gastrins and Achlorhydria

Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers.. The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice.. In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria.. Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.

Topics: Achlorhydria; Antibodies, Bacterial; Biomarkers; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Mass Screening; Pepsinogen A; Pepsinogen C; Stomach Neoplasms; Vitamin B 12

Proton pump inhibitors (PPI) are one of the most widely used groups of drugs and their potential toxicity is periodically reviewed, emphasizing aspects originally considered secondary. The present review analyzes the physiological and pharmacological bases and the scarce clinical evidence for a potential association between the continued administration of PPI and the development of osteoporosis and bone fractures. Both disorders are clearly related to calcium homeostasis and are highly important in elderly patients due to their poor general prognosis and disabling consequences.

Topics: Achlorhydria; Aging; Calcium; Calcium, Dietary; Comorbidity; Disease Susceptibility; Fractures, Spontaneous; Gastric Acid; Gastrins; Homeostasis; Humans; Hyperparathyroidism, Secondary; Intestinal Absorption; Malabsorption Syndromes; Models, Biological; Osteoporosis; Proton Pump Inhibitors; Risk

Gastric hypoacidity and hypergastrinaemia are seen in several conditions associated with an increased risk of gastric malignancy. Hypoacidity and hypergastrinaemia are closely related and their long-term effects are difficult to study separately in patients. Studies using animal models can provide valuable information about risk factors and mechanisms in gastric cancer development as the models allow a high degree of intervention when introducing or eliminating factors possibly affecting carcinogenesis. In this report, we briefly review findings from relevant animal studies on this topic. Animal models of gastric hypoacidity and hypergastrinaemia provide evidence hypergastrinaemia is a common causative factor in many otherwise diverse settings. In all species where sufficient hypoacidity and hypergastrinaemia have been induced, a proportion of the animals develop malignant lesions in the gastric oxyntic mucosa.

Topics: Achlorhydria; Animals; Cell Proliferation; Cell Transformation, Neoplastic; Disease Models, Animal; Enterochromaffin-like Cells; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Receptor, Cholecystokinin B; Risk Assessment; Risk Factors; Stomach; Stomach Neoplasms

The gastrointestinal hormone, gastrin, was discovered a century ago as the second hormone in history. Subsequently, gastrin peptides have been identified and the genes encoding the hormone as well as its receptor have been cloned in several mammalian species including the mouse. This has facilitated the development of gastrin and gastrin receptor deficient mice as models for genetic dissection of the role of gastrins in maintaining gastric homeostasis and control of acid secretion. The gastrin knockout mice are achlorhydric due to inactivation of the ECL and parietal cells. Moreover, this achlorhydria is associated with the development of intestinal metaplasia and bacterial overgrowth, which ultimately lead to development of gastric tumors. Outside the stomach, gastrin deficiency alters pancreatic islet physiology and is associated with a moderate fasting hypoglycemia in the fasting state. But lack of gastrin does not impair islet regeneration. The association between progastrin, progastrin-derived processing intermediates and colorectal carcinogenesis has also been examined through genetic or chemical cancer induction in several mouse models, although the clinical relevance of these studies still remains to be proven. While others have focused on models of increased gastrin production, the present review will describe the lessons learned from the gastrin deficient mice. These mice help understand how dysregulation of gastrin secretion may be implicated in human disease.

Topics: Achlorhydria; Animals; Gastric Acid; Gastrins; Humans; Intestines; Metaplasia; Mice; Mice, Knockout; Models, Biological

Gastrin and gastrin receptor-deficient mice have been used for genetic dissection of the role of gastrins in maintaining gastric homeostasis and control of acid secretion. The gastrin knockout mice are achlorhydric due to inactivation of the ECL and parietal cells. Moreover, this achlorhydria is associated with intestinal metaplasia and bacterial overgrowth, which ultimately leads to the development of gastric tumours. The association between progastrin, progastrin-derived processing intermediates and colorectal carcinogenesis has also been examined through genetic or chemical cancer induction in several mouse models, although the clinical relevance of these studies remains unproven. While others have focused on models of increased gastrin production, the present review describes the lessons learned from gastrin-deficient mice. Study of these mice helps our understanding of how dysregulation of gastrin secretion may be implicated in human disease.

Topics: Achlorhydria; Animals; Gastric Acid; Gastric Mucosa; Gastrins; Gene Expression Regulation; Intestinal Diseases; Metaplasia; Mice; Mice, Knockout; Models, Biological; Receptor, Cholecystokinin B; Stomach Neoplasms

Since hypochlorhydria can induce hypergastrinemia, and gastrin has a trophic effect on some gastrointestinal cells, states that cause elevated plasma gastrin levels are of interest in terms of effects on cell growth and function. This article reviews the relationship between gastric mucosal cells during periods of acid stimulation and inhibition and analyses the effects of hypochlorhydria and hypergastrinemia on gastric and colonic cells and tumors. Hypochlorhydria releases the inhibitory effect of antral gastrin cells, inducing them to release gastrin in the presence of peptides or amino acids in the gastric lumen or in response to antral distension. Gastrin stimulates the oxyntic mucosa, which may lead to hyperplasia of enterochromaffin-like cells, resulting in enterochromaffin-like carcinoid tumors in aged rats and, rarely, in patients with chronic atrophic gastritis or gastrinomas. In addition to hypergastrinemia, other factors appear to be required for the progression of enterochromaffin-like hyperplasia to carcinoids; genetic factors may be involved. Gastrin elevations due to antisecretory drug therapy are indirectly proportional to the degree of acid inhibition and are reversible upon cessation of therapy. The gastrin levels during omeprazole therapy are similar to those caused by gastric vagotomy. Available evidence does not support a relationship between hypergastrinemia and the occurrence or growth of gastric carcinoma or colonic tumors.

Topics: Achlorhydria; Animals; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Omeprazole; Rats

Topics: Achlorhydria; Antacids; Anti-Ulcer Agents; Gastric Acid; Gastrins; Gastroesophageal Reflux; Humans; Peptic Ulcer; Time Factors

Achlorhydria has been discussed as a possibly dangerous consequence of therapeutic inhibition of gastric acid secretion since the introduction of H2-receptor antagonists. The risk of long-term hypergastrinaemia has only been considered for about 5 years. The reason for this was the demonstration that gastric carcinoids (ECLomas) observed after life-long treatment of rats with the proton pump inhibitor omeprazole could also be produced in rats by other methods leading to long-lasting profound hypergastrinaemia. Such methods were the 80% resection of the oxyntic mucosa or feeding of ranitidine (2000 mg/day) for 2 years. The endocrine tumours corresponded to the gastric carcinoids found in patients with long-lasting hypergastrinaemia due to pernicious anaemia or with a gastrinoma as part of the MEN I syndrome. Neither in animals nor in man could other endocrine tumours or adenocarcinomas of the gastrointestinal tract be related to hypergastrinaemia. Epidemiologic data do not support gastrin dependence of adenocarcinoma of the stomach or the colon. Experimental findings of gastrin effects on tumour growth in vivo and in vitro have been contradictory and may be explained by the presence of gastrin receptors on tumour cells and the role of gastrin as an autocrine growth factor in some of these tumours. Since acid blockade by proton pump inhibitors or H2-receptor blockers dose-dependently increase serum gastrin levels, patients with ranitidine-resistant peptic ulceration receiving long-term treatment with high-dose omeprazole have been followed up with serial gastric biopsy specimens for up to 5 years. Complete healing, moderate hypergastrinaemia, and a slight hyperplasia but no dysplasia of the ECL cells in the oxyntic mucosa have been observed, which seemed to be correlated to chronic gastritis progressing over the years. Despite these negative findings excessive hypergastrinaemia by overdosage of potent drugs for inhibition of gastric secretion should be avoided and monitoring of plasma gastrin levels is recommended in case of long-term treatment.

Topics: Achlorhydria; Adenocarcinoma; Colonic Neoplasms; Enterochromaffin Cells; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Histamine H2 Antagonists; Humans; Stomach Neoplasms

Topics: Achlorhydria; Endoscopy, Gastrointestinal; Gastrins; Humans; Hypertension, Portal; Prevalence; Stomach Diseases

Topics: Achlorhydria; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Histamine; Humans; Hyperplasia; Pyloric Antrum; Stomach

Topics: Achlorhydria; Carcinoid Tumor; Gastrectomy; Gastrins; Gastritis, Atrophic; Humans; Stomach Neoplasms

Several gastric mucosal diseases and the response to powerful gastric secretory inhibitors are accompanied by hypergastrinaemia. When the gastric mucosa is functioning normally, hypergastrinaemia may be dangerous as a consequence of gastric hypersecretion. When the gastric mucosa is functionally abnormal, hypergastrinaemia produces no apparent adverse effects on health. However, the diseases giving rise to hypergastrinaemia are very dangerous because they are often the precursors of gastric cancer. In view of the probable mechanisms of gastric carcinogenesis, it is argued that therapeutic achlorhydria is also potentially dangerous irrespective of the absence or presence of 'hypergastrinaemia'.

