and intensely during the period. Hypersecretion of acid is well known to be the specific feature of this disease. However, the present study clearly indicates that spontaneous acid secretion per se or vagally induced acid secretion during phase II disturbs the interdigestive motor cycle and, in consequence, leads to the development of ulcers due to the fact that acid contents alone are continuously mixed in the stomach over the prolonged period of phase II activity. These findings lead us to a better understanding of the true pathogenesis of this disease as well as effective treatment of patients from a radical as well as symptomatic standpoint.

Topics: Adult; Animals; Digestion; Digestive System Physiological Phenomena; Dogs; Duodenal Ulcer; Food; Gastrins; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Motilin; Muscle Contraction; Secretin

There are few detailed studies of patients with pathological hypergastrinaemia of antral origin. We have identified four patients with severe acid hypersecretion associated with peptic ulcer disease and in whom no evidence for gastrinoma or isolated retained antrum could be found. Three of these patients also had hypergastrinaemia. In two patients, one with gastric ulcers and one with duodenal ulcer disease, the hypergastrinaemia appeared to be due to antral gastrin cell hyperfunction and there was also evidence for mild antral gastrin cell hyperplasia. In the other hypergastrinaemic patient, a primary intestinal gastrin cell hyperfunction syndrome was suspected, but a hidden gastrinoma could not be excluded. The remaining patient had nearly fatal hypersecretory ulcer disease and cimetidine failed to control the hypersecretory state. In this patient the hypersecretion responded to a more potent H2 antagonist with resolution of a metabolic encephalopathy. No general pathophysiological mechanism could be identified in these patients or in larger groups of patients with gastric or duodenal ulcer disease.

Topics: Adult; Aged; Duodenal Ulcer; Duodenum; Gastric Acid; Gastrins; Humans; Male; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Zollinger-Ellison Syndrome

During a 3-year period proximal gastric vagotomy without drainage and selective gastric vagotomy with drainage were performed in 61 patients with duodenal ulcer. Of these, 57 patients were followed for 3-6 years. 77% were symptom-free (Visick I); 8,3% were improved but still have periods of dyspepsia (Visick II) and 14% were failures because of recurrent ulcer (Visick III). There were seven duodenal recurrences in the bulb, and one prepyloric recurrence. There were no operative deaths or major complications. The side effects, like diarrhoea and dumping, after proximal gastric vagotomy and selective vagotomy were mild and rare. The majority of our patients gained their ideal body weight within the first six months from surgery. Blood chemistry did not show any deficiency in haemoglobin secondary to vagotomy, but plasma basal level of gastrin was constantly higher after surgery. It is concluded that 3-6 years after proximal gastric vagotomy and selective gastric vagotomy for duodenal ulcer there was a 14% recurrence rate, but the absence of mortality, severe complications or significant side effects seems to be at least as important as the high recurrence rate.

Topics: Adolescent; Adult; Aged; Body Weight; Diarrhea; Drainage; Duodenal Ulcer; Follow-Up Studies; Gastrins; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Recurrence; Retrospective Studies; Vagotomy; Vagotomy, Proximal Gastric

Topics: Animals; Cat Diseases; Cats; Duodenal Ulcer; Female; Gastrins; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Molecular Weight; Radioimmunoassay

The prevalence of gastrinomas and the Zollinger-Ellison syndrome is unknown. In order to examine a high risk group of patients, basal and secretin-provoked plasma gastrin levels were determined in 50 consecutive patients, predominantly from the west of Scotland. All had endoscopically proven recurrent peptic ulceration following duodenal ulcer surgery. This resulted in three cases strongly suspected of having a gastrinoma. Further investigations including exploratory laparotomy were unable to demonstrate a gastrinoma in two, but the evidence suggested an occult tumour in one. In this remaining unoperated patient, the serum gastrin returned to normal. The reference range for both basal and secretin stimulated gastrin response and percentage change has been determined in normal control subjects (n = 10) and in primary ulcer patients (n = 20). It is concluded that in this study, gastrinomas had a less than 2 per cent prevalence in patients presenting with recurrent peptic ulceration. As the diagnosis of a gastrinoma changes the surgical approach, conducting screening tests still seems warranted.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Recurrence; Scotland; Secretin; Zollinger-Ellison Syndrome

A population of 8 children aged 7 to 13 and radiologically and/or endoscopically diagnosed of duodenal ulcer is compared with another made up of 12 normal children of similar ages and weights. In both groups gastric secretion, basal and after pentagastrin stimulation, and serum levels of gastrin and pepsinogen I, basal and after pentagastrin stimulation, and serum levels of gastrin and pepsinogen pepsinogen basal and after pentagastrin stimulation, and serum levels of gastrin and pepsinogen I, basal and after proteic meal, were studied. BAO, MAO and PAO were significantly higher in ulcer patients. Gastrinemia, both basal and stimulated, were rather similar in both groups. Serum pepsinogen I was always higher in ulcer patients in the basal state than in their healthy counterparts (greater than ng/ml vs. 30-50 ng/ml), but was not modified by proteic meal in either group. The fact that all ulcer children had a familial history and a basal pepsinogen I elevated, aside with the secretory response to stimulation, suggests that ulcer can be result either of an increased mass or of a higher sensitivity of gastric parietal cells that could be related to genetic factors.

Topics: Adolescent; Child; Dietary Proteins; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Pentagastrin; Pepsinogens

After a meal the serum concentrations of the N-terminal tridecapeptide-like fragment of gastrin-17, (1-13)G-17, increased markedly in patients with active duodenal ulcer, but less so in healthy subjects. Consequently the synthetic (1-13)G-17 was infused intravenously in doses that resulted in concentrations similar to those measured in duodenal ulcer patients in order to examine whether the N-terminal fragment influences gastric acid secretion. Doses of 125 and 400 pmol (1-13)G-17/kg per h inhibited the meal-stimulated acid secretion by 36% (P less than 0.05) and 66% (P less than 0.05) respectively. The release of endogenous C-terminal gastrin immunoreactivity was not influenced. The infusion of (1-13)G-17 also inhibited the acid response to exogenous gastrin-34, gastrin-17 and Peptavlon, but not to gastrin-4. The results suggest that the N-terminal gastrin-17 fragment--although devoid of the hitherto considered only active site of gastrin--plays a significant role in the regulation of the gastric acid secretion in patients with active duodenal ulcer.

Topics: Adult; Binding Sites; Depression, Chemical; Duodenal Ulcer; Fasting; Female; Food; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptide Fragments

Six cases of duodenal ulcer were studied in male children (mean age 8.8 yrs., range 6-12 yrs., mean weight 29.8 kg). All were submitted to X-ray examination and/or digestive endoscopy. Ten healthy children, matched by weight, age and sex were chosen as controls. All children underwent a standardized protein meal to evaluate serum gastrin and pepsinogen I response and the pentagastrin test for acid secretion. The serum gastrin level was found to be similar in the two groups (normal children and duodenal ulcer) both in the fasting state and after food stimulation, whereas the basal and after-meal serum pepsinogen I values were statistically higher in the duodenal ulcer group (p less than 0.01). The pentagastrin test showed a basal, maximal and peak acid output significantly lower in controls than in the subjects with primary duodenal ulcer. The results confirm that elevated gastric acid response is already present in duodenal ulcer of childhood and seems to be its cause rather than its consequence. Our finding of an already elevated pepsinogen I level, coupled with the already reported family histories of the disease, further support an inherited basis for duodenal ulcer in childhood.

Topics: Child; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Humans; Male; Pentagastrin; Pepsinogens

Sham feeding resulted in a significant increase of gastric acid secretion in 12 male patients with duodenal ulcer. No significant change in serum gastrin concentration was produced by sham feeding. Reproducibility of gastric acid response to sham feeding was very good (r = 0.74). The mean peak 30 min acid output amounted to 9.5 +/- 1.0 mmol/30 min following sham feeding. That was 46.5% of the 30 min peak acid output elicited by pentagastrin infusion administered in a dose of 1.5 micrograms/kg/h. Cimetidine in a dose of 2 mg/kg/h almost completely reduced (by 85%) the gastric acid secretion induced by sham feeding. Cimetidine did not cause any change in serum gastrin concentration during and after sham feeding.

Topics: Adult; Cimetidine; Duodenal Ulcer; Feeding Behavior; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Time Factors

The metabolism of the NH2-terminal tridecapeptide fragment of gastrin-17 (1-13)G-17) was examined in normal subjects and duodenal ulcer patients. A dose of 65 pmol synthetic human (1-13)G-17/kg/h was infused intravenously for 90 min. After cessation of infusion the disappearance curve was similar in the two groups. The mean half-life, volume of distribution, and clearance rate were, for normal and duodenal ulcer subjects, 6.3 and 6.3 min, 100 and 93 ml/kg, and 11.0 and 10.2 ml/kg/h, respectively. The gastric acidity decreased during the infusion in duodenal ulcer patients (54 +/- 11 to 40 +/- 10 meq/l (p less than 0.02] but not in normal subjects. The results suggest that the increased serum concentrations of the NH2-terminal fragment of gastrin-17 in duodenal ulcer patients are not caused by a decreased metabolism of (1-13)G-17. Moreover, the data show that (1-13)G-17 reduces gastric acid secretion.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Peptide Fragments

The concentration of the NH2-terminal fragment of gastrin-17 in serum was determined by radioimmunochemistry. Two antisera were used, one specific for the COOH-terminus and the other for the NH2-terminus of gastrin-17. The NH2-terminal gastrin-17 immunoreactivity in unfractionated serum correlated well with the amount of fragment found after gel filtration of the same sera (p less than 0.001). In healthy subjects (no. = 100), the NH2- and COOH-terminal gastrin immunoreactivity was 8 +/- 1 and 20 +/- 1 pmol/l (mean +/- SEM), respectively. In patients with acute duodenal ulcer (no. = 30) and acute gastritis (no. = 10) the NH2-terminal immunoreactivity was fourfold increased compared with in healthy subjects (p less than 0.001), whereas the COOH-terminal was identical, the NH2- and COOH-terminal concentrations being 33 +/- 7 and 22 +/- 2 pmol/l in duodenal ulcer and 35 +/- 6 and 21 +/- 1 pmol/l in acute gastritis. Other groups of patients had NH2- and COOH-terminal gastrin concentrations in serum similar to those measured in healthy subjects. The results suggest that gastrin cells process gastrin-17 abnormally during the acute phase of duodenal ulcer and gastritis.

Topics: Acute Disease; Adolescent; Adult; Aged; Amino Acid Sequence; Chromatography, Gel; Duodenal Ulcer; Female; Gastrins; Gastritis; Humans; Male; Middle Aged; Peptide Fragments; Radioimmunoassay

The effects of carprofen (Roche), a nonsteroid antiinflammatory agent, on gastric secretion, serum gastrin level, electropotential difference (PD), gastric microbleeding, DNA loss, and the generation of mucosal prostaglandins (PGs) were examined in 20 duodenal ulcer patients with active ulcer (15 patients) or in remission (5 patients). Carprofen administered for one-week period at a therapeutic dose (300 mg/day) was well tolerated by all ulcer patients and no adverse effects were observed during or after treatment. Endoscopy performed after carprofen treatment showed complete ulcer healing in 9 out of 15 patients and no exacerbations were observed in the rest of patients. No significant changes were observed in basal or pentagastrin-induced secretion, PD, gastric microbleeding and DNA loss. The generation of PGE2, 6-keto-PGF1 alpha and thromboxane B2 was not affected by the treatment with carprofen. This study indicates that carprofen shows excellent gastrointestinal tolerance in ulcer patients, and it might be useful in the treatment of arthritic patients with peptic ulcer disease.

Topics: Action Potentials; Adult; Anti-Inflammatory Agents; Carbazoles; DNA; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Peptic Ulcer Hemorrhage; Prostaglandins

We studied effects of graded concentrations of intragastric calcium on acid secretion, residual gastric volume, and serum gastrin and calcium levels. Intragastric titration was performed with solutions of isotonic mannitol or mannitol plus 2.5, 6, 16, 39, and 97 mM CaCl(2) in 10 normal and eight duodenal ulcer subjects. Acid secretion was significantly increased above control values by the two highest CaCl2 concentrations in normal subjects and by the three highest CaCl2 concentrations in ulcer subjects. Highest observed acid output to any concentration of CaCl2 was 55% of peak acid output to pentagastrin in normal subjects and 75% in ulcer subjects. Intragastric calcium also released gastrin; correlation between acid secretion and circulating gastrin was weak (r = 0.43, P less than 0.05). Serum calcium was slightly increased but did not correlate with acid secretion. Residual intragastric volume after both control and CaCl2 solutions was much less in ulcer than in normal subjects; calcium did not alter residual volumes.

Topics: Adult; Aged; Animals; Calcium; Duodenal Ulcer; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Male; Middle Aged; Milk; Pentagastrin

Serum gastrin was studied before meals in 71 patients with duodenal ulcer, treated with various doses of simetidin and pyrensepin. Gastrin level was elevated after a treatment with 1 g simetidin daily and 125 mg pyrensepin, and remained unchanged with pyrensepin treatment (50 and 100 mg daily). A tendency to decreased gastrin level was observed after the treatment with simetidin 400 mg daily. Under those circumstances the attempt at duodenal ulcer treatment with lower simetidin doses, than the usual, is justified.

Topics: Adult; Anti-Ulcer Agents; Benzodiazepinones; Cimetidine; Drug Evaluation; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Pirenzepine; Time Factors; Wound Healing

Topics: Adult; Animals; Diet; Duodenal Ulcer; Gastrins; Humans; India; Male; Milk; Oryza

Plasma adrenaline, plasma noradrenaline and serum gastrin concentrations were measured before and after sham feeding in eight patients with duodenal ulcer and in four normal subjects. No significant change in the concentrations was observed after sham feeding. In three patients with duodenal ulcer an insulin test resulted in a 25-fold rise in plasma adrenaline. The ulcer patients showed significantly higher levels of plasma adrenaline and plasma noradrenaline than the normal subjects both before and after sham feeding, and this difference was probably not caused only by age difference in the two groups. It is concluded that sympathetic nervous activity and serum gastrin concentrations are not influenced by sham feeding in contrast to the influence of insulin hypoglycemia.

Topics: Adult; Blood Glucose; Catecholamines; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Male; Middle Aged

The secretory and motor function of the stomach and gastrin incretion were investigated in 68 patients with peptic ulcer of variable localization. In addition, a retrospective analysis of the course of prepyloric gastric ulcer and Billroth I resection was performed in 62 patients. Results show that gastric acid secretion and velocity of gastric emptying diminish significantly with increasing height of the localization of the ulcer. Prepyloric gastric ulcer cannot be likened to the duodenal ulcer. Moreover, experimental and clinical results suggest that prepyloric ulcer represents a disease entity per se requiring separate therapeutic approaches (gastric resection following Billroth I).

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrectomy; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer

The use of secretin in the biochemical and roentgenologic diagnoses of a duodenal gastrinoma has been described. Preoperatively, the secretin test indicated that a gastrinoma and not a retained antrum was the cause of hypergastrinemia in a patient who had previously undergone Billroth II gastrectomy. Intravenous infusion of secretin during selective angiography resulted in greatly enhanced visualization of the tumor which allowed it to be localized to the duodenal stump. Several months postoperatively, the secretin test result had become negative, which presumably suggested that the tumor had been excised completely. Our experience has revealed that intravenous secretin might improve the diagnostic usefulness of selective angiography.

Topics: Aged; Duodenal Ulcer; Gastrins; Humans; Male; Radiography; Secretin; Zollinger-Ellison Syndrome

Between February 1972 and December 1976 100 proximal gastric vagotomies (PGV) were performed on duodenal ulcer patients after failure of conservative treatment. The diagnosis was verified by preoperative barium meal and endoscopy and by peroperative examination. There was no operative mortality. Mean duration of postoperative hospital stay was 9.6 days. The percentual distribution in Visick-grading at the 1-year follow-up was 90% in class I + II, and 10% in class III + IV. The corresponding figures at the 5-year follow-up were 82% and 18%. The mean postoperative basal acid output did not change from one to five years. The reduction in pentagastrin stimulated acid output was unchanged at the 1- and 5-year follow-up. Neither did the mean acid output after insulin stimulation change between one and five years postoperatively. The mean concentration of serum gastrin was raised at one year but decreased to normal at the 5-year follow-up. Ten patients (10%) had ulcer recurrence during follow-up. Seven of these were successfully treated by gastric resection and three by antacids and cimetidine.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Prognosis; Recurrence; Vagotomy; Vagotomy, Proximal Gastric

Our aim was to develop proximal gastric vagotomy with mucosal antrectomy as an operative approach to duodenal ulcer. We performed mucosal antrectomy in four dogs by excising the antral mucosa via a circular corporal myotomy, removing a circumferential band of corporal seromuscularis, anastomosing the corporal and pyloric mucosas endoantrally, and reapproximating the corporal and antral seromuscularis. Gastric emptying and serum gastrin were assessed before and 4 weeks after operation. A second operation, proximal gastric vagotomy, was then done, and the tests were repeated 4 weeks later. The concentration of gastrin in the serum during fasting was lower after mucosal antrectomy than before operation, as was the postprandial concentration; the values remained low after proximal gastric vagotomy. Gastric emptying of liquids and indigestible solids was unaltered by mucosal antrectomy or mucosal antrectomy plus proximal gastric vagotomy. The emptying of digestible solids was slowed somewhat by mucosal antrectomy to 75% of the control rate, but no further change was found after proximal gastric vagotomy. We concluded that mucosal antrectomy eliminated the gastrin-producing antral mucosa and, in combination with proximal gastric vagotomy, did not greatly alter gastric emptying of liquids or solids. The combined operation might have a role in the surgical treatment of duodenal ulcer.

Topics: Animals; Dogs; Duodenal Ulcer; Female; Gastric Emptying; Gastric Mucosa; Gastrins; Methods; Pyloric Antrum; Vagotomy; Vagotomy, Proximal Gastric

The mucosa of the proximal stomach contains a powerful inhibitor of acid secretion and gastrin release. The release of this inhibitor is dependent on intact vagal innervation of the proximal stomach. Thus, proximal gastric vagotomy interferes with the release of the inhibitor. After proximal gastric vagotomy for peptic ulcer, recurrence rates increase over time. In addition, there is some recovery of acid secretion. Although nerve regeneration or sprouting has been suggested as the possible explanation for these events, we propose that interference with the inhibitory mechanism of the proximal stomach may be another possible explanation for the increasing ulcer recurrence rates after proximal gastric vagotomy. At present, this is only a hypothesis and is suggested only by indirect evidence. Direct testing of the hypothesis will require complete purification of the inhibitor and the development of a specific radioimmunoassay.