Topics: Achlorhydria; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Omeprazole

Newer potent and long-acting inhibitors of acid secretion, such as the proton pump inhibitor omeprazole, are becoming available for general use. These drugs promise to control acid-peptic disease effectively in patients who do not respond adequately to conventional short-acting H2-receptor antagonists. The safety of chronic administration of these drugs has come into question, however. Lifelong profound inhibition of acid secretion in rats induced by superpotent inhibitors of acid secretion or subtotal fundectomy is associated with the development of carcinoid tumors of enterochromaffin-like (ECL) cells in the gastric corpus. Available evidence supports a role of gastrin, which becomes chronically elevated in animals subjected to prolonged and profound hypochlorhydria. In humans, hypergastrinemic states such as Zollinger-Ellison syndrome and atrophic gastritis are associated with an increased risk of ECL-cell carcinoid tumors. Such observations have raised concern that humans may also be susceptible to carcinoid tumor formation in response to potent inhibitors of acid secretion. To date, however, no cases of carcinoid tumor have been attributed to the use of omeprazole in humans. If achlorhydric doses are not used, significant hypergastrinemia can be avoided while effectiveness of treatment is maintained. Such measures should minimize any risk of ECL-cell carcinoid tumors in humans taking potent long-term antisecretory drugs.

Topics: Achlorhydria; Animals; Carcinoid Tumor; Cell Transformation, Neoplastic; Enterochromaffin Cells; Gastrins; Humans; Omeprazole; Rats; Stomach Neoplasms

Three cases of gastric carcinoid polypi associated to atrophic gastritis and high levels of seric gastrin, are presented. One of the cases was a multiple micropolyposis the literature regarding this association is reviewed and the therapy discussed. Tumors of greater than 2 cm have to be considered potentially malignant and be treated likewise. The treatment of the micropolyposis is not well established.

Topics: Achlorhydria; Adult; Autoimmune Diseases; Carcinoid Tumor; Female; Follow-Up Studies; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Polyps; Pyloric Antrum; Stomach Neoplasms

Based on the experience from more than 10,000 individuals omeprazole has been found to be safe and is well tolerated. Side effects are few and do not differ from those observed during H2-blocker treatment. Effects on endocrine cells observed in animals during toxicological studies include increase of antral G cells, decrease of antral D cells and increase of fundic ECL cells. The increase of G cells and the decrease of D cells is the consequence of achlorhydria achieved by very high omeprazole dosages and results in hypergastrinaemia. Hypergastrinaemia is responsible for ECL cell hyperplasia. Lifelong hypergastrinaemia in rats has been found to induce carcinoid tumours. This gastrin-carcinoid sequence is unlikely to occur in man with an omeprazole dosage recommended for treatment of peptic diseases. Therapeutic doses in man do not produce complete achlorhydria. Therefore, serum gastrin levels increase in man during omeprazole treatment only moderately and are similar in magnitude as after selective proximal vagotomy. Available results on gastric endocrine cells in patients treated with omeprazole for up to 2 years could not demonstrate significant changes in G, D and ECL cell densities. It is concluded that omeprazole is, in man, as safe as H2 blockers if administered in doses recommended for treatment of peptic diseases.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Achlorhydria; Animals; Carcinoid Tumor; Clinical Trials as Topic; Drug Administration Schedule; Enterochromaffin Cells; Gastrins; Humans; Omeprazole

Topics: Achlorhydria; Adenocarcinoma; Animals; Anti-Ulcer Agents; Carcinoid Tumor; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Rats; Serotonin; Stomach Neoplasms

We have described a 40-year-old woman whose classic adrenal insufficiency, achlorhydria, and hypergastrinemia was complicated by the development of a gastric carcinoid. There is now evidence that patients with elevated serum gastrin levels are at increased risk for this rare tumor.

Topics: Achlorhydria; Addison Disease; Adult; Carcinoid Tumor; Female; Gastrins; Humans; Stomach Neoplasms

This paper reviews the relationship between gastric acid secretion and infection and the protective role of gastric acid as a primary bactericidal barrier and modulator of gastrin section. Gastric acid is bactericidal at pH 3 or less, but reduction of acidity predisposes to infection with a wide variety of bacteria. Bacterial infections or hyperpyrexia may be associated with a marked reduction in gastric acid secretion, and Campylobacter pylori has been suggested as one cause of epidemic hypochlorhydria. Achlorhydria is also associated with hypergastrinaemia with levels 20-fold higher in pernicious anaemia patients than normal subjects. Treatment with antisecretory drugs is associated with hypergastrinaemia with gastrin levels 2- to 5-fold higher than with placebo, and the gastrin levels correlate with the degree of acid suppression. The possible relationship among infection, acid suppression, hypergastrinaemia, and the development of enterochromaffin cell hyperplasia and possible carcinogenesis is reviewed.

Topics: Achlorhydria; Bacterial Infections; Campylobacter Infections; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration

Topics: Achlorhydria; Animals; Gastric Mucosa; Gastrins; Humans; Rats; Stomach Neoplasms

The accumulating evidence of an association between antrum-sparing hypergastrinaemic atrophic gastritis, frequently associated with pernicious anaemia, and the occurrence of gastric carcinoid tumours is briefly reviewed. The development of argyrophil cell carcinoid tumours in the atrophic fundic mucosa seems to be related to argyrophil cell hyperplasia caused by hypergastrinaemia. Epidemiologic considerations indicate that the gastric carcinoid generally is underdiagnosed and that the incidence of this tumour is higher than previously recognized. The clinical relevance of minute gastric carcinoids, or endocrine cell 'adenomas', is obscure. However, larger tumours should be regarded as potentially malignant. These findings are relevant to the aspect of long-term medically induced achlorhydria leading to hypergastrinaemia.

Topics: Achlorhydria; Adenoma; Anemia, Pernicious; Atrophy; Carcinoid Tumor; Cell Division; Epidemiologic Methods; Gastrins; Gastritis; Humans; Stomach Neoplasms

Topics: Achlorhydria; Acromegaly; Adenoma; Adenoma, Islet Cell; Adolescent; Adult; Aged; Calcium; Cushing Syndrome; Diarrhea; Female; Gastric Acid; Gastrins; Glucagon; Humans; Hyperinsulinism; Hyperparathyroidism; Hypoglycemia; Hypokalemia; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Polypeptide; Pancreatitis; Parathyroid Glands; Parathyroid Neoplasms; Pituitary Neoplasms; Syndrome; Thyroid Diseases; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Adrenocorticotropic Hormone; Animals; Dogs; Gastric Juice; Gastrins; Gonadotropins, Pituitary; Growth Hormone; Haplorhini; Humans; In Vitro Techniques; Insulin Antagonists; Pancreatic Hormones; Rats; Somatostatin; Thyrotropin

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

The Verner-Morrison Syndrome is a clinically defined entity caused by an islet cell tumor of the pancreas. More than 60 cases have been described so long. The syndrome is characterized by diarrhea, hypokalemia and hypochlorhydria. In addition to a diabetic disposition, raised calcium levels and skin alterations may be present. The diagnosis is a clinical one. A pancreatic tumor should be searched for and removed. Morphologically a benign and a maligne islet cell tumor or a diffuse hyperplasia of the islets of Langerhans can be found. Until now identification of the tumor cells has not been possible. There seems no doubt that the tumor cells produce a peptide hormone. Secretin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide and combinations of hormones are discussed. The results are contradictory. Theories concerning the formal and causal pathogenesis are only incomplete and unproved up to now.

Topics: Achlorhydria; Adenoma, Islet Cell; Adolescent; Adult; Aged; Diarrhea; Female; Gastrins; Glucagon; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Pancreatic Neoplasms; Peptides; Pregnancy; Secretin; Syndrome

The islet cell tumors of the pancreas are now known to produce a variety of polypeptides in addition to insulin. These include glucagon, serotonin, corticotropin, melanocyte-stimulating hormone, gastrin and a secretinlike hormone that may be VIP or a combination of such polypeptides. The development and wide availability of the newer immunoassays for the various recognized hormones as well as candidate hormones of the gut will simplify the diagnosis of these challenging tumors, which up until this time have produced symptoms that were bizarre and often fatal to the patient.

Topics: Achlorhydria; Adenoma, Islet Cell; Angiography; Calcium; Diagnosis, Differential; Diarrhea; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hyperinsulinism; Hyperparathyroidism, Secondary; Neoplasm Metastasis; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Acute Kidney Injury; Adenoma, Islet Cell; Adult; Cholecystokinin; Dehydration; Diarrhea; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypercalcemia; Hypokalemia; Kidney Diseases; Male; Pancreatic Neoplasms; Protein Precursors; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Animals; Calcitonin; Calcium; Dogs; Gastric Juice; Gastrins; Glucagon; Humans; Hyperparathyroidism; Magnesium; Parathyroid Glands; Parathyroid Hormone; Peptic Ulcer; Phosphates; Rats

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: 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

Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size of the largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalized circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the source of the tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type 1 gastric NETs.. After a mean 14 months off netazepide, 13 of the 16 patients took it for another 52 weeks. Assessments were: gastroscopy; gene-transcript expression in corpus biopsies using quantitative polymerase chain reaction; blood CgA and gastrin concentrations; and safety assessments.. While off-treatment, the number of tumours, the size of the largest one, and CgA all increased again. Netazepide for 52 weeks: cleared all tumours in 5 patients; cleared all but one tumour in one patient; reduced the number of tumours and size of the largest one in the other patients; normalized CgA in all patients; and reduced mRNA abundances of CgA and histidine decarboxylase in biopsies. Gastrin did not increase further, confirming that the patients had achlorhydria. Netazepide was safe and well tolerated.. A gastrin/cholecystokinin 2 receptor antagonist is a potential medical and targeted treatment for type 1 gastric NETs, and an alternative to regular gastroscopy or surgery. Treatment should be continuous because the tumours will regrow if it is stopped. Progress can be monitored by CgA in blood or biomarkers in mucosal biopsies.

Topics: Achlorhydria; Aged; Autoimmune Diseases; Benzodiazepinones; Chromogranin A; Gastrins; Gastritis, Atrophic; Histidine Decarboxylase; Humans; Middle Aged; Neuroendocrine Tumors; Phenylurea Compounds

Gastric analysis is useful for diagnosing and monitoring the control of hypersecretory conditions and to distinguish appropriate from inappropriate causes of hypergastrinaemia. Pentagastrin, used to measure maximal acid output (MAO), is no longer available in the USA.. We examined the University of Pennsylvania Health System gastric analysis database, which includes demographic data, study indications, gastric analysis, and serum gastrin and secretin testing results according to referral indications, paying specific attention to discordant basal acid output (BAO) and MAO measurements.. One hundred and twenty-four gastric analyses were performed in 103 patients (42 males, mean age 47.5 years, 14 with prior acid-decreasing surgery). Recurrent ulceration or pain unresponsive to antisecretory therapy was the indication in 42 patients. Twelve were hypersecretory, including three each with isolated elevations of BAO or MAO. Hypergastrinaemia was the indication in 35 patients. Five were hypersecretory (four with Zollinger-Ellison syndrome), three had isolated MAO elevations and 16 were hypo- or achlorhydric, indicating appropriate hypergastrinaemia. Of the seven patients with isolated MAO elevations, two had clear benefit from the stimulated portion of the study (four additional patients had equivocal benefit).. Gastrin concentrations cannot be interpreted without knowledge of acid secretory capacity. MAO measurement has a small but significant benefit over measuring BAO alone.

Topics: Achlorhydria; Adolescent; Adult; Aged; Enzyme Inhibitors; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Proton Pump Inhibitors; Recurrence; Retrospective Studies; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

The bioavailability of dipyridamole, a poorly soluble weak base, was evaluated in 11 healthy, older subjects (> or = 65 years), 6 with a low fasting gastric pH (control) and 5 with a fasting gastric pH > 5 (achlorhydric), in a randomized, crossover design. Subjects received 50 mg dipyridamole as a single oral dose both with and without pretreatment with 40 mg famotidine (control subjects) or 1360 mg glutamic acid HCl (achlorhydric subjects). Gastric pH was monitored by Heidelberg radiotelemetric capsule. Gastric emptying of 99mTc-radiolabeled orange juice was measured. Gastric pH appeared to be a primary determinant in dipyridamole absorption in the elderly. Elevated gastric pH resulted in compromised dipyridamole absorption compared to low-gastric pH conditions in all cases. The administration of glutamic acid hydrochloride to achlorhydric subjects prior to the dose of dipyridamole corrected for the decreased Cmax and AUC(0-36) exhibited in achlorhydric subjects without pretreatment. Tmax and ka were slower in achlorhydrics, although pretreatment with glutamic acid HCl tended to normalize these parameters. Based on these results, it would be beneficial for achlorhydrics to take glutamic acid hydrochloride prior to taking dipyridamole and other medications which need a low gastric pH for complete absorption. The administration of 40 mg famotidine was successful in elevating the gastric pH to > 5 in all subjects and maintained it at > 5 for at least 3 hr in all subjects tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Achlorhydria; Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Dipyridamole; Famotidine; Female; Gastric Acid; Gastric Emptying; Gastrins; Glutamates; Glutamic Acid; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Male

The mechanisms of hypergastrinaemia during H2-receptor antagonist therapy remain unclear. In addition, the effect of food stimulation in conditions of hypergastrinaemia is poorly understood. These effects may be important when considering long-term therapy with potent acid inhibitory agents. To investigate this we studied the effect of H2-receptor antagonist therapy on basal and meal-stimulated plasma gastrin concentrations in 9 patients with pentagastrin fast gastric achlorhydria associated with pernicious anaemia. The subjects received in double-blind randomized fashion 28-day courses of 300 mg ranitidine q.d.s. and placebo, with one-month wash-out between. The fasting and peptone meal-stimulated gastrin concentrations were studied on the final day of each course of treatment. The median fasting gastrin concentrations (ng/L) were similar following placebo (1100, range 25-2100), and 300 mg ranitidine q.d.s. (1075, range 15-2600) and both markedly elevated when compared with our laboratory's normal range of 0-100. Despite the elevated basal levels the pernicious anaemia patients still showed a further increase in response to the peptone meal. Their median peak percentage rise over basal in response to the meal was similar following placebo (96%, range 0-375) and 300 mg ranitidine q.d.s. (100%, range 25-425) (both P less than 0.02 c.f. basal). This study shows that: (a) in hypergastrinaemia in pernicious anaemia subjects, meal stimulation leads to a marked and prolonged increase in plasma gastrin concentrations; (b) H2-receptor antagonists have no effect on plasma gastrin in the neutral stomach and this is consistent with their gastrin effect being entirely secondary to acid inhibition.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Double-Blind Method; Fasting; Female; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Peptones; Ranitidine

Based on the experience from more than 10,000 individuals omeprazole has been found to be safe and is well tolerated. Side effects are few and do not differ from those observed during H2-blocker treatment. Effects on endocrine cells observed in animals during toxicological studies include increase of antral G cells, decrease of antral D cells and increase of fundic ECL cells. The increase of G cells and the decrease of D cells is the consequence of achlorhydria achieved by very high omeprazole dosages and results in hypergastrinaemia. Hypergastrinaemia is responsible for ECL cell hyperplasia. Lifelong hypergastrinaemia in rats has been found to induce carcinoid tumours. This gastrin-carcinoid sequence is unlikely to occur in man with an omeprazole dosage recommended for treatment of peptic diseases. Therapeutic doses in man do not produce complete achlorhydria. Therefore, serum gastrin levels increase in man during omeprazole treatment only moderately and are similar in magnitude as after selective proximal vagotomy. Available results on gastric endocrine cells in patients treated with omeprazole for up to 2 years could not demonstrate significant changes in G, D and ECL cell densities. It is concluded that omeprazole is, in man, as safe as H2 blockers if administered in doses recommended for treatment of peptic diseases.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Achlorhydria; Animals; Carcinoid Tumor; Clinical Trials as Topic; Drug Administration Schedule; Enterochromaffin Cells; Gastrins; Humans; Omeprazole

In healthy human volunteers, a single oral dose of enprostil (35 micrograms) inhibited basal gastric acid output by a mean of 71 percent, pentagastrin-stimulated output by 46 percent, sham-meal-stimulated output by 48 percent, and histamine-stimulated output by 16 percent. In each case, there was a reduction in both the volume and acidity of the gastric juice. Pepsin output was unchanged. Although enprostil increased the gastric pH, it did not induce basal or post-prandial hypergastrinemia. In patients with hypergastrinemia secondary to achlorhydria, enprostil lowered the basal gastrin level and reduced or abolished the post-prandial gastrin rise in a dose-related fashion. Enprostil reduces basal and stimulated gastric acid secretion and inhibits gastrin release.

Topics: Achlorhydria; Adult; Anemia, Pernicious; Enprostil; Gastric Acid; Gastric Juice; Gastrins; Histamine; Humans; Hydrogen-Ion Concentration; Male; Pentagastrin; Pepsin A; Prostaglandins E, Synthetic

Methods for the measure of gastric acid secretion include invasive and non-invasive tests. The gold-standard to measure the acid output is the collection of gastric after in basal condition (Basal Acid Output, B.A.O.) and after an i.m. injection of pentagastrin (Maximal Acid Output, M.A.O.). However, direct measurement of gastric acid production is out of order in clinical practice, but many GI symptoms are claimed to be related with acid disorders and empirically cured. Hypochlorhydria is associated with precancerous conditions such as chronic atrophic gastritis (CAG). Acid measurement with non-invasive methods (pepsinogens) is supported by international guidelines.