Topics: Animals; Dogs; Duodenal Ulcer; Gastric Acid; Gastric Fundus; Gastrins; Humans; Peptic Ulcer; Recurrence; Vagotomy; Vagotomy, Proximal Gastric

The number of G- and D-cells per area and the ratio of G/D-cells were investigated in biopsy specimens of the pyloric antrum from normochlorhydric subjects without peptic ulcer, from patients with duodenal ulcer, gastrinoma, pernicious anaemia, and after selective proximal vagotomy. Compared with normochlorhydric subjects antral G-cell density was significantly raised in pernicious anaemia, unchanged in duodenal ulcer, and diminished in gastrinoma patients. After vagotomy G-cell density was found to be raised if compared with patients with duodenal ulcer. D-cell density was significantly increased in gastrinoma patients, unchanged in duodenal ulcer, and diminished in pernicious anaemia and after vagotomy. The G/D-cell ratio was increased in pernicious anaemia and after vagotomy, unchanged in duodenal ulcer, and decreased in gastrinoma patients. It is concluded that the antral pH governs the ratio of G- and D-cells. Therefore, the G/D cell ratio increases in states of reduced acid secretion and decreases in massive hyperchlorhydria. Hypergastrinaemia as such does not affect the G/D-cell ratio.

Topics: Adult; Anemia, Pernicious; Cell Count; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Somatostatin

The technique and validation of the cytochemical section bioassay for gastrin-like activity are described. This assay utilises the measurement of hormone-induced changes of carbonic anhydrase activity in guinea-pig gastric parietal cells. The clinical use of the assay as identified elevated levels of fasting gastrin-like biological activity in the plasma of patients with duodenal ulcer and has also demonstrated discrepancies between radioimmunoreactive gastrin levels, biological activity, and the clinical presentation of peptic ulcer disease.

Topics: Adult; Animals; Aprotinin; Duodenal Ulcer; Fasting; Female; Gastric Mucosa; Gastrins; Guinea Pigs; Histocytochemistry; Humans; Male; Middle Aged; Radioimmunoassay; Zollinger-Ellison Syndrome

The effect of highly selective vagotomy on pancreatic exocrine function and the release of gastrin and cholecystokinin was studied in 10 patients with endoscopically-proven duodenal ulceration. Cholecystokinin and gastrin concentrations in serum both increased significantly after highly selective vagotomy. Amylase concentration in the duodenal aspirate increased significantly after vagotomy, but trypsin concentration remained unchanged. The expected reductions in gastric acid secretion were noted. Thus highly selective vagotomy reduces acid secretion effectively in patients with duodenal ulcer without impairing the exocrine function of the pancreas.

Topics: Amylases; Cholecystokinin; Duodenal Ulcer; Duodenum; Gastric Acid; Gastrins; Humans; Intestinal Secretions; Pancreas; Postoperative Period; Trypsin; Vagotomy; Vagotomy, Proximal Gastric

Topics: Acupuncture Therapy; Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Adrenocorticotropic Hormone; Chronic Disease; Dietary Proteins; Duodenal Ulcer; Fasting; Female; Gastrins; Gastritis; Humans; Insulin; Male; Middle Aged; Time Factors

Topics: Cimetidine; Drug Administration Schedule; Duodenal Ulcer; Gastric Acid; Gastrins; Guanidines; Humans

Topics: Adult; Deoxyglucose; Duodenal Ulcer; Gastric Acid; Gastric Acidity Determination; Gastrins; Growth Hormone; Histamine; Humans; Insulin; Male; Middle Aged; Stimulation, Chemical

Results of this study showed that in a considerable number of patients with duodenal ulcer a globulin of the IgG class was responsible for the enhancement of HCl secretion. This secretagogue globulin appeared to combine directly with the H2 receptors of the parietal cells thereby increasing hydrochloric acid output without the formation of antigen-antibody complex.

Topics: Anemia, Pernicious; Animals; Cimetidine; Duodenal Ulcer; Fluorescent Antibody Technique; Gastric Acid; Gastrins; Humans; Hydrochloric Acid; Immunoglobulin G; Immunoglobulins; Rats; Rosette Formation; Secretory Rate; Time Factors

Topics: Anti-Ulcer Agents; Duodenal Ulcer; Gastric Acid; Gastric Fundus; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Neurosecretory Systems; Pepsin A; Pyloric Antrum; Vagotomy, Proximal Gastric; Vagus Nerve

A one-hour infusion of 0.25 micrograms/kg urogastrone administered to seven patients with duodenal ulceration resulted in significant reduction of basal acid secretion (p less than 0.05) but was without significant effect on basal pepsin and intrinsic factor secretion or on serum gastrin concentration. In another group of five patients with duodenal ulceration a one-hour infusion of urogastrone was given on five successive days. On day 1 and 5 urogastrone was administered after establishing a plateau response to intravenous pentagastrin 1.2 micrograms/kg/h. A mean reduction of 65% in acid output during the urogastrtone infusion was seen on day 1 and this was maintained during the next hour. On day 5 the pentagastrin-stimulated acid output was less than on day 1 and a further significant decrease was noted after urogastrone. Pepsin and intrinsic factor output were also significantly inhibited. There was no change in fasting serum gastrin or urogastrone concentration.

Topics: Adult; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Juice; Gastrins; Humans; Intrinsic Factor; Male; Middle Aged; Pentagastrin; Pepsin A; Secretory Rate; Time Factors

The role of gastrin as a cause of duodenal ulceration has been generally overestimated. The serum gastrin level cannot be used as a criterion for choosing either partial gastrectomy or non-resecting surgery. In the postoperative course the stimulated serum gastrin release differs significantly after selective proximal vagotomy plus pyloroplasty and without pyloroplasty. This fact demonstrates the influence of pyloroplasty on the serum gastrin concentration. In case of duodenal ulcer the stimulated serum gastrin test presents a reliable method to control the results obtained after performing a highly selective vagotomy. Compared with the Hollander-test it is without any complication however more efforts are required.

Topics: Adult; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Insulin; Male; Pentagastrin; Pyloric Antrum; Vagotomy; Vagotomy, Proximal Gastric

Gastric emptying was delayed preoperatively in 9 of 19 patients with duodenal ulcer disease, but all 9 patients with evidence of retention by scan were asymptomatic; gastric emptying was normal in the remaining 10 patients. A significant delay in gastric emptying was documented by scan in 17 of 19 patients immediately after parietal cell vagotomy (despite the absence of symptoms of gastric retention). Delayed emptying was demonstrated in three patients who were restudied more than 1 year after parietal cell vagotomy; again these patients had no symptoms of gastric retention at any time. A sustained reduction in basal and stimulated acid secretion in both the early and late postoperative period was documented in all 19 patients, and serum gastrin levels also remained low. This absence of acid or gastrin stimulation is corroborated by the fact that there was no recurrence of ulcers in these patients during a follow-up period of up to 37 months.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Emptying; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Postoperative Complications; Vagotomy; Vagotomy, Proximal Gastric

In a small percentage of patients with ulcer disease, a gastrinoma may be ultimately discovered. In most institutions, a fasting serum gastrin determination and gastric analysis are as first-line tests to identify this subgroup of patients with ulcer disease. The blood test is relatively inexpensive and well accepted by patients. Gastric analysis is uncomfortable and required a well-equipped facility staffed by skilled personnel. A prospective study designed to assess the diagnostic usefulness of these tests and, particularly, whether combining both tests adds to the individual value of each, revealed that gastric analysis does not improve the diagnostic ability of the fasting serum gastrin test. Therefore, gastric analysis probably is not indicated for determining whether a patient with active ulcer disease has a gastrinoma. The fasting serum gastrin test will suffice, and abnormal values on this test should be verified by the use of other tests such as responses to gastrin provocative tests.

Topics: Adolescent; Adult; Aged; Child; Diagnosis, Differential; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Cimetidine; Diagnosis, Differential; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Humans; Prospective Studies; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged

The course of gastric acid secretion and serum gastrin level before and after operation was studied in 41 patients suffering from a gastroscopically determined ulcer disease. In 15 patients suffering from duodenal ulcer, a highly selective vagotomy without pyloroplasty was performed and in 26 patients suffering from peptic ulcer (duodenal or gastric ulcer) a partial gastrectomy (Billroth I). After a highly selective vagotomy without pyloroplasty a reduction in the secretory response to pentagastrin and a significant rise of the basic and postprandial gastrin concentration could be observed. Both methods are suitable to determine the completeness of vagotomy. The estimation of the course of serum gastrin level after vagotomy only reveals a temporary disorder of the antrum-pylorus mechanism. In our opinion a pyloroplasty is not necessary.

Topics: Adult; Duodenal Ulcer; Gastrectomy; Gastric Acid; Gastrins; Humans; Middle Aged; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Vagotomy; Vagotomy, Proximal Gastric

Topics: Chromatography, Affinity; Chromatography, Gel; Duodenal Ulcer; Duodenum; Gastrectomy; Gastrins; Humans; Protein Precursors; Pyloric Antrum; Radioimmunoassay

In order to explore secretory mechanisms in peptic ulcer, the plasma secretin response to an intraduodenal load of gastric acid stimulated with tetragastrin was studied in 10 patients with duodenal ulcer, nine with gastric ulcer, and five young healthy volunteers. After the injection of tetragastrin plasma secretin level was significantly increased in all subjects. The integrated incremental secretin output significantly correlated with the incremental acid output in the duodenal ulcer group as well as the gastric ulcer group. THere was no significant difference in the integrated incremental secretin output among the three groups. However, the integrated incremental secretin output per unit amount of gastric acid loaded in the duodenum was significantly lower in the duodenal ulcer group than in the other two groups. These results suggest that in patients with duodenal ulcer the secretin release in response to an intraduodenal load of endogenous acid is impaired.

Topics: Adult; Duodenal Ulcer; Duodenum; Female; Gastric Acid; Gastrins; Humans; Hydrochloric Acid; Male; Middle Aged; Peptic Ulcer; Secretin; Stomach Ulcer; Tetragastrin; Time Factors

Responses of serum gastrin to both intravenous infusion of secretin (GIH secretin 3 CU/kg/hr) and intravenous bolus injection (GIH secretin 1 CU/kg) were studied in 2 Zollinger-Ellison syndrome (ZE) patients and 27 duodenal ulcer (DU) patients. In all of the DU patients, the stage of the ulcer was determined endoscopically, prior to testing, as either active or healed. We found that the responses of serum gastrin to secretin were closely related to the stage of the duodenal ulcer; serum gastrin increased in the active stage and decreased in the healed stage. In patients with active duodenal ulcer, a false positive (ZE-like) response to exogenous secretin was observed. Comparing the results of intravenous infusion and bolus administration of secretin in terms of maximal percent change of serum gastrin, there was no significant difference between the two methods, confirming the works reported by others.

Topics: Adult; Diagnosis, Differential; Duodenal Ulcer; False Positive Reactions; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

The gastric anatomic-functional behaviour (gastric acid secretion, gastrinemia parietal cell mass, histological pattern of the fundic mucosa) was evaluated in 50 duodenal ulcer patients in the active stage of the disease. After 28 days of treatment with cimetidine (1 g/day), the 42 healed patients stopped therapy completely for three months. At the end of the follow-up the anatomic-functional behaviour was monitored and compared with the initial data in the 24 subjects who were still symptomless, as well as in the 18 patients whose duodenal ulcer relapsed. The analysis of the data obtained demonstrated that gastric acid secretion, gastrinemia and morphology of the fundic mucosa do not vary with the different activity phase of duodenal ulcer; therefore additional factors, and in particular alterations of mucosa resistance, are presumed to be responsible for the development of ulcerous lesions. Moreover, a comparison between the initial data of patients with ulcer healing after cimetidine therapy, and of those with unhealed ulcer, failed to reveal any significant differences, thus denying a prognostic value of acid secretion tests in duodenal ulcer disease.

Topics: Adult; Cimetidine; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Prognosis

A study was made of the effect of a synthetic enkephalin analog and cimetidinee on experimental duodenal ulcer in rats induced by cysteamine administration. The ulcers were demonstrated to heal within 4 weeks. It was noted that ulcer occurrence was preceded by the increased serum gastrin level. Administration to rats of the enkephalin analog accelerated ulcer healing to a greater extent than that of cimetidin. It is suggested that one of the mechanisms of enkephalin analog protective action might involve the prevention of the gastrin increased level.

Topics: Animals; Cimetidine; Cysteamine; Drug Evaluation, Preclinical; Duodenal Ulcer; Endorphins; Enkephalins; Gastrins; Guanidines; Male; Rats; Rats, Inbred Strains; Time Factors

In order to evaluate whether prepyloric ulcer (PPU) could be classified as an intermediate ulcer type between duodenal ulcer (DU) and gastric ulcer (GU), fasting serum gastrin as well as basal and pentagastrin-stimulated acid secretion were studied. The fasting serum gastrin values in the three groups were not significantly different. Patients with PPU and DU showed a higher basal acid output compared to GU patients. The basal acid output in DU patients increased in the last two periods before stimulation, and in the last basal period it was significantly higher compared to PPU patients. Patients with GU showed the lowest basal and stimulated acid output. However, the higher stimulated acid output in DU patients was insignificantly different from that of PPU patients. The results indicate that basal and stimulated gastric acid secretion values in PPU patients are closer to those of DU patients than of GU patients. Furthermore, it is concluded that PPU is a homogeneous ulcer type without secretory overlap with the GU group.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Stomach Ulcer

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

Clinical and laboratory results are presented of 229 patients treated by highly selective vagotomy for duodenal ulcer in a non-university teaching hospital. Sixty-two per cent of the operations were performed by residents as part of their training. After 1-8 years follow-up (97 per cent complete) there were 22 recurrences (9.6 per cent). The residents had fewer recurrences than the consultants, but their patients follow-up was shorter. The usual Visick grading is presented (1, 2: 83.5 per cent; 3, 4: 16.5 per cent) as well as an additional way of grading described by Visick in 1948 which suggests that 4 per cent appear to be permanent failures. Mortality rate was 0.4 per cent, complications rate was low and side effects were in general of minor importance. Laboratory results are presented showing that the basal acid output (BAO) was reduced permanently by 65 per cent, and the PAO by 50 per cent. In patients with recurrences BAO was not reduced and the PAO was less reduced than in the non-recurrence group. Metabolic parameters did not deteriorate. Basal serum gastrin rose after operation while serum vitamin B12 remained constant with a minimal tendency to decrease.

Topics: Adolescent; Adult; Aged; Consultants; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Internship and Residency; Male; Middle Aged; Postoperative Complications; Recurrence; Reoperation; Time Factors; Vagotomy; Vagotomy, Proximal Gastric

Topics: ABO Blood-Group System; Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Seasons

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Secretin; Stomach Ulcer

A series of duodenal ulcer patients was studied to determine the relationship of the integrated postprandial gastrin response with the maximal acid secretory capacity, the ABO blood groups, age of onset of ulcer dyspepsia, and the family history of ulcer dyspepsia of the patients. It was found that: 1. The A, B, AB duodenal ulcer patients had a significantly higher maximal acid gastric secretory capacity (P less than 0.001), significantly earlier age of onset of ulcer dyspepsia (P less than 0.001) and significantly stronger family history of dyspepsia (P less than 0.05) than those patients with O blood group. 2. The integrated gastrin response was significantly higher in "hipersecreting" duodenal ulcer patients (secreted more than 25 mMol/h in response to histamine) than in "normosecreting" duodenal ulcer patients (secreted less than 25 mMol/h) (P less than 0.001) but the values for the latter were not different from normal subjects. 3. There was not statistical significant difference between the mean values of the basal serum gastrim levels of normosecreting duodenal ulcer patients, the hypersecreting duodenal ulcer patients and the normal subjects. 4. A significant positive correlation exists between the maximal acid output and integrated postprandial gastrin response in duodenal ulcer patients. (P less than 0.001). This correlation was negative in the normal subjects (P less than 0.01). 5. This finding supports the existence of a positive relationship between the functioning parietal cell and gastrin cell masses.

Topics: ABO Blood-Group System; Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum

In 19 DU-patients and in 15 control subjects acid secretion tests were performed by continuous aspiration or by intragastric titration. Pentagastrin (6 micrograms/kg subcutaneously) or a 20% peptone solution (intragastric instillation) were used for stimulation. In 10 control subjects pentagastrin stimulated acid secretion was within the normal range, hypersecretion (greater than 32 mmol/h) was found in the other 5. 14 DU-patients showed hypersecretion, 5 had normal acid secretion. In contrast to these findings intragastric peptone stimulation caused a very uniform acid secretion within each group. Based on these results ulcer patients and healthy controls could be discriminated more exactly. Acid secretion and serum gastrin concentration were significantly higher in DU patients than in controls. There was a significant correlation between maximal gastrin concentrations and peak acid output after peptone stimulation.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Pentagastrin; Peptones; Solutions

Changes in plasma concentrations of adrenaline, noradrenaline, dopamine and gastrin in response to a standard meal were studied in 6 normal volunteers and 8 patients with chronic duodenal ulcer (DU) disease. Before the meal plasma gastrin and noradrenaline, but not adrenaline or dopamine, were higher in DU patients than in the controls. Food induced significant increments in plasma gastrin and noradrenaline concentration in both groups, whereas plasma adrenaline and dopamine levels remained unchanged. Plasma gastrin and noradrenaline concentrations were higher in DU patients than in the normal controls both during and after the meal. The results do not support the hypothesis that adrenaline is involved in the pathogenesis of duodenal ulcer disease, whereas the role of the increased plasma noradrenaline concentrations in this disease remains unclear.