Topics: Achlorhydria; Biomarkers; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastritis, Atrophic; Humans; Pentagastrin; Pepsinogens; Peptic Ulcer; Precancerous Conditions

Ezrin, an adaptor protein that cross-links plasma membrane-associated proteins with the actin cytoskeleton, is concentrated on apical surfaces of epithelial cells, especially in microvilli of the small intestine and stomach. In the stomach, ezrin is predominantly expressed on the apical canalicular membrane of parietal cells. Transgenic ezrin knockdown mice in which the expression level of ezrin was reduced to <7% compared with the wild-type suffered from achlorhydria because of impairment of membrane fusion between tubulovesicles and apical membranes. We observed, for the first time, hypergastrinemia and foveolar hyperplasia in the gastric fundic region of the knockdown mice. Dilation of fundic glands was observed, the percentage of parietal and chief cells was reduced, and that of mucous-secreting cells was increased. The parietal cells of knockdown mice contained dilated tubulovesicles and abnormal mitochondria, and subsets of these cells contained abnormal vacuoles and multilamellar structures. Therefore, lack of ezrin not only causes achlorhydria and hypergastrinemia but also changes the structure of gastric glands, with severe perturbation of the secretory membranes of parietal cells.

Topics: Achlorhydria; Animals; Antibodies; Cytoskeletal Proteins; Epithelium; Gastric Mucosa; Gastrins; Gene Expression Regulation; Gene Knockdown Techniques; Lectins; Mice; Mice, Transgenic; Microscopy, Fluorescence; Mucin-6; Mucins; Muscle Proteins; Parietal Cells, Gastric; Peptides; RNA; Trefoil Factor-2; Up-Regulation

It is known, that long decrease in gastric secretion leads to the development of hypergastrinemia, dysbiosis and to pathological changes in digestive organs. Very important there is a search of ways to correction of these undesirable consequences. Long-term usage of omeprazole leads to metabolic disorders in periodontium tissues and salivary glands, such as development of NO-ergic system disbalance and activation of free-radical oxidation, that are positively corrected by multiprobiotic of new generation "Symbiter acidophilic".

Topics: Achlorhydria; Animals; Anti-Ulcer Agents; Free Radicals; Gastric Juice; Gastric Mucosa; Gastrins; Glycation End Products, Advanced; Humans; Injections, Intraperitoneal; Male; Mouth; Nitric Oxide Synthase Type II; Omeprazole; Oxidative Stress; Periodontium; Probiotics; Rats; Rats, Wistar; Salivary Glands; Stomach

Mutations in TRPML1, a lysosomal Ca(2+)-permeable TRP channel, lead to mucolipidosis type IV, a neurodegenerative lysosomal storage disease. An unusual feature of mucolipidosis type IV is constitutive achlorhydria. We produced Trpml1(-/-) (null) mice to investigate the requirement for this protein in gastric acid secretion.. Trpml1-null mice were generated by gene targeting. The expression of Trpml1 and its role in acid secretion by gastric parietal cells were analyzed using biochemical, histologic, and ultrastructural approaches.. Trpml1 is expressed by parietal cells and localizes predominantly to the lysosomes; it was dynamically palmitoylated and dephosphorylated in vivo following histamine stimulation of acid secretion. Trpml1-null mice had significant impairments in basal and histamine-stimulated gastric acid secretion and markedly reduced levels of the gastric proton pump. Histologic and ultrastructural analyses revealed that Trpml1(-/-) parietal cells were enlarged, had multivesicular and multi-lamellated lysosomes, and maintained an abnormal intracellular canalicular membrane. The intralysosomal Ca(2+) content and receptor-mediated Ca(2+) signaling were, however, unaffected in Trpml1(-/-) gastric glands, indicating that Trpml1 does not function in the regulation of lysosomal Ca(2+).. Loss of Trpml1 causes reduced levels and mislocalization of the gastric proton pump and alters the secretory canaliculi, causing hypochlorhydria and hypergastrinemia. The lysosomal enlargement and defective intracellular canaliculi formation observed in Trpml1(-/-) parietal cells indicate that Trpml1 functions in the formation and trafficking of the tubulovesicles. This study provides direct evidence for the regulation of gastric acid secretion by a TRP channel; TRPML1 is an important protein in parietal cell apical membrane trafficking.

Topics: Achlorhydria; Animals; Calcium; Disease Models, Animal; Gastric Acid; Gastrins; H(+)-K(+)-Exchanging ATPase; Histamine; Hypertrophy; Lipoylation; Lysosomes; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucolipidoses; Parietal Cells, Gastric; Phosphorylation; Protein Transport; Time Factors; Transient Receptor Potential Channels; TRPM Cation Channels

Hypochlorhydria during Helicobacter pylori infection inhibits gastric Sonic Hedgehog (Shh) expression. We investigated whether acid-secretory mechanisms regulate Shh gene expression through intracellular calcium (Ca2(+)(i))-dependent protein kinase C (PKC) or cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation.. We blocked Hedgehog signaling by transgenically overexpressing a secreted form of the Hedgehog interacting protein-1, a natural inhibitor of hedgehog ligands, which induced hypochlorhydria. Gadolinium, ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) + 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), PKC-overexpressing adenoviruses, and PKC inhibitors were used to modulate Ca(2+)(i)-release, PKC activity, and Shh gene expression in primary gastric cell, organ, and AGS cell line cultures. PKA hyperactivity was induced in the H(+)/K(+)-β-cholera-toxin-overexpressing mice.. Mice that expressed secreted hedgehog-interacting protein-1 had lower levels of gastric acid (hypochlorhydria), reduced production of somatostatin, and increased gastrin gene expression. Hypochlorhydria in these mice repressed Shh gene expression, similar to the levels obtained with omeprazole treatment of wild-type mice. However, Shh expression also was repressed in the hyperchlorhydric H(+)/K(+)-β-cholera-toxin model with increased cAMP, suggesting that the regulation of Shh was not solely acid-dependent, but pertained to specific acid-stimulatory signaling pathways. Based on previous reports that Ca(2+)(i) release also stimulates acid secretion in parietal cells, we showed that gadolinium-, thapsigargin-, and carbachol-mediated release of Ca(2+)(i) induced Shh expression. Ca(2+)-chelation with BAPTA + EGTA reduced Shh expression. Overexpression of PKC-α, -β, and -δ (but not PKC-ϵ) induced an Shh gene expression. In addition, phorbol esters induced a Shh-regulated reporter gene.. Secretagogues that stimulate gastric acid secretion induce Shh gene expression through increased Ca(2+)(i)-release and PKC activation. Shh might be the ligand transducing changes in gastric acidity to the regulation of G-cell secretion of gastrin.

Topics: Achlorhydria; Animals; Calcium; Carrier Proteins; Cyclic AMP-Dependent Protein Kinases; Gastric Acid; Gastrins; Gene Expression Regulation; H(+)-K(+)-Exchanging ATPase; Hedgehog Proteins; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Protein Kinase C; Signal Transduction

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2-64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128DeltacagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4-8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies.

Topics: Achlorhydria; Animals; Antigens, Bacterial; Bacterial Proteins; Cytokines; Gastrins; Gastritis; Genomic Islands; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Hypertrophy; Immunoenzyme Techniques; Precancerous Conditions; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatostatin; Stomach Neoplasms; Stomach Ulcer

To evaluate a 15-year-old boy with MLIV (mucolipidosis type IV) and clinical abnormalities restricted to the eye who also had achlorhydria with elevated blood gastrin levels.. In addition to a detailed neuro-ophthalmic and electrophysiological assessment, his mutant mucolipin-1 was experimentally expressed in liposomes and its channel properties studied in vitro.. The patient was a compound heterzygote for c.920delT and c.1615delG. Detailed neuro-ophthalmic examination including electroretinography showed him to have a typical retinal dystrophy predominantly affecting rod and bipolar cell function. In vitro expression of MCOLN1 in liposomes showed that the c.1615delG mutated channel had significantly reduced conductance compared with wild-type mucolipin-1, whereas the inhibitory effect of low pH and amiloride remained intact.. These findings suggest that reduced channel conductance is relatively well tolerated by the brain during development, whereas retinal cells and stomach parietal cells require normal protein function. MLIV should be considered in patients with retinal dystrophy of unknown cause and screened for using blood gastrin levels.

Topics: Achlorhydria; Adolescent; Electroretinography; Gastrins; Gene Deletion; Guanine; Heterozygote; Humans; Male; Mucolipidoses; Mutation; Retinal Bipolar Cells; Retinal Diseases; Retinal Rod Photoreceptor Cells; Thymine; Transient Receptor Potential Channels; TRPM Cation Channels

The KCNQ1 gene encodes a voltage-dependent potassium ion channel, and mutations in this gene are the most common cause of congenital long QT syndrome (LQTS). In the present study, we investigated the various phenotypic characteristics of vertigo 2 Jackson (C3H/HeJCrl-Kcnq1(vtg-2J)/J) mice with a Kcnq1 mutation. Both heterozygotes (vtg-2J/+) and homozygotes (vtg-2J/vtg-2J) showed prolonged QT intervals in electrocardiograms (ECGs) compared to C3H/HeJ control (+/+) mice. Furthermore, vtg-2J/vtg-2J mice showed gastric achlorhydria associated with elevation of their serum gastrin levels. The serum corticosterone levels were also significantly increased in vtg-2J/vtg-2J mice. In addition, vtg-2J/vtg-2J mice exhibited significantly higher blood pressure. These findings indicate that the Kcnq1 mutation in vtg-2J mice alters various physiological functions in the cardiac, gastric and adrenocortical systems, and suggest that vtg-2J mice may represent a useful model for studying Kcnq1 functions.

Topics: Achlorhydria; Animals; Corticosterone; Disease Models, Animal; Electrocardiography; Female; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Genotype; Hypertension; KCNQ1 Potassium Channel; Long QT Syndrome; Male; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Mutation; Phenotype; Stomach

Genes in the KCNE family encode single transmembrane domain ancillary subunits that co-assemble with voltage-gated potassium (Kv) channel alpha subunits to alter their function. KCNE2 (also known as MiRP1) is expressed in the heart, is associated with human cardiac arrhythmia, and modulates cardiac Kv alpha subunits hERG and KCNQ1 in vitro. KCNE2 and KCNQ1 are also expressed in parietal cells, leading to speculation they form a native channel complex there. Here, we disrupted the murine kcne2 gene and found that kcne2 (-/-) mice have a severe gastric phenotype with profoundly reduced parietal cell proton secretion, abnormal parietal cell morphology, achlorhydria, hypergastrinemia, and striking gastric glandular hyperplasia arising from an increase in the number of non-acid secretory cells. KCNQ1 exhibited abnormal distribution in gastric glands from kcne2 (-/-) mice, with increased expression in non-acid secretory cells. Parietal cells from kcne2 (+/-) mice exhibited normal architecture but reduced proton secretion, and kcne2 (+/-) mice were hypochlorhydric, indicating a gene-dose effect and a primary defect in gastric acid secretion. These data demonstrate that KCNE2 is essential for gastric acid secretion, the first genetic evidence that a member of the KCNE gene family is required for normal gastrointestinal function.

Topics: Achlorhydria; Animals; Cells, Cultured; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gene Targeting; Hyperplasia; Hypertrophy; KCNQ1 Potassium Channel; Mice; Mice, Inbred C57BL; Mice, Knockout; Parietal Cells, Gastric; Potassium Channels, Voltage-Gated; Protein Subunits; Stomach; Up-Regulation

Pernicious anemia (PA), as many other autoimmune disorders, has a trend to appear in other members of the family of the affected patients. Although this fact has been recognized since some decades ago, less is known about the frequency with which the abnormalities detected in the patients appear also in their relatives, the correlations that exist among these abnormalities and to what extent these markers of the disease relate to serum cobalamin concentration.. For these reasons we studied the values of some markers of PA in a group of 79 first-degree relatives and we detected that the most frequent abnormalities are a decrease in serum pepsinogen I (22.7% of cases), an increase in serum gastrin (16.5% of cases) and in parietal cell antibody at a titer >or=40 (23.4% of cases). From a functional point of view, a decrease in hydrogen excretion in a magnesium breath test, indicative of achlorhydria, is also frequent (29.1%). The fall in cobalamin concentration runs in parallel with these abnormalities. The concentration of this vitamin was below normal levels in as much as 15.2% of cases.. These findings emphasize the need for searching for the presence of occult or latent PA in relatives of patients with this diagnosis, not only to prevent the development of anemia but also to avoid other undesirable consequences of cobalamin deficiency.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Breath Tests; Family Health; Female; Gastrins; Humans; Hydrogen; Male; Middle Aged; Pepsinogen A; Risk; Vitamin B 12 Deficiency

The NHE4 Na+/H+ exchanger is abundantly expressed on the basolateral membrane of gastric parietal cells. To test the hypothesis that it is required for normal acid secretion, NHE4-null mutant (NHE4-/-) mice were prepared by targeted disruption of the NHE4 (Slc9a4) gene. NHE4-/- mice survived and appeared outwardly normal. Analysis of stomach contents revealed that NHE4-/- mice were hypochlorhydric. The reduction in acid secretion was similar in 18-day-old, 9-week-old, and 6-month-old mice, indicating that the hypochlorhydria phenotype did not progress over time, as was observed in mice lacking the NHE2 Na+/H+ exchanger. Histological abnormalities were observed in the gastric mucosa of 9-week-old NHE4-/- mice, including sharply reduced numbers of parietal cells, a loss of mature chief cells, increased numbers of mucous and undifferentiated cells, and an increase in the number of necrotic and apoptotic cells. NHE4-/- parietal cells exhibited limited development of canalicular membranes and a virtual absence of tubulovesicles, and some of the microvilli had centrally bundled actin. We conclude that NHE4, which may normally be coupled with the AE2 Cl-/HCO3- exchanger, is important for normal levels of gastric acid secretion, gastric epithelial cell differentiation, and development of secretory canalicular and tubulovesicular membranes.

Topics: Achlorhydria; Alleles; Alternative Splicing; Animals; Apoptosis; Blotting, Northern; Blotting, Western; Cell Differentiation; DNA, Complementary; Dose-Response Relationship, Drug; Exons; Gastric Acid; Gastrins; Hydrogen-Ion Concentration; Immunoblotting; In Situ Nick-End Labeling; Mice; Mice, Transgenic; Microscopy, Electron; Models, Biological; Models, Genetic; Mutation; Necrosis; Parietal Cells, Gastric; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Sodium-Hydrogen Exchangers; Time Factors

Epidemiological studies suggest that atrophic corpus-dominant gastritis is an increased risk factor for gastric carcinogenesis. The role of the Helicobacter pylori type IV secretion system (T4SS) for pathogenesis in the Mongolian gerbil model was explored.. Mongolian gerbils were infected for 32 weeks either with H. pylori type I strain B128 or with isogenic mutant strain B128delta cytotoxin-associated gene (cagY) or B128delta cagA , defective in T4SS or in the production of its effector protein CagA, respectively. Quantitative H. pylori reisolation was performed from the gastric antrum and corpus separately, cytokines were measured by quantitative reverse-transcription polymerase chain reaction, and gastric pH and hormones were determined.. B128-infected gerbils harbored high numbers of bacteria in the gastric antrum and corpus, whereas B128delta cagY and B128delta cagA colonized the antrum more densely than the corpus. All infected animals showed a strong antral inflammation and epithelial cell proliferation. B128-infected, rather than mutant-infected, gerbils presented a severe transmural inflammation with huge lymph aggregates, increased proliferation, significant atrophy, and mucous gland metaplasia in the corpus. Plasma gastrin levels and gastric pH values were significantly increased only in B128-infected gerbils. In all infected animals, the expression of the proinflammatory cytokines interleukin 1beta, interferon gamma, and growth-regulated protein was considerably increased in the antrum, but only in wild type-infected animals was an increase seen in the corpus mucosa.. The presence of an intact T4SS allows H. pylori to colonize the gastric corpus. This results in atrophic corpus-dominant gastritis, a severe precancerous condition, thus highlighting T4SS and CagA as major risk factors for gastric cancer development.