Topics: Adult; Aged; Catecholamines; Dopamine; Duodenal Ulcer; Epinephrine; Female; Food; Gastrins; Humans; Male; Middle Aged; Norepinephrine

Morphometric estimation of the antral G-cells, radioimmunoassay estimation of the antral tissue gastrin, estimation of the antral mucosal volume and gastric acid secretion have been carried out on 10 duodenal ulcer patients. The total antral tissue gastrin varied from 52.4 to 245.1 micrograms and the mean G-cell gastrin from 0.5 to 1.8 pg. No constant relationship was found between G-cell densities and antral gastrin concentration, suggesting that no constant relationship exists between G-cell numbers and G-cell function. Furthermore, no constant relationship was observed between total antral gastrin and acid secretion.

Topics: Adult; Cell Count; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum

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.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Vagotomy; Vagotomy, Proximal Gastric

Duodenal ulcer can be induced in rats by a single dose of cysteamine. The ulcer formation is accompanied by acid hypersecretion and elevated serum gastrin levels. This study was performed to elucidate the mechanisms of gastrin release after an ulcerogenic dose of cysteamine. Cysteamine induced a rise in serum gastrin from 29 +/- 5 pg/ml to a maximum of 203 +/- 62 pg/ml after 3 h in unoperated rats, whereas no rise was seen in vagotomized or antrectomized rats. The beta-adrenergic blocking agent propranolol strongly inhibited cysteamine-induced gastrin release, whereas atropine dependent on an intact vagus and may be mediated by beta-adrenergic receptors.

Topics: Animals; Atropine; Cysteamine; Duodenal Ulcer; Female; Gastrins; Propranolol; Rats; Rats, Inbred Strains

Intravenous infusion of bombesin (0.9 micrograms/kg/hour) caused a significant increase in gastric acid secretion and serum gastrin concentration in 8 duodenal ulcer patients. Intravenous infusion of calcitonin (2 MRCU/kg/hour) produced a significant decrease in gastric acid output and in integrated gastrin output produced by bombesin infusion (0.9 micrograms/kg/hour) in the same 8 patients with duodenal ulcer. Percentage of inhibition was 49.7 and 40.8, respectively. Simultaneous infusion of calcitonin and bombesin caused no significant difference in serum calcium concentration. It is suggested that the inhibitory effect of calcitonin on acid secretion elicited by bombesin is produced, at least in part, by a fall in serum gastrin caused by bombesin. In addition, calcitonin might directly inhibit the parietal cells by releasing endogenous gastric somatostatin.

Topics: Adult; Bombesin; Calcitonin; Calcium; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptides; Time Factors

In 30 healthy subjects distension of the antrum by a 150-cm3 balloon reduced the acid and volume responses to submaximal stimulation achieved by a continuous intravenous infusion of pentagastrin. The inhibition persisted during perfusion of the stomach with alkaline buffer. The plasma somatostatin concentration did not increase during distension and no somatostatin was detected in the gastric contents. Balloon distension of the antrum during laparotomy did not affect the concentration of somatostatin and gastrin in portal blood in patients with gallbladder disease or duodenal ulcer. The results confirm that antral distension stimulates acid secretion in duodenal ulcer patients without involvement of the gastrin mechanism. Moreover, the inhibition of acid secretion by antral distension in healthy subjects is independent of luminal pH and does not appear to be mediated by somatostatin.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Pentagastrin; Pyloric Antrum; Somatostatin

Glucagon provocation test was performed in the patients with hypergastrinemia and hyperchlorhydria to investigate its diagnostic value. A paradoxical response of plasma gastrin level in the patients with the Zollinger-Ellison syndrome and a marked decrease of plasma gastrin level in the patients with gastric ulcer, duodenal ulcer, excluded gastric antrum, multiple endocrine adenomatosis, pernicious anemia and chronic renal failure were demonstrated by glucagon infusion. Glucagon provocation test, therefore, was considered to be of great value in the diagnosis of the Zollinger-Ellison syndrome, particularly, in the case of an excluded gastric antrum in which secretin provocation test caused the false positive result because of a marked increase of pancreatic secretion. Glucagon provocation test in combination with secretin provocation test, therefore, is at present the most preferable diagnostic procedure for detecting the Zollinger-Ellison syndrome.U

Topics: Adult; Diagnosis, Differential; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Glucagon; Humans; Kidney Failure, Chronic; Middle Aged; Multiple Endocrine Neoplasia; Pyloric Antrum; Secretin; Stomach Ulcer; Zollinger-Ellison Syndrome

It is now evident that hypersecretion of gastric hydrochloric acid is an important pathogenetic element among a variety of heterogeneous factors responsible for the production of common duodenal ulcer. Hypersecretion of gastric acid due to usually strikingly increased circulating levels of gastrin released from gastrinoma tissue is characteristics of patients with to Zollinger-Ellison Syndrome. In contrast, fasting serum gastrin levels are normal in patients with common duodenal ulcer. The polypeptide hormone, gastrin does, however, appear to play subtle and multiple roles in enhancement of gastric acid secretion in duodenal ulcer. Recent evidence suggests that abnormalities in gastrin release and action may be influenced by participation of somatostatin. The hypothesis is proposed for consideration and for further investigation that the multiple subtle abnormalities in gastrin release and parietal cell sensitivity to gastrin may be due to disturbances in the actions or concentrations of locally acting polypeptides, substances which are capable of suppressing gastrin release and its effects (somatostatin), or alternatively, are capable of stimulating release of gastrin into the circulation (bombesin).

Topics: Bombesin; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Somatostatin; Zollinger-Ellison Syndrome

As an attempt to approach the pathogenesis of peptic ulcer disease, antral gastrin and somatostatin concentrations were studied in normal subjects, patients with duodenal ulcer and gastric ulcer. In the patients with peptic ulcer, antral somatostatin concentrations were significantly lower than those in normal subjects. In non-ulcer subjects, including normal subjects and patients with atrophic gastritis, antral somatostatin concentrations were correlated inversely with the degree of antral gastritis, while in the patients with peptic ulcer, especially in duodenal ulcer, they were low, irrespective of histological picture of antral mucosa. In the patients with duodenal ulcer, low antral somatostatin concentrations with high antral gastrin/somatostatin ratio may cause increased serum gastrin levels and increased gastric acid secretion. From the above findings, it has been concluded that low antral somatostatin levels may be related to the pathogenesis of duodenal ulcer disease.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Middle Aged; Pyloric Antrum; Somatostatin; Stomach Ulcer

Topics: Adolescent; Adult; Aged; C-Peptide; Cyclic AMP; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Glucagon; Humans; Insulin; Male; Middle Aged; Pancreatic Hormones; Stomach Ulcer

Topics: Drug Tolerance; Duodenal Ulcer; Gastrins; Glutamine; Humans; Patient Compliance; Proglumide; Receptors, Cell Surface; Stomach Ulcer

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Histological Techniques; Humans; Reference Values

Gastric acid and serum gastrin, pancreatic polypeptide, and insulin responses to cephalic vagal stimulation were studied in eight patients with duodenal ulcer using modified sham-feeding for periods varying from four to 30 minutes. In addition, the maximal acid response to sham-feeding was compared with that induced by pentagastrin in 10 healthy subjects and 14 patients with duodenal ulcer. It was found that the gastric acid response to modified sham-feeding reached the maximal value after 15 minutes of sham-feeding and amounted to about 68% of the pentagastrin maximum. The serum pancreatic polypeptide response was also increased after modified sham-feeding and depended on the duration of this procedure, whereas gastrin and insulin responses were not significantly affected by modified sham-feeding. When the peak acid output induced by modified sham-feeding was normalised as percentage of the peak response to pentagastrin, it was similar in healthy subjects and in patients with duodenal ulcer; this indicates that the increased peak acid response to modified sham-feeding observed in patients with duodenal ulcer corresponded with their greater parietal cell mass rather than with increased vagal tone.

Topics: Adult; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Hormones; Humans; Insulin; Male; Pancreatic Polypeptide; Pentagastrin; Pepsin A; Time Factors

The cause of duodenal ulcer (DU) is unknown, but gastric acid and pepsin must be involved in the pathogenesis of the disorder: (1) Patients with massive acid hypersecretion due to gastrinoma almost develop peptic ulcer, usually duodenal; (2) ordinary DU patients, on the average, secrete much more acid basally and also have larger acid secretory capacities than healthy people; and (3) reduction of gastric acid secretion (e.g., with cimetidine) accelerates DU healing and prevents DU from recurring. Although factors responsible for increased basal acid secretion rates and for increased maximal secretory capacity (parietal cell mass) in many DU patients are not completely understood, it is likely that neural and hormonal factors are involved: The stomachs of some DU patients may be under increased vagal drive in the basal state. Parietal cells of DU patients are more sensitive to the hormone gastrin, which is released by food. In this review, evidence for abnormalities in vagal function and gastrin physiology in DU will be discussed, with emphasis on recent developments.

Topics: Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Pepsin A; Vagus Nerve

In 8 outpatients with duodenal ulcer the effect of a single dose of 50 mg pirenzepine is compared to a 3-7 days treatment with 2x50 mg. Basal and peptone-stimulated acid output is measured. A single dose of 50 mg pirenzepine reduced basal acid output by 39,9% and the stimulated acid secretion by 21,3%. Treatment for 3-7 days with 2x50 mg pirenzepine is significantly more effective. Basal acid output is reduced by 75,1% and stimulated acid output by 54,0%. No acid inhibition can be demonstrated 12 hours after the last drug administration. Basal serum gastrin levels are little but significantly increased after chronic treatment.

Topics: Administration, Oral; Benzodiazepinones; Drug Administration Schedule; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Piperazines; Pirenzepine

The study investigated the relationships between specific demographic, psychosocial, and physiological variables and the severity of duodenal ulcer disease in a population of patients with proved duodenal ulcer. Intercorrelations between psychosocial and physiological variables were also studied. The study design was cross sectional and retrospectively assessed life change units and DUD severity during the previous 6 months in 39 male ulcer clinic outpatients. Anxiety, depression, life change units, the family environment, ABO blood type, secretor status, serum pepsinogen, and serum fasting gastrin were evaluated. A DUD severity score was calculated from self-reported ulcer pain symptoms and ulcer complications. Gastrin levels correlated significantly with three Family Environment Scale (FES) subscales, including: (a) independence, (b) achievement orientation, and (c) expressiveness. Duodenal ulcer disease severity scores correlated with Zung SDS scores, but not with state or trait anxiety, life change units, or the FES.

Topics: Achievement; Adult; Aged; Anxiety; Communication; Cross-Sectional Studies; Dependency, Psychological; Duodenal Ulcer; Family; Gastrins; Humans; Life Change Events; Male; Middle Aged; Personality; Retrospective Studies

Of 114 patients with chronic pancreatitis, 19 (16.7%) has gastric or duodenal ulcers. Patients with moderate pancreatic exocrine dysfunction tended to show high acid output and low serum gastrin levels, while those with severe dysfunction had slightly lower acid output and higher serum gastrin levels. The higher the degree of pancreatic fibrosis, the higher tended to be the acid output and serum gastrin levels. Not all patients with ulcers developed hypergastrinemia. The mechanism of acid hypersecretion and ulcer formation in patients with chronic pancreatitis cannot be explained solely by pancreatic deterioration, fibrosis or gastrin release; a decrease in the production and release of gastric inhibitory hormone should be taken into consideration.

Topics: Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreas; Pancreatitis; Stomach Ulcer

Topics: Adult; China; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Singapore; Stomach Ulcer

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

Topics: Adult; Arginine; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Glucagon; Humans; Male; Middle Aged; Pentagastrin; Postoperative Period; Vagotomy; Vagotomy, Proximal Gastric

Topics: Duodenal Ulcer; Food; Gastrins; Humans; Protein Precursors

Antral G-cell hyperfunction is a rare cause of hypergastrinemia, hyperchlorhydria, and duodenal ulcer disease. We found evidence for a familial basis for this disorder. The probands were two young men with aggressive duodenal ulcer who had basal and postprandial hypergastrinemia, hyperpepsinogenemia I, and basal and pentagastrin-stimulated hyperchlorhydria. All characteristics returned to normal after antrectomy and vagotomy. Antral gastrin concentrations and quantitative G-cell counts were normal, indicating hyperfunction of G-cells rather than hyperplasia. Four of 10 first-degree relatives of the two patients shared with them the combination of postprandial hypergastrinemia and hyperpepsinogenemia I. The aggregation of these abnormalities in tow families, each identified by a proband with hypergastrinemic, hyperpepsinogenemic l duodenal ulcer, suggests that antral G-cell hyperfunction may have a genetic basis.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Pedigree; Pepsinogens

The purpose of the investigation was to detect ulcer patients having nontumorous hypergastrinemic hyperchlorhydria and to diagnostically differentiate this pseudo-Zollinger-Ellison syndrome from neurogenic duodenal ulcer disease and pancreatic gastrinomas. Nine patients having clinical, radiologic and humoral findings simulating the Zollinger-Ellison syndrome or severe duodenal ulcer disease were studied by physiologic provocative testing. The patients, not having pancreaticoduodenal gastrinomas, had an antral mucosal source of their moderate hypergastrinemia even after vagotomy with drainage, which was eliminated in eight patients treated by surgical antrectomy, resulting in normal serum gastrin concentrations. The pseudo-Zollinger-Ellison syndrome is, thus, characterized physiologically by an exaggerated gastrin response to meals, no response to secretin stimulation and pathologically by hyperfunctioning hyperplastic G cells of the antrum. The clinical, physiologic, pathologic and surgical features were integrated for accurate diagnosis and treatment.

Topics: Adult; Aged; Calcium; Diagnosis, Differential; Duodenal Ulcer; Eating; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Secretin; Stomach Diseases; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Glutamine; Humans; Middle Aged; Proglumide

Topics: Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans

Examination of the antral G-cell density, acid secretion and fasting levels of serum-gastrin were carried out on 20 patients with prepyloric ulcer (within 2 cm of the pyloric ring) and 76 patients with duodenal bulb ulcer. No difference was found in respect to the G-cell density between the group of prepyloric and that with duodenal bulb ulcer, although a lower pentagastrin stimulated acid output and consequently a smaller parietal cell mass appeared to be present in the first group as compared to the second. No relationship was found in either group between fasting levels of serum-gastrin and G-cell density, suggesting that no constant relationship exists between G-cell density and activity under basal conditions. A positive relationship, although statistically insignificant (0.05 less than P less than 0.1) between peak acid output and G-cell density in patients with duodenal bulb ulcer, indicates that in these patients the parietal cell mass and G-cell density are interrelated. The present study could not confirm the entity of antral G-cell hyperplasia in duodenal ulcer patients.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum

Estimates of the border between antral and fundic mucosa, antral size, antral G-cell density, G-cell population, and total G-cell volume were made from multiple biopsies taken from the gastric curves during parietal cell vagotomy for duodenal ulcer in 33 patients. No relation was found between the landmarks of Latarjet's nerve and the border. The fundic mucosa was underdenervated in 20% of the patients, and the postoperative acid response to sham feeding in these was higher than in patients with an overdenervated or optimally denervated border. No relation was found between antral size, defined as antral mucosal volume containing G-cells, and preoperative acid secretion. However, an inverse relation was found between antral size, defined as antral mucosal volume containing no parietal cells, and preoperative maximum acid secretion, suggesting an inverse relation between areas with and without parietal cells. No relation was found between acid secretion and G-cell densities, G-cell population, or total G-cell volume.

Topics: Cell Count; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum; Vagotomy; Vagus Nerve

Praomys (Mastomys) natalensis, an African rodent ranging in size between a mouse and a rat, is more susceptible to the induction of duodenal ulcers by constant infusion of exogenous histamine through an osmotic minipump implanted subcutaneously than other rodent species tested such as mouse, rat, or guinea-pig. By increasing the doses of infused histamine, there were increases in the incidence, intensity, and perforation rate of duodenal ulcers in Mastomys. The induction of duodenal ulcers in Mastomys by tetra- and pentagastrins was unsuccessful, probably because of the limited releasing capacity of the present minipump for use of these two peptides which were sparingly soluble in water. More soluble human synthetic gastrin I was approximately three to four times as potent as histamine for inducing duodenal ulcers in Mastomys. The susceptibility of Mastomys to the induction of duodenal ulcer by cysteamine appears to be comparable to that of rat. The complete suppression of histamine-induced duodenal ulcers of Mastomys was possible by repeated subcutaneous injections of cimetidine.

Topics: Animals; Cimetidine; Cysteamine; Disease Models, Animal; Duodenal Ulcer; Female; Gastrins; Guinea Pigs; Histamine; Male; Mice; Mice, Inbred DBA; Pentagastrin; Rats; Rodentia; Species Specificity; Tetragastrin

This paper presents a comparative retrospective analysis of the effects of vagotomy and drainage, parietal cell vagotomy (PVC) and maintenance H2 receptor antagonist (H2RA) therapy on ulcer recurrence rates, clinical status, gastric acid secretion, serum gastrin responses and gastric structure in the elective treatment of duodenal ulcer. The results indicate that the operations offered greater protection against recurrent ulceration, and that H2RA therapy provides some protection against recurrence while the patient is on continued treatment but does not alter the natural history of the disease when treatment is stopped. The evidence to date suggests that neither PCV nor H2RA therapy has altered the conventional indications for surgical treatment in duodenal ulceration.

Topics: Drainage; Duodenal Ulcer; Eating; Fasting; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Mortality; Recurrence; Stomach; Vagotomy

Gastrin and somatostatin were measured in alkaline gastric instillates in normal subjects, patients with duodenal ulcer disease in quiescent state and in patients with achlorhydria. Both peptides were released into the lumen. The gastrin-somatostatin ratio (G/S) in healthy subjects was approximately three. Duodenal ulcer patients had significantly lower G/S ratio due to lower gastrin and higher somatostatin levels whereas in patients with achlorhydria, the G/S ratio did not differ from normal subjects.

Topics: Achlorhydria; Adult; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Middle Aged; Somatostatin

The effects of ranitidine, a new H2-receptor antagonist which does not contain an imidazole ring, and cimetidine have been determined on histamine, meal-induced gastric acid secretion, and serum gastrin levels in duodenal ulcer patients. Compared with cimetidine, ranitidine was found to be about eight times more potent an inhibitor of histamine-induced secretion and four to five times more potent an inhibitor of sham-feeding, and real feeding induced acid secretion without effecting serum gastrin levels.

Topics: Adult; Cimetidine; Duodenal Ulcer; Furans; Gastric Juice; Gastrins; Guanidines; Histamine; Histamine H2 Antagonists; Humans; Ranitidine

Topics: Acute Disease; Animals; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Pylorus

Topics: Betazole; Blood Glucose; Duodenal Ulcer; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Metoclopramide; Neurotensin; Pentagastrin; Peptides; Pyloric Antrum; Secretory Rate; Somatostatin; Vasoactive Intestinal Peptide

The effect of intravenous secretin on plasma immunoreactive gastrin is presumed to improve diagnostic accuracy in patients with a gastrinoma. To investigate this further, the secretin provocation test was performed in control patients (n = 10), patients with a primary duodenal ulcer (n = 10), patients who had previously had surgery for a duodenal ulcer (n = 20), patients with symptomatic recurrent peptic ulceration (n = 50) and 2 patients with a histologically proved gastrinoma. It was found that the secretin test gave a false positive result in 3 out of 10 symptomatic duodenal ulcer patients, 2 out of 20 patients who had had previous duodenal ulcer surgery and were now asymptomatic and 15 out of 50 patients with recurrent peptic ulceration. Both gastrinoma patients had positive secretin tests but there were no obvious criteria that separated the gastrin response of a gastrinoma patient from those with primary or recurrent peptic ulceration. It is concluded that the secretin test is probably of little value in both the screening and the diagnosis of a gastrinoma.

Topics: Adenoma, Islet Cell; Diagnosis, Differential; Duodenal Ulcer; Gastrins; Humans; Pancreatic Neoplasms; Peptic Ulcer; Recurrence; Secretin

Topics: Adolescent; Adult; Animals; Calcitonin; Calcium; Cattle; Cyclic AMP; Cyclic GMP; Duodenal Ulcer; Gastric Juice; Gastrins; Glucagon; Humans; Insulin; Middle Aged; Parathyroid Hormone; Phosphorus

Topics: Duodenal Ulcer; Gallbladder; Gastric Acid; Gastrins; Humans; Liver; Pancreas; Pepsin A; Vagotomy; Vagotomy, Proximal Gastric

We have studied the relationships between the main molecular forms of gastrin (G17 and G34) in the serum, antral and duodenal mucosa of duodenal (DU) and gastric (GU) ulcer patients. Fasting serum G17 was similar in both DU and GU (about 6 pmol/l) and in both groups increased about three-fold with feeding. In contrast, basal serum G34 was significantly higher in GU (29 pmol/l) than in DU (12 pmol/l) and the peak post prandial increase over basal of G34 was also higher in GU (57 pmol/l) compared with DU (10 pmol/l). In sharp contrast, in the same groups of DU and GU patients mean total antral gastrin concentrations were similar (about 12 nmol/g), and in both groups 95% of antral gastrin was G17, most of the remainder being G34. In both groups total duodenal gastrin concentrations were about 20% those in antral mucosa and about 70% of duodenal gastrin was attributable to G34. The higher serum G34 in GU could therefore be explained by increased secretion of duodenal gastrin, but further work is needed to examine whether there might also be preferential secretion of antral G34 in GU, or a difference in the metabolism (or volume of distribution) of gastrin variants in GU and DU.

Topics: Adult; Aged; Chromatography, Gel; Duodenal Ulcer; Duodenum; Fasting; Female; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Peptic Ulcer; Pyloric Antrum; Radioimmunoassay

The gastric acid secretion, fasting serum gastrin and serum concentration of trimipramine were studied in 20 patients with duodenal ulcer during a 6 weeks treatment with trimipramine. Ulcer healing was examined endoscopically. In the group of 11 patients with healed ulcers the gastric acid secretion decreased significantly at 3 and 6 weeks in contrast to the 9 patients in whom ulcers did not heal, indicating a different antisecretory response in the two groups. The serum concentration of trimipramine was similar in both groups during treatment. Possible mechanisms of action of trimipramine in peptic ulcer disease and problems concerning clinical response and dose are discussed.

Topics: Adult; Aged; Dibenzazepines; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Middle Aged; Trimipramine

Using an in vitro perfusion technique, the release of immunoreactive gastrin (IRG) from human antral mucosa has been investigated, and comparisons made between the release of IRG and the G cell numbers within the tissue. Serosal stimulation with acetyle choline (5.504 x 10(-12)M conc.) resulted in a significantly greater release of IRG from the tissue when compared with release from unstimulated tisse from the same patient (4666 +/- 1656 fM/ml. stimulated; 274 +/- 130 fM/ml. unstimulated (T = 2.64; P < 0.02). A wide variation in G cell numbers was found between tissues and within tissue, and there was no significant correlation between the gastrin secreted and the G cell population. Stimulation with acetyl choline resulted in a 68.8% reduction in G cell numbers compared with a 56.7% reduction in unstimulated tissue, but these were not significantly different (T = 1.68; P > 0.1). No significant correlation was found between the reduction in G cell numbers detected by immunohistology and the IRG secreted by the tissues.

Topics: Acetylcholine; Cell Count; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; In Vitro Techniques; Perfusion; Pyloric Antrum; Radioimmunoassay

The effects of atropine and pirenzepine on sham-feeding stimulated gastric secretion and serum gastrin and pancreatic polypeptide levels have been studied in 12 patients with duodenal ulcer. Both atropine and pirenzepine caused a dose-dependent decrease in acid and pepsin secretion induced by sham-feeding. Serum gastrin response to sham-feeding was negative and it was enhanced by atropine but suppressed by pirenzepine. Plasma pancreatic polypeptide level, which was markedly increased by sham-feeding, was abolished both by atropine and pirenzepine. This study shows that pirenzepine is a more selective inhibitor of gastric secretory and serum hormonal responses to sham-feeding than atropine and that it may be a useful tool for studying the cholinergic innervation of the oxyntic glands and the G-cells in man.

Topics: Adult; Atropine; Benzodiazepinones; Dose-Response Relationship, Drug; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Humans; Pancreatic Polypeptide; Piperazines; Pirenzepine

Endoscopy of the upper gastrointestinal tract was performed on 84 patients with end-stage chronic renal failure undergoing hemodialysis. Gastric acid secretion and fasting plasma gastrin levels were also examined in these patients. Hemorrhagic gastritis was most frequently observed (23 cases) followed by erosive gastritis (18 cases). No patients had gastric ulcers. Duodenal ulcers were observed in only two patients. Gastrointestinal bleeding was observed in 15 cases (17.9%). Thirteen of these 15 cases had hemorrhagic gastritis, one of which had a duodenal ulcer as a complication. Fasting plasma gastrin levels (359.6 +/- 336.5 pg/ml) were significantly higher than those of normal subjects (35.2 +/- 37.1 pg/ml), but no acceleration in gastric acid secretion was observed either in the basal condition (BAO 0.8 +/- 0.7 mEq/h) or following tetragastrin stimulation (MAO 9.0 +/- 6.9 mEq/h). Our results were inconsistent with the previous reports that high frequencies of peptic ulcers and increased gastric acid secretion were observed in patients with chronic renal failure. Our data suggest that the defensive factors rather than the aggressive factors of the gastroduodenal mucosa may be involved in chronic renal failure.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Gastritis; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Kidney Failure, Chronic; Male; Middle Aged

The G-cell population in the pyloric antrum and proximal duodenum was studied quantitatively by immunofluorescence in specimens from 10 gastric and 12 duodenal ulcer patients. In both groups, G-cell density was highest in the pyloric antrum and much lower in the intermediate zone and proximal duodenum, and G-cell counts were statistically higher at the greater than the lesser curvature. The estimated total number of G cells in the whole pyloric antrum including the intermediate zone in the duodenal ulcer group was (1.806 +/- 0.347) x 10(7), this value was significantly greater (P less than 0.05) than that of (0.872 +/- 0.207) x 10(7) in the gastric ulcer group. This difference was due to a higher incidence of intestinal metaplasia and a decrease in the thickness of the antral mucosa in the latter group. The estimated total number of G cells showed a significant negative correlation not only with the patient age (P less than 0.01) but also with the degree of intestinal metaplasia of the antral mucosa (P less than 0.01) in both duodenal and gastric ulcer patients.

Topics: Adult; Cell Count; Chromaffin System; Duodenal Ulcer; Duodenum; Enterochromaffin Cells; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Metaplasia; Middle Aged; Pyloric Antrum; Stomach Ulcer

We have previously demonstrated that insulin hypoglycemia releases antral gastrin by a pH sensitive mechanism in duodenal ulcer (DU) patients. The effect of vagotomy per se on the hypoglycemic release of gastrin therefore might be obscured by alterations in antral pH. In the present study on 11 DU patients, the gastric acid response to intravenously administered insulin (0.2 units/kg-1) was determined before and after selective vagotomy with pyloroplasty (SV + PP). In another preoperative and postoperative test on each patient, the serum gastrin test, the serum gastrin response (radioimmunoassay) to insulin was determined during gastric perfusion with citrate-phosphate buffer pH 7.0. By adjusting the perfusion rate, the intragastric pH was maintained at 5.0 or higher. SV + PP abolished the acid response to insulin in four and reduced the response by 80% to 95% in another six patients. Gastric buffer perfusion or SV + PP did not alter the basal serum gastrin level. The increase of serum gastrin level after insulin was significantly (P less than 0.01) reduced by SV + PP. Before operation the integrated serum gastrin response to insulin was significant (P less than 0.01). SV + PP reduced the response to one-third. The effect of SV + PP on the hypoglycemic release of gastrin varied among the patients but no relationship was found to the effect on the acid response, nor to the variations of the volume or pH of the perfusate (pH range, 5.0 to 7.5). It is concluded that insulin hypoglycemia releases antral gastrin by a vagal and probably also by a nonvagal mechanism and that both mechanisms are pH sensitive.

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Perfusion; Pyloric Antrum; Vagotomy

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Humans; Insulin; Male; Middle Aged; Pyloric Stenosis; Stimulation, Chemical; Stomach Ulcer

Topics: Deoxyglucose; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Hydrogen-Ion Concentration; Insulin; Pentagastrin; Recurrence; Specimen Handling; Vagotomy; Zollinger-Ellison Syndrome

Changes in fasting blood levels of glucose, insulin, glucagon and gastrin were determined in duodenal ulcer patients (n equal to 59) before and up to 1 year after highly selective vagotomy (HSV). There was an increase in glucose values after HSV by approximately 6 mg/dl. The rise in gastrin levels was variable depending on the maximal preoperative acid secretion during pentagastrin stimulation. Insulin values remained unchanged after HSV while there was a significant drop of glucagon levels after 1 year. There is no relationship between the extent of post-HSV gastrinemia and glucose or between the latter and glucagon. It can be assumed that HSV causes additional metabolic changes besides reducing acid production.

Topics: Adolescent; Adult; Aged; Blood Glucose; Duodenal Ulcer; Female; Gastrins; Glucagon; Humans; Insulin; Male; Middle Aged; Postoperative Period; Vagotomy; Vagotomy, Proximal Gastric

A density study of the antral gastrin-producing cells has been performed, before and after eight weeks of treatment with a histamine H2-receptor antagonist (cimetidine 1 g per day), in a series of 38 patients suffering from chronic duodenal ulcer. The treatment produced a significant increase in numerical density and a decrease in mean cell volume. The volume density of the cells was unchanged, suggesting that the elevated serum-gastrin during treatment may be the result of gastrin-cell hyperplasia, without change in the total gastrin-cell volume. The authors suggest that G-cell hyperplasia demonstrated during cimetidine treatment may be a factor of importance with regard to the rapid recurrence of many ulcers after discontinuation of the treatment.

Topics: Adult; Aged; Cell Division; Cimetidine; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Hyperplasia; Immunoenzyme Techniques; Male; Middle Aged; Pyloric Antrum

Topics: Duodenal Ulcer; Gastrins; Humans; Secretin; Stomach Ulcer; Zollinger-Ellison Syndrome

The serum gastrin responses after ingestion of hard boiled eggs and Nutrient Broth solution were examined in peptic ulcer patients and normal subjects. The values observed of the serum gastrin response to these test meals were compared and contrasted. A significant enhancement of gastrin release in response to protein was obtained. There were no significant differences between the releases of gastrin after the two test meals.

Topics: Adult; Dietary Proteins; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Stomach Ulcer

Duodenal ulcer patients with normal (n = 36) or increased (n = 24) gastric acid production during maximal pentagastrin stimulation, were examined preoperatively and at different intervals (up to 1 year) after highly selective vagotomy (HSV). Fasting levels of gastrin, parathormone, calcitonin, proteins, calcium and magnesium fractions, inorganic phosphate and alkaline phosphatase were determined in serum, those of glucagon in plasma. Both types of patients have the same gastrin levels preoperatively (approx. 36 pg-equiv./ml). Magnesium and alkaline phosphatase are significantly higher in patients with a normal secretory response than in those with hypersecretion. The postoperative gastrin increase is significantly higher in the former than in the latter, while postoperative glucagon levels drop in both groups. The analysis of calcium fractions and the dissociation constant did not show any HSV-mediated change in calcium metabolism. The magnesium levels, however, are lower one year after the operation than in the pre-operative period in patients with normosecretion. In this group parathormone and calcitonin remain unchanged while in patients with a hypersecretory response a slight (parathormone) or moderate (calcitonin) tendency towards low values can be recognized in the post-operative period. We conclude that the duodenal ulcer patients probably belong to groups with different pathophysiological behaviour which do not have identical reactions to HSV. Imbalances in the metabolism of minerals and that of related hormones could not be demonstrated up to one year after HSV.

Topics: Adult; Aged; Calcitonin; Calcium; Duodenal Ulcer; Gastrins; Glucagon; Humans; Magnesium; Male; Middle Aged; Minerals; Parathyroid Hormone; Postoperative Period; Vagotomy

Twenty-two duodenal and 16 gastric ulcer patients were treated with 400 mg cimetidine twice daily for one year after their ulcers had healed. No change in gastric acid secretion was observed before and after treatment in 20 duodenal and 13 gastric ulcer patients. Similarly, the inhibitory effect of 200 mg cimetidine on gastric acid secretion was unaltered in 11 duodenal and 6 gastric ulcer patients studied and cimetidine blood concentration were unchanged in 9 duodenal and 4 gastric ulcer patients after one year. In 7 duodenal and 6 gastric ulcer patients the serum gastrin response to a standard test meal before and after treatment was identical.

Topics: Cimetidine; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Guanidines; Humans; Middle Aged; Recurrence; Stomach Ulcer

In large groups of control subjects and gastric, prepyloric, and duodenal ulcer patients basal gastrin concentration as basal and maximal acid output was measured. All groups had equal basal gastrin concentrations, except gastric ulcer patients, who had higher values (p less than 0.001). A significant negative correlation was found between acid output and basal gastrin in controls and prepyloric ulcer patients. In duodenal ulcer a similar correlation was seen only after exclusion of gastrin and basal acid hypersecretors, and in gastric ulcer no correlation could be found. The characteristic pattern for gastrin and acid secretion was in prepyloric ulcer patients almost like that in controls, whereas gastric ulcer patients seemed more heterogeneous. In duodenal ulcer differences may be explained by a defective feedback inhibition of acid.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Stomach Ulcer

Using a technique adapted from the intragastric titration method of Fordtran and Walsh, food-stimulated acid secretion, gastrin release and gastric emptying have been investigated before and after proximal vagotomy in 11 duodenal ulcer patients. Vagal denervation of the proximal stomach resulted in (i) a 40 p. 100 decrease in acid secretion in response to a protein meal; this response was of the same magnitude as the reduction in pentagastrin-stimulated acid output, (ii) a marked increase in food-induced gastrin release, suggesting a relationship between antral gastrin release and fundal vagal innervation since antral pH remained constant and the amount of protein and the distension volume within the antrum were the same as before proximal vagotomy, (iii) a slowing down of the initial phase of gastric emptying of the liquid protein meal in 5 patients, a slight acceleration in 4 and no change in 2. The clinical relevance of these findings is discussed.

Topics: Adult; Aged; Dietary Proteins; Duodenal Ulcer; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Male; Middle Aged; Solutions; Vagotomy; Vagotomy, Proximal Gastric

Reports on increased duodenal ulceration after bile diversion prompted the present investigation of gastric acid secretion and gastrin in 16 patients with a Roux-en-Y hepaticojejunostomy and 11 patients with a choledochoduodenostomy. Basal and pentagastrin stimulated acid output, gastrin in serum and gastrin in the antral mucosa were all significantly elevated in patients with a Roux-en-Y compared with those patients having a choledochoduodenostomy. In patients with a Roux-en-Y, bile bypassed the duodenum and the most proximal part of the jejunum; it is hypothesized that the bypass of bile may induce gastric acid hypersecretion secondary to an altered biosynthesis and release of gastrin.