Topics: Achlorhydria; Animals; Antigens, Bacterial; Atrophy; Bacterial Proteins; Cytokines; Female; Gastric Mucosa; Gastrins; Gastritis; Gerbillinae; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Helicobacter pylori; Hypertrophy; Mutation; Precancerous Conditions; Promoter Regions, Genetic; Pyloric Antrum; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Virulence

Apart from its importance as an acid secretogogue, the role of histamine as a downstream target of gastrin has not been fully explored. Previous studies have shown that the combination of hypergastrinemia and Helicobacter infection resulted in accelerated gastric cancer in mice. We used this model to examine the role of cholecystokinin 2 (CCK2)/gastrin receptor and histamine H2-receptor signaling in the development of gastric atrophy and cancer.. Male hypergastrinemic mice (INS-GAS mice) were infected with Helicobacter felis and given the CCK2/gastrin receptor antagonist YF476 and/or the histamine H2-receptor antagonist loxtidine for 3 or 6 months. In addition, mice were treated with omeprazole alone or in combination with either YF476 or loxtidine for 3 months.. Mice treated with YF476 or loxtidine alone showed partial suppression of both gastric acid secretion and progression to neoplasia. The combination of YF476 plus loxtidine treatment resulted in nearly complete inhibition of both parameters. YF476 and/or loxtidine treatment did not alter the overall level of H. felis colonization but did result in significant down-regulation of the growth factors regenerating gene I and amphiregulin. Loxtidine treatment, with or without YF476, induced a mild shift in T-helper cell polarization. In contrast, omeprazole treatment resulted in mild progression of gastric hyperplasia/dysplasia, which was ameliorated by the addition of YF476 or loxtidine.. The combination of CCK2/gastrin- and histamine H2-receptor antagonists has synergistic inhibitory effects on development of gastric atrophy and cancer in H. felis/INS-GAS mice, while the proton pump inhibitor showed no such effects. These results support an important role for the gastrin-histamine axis in Helicobacter-induced gastric carcinogenesis.

Topics: Achlorhydria; Animals; Atrophy; Benzodiazepinones; Disease Models, Animal; Gastrins; Helicobacter felis; Helicobacter Infections; Histamine H2 Antagonists; Male; Mice; Mice, Transgenic; Phenylurea Compounds; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Receptors, Histamine H2; Stomach Neoplasms; Triazoles

Histamine plays an important role in the regulation of gastric acid secretion; however, its role in maintenance of gastric morphology remains unclear. To clarify the necessity of histamine for gastric mucosal development and maintenance, we evaluated two different kinds of mice that lacked either mast cells (one of the gastric histamine-producing cell types) or histidine decarboxylase (HDC; a histamine-synthesizing enzyme). Measurements of stomach weight, intragastric pH, mucosal histamine levels, as well as serum gastrin and albumin levels were performed in mice. Gastric mucosal appearance was examined by immunohistochemical techniques. Although gastric mucosal histamine levels in mast cell-deficient mice were half of those observed in the wild-type mice, intragastric pH, serum gastrin levels, and gastric morphology at 12 mo were unchanged compared with the wild-type mice. In contrast, HDC-deficient mice possessed no detectable gastric histamine, but did exhibit hypergastrinemia, as well as marked increases in intragastric pH and stomach weight compared with the wild-type mice. Histological analysis revealed that 9-mo-old HDC-deficient mice demonstrated hyperplasia in the oxyntic glandular base region, as well as increased numbers of parietal and enterochromaffin-like cells. These results indicate that enterochromaffin-like cell-derived histamine is potentially involved in gastric mucosal morphology regulation.

Topics: Achlorhydria; Animals; Enteroendocrine Cells; Gastric Mucosa; Gastrins; Histamine; Histidine Decarboxylase; Hyperplasia; Male; Mast Cells; Mice; Mice, Knockout; Mice, Mutant Strains; Parietal Cells, Gastric

The histidine decarboxylase enzyme (HDC) is responsible for the synthesis of histamine in mammals. Histidine decarboxylase-deficient (HDC-/-) mice have recently been developed by targeted mutation of the HDC gene.. The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a wash-through method for basal gastric acid secretion and by pylorus ligation for stimulated gastric acid secretion) and gastrin levels (by radioimmunoassay) in homozygous HDC-/- mice kept on a low-histamine diet.. A double maximal gastric acid secretory response was found in knockouts after exogenous histamine administration. In contrast, the gastric acid secretion was significantly reduced after gastrinergic and cholinergic stimulation in the absence of histamine. The oxynthic gland area of HDC-/- mice was thickened with an increased parietal cell count compared to wild types. Substantially elevated serum and antral tissue gastrin levels of HDC-/- mice could be possible indications of both an expanded parietal cell mass and/or an increased histamine-induced maximal gastric acid secretory capacity of this genotype.. These data suggest that not enough compensatory mechanisms develop in HDC-/- mice during a prolonged low-histamine diet to maintain/restore normal gastric acid secretion. An expanded parietal cell pool was also demonstrated in HDC-/- mice kept on a low-histamine diet, probably caused by a trophic effect of sustained hypergastrinaemia. The HDC-/- strain is a suitable model for studying the effects of achlorhydria and consequent hypergastrinaemia as an approach to human conditions such as atrophic gastritis or long-term antisecretory therapies.

Topics: Achlorhydria; Animals; Bethanechol; Diet; Gastric Acid; Gastrins; Histamine; Histidine Decarboxylase; Homozygote; Immunohistochemistry; Male; Mice; Mice, Knockout; Muscarinic Agonists; Parietal Cells, Gastric; Pentagastrin

Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess the effects of these variables comparisons were carried out in patients with the acid related Zollinger-Ellison syndrome (ZES) versus patients with progressive systemic sclerosis (PSS) and gastro-oesophageal reflux disease.. Twenty-five patients with PSS and 16 patients with ZES were included and received continuous omeprazole treatment for a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients were titrated by 24 h pH-metry to oesophageal pH>4, and all ZES patients were titrated to a basal acid output of zero H+.. Changes towards diffuse and linear ECL cell hyperplasia were observed in 41% of the PSS patients. Micronodular hyperplasia and neoplasia were not seen. In the ZES patients changes towards linear and micronodular hyperplasia were observed in all patients. Two patients developed ECL cell carcinoids; one of these had MEN-1 syndrome. Also parietal cell changes were more pronounced in the ZES group than in the PSS group.. In patients without intrinsic acid hypersecretion and hypergastrinaemia significant proliferation of ECL cells is not an issue irrespective of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection.

Topics: Achlorhydria; Aged; Aged, 80 and over; Anti-Ulcer Agents; Cell Division; Drug Administration Schedule; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Neurosecretory Systems; Omeprazole; Parietal Cells, Gastric; Scleroderma, Systemic; Zollinger-Ellison Syndrome

Reduced gastric acid predisposes the stomach to colonization by bacteria and inflammation. Therefore, we investigated how the chronic gastritis in mice made hypochlorhydric by either gastrin deficiency or omeprazole treatment modulates epithelial cell function.. The gastric pathology of 16-week-old wild-type gastrin-expressing (G+/+) and gastrin-deficient (G-/-) mice maintained in conventional housing was compared. G-/- mice were then treated with antibiotics for 20 days. In a separate experiment, G+/+ mice were treated with omeprazole for 2 months or treated with omeprazole and antibiotics.. Compared with the G+/+ animals, the hypochlorhydric G-/- mice showed significant inflammation that resolved after 20 days of antibiotic treatment and correlated with a decrease in bacterial overgrowth. Elevated G- and parietal-cell numbers in the G-/- mice, quantified by flow cytometry, normalized after antibiotic treatment. G+/+ mice treated with omeprazole had increased bacteria and mucosal lymphocytes that resolved after antibiotic therapy. Quantitation of the gastric cells in these omeprazole-treated mice revealed a significant increase in G- and parietal-cell numbers. On resolution of the gastritis, a decrease in parietal and gastrin-expressing (G) cells was observed despite sustained hypochlorhydria in the presence of omeprazole.. Genetic or chemical hypochlorhydria predisposes the stomach to bacterial overgrowth resulting in inflammation. The specific changes in parietal and G cells correlate with the presence of inflammation and not directly with gastric acid. Thus, the normal stomach responds to inflammation by increasing the number and function of cell types that are able to maximize gastric acid output.

Topics: Achlorhydria; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; B-Lymphocytes; Bacteriological Techniques; Campylobacter; Campylobacter Infections; Female; Flow Cytometry; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Male; Mice; Omeprazole; Parietal Cells, Gastric; T-Lymphocytes

Carboxypeptidase E deficiency as seen in the fat/fat mice is associated with reduced antral somatostatin content but tripling of the progastrin product. Thus, fat/fat mice are able to maintain normal tissue concentrations of bioactive alpha-amidated gastrin in spite of grossly attenuated progastrin processing. After induction of achlorhydria, however, neither the amount of alpha-amidated gastrin nor the total progastrin product increased in the fat/fat mice. This is contrary to what is seen in wild-type mice. Furthermore, the synthesis of antral somatostatin and fundic chromogranin A is also abnormal. Hence the results suggest a breakdown in the feedback loop that regulates gastric acid secretion.