Topics: Adult; Aged; Cholestasis, Extrahepatic; Common Bile Duct; Duodenal Ulcer; Duodenum; Female; Follow-Up Studies; Gastric Juice; Gastrins; Hepatic Duct, Common; Humans; Jejunum; Male; Methods; Middle Aged; Postoperative Complications

We studied 25 duodenal ulcer patients and 14 age- and sex-matched normal controls to determine whether gastric acid secretion in duodenal ulcer patients is abnormally sensitive to stimulation by gastrin endogenously released in response to meals. Acid response to saline and to 0.5, 1.0, 2.0, 4.0, and 8.0% peptone infused into the stomach was measured by 30 min intragastric titration. Total serum gastrin (G-total) and serum heptadecapeptide gastrin (G17), fasting and 30 min after each test meal, were measured by specific radioimmunoassays. In 19 ulcer patients and 11 normal subjects (controls), acid response to graded doses (11, 33, 100, and 300 pmol kg(-1) h(-1)) of G17-I were also measured. Mean acid output in response to each dose of peptone was significantly higher in duodenal ulcer patients than in the controls. Gastrin levels in ulcer patients and controls were not significantly different. Within individual patients and controls, both G-total and G17 were significantly correlated with meal-stimulated acid output regardless of whether the absolute, basal-corrected, or distention-corrected values for acid output were examined (median r ranged from 0.82 to 0.94, P < 0.001). From the individual regression lines, the gastrin concentrations corresponding to half of the highest observed meal-stimulated acid response (D(50m)) were calculated. Mean D(50m) for G-total and G17 were significantly lower in duodenal ulcer patients than in controls both in the overall group and in pairs of ulcer patients and controls matched on the basis of highest observed meal-stimulated acid responses, or on the basis of maximal acid output in response to synthetic human G17. The dose of exogenously administered G17 required for half maximal G17 acid response mean D(50g), was significantly less in patients than in control subjects. In both ulcer and control subjects, D(50g) correlated significantly with D(50m). This and the significant correlation between meal-stimulated G17 and acid response strongly suggest that the endogenously released gastrin was responsible for most, if not all, of the postpeptone acid output.We conclude that after peptone test meals, gastric acid secretion in duodenal ulcer patients was abnormally sensitive to stimulation by endogenously released gastrin.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Food; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Peptones; Remission, Spontaneous; Time Factors

Topics: Bed Rest; Brain Stem; Diabetes Complications; Duodenal Ulcer; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Hernia, Hiatal; Humans; Scleroderma, Systemic

Topics: Adult; Chronic Disease; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Peptic Ulcer; Postgastrectomy Syndromes; Postoperative Period

The total number of gastrin (G) cells in the stomach was determined by using a histologic counting method and planimetry in ulcerous and nonulcerous patients. The preoperative basal and postprandial serum gastrin values and the gastrin cell mass in the gastrectomy specimen could be compared in 16 surgical patients. There was a significant correlation between the integrated gastrin response to feeding and the total gastrin cell number in the stomach. No correlation was found between the basal serum gastrin level and the total gastrin cell count. A total gastrin cell number higher than 50 million was found in the stomach of three duodenal ulcer patients with preoperative postprandial hypergastrinemia as well as in one patient with normal serum gastrin values. Gastrin cell counts between 6 and 42 million were found in control stomachs and in patients with gastric ulcer. Preoperative feeding tests could be useful to select patients with an elevated antral G cell number.

Topics: Cell Count; Duodenal Ulcer; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Pyloric Antrum; Recurrence; Stomach Ulcer; Vagotomy

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.

Topics: Amino Acid Sequence; Chromatography, Gel; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Peptide Fragments; Radioimmunoassay

Topics: Adolescent; Adult; Duodenal Ulcer; Fasting; Gastrins; Growth Hormone; Humans; Male; Middle Aged; Radioimmunoassay

The relationship between histopathological alterations and G-cell population in the stomach was studied in l4 resected stomachs from patients with chronic peptic ulcer disease (6 with duodenal ulcer and 8 with gastric ulcer). G-cells were identified by indirect immunoperoxidase method. When atrophy was graded three steps (0, 1, 2), the average grade of DU and GU was 0.23 and 0.89, respectively. There was a significant correlation (r=0.871, p less than 0.005) between atropic grade and G-cell population in each stomach. The mean occupation rate with intestinal metaplasia was 0.9% in DU and 35.8% in GU. There was no correlation between total pyloric area and G-cell population, however residual pyloric area excluding intestinal metaplasia correlated significantly with G-cell population (r=0.557, p less than 0.05). There was a significant difference in the mean G-cell population which were 26.5 millions in DU and 8.9 millions in GU. The mean integrated gastrin response to Cimetidine-OXO test meal were 559+/-236 pg/ml in DU and 216+/-124 pg/ml in GU, and there was significant correlation (r=0.889, p less than 0.005) between G-cell population and integrated gastrin response. The average age of both groups, however, was 27.7 in DU and 52.8 in GU, so that these differences of G-cell population and functional G-cell mass in both groups might originate in the histopathological alterations accompanying with the aging.

Topics: Adolescent; Adult; Aged; Chromaffin System; Cimetidine; Duodenal Ulcer; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Guanidines; Humans; Middle Aged; Peptic Ulcer; Pylorus; Stomach; Stomach Ulcer

Topics: Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Urticaria Pigmentosa; Vagotomy; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Liver Cirrhosis; Male

Gastrin 1--17 protected against physiological proteolysis does not change gastric acid secretion and serum gastrin level even if present in the duodenal and gastric lumen in excessive amounts. Consequently gastric juice gastrin has no local effect on the parietal cell. There is no measurable resorption of gastrin from the gastric or duodenal lumen. Gastrin 1--17 does not liberate endogenous gastrin from the antral and duodenal mucosa. Thus, an indirect systemic influence of gastric juice gastrin on the function of the parietal cell can be excluded. Gastric juice gastrin seems to be a waste-product of a bidirectional G-cell secretion. Gel filtration and starch block electrophoresis revealed considerable amounts of immunoreactive material in the duodenal perfusate resembling gastrin 1--34. Thus, the duodenal G-cells seem to liberate gastrin into the duodenal lumen.

Topics: Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Zollinger-Ellison Syndrome

Dose-response studies to tetragastrin were performed in patients with duodenal ulcer before and after highly selective vagotomy, hemigastrectomy and truncal vagotomy plus antrectomy. The calculated maximal response and the dose necessary to elicit 50 percent of that response (D50) were calculated by linear transformation of the results. Both highly selective vagotomy and hemigastrectomy were followed by a significant decrease in the stimulated acid output, characterized by a decrease in the calculated maximal response, but no change in the sensitivity of the parietal cells (D50) was observed. This indicates a noncompetitive reduction in the acid output. The calculated maximal response could not be restored to preoperative values by increasing the dose of stimulant. Truncal vagotomy plus antrectomy was followed by severe alteration in gastric physiology, and no linear transformation of the acid output could be made. This investigation shows that maximal acid output was obtained by the same dose of stimulant before and after all three operations studied. Therefore it is not necessary to increase the dose in postvagotomy acid studies.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Pyloric Antrum; Random Allocation; Tetragastrin; Vagotomy

Sham feeding is thought to stimulate gastric acid secretion solely via vagal pathways. We evaluated whether sham feeding can be used as a test for vagotomy. From results in 50 nonvagotomized subjects (28 unoperated duodenal ulcer patients and 22 healthy controls), a ratio of sham feeding-stimulated acid output to peak acid output of 0.10 or less was defined as abnormally low (with 95% confidence). The ratio of sham feeding to peak acid output was abnormally low in 28 of 41 (68%) vagotomized duodenal ulcer patients without clinical evidence of recurrent ulcer, suggesting that most of these patients had indeed had an effective reduction in vagal innervation of the stomach. On the other hand, 11 of 15 (73%) vagotomized duodenal ulcer patients with symptomatic, recurrent ulcers had normal ratios of sham feeding to peak acid secretion. That a normal ratio represented an incomplete vagotomy was independently suggested in 5 of these patients; in 1 an intact vagal trunk was confirmed at a second operation; in the other 4, acid secretion fell strikingly after transthoracic vagotomy, which would not have been expected to happen if vagotomy had initially been complete. In 5 vagotomized patients tested on two occasions, the ratio was reasonably reproducible. We conclude that a ratio of sham feeding-stimulated to peak acid output greater than 0.10 after an attempted vagotomy suggests persistent vagal innervation, whereas a ratio of 0.10 or less suggests, with at least 95% confidence, that vagotomy has been successful.

Topics: Adult; Aged; Duodenal Ulcer; Eating; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Physical Stimulation; Recurrence; Vagotomy; Vagus Nerve

Sham feeding augments gastric acid secretion by activating efferent vagal pathways to the stomach. If increased vagal activity in the basal state were the cause of increased basal acid secretion in some patients with duodenal ulcer, these patients might be expected to secrete little or no additional acid in response to sham feeding. To test this, we measured basal and sham feeding-stimulated acid secretion (as well as peak pentagastrin-stimulated acid output) in 29 duodenal ulcer patients and 22 healthy subjects. Four ulcer patients who had markedly increased basal acid secretion (basal/peak acid output > 0.30) and normal basal serum gastrin concentrations failed to augment acid secretion in response to sham feeding. On the other hand, patients with marked basal acid hypersection owing to hypergastrinemia (Zollinger-Ellison syndrome) responded to sham feeding with a large increase in acid secretion above basal rates. Every normal subject responded to sham feeding with an increase in acid secretion above basal rates, even when acid secretion had been stimulated by an intravenous pentagastrin infusion before beginning sham feeding. These findings suggest that in some patients with duodenal ulcer (4 of 29 in this study) increased basal acid secretion is caused by increased vagal tone.

Topics: Adult; Aged; Duodenal Ulcer; Eating; Efferent Pathways; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Physical Stimulation; Vagotomy; Vagus Nerve

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrectomy; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Secretory Rate; Stomach Ulcer

Maximal acid output (MAO) after pentagastrin stimulation and gastrin response to a standard meal was studied in 100 control and 200 duodenal ulcer subjects from each of two ethnic groups, Scots and Chinese. The acid output was significantly higher in the Scots than in the Chinese for both controls and duodenal ulcer patients. Despite correction for differences in body stature by expressing MAO as a function of the body weight, these differences persisted. In 45 pairs of closely matched patients with duodenal ulcer, the differences between the two ethnic groups remained significant, irrespective of whether MAO was expressed in absolute or weight corrected values. This indicates that differences in age, sex, family history, or duration of illness did not account for differences in acid output. In 20 pairs of normal control and 45 pairs of duodenal ulcer patients the fasting and post-prandial serum gastrin levels did not differ, significantly between the two ethnic groups. The proportion of acid normosecretors was significantly higher in the Chinese duodenal ulcer patients than in the Scottish. The reason for these differences in the gastric acid output between the two ethnic groups is not known and needs to be studied further.

Topics: Adult; China; Duodenal Ulcer; Female; Food; Gastric Juice; Gastrins; Hong Kong; Humans; Male; Middle Aged; Pentagastrin; Scotland

Integrated postprandial serum gastrin levels were studied in a prospective series of 144 Chinese patients with duodenal ulcer in relation to sex, total body weight, age of onset and duration of ulcer symptoms, blood group status, and positivity for familial dyspepsia. Postprandial gastrin was unrelated to sex, total body weight, duration of symptoms, and blood group status. Patients whose onset age was in the first two decades (early onset group) had significantly higher postprandial gastrin than those with onset age in the 4th and 6th decades (P less than 0.01). This was found to be associated with the presence in the early onset group (n = 35) of a high proportion of patients with positive family history of ulcer dyspepsia (n = 24), in whom postprandial gastrin was significantly higher than those without such history (P less than 0.01). These results suggest that early onset patients who are positive for family history of ulcer dyspepsia segregate to form one subgroup of duodenal ulcer. They also offer a clue that familial hypergastrinaemia may be one marker for familial duodenal ulcer.

Topics: Adolescent; Adult; Age Factors; Blood Group Antigens; Body Weight; Child; Duodenal Ulcer; Dyspepsia; Female; Food; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Sex Factors; Time Factors

Provided the intragastric pH is greater than 6 and the collected gastric juice is boiled and neutralised immediately, considerable amounts of gastrin-like immunoreactivity can be found in human gastric juice. Characterisation according to size and charge reveals that nearly all the gastrin-like immunoreactivity is similar to gastrin 1-17. Direct stimulation of the G-cells with protein solution is followed by a significant and simultaneous increase of acid secretion, serum gastrin, and gastrin output into the lumen of the stomach in control subjects and patients with duodenal ulcer.

Topics: Chromatography, Gel; Duodenal Ulcer; Electrophoresis, Starch Gel; Gastric Juice; Gastrins; Humans; Radioimmunoassay

The sympathetic nervous system is of major importance for the regulation of several physiologic functions. Drugs that inhibit the actions of catecholamines and adrenergic drugs are used in the treatment of many clinical disorders. The potential role of catecholamines in a number of human diseases has, however, until recent years been studied to a limited extent only due to lack of methods for quantitation of sympathetic nervous activity. After the development of enzymatic isotope-derivative assays, reliable measurements of noradrenaline and adrenaline became available. Studies in man have shown that plasma noradrenaline is an index of sympathetic nervous activity. The present survey deals with noradrenaline and adrenaline concentrations in blood, tissue, and cerebrospinal fluid in a number of clinical disorders viz. arterial hypertension, duodenal ulcer, malignant tumors, primary depressive illness, and ketotic hypoglycemia.

Topics: Adult; Blood Pressure; Child; Clonidine; Depression; Duodenal Ulcer; Epinephrine; Female; Gastrins; Heart Rate; Humans; Hypertension; Hypoglycemia; Ketosis; Male; Middle Aged; Neoplasms; Norepinephrine; Sympathetic Nervous System

Pentagastrin-stimulated maximal acid output and postprandial integrated gastrin response (sigma gastrin) were measured in 170 consecutive patients with duodenal ulcers. Within both acid normosecretor and hypersecretor groups, patients with positive family history of ulcer dyspepsia had significantly higher mean maximal acid output than did those without such history. In early-onset (symptoms before age 30) but not late-onset (symptoms after age 30) patients, mean sigma gastrin was significantly greater in those with positive than in those with negative family histories, and in normosecretors than in hypersecretors. Among early-onset patients, family-history-positive normosecretors had a significantly positive correlation between maximal acid output and sigma gastrin, whereas family-history-positive hypersecretors had a significantly negative correlation between these variables. Thus, two subgroups of familial ulcers were identified among early-onset patients. A drive mainly on the G cells may be present in the former group, whereas a drive mainly on the parietal cells may be present in the latter.

Topics: Adult; Age Factors; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Prospective Studies

Changes in the numbers of G cells and the formation and release of gastrin granules have been studies by means of radioimmunoassay and quantitative electron microscopy. The appearance of G-cell granules was affected by the pH and duration of fixation, and after prolonged fixation immature newly formed granules could be identified. In rats fasting up to 3 days first the release and then in turn the maturation and synthesis of granules were depressed. Ultimately the renewal of G cells was inhibited and their numbers declined. During an acute stimulus only a small proportion of total antral gastrin was released and the appearance of G cells was unaltered. In patients treated with cimetidine for 12 months there was no G-cell hyperplasia despite raised stimulated gastrin levels.

Topics: Animals; Cell Count; Cimetidine; Duodenal Ulcer; Gastrins; Humans; Male; Microscopy, Electron; Pyloric Antrum; Radioimmunoassay; Rats

The function of residual parietal cells and G cells following selective vagotomy with pyloroplasty (SV + P) in 21 duodenal ulcer patients was assessed by light-electron microscopical studies of gastroendoscopic biopsy material and determination of gastric acid secretion and serum gastrin levels. The postoperative decrease in number of parietal cells was not so great when compared with the reduction of acid secretion. However, the ultrastructural changes of parietal cells suggested hypofunction of the cells. In addition, the response of parietal cells to histalog stimulation was also decreased according to morphological observations under electron microscope. Basal plasma gastrin was significantly increased (p < 0.01) one month after surgery. Integrated gastrin response (IGR) to meat extract and insulin hypoglycemia stimulation was also increased significantly (p < 0.01) six months postoperatively. The G cells were still increasing in number six months after SV + P, and G cell hyperplasia became more remarkable after one year. Emiocytotic figures were observed in denervated G cells which were stimulated by meat extract or insulin hypoglycemia. On the basis of the findings of this study, it is considered necessary to conduct complete vagotomy on the parietal cell region when SV + P is performed.

Topics: Adult; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Microscopy, Electron; Middle Aged; Pylorus; Vagotomy

Electron microscopic and specific immunofluorescent studies revealed enhanced hormonal activity of the antral part of the stomach manifested in hyperplasia of gastrin-producing cells in patients with duodenal ulcer. A relationship between the level of stimulated gastric secretion, number of gastrin-producing cells and their functional activity was established. No correlation was found between the values of acidity and levels of basal and stimulated gastrin or the dependence of the latter parameters on the number and functional activity of gastrin-producing cells.

Topics: Adolescent; Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Pyloric Antrum

It is unknown whether the gastrin response to secretin (secretin test) can distinguish hypergastrinemia due to vagotomy from hypergastrinemia due to Zollinger-Ellison syndrome (ZES). Therefore, we measured serum gastrin concentrations basally and in response to intravenous secretin in 13 vagotomized duodenal ulcer patients without preoperative evidence evidence of ZES and in 5 vagotomized patients with ZES. Following secretin, serum gastrin concentrations increased 40 pg/ml or less [mean (+/- SE) rise 23 +/- 3 pg/ml] in the vagotomized patients without ZES. On the other hand, in the patients with ZES serum gastrin increments after secretin ranged from 105 to 1224 pg/ml. Thus, a large (> 100 pg/ml) rise in serum gastrin concentrations following secretin in a vagotomized patient should suggest Zollinger-Ellison syndrome and not be attributed to vagotomy per se.

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastrins; Hormones; Humans; Injections, Intravenous; Secretin; Vagotomy; Zollinger-Ellison Syndrome

Basal and histalog-stimulated gastric acid secretion and serum gastrin levels before and after a standard protein meal were compared in eight children with active duodenal ulcer (DU), four with active gastric ulcer (GU), and in seven children with recurrent abdominal pain (RAP) of undetermined etiology. There was no discernible difference in the pattern of abdominal pain in DU, GU, and RAP. Basal acid output, peak and maximal acid output, whether expressed as milliequivalents per hour or as milliequivalents per kilogram per hour, were comparable in children with DU, GU, and RAP. In contrast, serum gastrin levels, 1 and 2 hours after standard protein meal, were significantly higher in the DU children than in the GU or RAP group. These studies have suggested that hypersecretion of gastric acid may not be associated with duodenal ulcer or gastric ulcer disease in children, and that increased gastrin secretion and possible reduced acid responsiveness coexist in children with duodenal ulcers.

Topics: Abdomen; Acute Disease; Adolescent; Child; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Pain; Recurrence; Stomach Ulcer

It is suggested on the ground of the present study that in a number of cases of duodenal ulcer it is an immunoglobulin of the class IgG which, as a stimulating factor, accounts for overproduction of gastric HCl. This immunoglobulin takes effect by direct attachment to the parietal cells.

Topics: Animals; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Immunoglobulin G; Lymphocyte Cooperation; Rats; Secretory Rate

Synthetic salmon calcitonin infused intravenously in a pharmacological dose of 2 MRCU/kg/hour resulted in an abrupt and profound inhibition of basal and pentagastrin and calcium induced gastric acid secretion in patients with duodenal ulcer. The inhibition in the sixth 15-minute period of the intravenous infusion of calcitonin amounted to 98.7% (basal acid secretion), 51.8% (pentagastrin-stimulated acid secretion) and 80.9% (calcium-induced acid secretion). There were no significant alterations in the serum calcium and gastrin levels during the intravenous infusion of calcitonin. The slight decrease in serum gastrin concentration in the first 30 minutes of calcitonin infusion cannot explain the strong inhibition of gastric acid secretion produced by calcitonin. It is assumed that calcitonin inhibits directly the parietal cells.