Topics: Achlorhydria; Animals; Base Sequence; Carboxypeptidase H; Carboxypeptidases; Chromogranin A; Chromogranins; DNA Primers; Feedback; Female; Gastric Acid; Gastrins; Male; Mice; Mice, Mutant Strains; Omeprazole; Protein Precursors; Proton Pump Inhibitors; Pyloric Antrum; Somatostatin

Our aim was to evaluate the relationship between gastric emptying and demographic, clinical, histological, and secretory features in patients with nonautoimmune fundic atrophic gastritis. Only 31% of 45 patients with fundic atrophic gastritis presented with achlorhydria. Scintigraphic gastric emptying of solids was delayed compared to healthy controls. Patients with achlorhydria showed gastric emptying rates lower than those with preserved acid secretion. Significant, but weak, correlations were observed between emptying rates and both peak acid output (Rs = 0.33) and serum gastrin levels (Rs = -0.36), but not with grading of mucosal atrophy. No symptom differences were observed between patients with or without achlorhydria, but a weak correlation was detected between peak acid output and the severity of epigastric pain (Rs = 0.40). In conclusion, patients with fundic atrophic gastritis present delayed gastric emptying that is weakly related to the reduction of the acid secretion and the raising of serum gastrin levels rather than to the severity of the atrophy.

Topics: Achlorhydria; Adult; Aged; Dyspepsia; Female; Gastric Acid; Gastric Emptying; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged

The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria.. To conduct a systematic comparative examination of gastric histology and function.. Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status.. All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection.. The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics.. Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.

Topics: Achlorhydria; Adult; Aged; Aged, 80 and over; Biopsy; Case-Control Studies; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter pylori; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Prospective Studies; Schilling Test; Vitamin B 12 Deficiency

To study circulating gastrin profile, both fasting and postprandially, in patients with achlorhydria due to auto-immune atrophic gastritis, comparing these with normal healthy controls.. Circulating gastrins were measured using three region-specific radio-immunoassays: amidated gastrins (R98), N-terminal G34 (R526) and N-terminal G17 (GP168). Samples were analysed further using gel chromatography.. Fasting gastrin concentrations were elevated in achlorhydria as measured using all three antisera: median 714 pmol/l (range 107-5176) in achlorhydria versus 12 pmol/l (2-33) in controls (R98), 343 pmol/l (45-4316) versus 10 pmol/l (5-41) (R526), and 720 pmol/l (14-6000) versus 2 pmol/l (1-10) (GP168). In patients, 47% of gastrin was amidated (95% in controls) and 30% was processed N-terminally only to G71 (4% in controls). Gastrin rose significantly postprandially: 1643 pmol/l (269-7142) in patients versus 24 pmol/l (5-142) in controls (R98), 432 pmol/l (113-4756) versus 15 pmol/l (7-45) (R526) and 2189 pmol/l (304-7150) versus 15 pmol/l (7-45) (GP168). Only 25% was amidated in the patient group (93.5% in controls) and 21% remained as component I (4% in controls).. This abnormal gastrin profile associated with hypergastrinaemia secondary to achlorhydria is consistent with saturation of the enzymes involved in the processing of the pro-hormone, in particular amidation of the C-terminus.

Topics: Achlorhydria; Aged; Aged, 80 and over; Chromatography, Gel; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Postprandial Period; Radioimmunoassay

Mucolipidosis type IV (ML-IV) is an autosomal recessive lysosomal storage disease that causes severe neurologic abnormalities. The brain disease is characterized by pigmented cytoplasmic granules in neurons and accumulation of lamellated membrane structures in lysosomes. The gastrointestinal disease in ML-IV was not previously recognized. Clinical examination of 20 patients with ML-IV (age range, 2-23 years) at the National Institutes of Health showed hypergastrinemia and constitutive achlorhydria. Endoscopic biopsy specimens from the gastric fundus, body, and antrum and from the duodenum of four such patients (ages 4, 6, 7, and 22 years) were evaluated histologically and by electron microscopy. Histologically, all gastric fundus and body biopsy specimens showed parietal cells in normal numbers. However, a striking cytoplasmic vacuolization of parietal cells was seen on hematoxylin and eosin stain. Electron microscopy showed the parietal cells to be markedly distended by large lysosomes containing lamellar, concentric, and cystic membranous inclusions. Additionally, chronic atrophic gastritis and enterochromaffin-like (ECL) cell hyperplasia were observed. Foveolar and chief cells in stomach and duodenum biopsy specimens were normal. We conclude that the cytoplasmic lysosomal inclusions in gastric parietal cells is a unique histologic feature of gastric biopsy in ML-IV.

Topics: Achlorhydria; Adult; Biopsy; Child; Child, Preschool; Enterochromaffin-like Cells; Female; Gastric Fundus; Gastrins; Gastritis, Atrophic; Gastroscopy; Humans; Hyperplasia; Inclusion Bodies; Lysosomes; Male; Mucolipidoses; Parietal Cells, Gastric

A now 54-year-old woman was 32 years ago found to have immune thrombocytopenia and 3 years ago ANA-positive and HBsAg-negative hepatitis with cirrhotic metaplasia. Numerous small asymptomatic carcinoids with marked hypergastrinaemia (1626 ng/l) were also first found 3 years ago. No gastrinoma could be found. Severe arthralgia was the main symptom on admission.. Gastroscopy revealed a polypoid carcinoid, 1 cm in diameter. There was total achlorhydria. No pernicious anaemia or carcinoid syndrome was found.. Total gastrectomy with construction of a jejunal substitute stomach was performed. Histology showed typical chronic-atrophic gastritis type A, all stages of an argyrophilic endocrine cell hyperplasia, as well as microcarcinoidosis and multicentric carcinoid, in part with submucosal infiltration and lymph node metastases. Immunohistology revealed immune reaction for the global endocrine marker. No specific hormones were demonstrable in the carcinoid cells. The postoperative course was without complications. Serum gastrin levels have since been normal.. The case confirms the possibility of an achlorhydria-hypergastrinaemia-carcinoid sequence. Now new stage-related therapeutic guidelines for this disease are needed.

Topics: Achlorhydria; Autoimmune Diseases; Carcinoid Tumor; Female; Follow-Up Studies; Gastrectomy; Gastrins; Gastritis, Atrophic; Gastroenterostomy; Humans; Jejunum; Lymphatic Metastasis; Middle Aged; Stomach; Stomach Neoplasms; Time Factors

Gastrin stimulates histidine decarboxylase (HDC) activity and proliferation of enterochromaffin-like (ECL) cells. Furthermore, it has been suggested that gastrin controls HDC gene expression. We therefore analysed the effect of gastrin receptor blockade by PD 136 450 (CAM 1189) on HDC gene expression. The influence of PD 136 450 on gastrin, somatostatin, and chromogranin A was also evaluated.. Gene expression of HDC, gastrin, somatostatin, and chromogranin A (CgA) was analysed by Northern blot analyses after 14 days' application of the proton pump inhibitor BY 308 and/or the gastrin/cholecystokinin B receptor antagonist PD 136 450.. PD 136 450 had no significant effect on gastrin mRNA or somatostatin mRNA in controls and during proton pump inhibition. BY 308 treatment resulted in a marked induction of HDC and CgA mRNA, whereas concomitant PD 136 450 in a concentration previously shown to suppress maximal pentagastrin-induced gastric acid secretion and to prevent BY 308-induced ECL cell proliferation did not result in significant alteration. PD 136 450 increased HDC significantly and CgA mRNA to a lesser extent in normogastrinaemic rats, whereas previous work showed a decreased ECL cell labelling index.. These data suggest that there are independent regulatory pathways for ECL cell proliferation and gene expression. Other factors besides gastrin may act through PD 136 450-insensitive pathways to control HDC and CgA gene expression.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Achlorhydria; Animals; Blotting, Northern; Chromogranin A; Chromogranins; Enzyme Inhibitors; Female; Gastrins; Gene Expression; Histidine Decarboxylase; Indoles; Omeprazole; Phenethylamines; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; RNA, Messenger; Somatostatin

The mechanism of hypergastrinaemia during omeprazole therapy is unclear, but is generally assumed to be entirely a consequence of acid suppression. However, direct stimulation of G cells by omeprazole could also be a factor. In order to further investigate the mechanism of omeprazole-induced hypergastrinaemia, we have studied the effects of the drug on plasma gastrin in patients with achlorhydria, in whom altered acid secretion cannot play a role.. We estimated fasting and peptone meal stimulated plasma gastrin in nine patients (seven female) with pernicious anaemia and achlorhydria, before and on the final day of 4 weeks' dosing with omeprazole 40 mg daily.. Despite the high fasting gastrin concentrations, the peptone meal produced a further elevation in plasma gastrin concentrations, median gastrin concentrations rising from 1500 ng/L (range 225-10,875 ng/L) to 3750 ng/L (range 585-15,600 ng/L) post-prandially (P = 0.004). The median post-prandial rise in plasma gastrin at this initial visit was 44% (3-260%), and the median time interval until plasma gastrin concentrations returned to fasting levels was 120 min (range 10- > 150 min). There was a significant negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation (Spearman correlation coefficient -0.79, P = 0.01). Fasting plasma gastrin concentrations were similar pre-omeprazole (median 1950 ng/L, range 240-16,500 ng/L) and post-omeprazole (median 1500 ng/L, range 315-7650 ng/L). Likewise, peak plasma gastrin concentrations were also similar pre-omeprazole (median 2700 ng/L, range 585-16,500 ng/L) and post omeprazole (median 3420 ng/L, range 720-11,250 ng/L).. (i) The hyperplastic G cell mass in patients with pernicious anaemia can be further stimulated by a peptone meal, which causes a prolonged rise in plasma gastrin concentrations. (ii) There is a negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation. (iii) Omeprazole has no effect on plasma gastrin in achlorhydric patients, which is consistent with its hypergastrinaemic effect being entirely secondary to acid inhibition.