Topics: Adult; Calcitonin; Calcium; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pentagastrin

The significance of antral pH for the basal serum level of immunoreactive gastrin and for the release of gastrin during insulin hypoglycemia has been studied in duodenal ulcer (DU) patients. To permit paired comparisons, 14 DU patients underwent two or three tests with insulin. Venous blood samples were collected at fixed intervals for determination of gastrin (radioimmunoassay). In the first insulin test, the gastric juice was aspirated; in the second test, the stomach was perfused with citrate-phosphate buffer, pH 7.0; and in the third test the stomach was perfused with 0.1M HCl, pH 1.0. The rate of buffer or acid perfusion was adjusted, and the pH of the perfusate was kept above 5.0 and below 1.3, respectively. Gastric perfusion with buffer or acid for 1 hour did not affect the basal serum gastrin level, nor did perfusion with buffer for 3 hours. Insulin hypoglycemia stimulated acid secretion and produced a significant integrated serum gastrin response during gastric aspiration, but the gastrin response was four times greater during buffer perfusion. Acid perfusion abolished the gastrin response. From our previous and present findings, it is concluded that the gastrin in serum during basal conditions is of extra-antral origin and is independent of antral pH. Insulin hypoglycemia releases antral gastrin by a pH-sensitive mechanism in DU patients; the release is suppressed at pH 1.3 or less and also is markedly inhibited when the gastric juice is aspirated.

Topics: Adult; Buffers; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Male; Middle Aged; Pyloric Antrum; Secretory Rate; Suction

We studied effects of selective proximal vagotomy on food-stimulated acid secretion and gastrin release in 7 duodenal ulcer patients. Food-stimulated acid secretion was evaluated by sham feeding patients and by infusing food directly into their stomachs. Vagotomy reduced sham feeding-stimulated acid secretion from 28.2 +/- 4.6 to 1.2 +/- 0.7 meq/hr (95% reduction) whereas infused food-stimulated secretion was decreased from 36.1 +/- 4.6 to 17.9 +/- 5.5 meq/hr (50% reduction). In contrast to the reductions in acid secretion, the gastrin response to infused food doubled after surgery. Although selective proximal vagotomy reduced the rate of acid secretion in response to infused food and also reduced by 64% the peak secretory capacity (peak acid output to pentagastrin), fractional secretion (i.e., the secretion rate in response to infused food expressed as a percentage of the peak secretory capacity) increased significantly after vagotomy from 63 +/- 7% to 91 +/- 11%. This increased fractional secretion in response to infused food was probably a result of exaggerated gastrin release after vagotomy.

Topics: Adult; Aged; Duodenal Ulcer; Eating; Enteral Nutrition; Gastric Emptying; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Vagotomy

Vagal activation produces a gastric acid secretory response by direct nervous stimulation of the parietal cell area and, at least in dogs, by gastrin released mainly from the antrum. In duodenal ulcer (DU) patients antrectomy reduces the acid response to sham feeding slightly more than the maximal acid output in response to pentagastrin, indicating that an antral factor contributes to the acid secretion induced by sham feeding. The marked acid response to sham feeding in antrectomized patients suggests that the direct nervous stimulation of the acid-secreting glands is the predominating stimulus in the vagal activation of acid secretion in man. In the present study vagal activation has been induced by adequate and modified sham feeding and insulin hypoglycemia in DU patients and healthy subjects. The acid response to adequate and modified sham feeding amounted to about 50% of the peak acid output in response to pentagastrin and corresponded to the acid response to an insulin dose of 0.1 U/kg b.w. Modified sham feeding seems to be a simple method of inducing physiological vagal activation of acid secretion. Sham feeding for 15 min increased only insignificantly the plasma concentrations of total gastrin immunoreactivity or heptadecapeptide gastrin. Prolonged sham feeding during intragastric neutralization or sham feeding after proximal gastric vagotomy did not significantly increase the plasma gastrin concentrations. Sham feeding is obviously a poor stimulus for release of gastrin in man. Either release effect of very small amounts of gastrin-17 or release of non-established gastrins may explain the biological effect of an antral factor. Pretreatment with benzilonium, an anticholinergic drug with minimal cerebral actions, increased the gastrin concentration after sham feeding in about half the experiments. This heterogeneous effect supports a non-cholinergic vagal release of gastrin and a cholinergic inhibition of gastrin release but also indicates a complex interaction at the level of the gastrin cells during vagal activation. Evidence for an inhibitory vagogastrone mechanism in DU patients has been found but its effect is weak and transient. Proximal gastric vagotomy abolished the acid responses to both insulin hypoglycemia and sham feeding, in accordance with the view that the direct nervous excitation of the acid-secreting glands is the predominating stimulus in the vagal activation of gastric acid secretion in man. Atropine in low doses or benzilonium

Topics: Adult; Aged; Animals; Dogs; Duodenal Ulcer; Duodenum; Ethics, Medical; Food; Gastric Juice; Gastrins; Humans; Insulin; Male; Middle Aged; Pentagastrin; Peptic Ulcer Perforation; Pyloric Antrum; Receptors, Cholinergic; Secretory Rate; Vagotomy; Vagus Nerve

The effect of a single dose of 400 mg of the H2-receptor antagonist cimetidine on protein meal stimulated immunoreactive gastrin was assessed in ten patients with gastric ulcer and ten patients with duodenal ulcer. In gastric ulcer patients, serum gastrin (mean +/- SE) rose from 34 +/- 2.2 pmol.l-1 to a peak of 80 +/- 5.0 pmol.l-1 at 45 minutes without and from 36 +/- 2.2 to 107 +/- 8.0 pmol.l-1 at 60 minutes with cimetidine; in duodenal ulcer it rose from 26 +/- 3.0 to 47 +/- 5.1 pmol.l-1 at 45 minutes without and 26 +/- 3.2 to 52 +/- 5.1 pmol.l-1 at 60 minutes with cimetidine. Integrated gastrin responses in gastric ulcer were 4900 +/- 800 pmol.l-1 120 minutes without and 7000 +/- 900 pmol.l-1 120 minutes with cimetidine and 1560 +/- 300 pmol.l-1 120 minutes without and 2620 +/- 400 pmol.l-1 120 minutes with cimetidine in duodenal ulcer patients. These gastrin increases after cimetidine are comparable to those achieved with continuous intragastric neutralisation with alkali.

Topics: Adult; Aged; Antigens; Cimetidine; Dietary Proteins; Duodenal Ulcer; Female; Food; Gastrins; Guanidines; Humans; Male; Middle Aged; Stomach Ulcer

Serum immunoreactive gastrin was measured in 14 patients with duodenal ulcer before and during a 12-month course of cimetidine 400 mg bd. All patients were symptomatically well during the cimetidine therapy and both basal gastrin and that in response to a protein rich meal were assessed before, at six months and at 12 months during therapy. The basal and post-prandial gastrin were significantly higher at six and 12 months on cimetidine than before cimetidine but the six and 12 month levels were similar. This study thus shows that the progressive increase in serum gastrin during six months of continuous cimetidine therapy does not occur beyond this time period.

Topics: Adult; Aged; Cimetidine; Dietary Proteins; Duodenal Ulcer; Eating; Female; Gastrins; Guanidines; Humans; Male; Middle Aged

Topics: Adolescent; Child; Chronic Disease; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Pepsin A; Peptic Ulcer

Measurements of serum cortisol and gastrin along with gastric acid-pepsin secretion in the resting state were carried out in gastric and duodenal ulcer patients. Increased basal corticosteroid concentrations were observed in patients with duodenal ulcer and gastric ulcer. Higher concentrations of the hormone were observed in the former group (P less than 0.05 for the latter). Fasting gastrin levels were significantly higher in gastric ulcer patients where gastric secretion is low than those in duodenal ulcer patients (P less than 0.001). These results suggest that the effect of adrenal cortical hormone on lowering the threshold of oxyntic gland cell reactivity against gastrin is an important factor in duodenal ulcer etiology. Extra-antral control mechanism(s) of gastric acid-pepsin secretion should not be overlooked.

Topics: Adrenal Cortex Hormones; Adult; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hydrocortisone; Middle Aged; Pepsin A; Stomach Ulcer

Topics: Brunner Glands; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Intestinal Mucosa; Kidney Transplantation; Postoperative Complications; Transplantation, Homologous

In 10 healthy subjects and 25 duodenal ulcer patients, gastric acid and pepsin and serum gastrin responses to cephalic-vagal stimulation induced by modified sham-feeding (MSF) were studied before and after vagotomy and atropinisation and compared with those to maximal stimulation with pentagastrin. When the MSF-induced peak acid output was normalised as a percentage of peak response to pentagastrin it was about 62% in healthy subjects and 66% in duodenal ulcer patients. Serum gastrin concentration was not changed significantly by modified sham-feeding either in normal subjects or in duodenal ulcer patients. Truncal vagotomy completely abolished gastric acid and pepsin responses to MSF in duodenal ulcer patients. Atropine almost completely suppressed gastric acid and pepsin responses to MSF in healthy subjects and reduced those in duodenal ulcer patients by about 62%. The combination of the modified sham-feeding and pentagastrin infusion resulted in augmentation of the acid output in duodenal ulcer patients but not in healthy subjects. This study shows that the cephalic phase results in a potent gastric acid and pepsin stimulation which is not accompanied by any change in serum gastrin concentration either in healthy subjects or duodenal ulcer patients and which is abolished by vagotomy and suppressed by atropine.

Topics: Adult; Atropine; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Male; Pentagastrin; Pepsin A; Pylorus; Secretory Rate; Time Factors; Vagotomy; Vagus Nerve

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Gastrins; Humans; Middle Aged; Stomach Ulcer

The number of gastrin-producing cells in biopsy specimens from the gastric and duodenal mucosae in 19 duodenal ulcer patients was quantitated using a morphometric method. The level of immunoreactive gastrin in a sample of fasting serum obtained at the time of the biopsy was measured by radioimmunoassay. The results show no significant difference when compared with those from a group of normal control volunteers. Moreover, there was no correlation between the numbers of gastrin-producing cells and the fasting serum gastrin level in either controls or duodenal ulcer patients.

Topics: Adolescent; Adult; Biopsy; Cell Count; Duodenal Ulcer; Duodenum; Female; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged

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.

Topics: Adult; Aged; Duodenal Ulcer; Eating; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pentagastrin

The effects of 100-microgram of 15(R)-15-methyl prostaglandin E2 on meal-stimulated acid secretion, serum gastrin, and pancreatic polypeptide concentrations were measured in patients with duodenal ulcer. The drug given in encapsulated or unencapsulated form significantly reduced gastric acid secretion by 59% or 70%, respectively. Rises in serum gastrin and pancreatic polypeptide concentrations after the meal were significantly blunted by 15(R)-15-methyl prostaglandin E2. This dose of prostaglandin led to no side effects and merits clinical evaluation in the treatment of peptic ulcer disease.

Topics: Adult; Capsules; Duodenal Ulcer; Eating; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Prostaglandins E, Synthetic

Basal and food-stimulated gastrin were measured in 16 patients with duodenal ulcer before and during long-term maintenance therapy with 400 mg cimetidine twice daily. Basal gastrin (mean +/- SE) rose significantly from 27.5 +/- 3.1 pmol/liter precimetidine to 32.8 +/- 2.1, 37.2 +/- 2.6, and 38.5 +/- 3.3 pmol/liter at 1, 3, and 6 months, respectively. The total integrated gastrin response to a protein meal was 1.67 +/- 0.18 nmol/liter/120 min pre-, and 2.54 +/- 0.35, 3.29 +/- 0.3, and 4.36 +/- 0.4 nmol/liter/120 min at 1, 3, and 6 months, respectively. These increases were significantly higher at each time period. This study has thus demonstrated a progressive increase in both basal and food-stimulated gastrin during cimetidine therapy, and this increase could theoretically lead to an increase in gastric acid secretion following cessation of cimetidine.

Topics: Aged; Cimetidine; Dietary Proteins; Drug Administration Schedule; Duodenal Ulcer; Eating; Female; Gastrins; Guanidines; Humans; Male; Middle Aged; Time Factors

Plasma concentrations of prostaglandins E and F have been measured by radioimmunoassay in patients undergoing diagnostic upper intestinal endoscopy. The results fail to support a previously reported deficiency of plasma PGE in duodenal ulcer patients. Plasma prostaglandin concentrations failed to correlate with the parameters of gastric secretion studied; and were unaffected by histamine H2-receptor blockade or the activity of duodenal ulceration. During combined pentagastrin and insulin secretory studies there was a significant correlation between the outputs of PGE and acid into gastric juice.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Stomach Ulcer

Gastric acid secretion, gastric emptying, fasting serum gastrin and the serum gastrin response to a meal were measured in duodenal ulcer patients before, and at least five days after completing prolonged treatment with cimetidine (1 or 2 g/day for four or eight weeks followed by 600 mg twice daily for six months). Fasting serum gastrin and the gastrin response were also measured during treatment. Compared with pretreatment values, fasting serum gastrin concentrations were raised both during and five to 31 days after stopping treatment (P less than or equal to 0.02). The integrated gastrin response and the rate of gastric emptying of the solid component of the meal were increased during treatment (P less than 0.001 and P less than 0.002 respectively) but returned to pretreatment levels after stopping therapy. No significant changes were observed in the basal or maximal acid outputs or the rate of emptying of the liquid component of the meal. The results imply that the hypergastrinaemia associated with long-term cimetidine therapy does not result in increased gastric acid secretion.

Topics: Cimetidine; Duodenal Ulcer; Fasting; Food; Gastric Emptying; Gastric Juice; Gastrins; Guanidines; Humans; Time Factors

Topics: Adult; Blood Pressure; Duodenal Ulcer; Epinephrine; Female; Gastrins; Heart Rate; Hemoglobins; Humans; Male; Middle Aged; Norepinephrine; Vagotomy

Relationships between hormonal secretions from the GI tract and gastric functional and/or pathological abnormalities could be studied according to 2 main lines : 1) gastric secretory changes could be the main symptom of hormonal secretory tumors, i.e. acid hypersecretion in the Zollinger Ellison syndrome, acid hyposecretion in pancreatic cholera and in somatostatinoma. In these cases, hormonal hypersecretion is directly responsible for the functional disturbances and the related symptoms; 2) gastric pathological conditions are sometimes accompanied by changes in hormonal secretion, but the level of interdependence is variable : high blood gastrin is directly depending upon the atrophic gastritis in pernicious anemia; this mechanism was also suggested in case of gastric carcinoma. Concerning ulcer disease, numerous problems are unsolved in respect to blood gastrin (basal and stimulated) abnormalities, as well as somatostatin and GIP secretions.

Topics: Aged; Anemia, Pernicious; Cholera; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Pancreatic Diseases; Pancreatic Neoplasms; Somatostatin; Stomach Diseases; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Child; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Reference Values; Stomach Ulcer

Topics: Duodenal Ulcer; Follow-Up Studies; Gastric Juice; Gastrins; Humans; Insulin; Pentagastrin; Recurrence; Secretory Rate; Vagotomy

Following selective proximal vagotomy (SPV) in duodenal ulcer patients basal acid output (BAO) and peak acid output (PAO) decrease by 79,3% and 41,8% respectively. Serum gastrin levels increase by 83% within the first five days after operation. Patients having had a SPV release evidently more gastrin after test meals as compared with the results before vagotomy. In consideration of the elevated praeoperative values insulin hypoglycaemia does not cause an augmented secretion of gastrin. There is no correlation between the fall in acid secretion and the increase in gastrin levels. Acidification of the gastric antrum (pH 2,0) did not influence the raised serum gastrin levels at the 10. day and one year after operation. There is a close correlation (r=0,94) between the percental increase in the basal gastrin concentration and the percental change of the vagal influence on the secretion of the parietal cell. It is postulated that together with the dissection of stimulating vagal fibres reaching the parietal cells other fibres are cut which cause an inhibition of gastrin release from the antral G-cells. Thus, the disinhibition of an oxyntopyloric reflex may account for the increase in serum gastrin levels after SPV.

Topics: Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Vagotomy

Truncal and selective proximal vagotomy cause in an increase of basal GIP-levels. There was no difference between the postprandial GIP release before and after vagotomy. However after extragastric vagotomy in dogs postprandial GIP-levels showed a significant increase in comparison to intact animals.

Topics: Animals; Blood Glucose; Dogs; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucose; Humans; Vagotomy

Topics: Animals; Anura; Bombesin; Dogs; Duodenal Ulcer; Gastrins; Gastritis; Gastrointestinal Diseases; Humans; Peptic Ulcer; Peptides; Stomach Ulcer; Zollinger-Ellison Syndrome

Several gastrointestinal peptides with proven or suggested endocrine or paracrine functions influence gastric acid secretion, gastrointestinal motility, and mucosal blood flow. Increased or decreased release of such factors could participate in the pathogenesis of duodenal ulcer disease by inducing increased gastric acid concentration in the duodenal bulb. To date, increased stimulation of parietal cells by gastrin has been demonstrated only in patients with gastrinoma, G-cell hyperplasia, gastric outlet obstruction, hyperparathyroidism, excluded antrum, and short bowel syndrome, but not in the usual duodenal ulcer disease. Also, a defective inhibition of parietal cell function by endocrine or paracrine factors, such as gastric inhibitory polypeptide, secretin, somatostatin and vasoactive intestinal polypeptide, seems not to exist in patients with duodenal ulcer disease. However, as long as the physiology of gastrointestinal peptides in gastric secretion and motility is not understood, a possible role of these factors in the pathogenesis of simple duodenal ulcer disease cannot be excluded.

Topics: Duodenal Neoplasms; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Different pathogenetic mechanisms lead to the formation of ulcers in stomach and duodenum. They must be taken into consideration, when selecting operative procedures. In the patient with duodenal ulcer we have with the selective proximal vagotomy a procedure at hand that in effective reduction of the secretion of the stomach and in preservation of the form and function of the stomach fulfills all criteria of a functional gastric surgery. At present in patients with gastric ulcers dominate still methods of resection with the aim of the removal of the ulcer and thus healing. The practicability and effectiveness of non-resecting methods is shown also in this case. But it should be controlled in larger clinical studies.

Topics: Adolescent; Adult; Aged; Child; Cimetidine; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastrins; Humans; Middle Aged; Pyloric Antrum; Recurrence; Stomach Ulcer; Vagotomy

The blood serum levels of gastrin and insulin and arterial blood levels of glucose were determined immediately before intravenous injection of 1 mg of glucagon, and 10, 20, 40 and 60 minutes later in 12 gastric ulcer patients, 14 duodenal ulcer patients and 12 controls using the radioimmunological and orthotoluidine methods respectively. Following glucagon administration the gastrin levels dropped in the controls and the gastrin patients, and increased in the duodenal patients by an average of 30%. Insulin levels increased in all three groups, but the increase was statistically significant in the two patients groups. Glucose levels in the blood also increased with no significant differences between the groups. It is suggested that the different effect of glucagon on gastrin levels may be due to gastrin-insulin interaction; the levels of the two hormones in the blood of duodenal patients were higher than in the other two groups studied.

Topics: Adolescent; Adult; Blood Glucose; Duodenal Ulcer; Gastrins; Glucagon; Humans; Insulin; Stomach Ulcer

In normal, duodenal ulcer, and gastric ulcer subjects the two main forms of gastrin, G17 and G34, were estimated by radioimmunoassay in fasting serum and after feeding. Two antisera were used: one showing high specificity for G17, the other specific for the common COOH-terminus of G17 and G34 and so allowing estimation of G34 by difference. Basal G17 was similar in gastric ulcer, duodenal ulcer, and normal subjects and the increases of G17 after feeding were also similar in these groups. In contrast, basal G34 was similar in normal and duodenal ulcer subjects but raised in gastric ulcer subjects. After a meal the G34 concentration in both gastric and duodenal ulcer patients was significantly higher than normal. It is concluded that the higher post-prandial gastrin responses in peptic ulcer that have been previously described are due largely to increased G34.

Topics: Adult; Antibody Specificity; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Gastritis; Humans; Male; Middle Aged; Monoamine Oxidase; Pylorus; Stomach Ulcer

Twenty-one consecutive patients with endoscopically proven recurrent ulcer were treated continuously with cimetidine, 1 g daily for 8 weeks. After 4 weeks' treatment 18 (86%) of the patients were free of symptoms, and the ulcers had healed in 17 (81%). At the 8th-week examination symptoms had disappeared, and ulcers were healed in 19 patients (91%). Within 6 weeks after withdrawal of cimetidine six patients (28%) presented recurrence of ulcers and symptoms. This study demonstrates that recurrent ulcer patients respond to cimetidine with regard to healing of ulcers and disappearance of symptoms, as do unoperated duodenal ulcer patients. Because operation for recurrent ulcer carries an increased mortality, we suggest that cimetidine should be attempted in the treatment.

Topics: Adult; Aged; Cimetidine; Drug Evaluation; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Guanidines; Humans; Male; Middle Aged; Recurrence; Stomach Ulcer

Topics: Adult; Aged; Duodenal Ulcer; Eating; Gastric Acidity Determination; Gastrins; Humans; Middle Aged

Six duodenal ulcer patients were investigated before and after truncal vagotomy and pyloroplasty. Four doses of gastrin-17 were injected intravenously (15.625, 31.25, 62.5, and 125 micrograms/kg body weight); the gastric secretory response and the disappearance rate of gastrin were measured. After vagotomy the basal level of gastrin increased from 64 pg/ml to 106 pg/ml. When corrected for the basal levels of gastrin, the peak levels and disappearance rate of gastrin-17 were observed to be the same after vagotomy as before (half-life before vagotomy, 5.6 min; after, 5.8 min). This indicates that vagus does not influence the metabolism of exogenous gastrin-17. The gastric secretion of acid was reduced to 30% after vagotomy, which shows that there is a synergism between vagus and gastrin-17.

Topics: Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Pyloric Antrum; Vagotomy

Topics: Adult; Duodenal Ulcer; Esophagitis, Peptic; Gastrins; Gastritis; Humans; Middle Aged

Relative chief and parietal cell volume densities were estimated morphometrically in the remnant mucosa of 98 male patients ("series"), operated on for duodenal ulcer by the Billroth II, and in the body mucosa of 55 subjects, age and sex matched, from a random series of a Finnish population ("controls"). The relative volumes of chief and parietal cells were significantly lower in the series than in the controls. The mean chief cell: parietal cell ratio was significantly higher in the series than in the controls. In the controls the ratio decreased with increasing loss of normal tubules. However, no such decrease was discernable in the series, owing to wide scatter of the individual ratios. High ratios (greater than or equal 2.0) were found in 17 cases of the series and in one of the controls. These 17 patients with high ratios had a significantly higher mean length of the foveoles and a significantly lower mean score of the round cell infiltration than the operated patients with lower ratios.

Topics: Adult; Atrophy; Cell Count; Cell Survival; Duodenal Ulcer; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Mitosis

The authors explored the gastric function of 20 volunteers by classical methods and by the assessment of gastric 99Tc pertechnetate clearance. From a comparison of results obtained with the various methods they come to the conclusion that the pertechnetate clearance method is dependable, easy to perform, and noninvasive; accordingly, they recommend its use as the method of choice for monitoring the treatment of duodenal ulcers and evaluating its results.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Stomach; Stomach Ulcer; Technetium

To delineate genetic factors involved in the pathogenesis of duodenal ulcer, serum pepsinogen I levels were determined by radioimmunoassay in two large kindreds with multiple members affected with duodenal ulcer. An elevated serum immunoreactive pepsinogen I concentration (greater than 100 ng per milliliter) segregated as an autosomal dominant trait in these families. Furthermore, 10 of 11 patients with clinical ulcer disease in these families had hyperpepsinogenemia. An elevated serum pepsinogen I concentration appears to be a subclinical marker of the ulcer diathesis in families with this autosomal dominant form of peptic-ulcer disease.

Topics: Duodenal Ulcer; Female; Gastric Juice; Gastrins; Genes, Dominant; Humans; Male; Pedigree; Pepsinogens; Radioimmunoassay

In 6 patients having duodenal ulcer disease plasma gastrin concentrations were determined before and after the oral administration of 0.5--2 g of calcium carbonate, 2--4 tablets of Camalox and 2 tablets of Novalucol. No significant influence on basal plasma gastrin levels was noted indicating that antacids, whether they contain calcium carbonate or not, do not influence the basal plasma concentration of gastrin at occasional administration.

Topics: Administration, Oral; Antacids; Calcium Carbonate; Dose-Response Relationship, Drug; Duodenal Ulcer; Female; Gastrins; Humans; Male

Pharmacokinetics and gastric secretion suppressing properties of a new drug, trithiozine (TR), were studied in man. Its availability, if taken orally, is prompt and very good; its blood plasma level lasts for over 5 hr. In basal conditions volume of gastric juice is suppressed by TR as it is by propantheline bromide (PPB). In contradistinction to PPB, TR reduces basal acid output. After histamine stimulation TR is not as effective as PPB in reducing both volume and acid output. TR did not appear to affect the plasma gastrin level. Lack of typical anticholinergic side-effects such as dryness in mouth, vision blurring, etc., on the one hand, and antisecretory activity limited to basal conditions on the other, seem to offer a new modification of the old approach to therapy of gastroduodenal ulcer. Clinical trials seem justified.

Topics: Adult; Anti-Ulcer Agents; Biological Availability; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Histamine; Humans; Kinetics; Male; Oxazines

In 10 healthy subjects and 10 duodenal ulcer patients the intestinal phase of gastric acid secretion was studied by intraduodenal infusion of a 10% liver extract meal (pH 7) at 400 ml/h for three hours. A gastroduodenal double lumen tube with two balloons was used to block the pylorus and to prevent duodenogastric reflux. Gastric acid response to a duodenal meal of liver extract reached a peak at the end of the first hour of infusion of the extract and was then followed by a relatively well-sustained plateau. When the figure was normalised as a percentage of peak response to pentagastrin it was about 45% in healthy subjects and 63% in duodenal ulcer patients. Serum gastrin concentration increased significantly during a duodenal meal of liver extract only in duodenal ulcer patients and not in healthy subjects. The combination of the duodenal meal of liver extract with pentagastrin infusion resulted in a significantly greater increase in acid output in duodenal ulcer patients than in healthy controls. Duodenal perfusion with a liver extract meal in which the pH was gradually decreased caused a pH-dependent reduction in acid output, but not in serum gastrin, both in the duodenal ulcer patients and in healthy subjects. This study shows that the intestinal phase in man results in a potent gastric acid stimulation which is pH-dependent, greatly augmented by pentagastrin, and more vigorous in duodenal ulcer patients than in healthy controls.

Topics: Adult; Duodenal Ulcer; Duodenum; Enteral Nutrition; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Intubation, Gastrointestinal; Male; Pentagastrin; Pepsin A

Topics: Adult; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pyloric Antrum; Pylorus; Vagotomy

Gastric acid secretion stimulated by a normally eaten beefsteak meal was measured for 4 h in 16 patients with duodenal ulcer disease (DU), in 9 patients with gastric ulcer disease (GU), and in 14 controls by intragastric titration with bicarbonate to a constant pH 5.5. Reproducibility of the method investigated in 6 DU and in 5 controls gave similar acid secretory values (var. coeff. = 7.5%). DU produced acid on a higher level and with longer duration after food than controls and GU (p less than 0.001). Apart from the second half of the first hour after food, when the acid secretion was higher in controls than in GU (p less than 0.025), there was no significant difference in acid output after food between GU and controls. Maximum gastrin values and 'total gastrin output' after food were significantly higher in GU than in controls, but these differences were not significant between GU and DU and between DU and controls. Fasting gastrin and gastrin levels after food were not correlated to basal acid output or acid output after pentagastrin or food in any of the groups. The maximal acid output after food was higher than the peak acid output after pentagastrin in controls, DU and GU. The relation between food- and pentagastrin-stimulated acid output was not statistically significantly different between the three groups. Instead, acid secretion after food was well correlated to acid secretion after pentagastrin in controls, DU and GU (r = 0.85).

Topics: Adult; Aged; Bicarbonates; Duodenal Ulcer; Female; Food; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Methods; Middle Aged; Secretory Rate; Stomach Ulcer

It is suggested that the early-morning growth-hormone release associated with slow-wave sleep is due to inhibition of somatostatin secretion from the hypothalamus. It is also associated with inhibition of gastrointestinal somatostatin, causing a release of gastrin and insulin. Because the levels of glucocorticoid hormones are concurrently low, the insulin effect is unopposed and increases gut motility through augmented vagal tone. This results in an increased delivery of acid to the duodenum. In duodenal-ulcer patients, whose duodenal buffering capacity is reduced because of a relative deficiency of secretin response, this leads to pain.

Topics: Animals; Cats; Circadian Rhythm; Duodenal Ulcer; Duodenum; Gastric Juice; Gastrins; Growth Hormone; Haplorhini; Humans; Insulin; Insulin Secretion; Pain; Pituitary Gland, Anterior; Sleep; Somatostatin

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Fluorescent Antibody Technique; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Male; Middle Aged; Peptic Ulcer; Pyloric Antrum; Staining and Labeling; Stomach; Stomach Neoplasms; Stomach Ulcer; Uremia

The distribution and numbers of G cells and of parietal cells were related to the distribution and severity of histopathological alterations (inflammatory cell infiltration, atrophy and intestinal metaplasia) in corresponding mucosal tissue blocks from resected stomachs (12 patients with gastric ulcer, 11 with duodenal ulcer, and 14 with duodenal ulcer and uremia). In all patients the histopathological features were more severe in the pyloric antrum than in the body, and the change in severity corresponded well with the disapperance of G cells at the body-antrum border. The transitional body-antrum zone was histopathologically similar to the remaining antrum. A marked individual heterogeneity of the histopathological alterations was observed. An increasing grade of atrophy was associated with increased severity of inflammation, and the presence of intestinal metaplasia was especially associated with atrophy. No significant correlation was found between the antral G-cell number and the grade of antral inflammatory cell infiltration, whereas there was a reduction in cell number with increasing grade of atrophy in all patient categories. The parietal-cell density in the body mucosa was decreased with increasing grade of inflammation as well as with increasing grade of atrophy. The presence of patchy intestinal metaplasia resulted in a complete absence of G cells and of parietal cells from the corresponding part of the mucosa in the antrum and body respectively.

Topics: Adult; Aged; Atrophy; Cell Count; Duodenal Ulcer; Female; Fluorescent Antibody Technique; Gastrectomy; Gastrins; Gastritis; Humans; Intestinal Mucosa; Intestines; Male; Metaplasia; Middle Aged; Pyloric Antrum; Pylorus; Staining and Labeling; Stomach Ulcer; Uremia

A case of malignant endocrine tumour of the jejunum, associated with severe duodenal ulcer is described. The tumour and a local metastasis were examined by immunohistochemistry and found to contain abundant somatostatin-immunoreactive cells together with less numerous cells displaying gastrin immunoreactivity. This is to our knowledge the first case of intestinal somatostatinoma. The presence of gastrin cells in the tumour may explain the ulcer diathesis.

Topics: Duodenal Ulcer; Female; Gastrins; Humans; Intestinal Neoplasms; Jejunum; Middle Aged; Neoplasm Metastasis; Somatostatin

The effect of Mucaine and Aludrox on basal and food stimulated immunoreactive gastrin has been assessed in normal control subjects and patients with duodenal or gastric ulcer. No differences in gastrin responses were observed either in the basal period or after the protein meal with the two antacids. As previously described, release of gastrin was greatest in gastric ulcer patients but in contrast to previous results,normal subjects seemed to show a greater response than duodenal ulcer patients but this was not statistically significant. Thus the combination of a local anaesthetic oxethazaine with aluminium hydroxide gel does not lead to diminished gastrin release and is not the prime mechanism of action of this agent.

Topics: Adult; Aged; Aluminum Hydroxide; Antacids; Duodenal Ulcer; Ethanolamines; Gastrins; Humans; Middle Aged; Peptic Ulcer; Stomach Ulcer

The total number of gastric and duodenal gastrin cells was determined in the gastrectomy specimens from eight patients with peptic ulcer. Planimetry was used to determine the antral and duodenal surface. The immunoperoxydase method with specific antigastrin antibodies was used for staining gastrin cells, and the mean concentration of nucleated gastrin cells per square millimeter of antral and duodenal surface was determined by light microscopy. The mean number of duodenal gastrin cells in the resected duodenum was 4.8 per cent of the total gastric gastrin cell mass. The concentration of gastrin cells in the antrum was quite variable from one mucosal site to another. The degree of extension of the antral gastritic areas was a major factor influencing the mean concentration value. The total number of gastrin cells in the stomach varied from approximately 7 to 74 million cells. Our data indicate that hyperplasia of gastrin cells cannot be demonstrated by studies performed in small specimens taken for biopsy.

Topics: Cell Count; Duodenal Ulcer; Duodenum; Gastrectomy; Gastrins; Humans; Immunoenzyme Techniques; Peptic Ulcer; Pyloric Antrum

The mucosal distribution of G cells was quantitatively mapped in resected stomachs from 42 patients (12 with gastric ulcer, 11 with duodenal ulcer, 14 with duodenal ulcer and uremia, and 5 with gastric cancer). Along the histological border of the proximal part of the pyloric antrum there was in all patient categories a transitional zone of varying extent, with a low G-cell density before the cells disappeared in the body of the stomach. The proximal end of the duodenum contained considerably fewer G cells than in the antrum, and the number was virtually equal in all groups. Within the antrum there was in the material as a whole a gradual increase in G-cell density from the proximal to the distal part, but this difference was not apparent for the gastric ulcer patients. When corresponding antral segments were compared between the various patient groups, the G-cell density was found to be significantly decreased in the distal antrum of the gastric ulcer patients. In all patient categories, except the duodenal ulcer group with uremia, the circumferential distribution of G cells showed reduced density along the curvatura minor. For the material as a whole there were great individual variations in the overall antral G-cell density, in the antral area corresponding to the distribution of G cells and in the total G-cell mass; these three variables were not significantly related to diagnosis, age or sex.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Fluorescent Antibody Technique; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Stomach Neoplasms; Stomach Ulcer; Uremia

Intraduodenal instillation of hypertonic glucose significantly inhibited tetragastrin-induced gastric acid and pepsin outputs in man. The secretory volume of gastric juice was markedly decreased, whereas, acid concentration remained unchanged. Pepsin concentration, on the contrary, was reduced significantly. The degree of inhibition of pepsin output, therefore, was greater than that of acid output. No significant difference in the extent of inhibition of acid or pepsin output was observed between control subjects and patients with duodenal ulcer.

Topics: Adult; Duodenal Ulcer; Duodenum; Female; Gastric Juice; Gastrins; Glucose; Humans; Hypertonic Solutions; Male; Middle Aged; Pepsin A

Topics: Adult; Dietary Fats; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Intestinal Secretions; Male; Middle Aged; Pepsin A

The concentration and molecular form of gastrin in urine were determined radioimmunochemically. Urine from hypergastrinaemic patients (Zollinger-Ellison syndrome and pernicious anaemia) contained gastrins corresponding to the serum components I and II. The excretion of gastrin increased with increasing gastrin concentrations in serum. Urine from six subjects with normal concentrations of gastrin in serum contained "apparent" gastrin immunoreactivity which could not be removed by specific immunoabsorption. No gastrin was detectable by gel filtration of desalted and concentrated urine from normal subjects. The apparent immunoreactivity was due partly to interference by sodium chloride. The results indicate that hypergastrinaemic patients, in contrast to normal subjects, excrete gastrins in the urine.

Topics: Anemia, Pernicious; Chromatography, Gel; Duodenal Ulcer; Gastrins; Humans; Immunosorbent Techniques; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Immunoenzyme Techniques; Pyloric Antrum

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Histological Techniques; Humans; Immunologic Techniques; Pyloric Antrum

Topics: Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastrins; Humans; Hyperplasia; Immunologic Techniques; Pyloric Antrum; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Blood Glucose; Cimetidine; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Guanidines; Humans; Insulin; Male; Middle Aged

Serum gastrin, serum insulin, plasma noradrenaline, plasma adrenaline, pulse rate and blood pressure were measured repeatedly during 24h in six patients with duodenal ulcer and in six control subjects. Mean serum gastrin concentration was 3-4 times higher in duodenal ulcer patients than in controls during both the day and at night. Serum insulin was the same in both groups of subjects. Overnight fasting and mean supine plasma noradrenaline as well as mean supine pulse rate were significantly higher in duodenal ulcer patients than in controls. Plasma adrenaline and arterial blood pressure were the same in patients and controls. These results suggest that sympathetic nervous activity is increased in patients with duodenal ulcer. The increased sympathetic nervous activity may mean that duodenal ulcer patients are subject to more stress than normal subjects or may be compensatory to increased vagal nervous activity presumed by some authors to be present in such patients.

Topics: Adult; Blood Pressure; Duodenal Ulcer; Eating; Fasting; Gastrins; Heart Rate; Humans; Male; Norepinephrine

The serum gastrin response to whole beef extract was measured in 14 duodenal ulcer patients before and after sulpiride administration. A significant inhibition of response was found both after acute intramuscular injection of the drug and after oral administration for 1 week. Fasting serum gastrin was also significantly reduced after chronic treatment; gastric acid secretion did not change. Although the mechanism of the gastrin-lowering action of sulpiride is unknown, it could be mediated by some known effects(s) of the drug, such as modifications in brain monoamine metabolism or perhaps reduced growth hormone secretion.

Topics: Administration, Oral; Adult; Animals; Cattle; Depression, Chemical; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Injections, Intramuscular; Male; Meat; Middle Aged; Sulpiride

Topics: Adult; Animals; Cattle; Duodenal Ulcer; Eating; Epinephrine; Fasting; Female; Gastrins; Humans; Male; Meat; Middle Aged; Norepinephrine; Physical Exertion; Propranolol; Pulse; Smoking; Vagotomy

Topics: Cimetidine; Duodenal Ulcer; Gastrins; Guanidines; Humans; Renal Dialysis

The inhibitory effects of cimetidine on gastric acid and pepsin secretion were studied before and after 1 month of treatment with 300 mg of cimetidine four times a day in 15 male duodenal ulcer patients. Cimetidine inhibited both pentagastrin- and peptone meal-stimulated acid secretion significantly better before, than after, 1 month of treatment. Similarly cimetidine inhibited pentagastrin-stimulated pepsin secretion significantly better before treatment. Meal-stimulated serum gastrin concentrations were significantly higher after treatment. The mechanism(s) of these effects was not apparent.

Topics: Cimetidine; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Guanidines; Humans; Male; Middle Aged; Pepsinogens; Time Factors

The effects of calcium and secretin were studied in 8 patients with the Zollinger-Ellison syndrome and 18 patients with duodenal ulcer disease. Intravenous infusion of calcium gluconate produced marked increases in serum gastrin levels in the patients with Zollinger-Ellison syndrome (4,350 +/- 1,625 pg/mg) and very slight increases in the patients with duodenal ulcer disease (140 +/- 49 pg/ml). Secretin given as a single intravenous injection also induced marked elevations in serum gastrin in the group with the Zollinger-Ellison syndrome (4,063 +/- 1,990 pg/ml). By contrast, intravenous secretin resulted in a progressive fall in serum gastrin levels in the duodenal ulcer group (from 119 to 97 pg/mg). These results suggest that both stimuli are very useful dagnostic tools in discriminating between Zollinger-Ellison and non-Zollinger-Ellison patients. The secretin challenge test is felt to be superior to the calcium infusions because it is simpler, safer and very rarely produces false-negative or-positive results.

Topics: Adult; Calcium; Diagnosis, Differential; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG), and insulin (IRI) were estimated in 41 normal weight patients with duodenal ulcer (DU) and 25 age-matched controls in response to a high calorie liquid test meal. 28 out of 41 DU patients had a hyperglycaemic glucose response during the test meal, and 15 had a pathological oral glucose tolerance test. Fasting and food-stimulated IR-GIP and IRG levels were significantly elevated in the DU patients. Serum IRI also increased to significantly higher levels in DU patients after the test meal. The degree of the greater hormone response was dependent on the glucose increase after the test meal in the case of insulin and GIP, but not in the case of gastrin. It is concluded: firstly, that a faster glucose absorption (possibly due to rapid initial gastric emptying or increased intestinal motility) is responsible for the high and short-lasting glucose peak and the increased GIP and insulin secretion; secondly, that the GIP response could well be causally related to the insulin response; thirdly, that hyposcretion of GIP is ruled out as a possible factor in the pathogenesis of gastric acid hypersecretion of duodenal ulcer patients.

Topics: Adult; Blood Glucose; Duodenal Ulcer; Energy Intake; Fasting; Female; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male

Topics: Blood Glucose; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Insulin

Secretin releasing response to intraduodenal acid infusion was investigated in 15 cases of diseased control, 7 cases of duodenal ulcer, 5 cases of chronic pancreatitis, and 6 cases of diabetes mellitus. Plasma secretin levels in response to duodenal acidification were less in duodenal ulcer and the appearance of the maximal peak was delayed compared with that found in control. It is suggested that the secretin release was impaired in duodenal ulcer in spite of hypersecretion of gastric acids. In chronic pancreatitis, secretin releasing response to acidification was markedly impaired, in addition, inhibition of secretin release by bicarbonate was diminished due to a lack of bicarbonate flow from the pancreas. On the other hand, although the response of secretin release in diabetes mellitus was also lower compared with that in control group, the capacity of secretin response showed values in-between control subjects and chronic pancreatitis. This research was supported in part by grant from the Ministry of Education, Science and Culture in Japan.

Topics: Adolescent; Adult; Chronic Disease; Diabetes Mellitus; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pancreatitis; Secretin

Gastric acid secretion basally and in response to intragastric meat extract instillation or to tetragastrin, and circulating gastrin concentration basally and after meat extract stimulation were studied in 67 patients with gastroduodenal ulcer, 30 patients after highly selective vagotomy or selective vagotomy for duodenal ulcer, 12 patients after antrectomy for or gastric ulcer and 10 control subjects. Circulating gastrin concentration increased significantly after meat extract stimulation in control subjects, patients with ulceration and patients after highly selective vagotomy, and acid secretion in each group was increased significantly above basal level. In patients after selective vagotomy, significant increase of circulating gastrin concentration was observed, but it was not associated with significant increase of acid secretion. After antrectomy, neither gastrin nor acid secretion increased significantly after meat extract stimulation. In conclusion, present study suggested that (1) gastric acid secretion in response to intragastric meat extract is chiefly affected by the responsiveness of oxyntic cells and release of antral gastrin and that (2) the presence of the antrum is almost essential for acid secretion after a test meal, and release of duodenal gastrin after antrectomy would not be so potent biologically as to result in an acid secretion.

Topics: Adult; Duodenal Ulcer; Eating; Gastric Juice; Gastrins; Humans; Meat; Middle Aged; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Vagotomy

Topics: Deoxy Sugars; Deoxyglucose; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hydrocortisone; Insulin; Secretory Rate

Gastrin antisera were raised by immunization of rabbits or guinea pigs with synthetic human gastrin I conjugated to bovine serum albumin by carbodiimide. Radioiodination of SHG: 2-17 was performed by the chloramine T-method and by an enzymatic procedure. AE-cellulose was used to get a monoiodinated tracer hormone. Antibody reactions with the different forms of gastrin and with CCK-PZ was characterized. Precision (VK = 6-8%) and reproducibility (VK less than 15%) of the gastrin values were comparable to the insulin assay. Gastrin stimulates the parietal cell and has trophic effects on gastric mucosa. Hypergastrinaemia in combination with hypersecretion exhibits clinical significance in patients suffering from Zollinger-Ellison-syndrome or excluded antrum-syndrome which are due to autonomous gastrin release. Some findings suggest a pathogenetic role of gastrin in duodenal ulcer disease. Those disease in which gastrin determinations are of clinical value are discussed.

Topics: Animals; Duodenal Ulcer; Gastric Mucosa; Gastrins; Guinea Pigs; Humans; Rabbits; Radioimmunoassay; Stimulation, Chemical; Zollinger-Ellison Syndrome

1. Maximal acid output after pentagastrin stimulation, and fasting and postprandial serum gastrin concentrations were determined in 25 normal subjects, 30 patients with corpus gastric ulcers, 10 patients with prepyloric ulcers and 30 patients with both duodenal and gastric ulcers. 2. Corpus ulcers and prepyloric ulcers formed one distinct group. Maximal acid output was abnormally low in the corpus ulcer patients and no different from normal in prepyloric ulcer patients, whereas fasting serum gastrin and postprandial integrated gastrin response was abnormally high in the former and no different from the normal in the latter. Furthermore, as in the normal subjects, a significant negative correlation between maximal acid output expressed in mmol h(-1) kg(-1) body weight and postprandial integrated gastrin response was observed in the corpus and prepyloric ulcer patients taken as a group. 3. In complete contrast patients with both duodenal and gastric ulcers, in whom postprandial integrated gastrin response was statistically highest amongst the three types of gastric ulcers, had a significantly positive correlation between maximal acid output and the integrated gastrin response. 4. These findings suggest the operation of different pathophysiological mechanisms in gastric ulcers with and without associated duodenal ulcers.

Topics: Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Secretory Rate; Stomach Ulcer

In a patient with a duodenal ulcer, with acid hypersecretion and moderately disturbed gastrin secretion tests, immunocytochemical examination of the vagotomy-antrectomy specimen revealed a pyloric microgastrinoma (clinically silent and apparently benign) and focal antropyloric gastrinosis. These localised lesions represent a new variant of abnormalities affecting the gastrin cells in the context of hypersecretory duodenal ulcers.

Topics: Adenoma; Carcinoid Tumor; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Pylorus; Stomach Neoplasms

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

Topics: Adult; Duodenal Ulcer; Eating; Esophagogastric Junction; Gastrins; Humans; Manometry; Middle Aged; Pressure; Pyloric Antrum; Vagotomy

Topics: Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Infusions, Parenteral; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

In the past 6 years 26 patients underwent operation for recurrent duodenal ulcer after what was considered to be an "adequate" initial operation. In such patients it is necessary first to demonstrate the recurrent ulcer and then to determine its cause. Endoscopy was the best means of confirming the diagnosis. The cause of recurrence was determined by tests for gastric acid secretion; 70% of patients had hyperacidity and 80% had positive results of the Hollander test. Treatment is always surgical but varies depending on the type of initial surgery, the primary cause of recurrence and the condition of the patient. Ten patients underwent vagotomy, 12 had vagotomy with antrectomy and 4 had antrectomy alone. There were no operative deaths but nine (35%) patients experienced 11 significant postoperative complications.

Topics: Adult; Aged; Drainage; Duodenal Ulcer; Endoscopy; Female; Gastrins; Humans; Male; Methods; Middle Aged; Pyloric Antrum; Recurrence; Retrospective Studies; Vagotomy

Topics: Adult; Cholecystokinin; Cimetidine; Duodenal Ulcer; Eating; Female; Gastrins; Humans; Male; Pancreatic Hormones; Peptides; Propantheline; Reflex; Stomach; Vagus Nerve

Estimates of the G cell population were made in 24 resected human pyloric antra from counts of cells in multiple samples and from measurements of antral size. Measurements had been made previously in 20 subjects of acid output (basal and after pentagastrin) and in 10 subjects of plasma gastrin (basal and after insulin + bicarbonate). G cells were most dense near the pylorus, but their circumferential distribution was even. The G cell populations ranged from 8 to 15 (mean 10) million in four control patients and from 3 to 43 (mean 18) million in 15 patients with duodenal ulcer. Those with recurrent ulcer after vagotomy had either a low G cell count and incomplete vagotomy, or a high G cell count and apparently complete denervation. Two patients with hypergastrinaemia and duodenal ulcer had moderate (29 X 10(6)) or marked (56 X 10(6)) excesses of G cells. 'G cell hyperplasia' may represent the extreme end of the normal range of G cell numbers in the antrum, and can be assessed by semi-quantitative grading of G cell hyperplasia in antral biopsies. There were significant direct correlations between antral area and G cell density, between peak acid output and G cell population, and between basal plasma gastrin and G cell density (but not population). We suggest that, in patients with duodenal ulcer, acid and gastrin secretion are interrelated and that both are related to the masses of parietal cells and of G cells.

Topics: Cell Count; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hyperplasia; Pyloric Antrum

Topics: Achlorhydria; Anemia, Pernicious; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum; Somatostatin

Topics: Cimetidine; Duodenal Ulcer; Food; Gastric Juice; Gastrins; Guanidines; Humans; Pentagastrin; Time Factors

Topics: Age Factors; Duodenal Ulcer; Female; Gastrins; Humans; Hypertrophy; Infant; Male; Pyloric Stenosis; Radioimmunoassay

Topics: Acute Disease; Animals; Chronic Disease; Cysteamine; Disease Models, Animal; Duodenal Ulcer; Duodenum; Female; Gastric Juice; Gastrins; Male; Rats

To assess the effectiveness of selective proximal vagotomy (SPV) in reducing the acid response to food, we have compared pre- and postoperative gastric acid and serum gastrin responses to a meal in 11 duodenal ulcer patients with intractable pain treated by SPV, with those of seven ulcer patients with gastric outlet obstruction treated by truncal vagotomy and drainage (TV + D). Acid secretion was measured by an intragastric titration method which measures acid response to food within the stomach (5% amino acid meal) adjusted to various pH levels (5.5, 2.5, and 1.5). Studies were performed before and two to six weeks after operation. The preoperative intragastric acid output (IGAO) was about 50% of maximal acid response to Histalog. The mean preoperative IGAO at pH 5.5 For 11 SPV patients was 17.4 +/- 3.1 mEq/hour; this was decreased by 72% to 4.3 +/- 1.1 mEq/hour after operation. The mean IGAO at pH 5.5 in nine patients treated by TV + D was 21.6 +/- 3.4 mEq/hour; this was decreased by 67% to 7.3 +/- 2.1 mEq/hour. Gastrin levels were significantly higher in postop than in preop SPV PATIENTS EVEN THOUGH PH values were constant. Gastrin levels were higher in postop TV + D patients than in postop SPV patients. This study demonstrates that acid reduction achieved by SPV is reliable and at least comparable with that achieved by turncal vagotomy. Postoperative elevation of gastrin in the SPV patients suggests that the vagus may release a humoral inhibitor of gastrin release from the gastric fundus; there may also be a further direct vagal inhibitor of antral gastrin release.

Topics: Adult; Drainage; Duodenal Ulcer; Evaluation Studies as Topic; Female; Follow-Up Studies; Food; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Methods; Middle Aged; Vagotomy

Topics: Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Intestinal Mucosa; Male; Serotonin; Stomach Diseases

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Duodenum; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Stomach Ulcer

Topics: Duodenal Ulcer; Gastrins; Humans; Peptic Ulcer; Stomach Ulcer

A case of recurrent duodenal ulcer, basal gastric hypersection, and hypergastrinemia of antral origin is presented. The diagnosis was suggested preoperatively by stimulation tests with secretin and food. Billroth II antrectomy led to normalization of serum gastrin within half an hour. The gastrin content of the antral mucosa was not increased, neither was antral G-cell hyperplasia demonstrable. Postoperatively the basal gastric acid output and fasting serum gastrin levels were normal, without a postprandial increase in serum gastrin concentrations. The case does not support the existence of a specific disease called antral G-cell hyperplasia.

Topics: Adult; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male; Pyloric Antrum; Recurrence; Secretory Rate

Topics: Animals; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Insulin; Insulin Secretion; Rats; Vagotomy

Topics: Adult; Calcium; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hypercalcemia; Middle Aged

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.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Fasting; Female; Food; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Stomach Ulcer; Uremia

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

Topics: Adolescent; Adult; Duodenal Ulcer; Esophagogastric Junction; Food; Gastrins; Humans; Manometry; Middle Aged; Pressure; Stomach Ulcer

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

Topics: Adult; Aged; Duodenal Ulcer; Esophagogastric Junction; Food; Gastrins; Humans; Middle Aged; Pressure; Pyloric Antrum; Vagotomy

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Neoplasms; Stomach Ulcer

Topics: Animals; Cimetidine; Dogs; Duodenal Ulcer; Gastrins; Histamine H2 Antagonists; Humans; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Liver Cirrhosis; Male; Middle Aged; Stomach Ulcer

Pigs develop gastric ulceration spontaneously and after bile duct ligation. Despite increased basal acid secretion, serum gastrin levels are not elevated, and a possible 'protective' role of gastrin was proposed. Continuous intravenous infusion of synthetic human gastrin did not protect from gastric ulceration, but was associated with simultaneous duodenal ulceration. Another ulcerogenic mechanism must be invoked.

Topics: Animals; Bile Ducts; Duodenal Ulcer; Gastrins; Infusions, Parenteral; Stomach Ulcer; Swine

1. In duodenal ulcer patients SPV results in an increase of basal and postprandial serum gastrin levels. There is no decrease of hypergastrinemia even five years after SPV. 2. After SPV there is a significant increase in basal serum GIP levels; postprandial GIP concentrations show a faster increase after food intake. 3. Serum insulin and blood glucose concentrations are not altered by SPV.

Topics: Chronic Disease; Digestion; Duodenal Ulcer; Follow-Up Studies; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Vagotomy

The distribution of parietal cells in the body mucosa, and of G cells in the antral mucosa, was quantitatively mapped in resected stomachs from 42 patients (12 with gastric ulcer, 11 with duodenal ucler, 14 with duodenal ulcer and uremia, and 5 with gastric cancer) who preoperatively had had their gastric acid secretion measured. In the material as a whole there was a significant positive correlation between the parietal-cell density and maximal acid output (MAO), and a significant negative correlation between the parietal-cell density and patient age. A significant positive correlation was found between the antral G-cell mass and basal acid output (BAO). When the individual patient categories were analyzed, the correlation between parietal-cell density and MAO were significant in the group with duodenal ulcer and uremia, and in the group with gastric cancer. Correlation between parietal-cell density and age was found only in the group with duodenal ulcer and uremia. There was no correlation between the parietal-cell density and various parameters of the antral G-cell population in the material as a whole or in any of the individual groups.

Topics: Adult; Aged; Cell Count; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Stomach; Stomach Neoplasms; Stomach Ulcer; Uremia