Topics: Achlorhydria; Administration, Oral; Aged; Aged, 80 and over; Anemia, Pernicious; Anti-Ulcer Agents; Eating; Fasting; Female; Gastric Acid; Gastrins; Humans; Middle Aged; Omeprazole

Immunoreactivities of urinary N-terminal big gastrin and serum C-terminal gastrin were determined in intact and antrectomized rats by radioimmunoassay using two antisera specific for N- and C-termini of big gastrin, respectively. Gel filtration of urine extract from intact rat showed a single giant peak of N-terminal big gastrin immunoreactivity eluted in a later position than 1-17 gastrin-34, indicating that N-terminal peptides smaller than 1-17 gastrin-34 are excreted in urine. Serum C-terminal gastrin concentration in antrectomized rats was about one sixth that in intact rats. Urinary excretion of N-terminal big gastrin in antrectomized rats was about one sixth that in intact rats. 2 week treatment with E3810, a proton pump inhibitor, (40 mg/kg/day, s.c.) induced urinary excretion of N-terminal big gastrin in parallel with a marked increase in serum C-terminal gastrin concentration in intact rats. Antrectomy completely prevented both the increase in urinary excretion of N-terminal big gastrin and the elevation of serum C-terminal gastrin induced by administration of E3810. There was an excellent correlation between serum concentration of C-terminal gastrin and urinary excretion of N-terminal big gastrin. These results suggest that urinary N-terminal big gastrin, which mostly originates from the gastric antrum, is a useful indicator of gastrin secretion in the rat.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Achlorhydria; Animals; Benzimidazoles; Female; Gastrectomy; Gastrins; Omeprazole; Peptide Fragments; Protein Precursors; Proton Pump Inhibitors; Pyloric Antrum; Rabeprazole; Rats; Rats, Sprague-Dawley

A 63-year-old woman was diagnosed as autoimmune gastritis by the presence of serum antibody against alpha-subunit of gastric H+,K(+)-ATPase. The patient did not have pernicious anemia, but showed achlorhydria, marked hypergastrinemia, enterochromaffin-like cell hyperplasia and an extremely high histidine decarboxylase activity in the gastric fundic mucosa. Intragastric acidification by infusion of hydrochloric acid via a nasogastric tube induced a transient reduction of serum gastrin level and fundic mucosal histidine decarboxylase activity. A marked increase in fundic mucosal histidine decarboxylase activity as well as hypergastrinemia appears to be the pathophysiologic response to achlorhydria caused by autoimmunity against gastric H+,K(+)-ATPase.

Topics: Achlorhydria; Autoimmune Diseases; Enterochromaffin Cells; Female; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis; Graves Disease; H(+)-K(+)-Exchanging ATPase; Histidine Decarboxylase; Humans; Hyperplasia; Middle Aged; Parietal Cells, Gastric; Polyps; Stomach Neoplasms

Gastric and duodenal pH levels were measured in 79 healthy, elderly men and women (mean +/- SD = 71 +/- 5 years) under both fasted and fed conditions using the Heidelberg capsule technique. The pH was recorded for 1 hr in the fasted state, a standard liquid and solid meal of 1000 cal was given over 30 min, then the pH was measured for 4 hr postprandially. Results are given as medians and interquartile ranges: fasted gastric pH, 1.3 (1.1-1.6); gastric pH during the meal, 4.9 (3.9-5.5); fasted duodenal pH, 6.5 (6.2-6.7); and duodenal pH during the meal, 6.5 (6.4-6.7). Although fasted gastric pH, fasted duodenal pH, and duodenal pH during the meal differ statistically from those observed in young subjects, the differences are not expected to be clinically significant in terms of drug absorption for the majority of elderly subjects. Following a meal, gastric pH decreased from a peak pH of 6.2 (5.8-6.7) to pH 2.0 within 4 hr in most subjects. This rate of return was considerably slower than in young, healthy subjects. Nine subjects (11%) had a median fasted gastric pH > 5.0, and in five of these subjects the median pH remained > 5.0 postprandially. In this group, drugs and dosage forms which require an acidic environment for dissolution or release may be poorly assimilated.

Topics: Achlorhydria; Aged; Aged, 80 and over; Digestive System; Duodenum; Fasting; Female; Gastric Acidity Determination; Gastrins; Humans; Hydrogen-Ion Concentration; Male; North America; Reference Values; Sex Characteristics

The effects of gastric fundectomy and antrectomy on the colonic mucosa were studied in hamsters over 5 and 25 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly increased after fundectomy and significantly decreased after antrectomy. Five days after fundectomy, there was a significant increase in scintigraphically determined colonic tissue [3H]-thymidine uptake and [3H]-thymidine labeling index of goblet cells, both of which were reduced 5 days after antrectomy. After fundectomy, the labeling index was maximal in differentiating-proliferative cells in the midportion of the colonic crypts, whereas the labeling index of the immature proliferative cells at the base of the crypts did not differ from that in the controls. On day 25, the crypt size and the number and percentage of goblet cells in the crypts were significantly increased in fundectomized animals. The number and percentage of goblet cells in antrectomized animals were significantly reduced on day 25. It is concluded that fundectomy in the hamster induces colonic mucosal hyperplasia with goblet cell proliferation, whereas antrectomy leads to retardation of colonic goblet cell proliferation.

Topics: Achlorhydria; Animals; Cell Division; Colon; Cricetinae; Gastrectomy; Gastric Fundus; Gastrins; Hyperplasia; Intestinal Mucosa; Male; Mesocricetus; Pyloric Antrum; Time Factors

Gastrin, somatostatin, H+/K(+)-ATPase and carbonic anhydrase are principal elements of acid secretion. We investigated in the conscious sheep the effect of 24 h omeprazole (an H+/K(+)-ATPase inhibitor) infusion on these elements at the level of synthesis, storage and secretion. Omeprazole inhibited acid secretion-pH increased from 3.0 to 7.1 at 24 h. Plasma amidated and glycine extended gastrin increased 3-fold while the ratio of amidated to glycine extended gastrins (4:1) remained unchanged. Despite the increase in circulating gastrin, antral gastrin concentration and mRNA did not change significantly. Gastrin-17 (amidated and glycine extended) was the predominant form in the circulation and antrum, although there were preferential increases in larger forms following omeprazole treatment. Omeprazole had no effect on somatostatin mRNA or peptide levels in the fundus. Similarly, plasma somatostatin remained unchanged. However, antral somatostatin increased significantly (63%) following omeprazole treatment accompanied by a 4-fold increase in its mRNA. Fundic H+/K(+)-ATPase mRNA was unchanged but a significant increase (87%) in carbonic anhydrase II mRNA was observed. Omeprazole induced hypergastrinaemia occurred without a measurable reduction in storage or increased synthesis of gastrin at 24 h. Increased antral somatostatin synthesis and storage may result from stimulation by plasma gastrin on antral D cells, independent of acid. The rise in carbonic anhydrase II mRNA in the absence of any change in H+/K(+)-ATPase mRNA may reflect the differential sensitivity of the genes encoding these two enzymes to the stimulatory action of gastrin.

Topics: Achlorhydria; Animals; Base Sequence; Blotting, Northern; Carbonic Anhydrases; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Gastrins; H(+)-K(+)-Exchanging ATPase; Kinetics; Molecular Sequence Data; Omeprazole; Radioimmunoassay; RNA, Messenger; Sheep; Somatostatin

Hyperplasia of the oxyntic enterochromaffinlike cells in response to long-lasting blockade of acid secretion is closely related to hypergastrinemia. In the present study, the effect of a specific gastrin receptor antagonist on proton pump inhibitor-induced changes on serum gastrin levels, mucosal height, as well as gastrin- and enterochromaffin-like cells was investigated in rats. The proton pump inhibitor BY 308 or the vehicle methylcellulose [Methocel (controls)] was administered for 2 weeks in the presence and absence of the gastrin receptor antagonist PD 136450 (CAM 1189). BY 308 significantly increased serum gastrin levels, gastrin cell density, and antral gastrin concentration. Concomitant application of PD 136450 did not alter this response. In the oxyntic stomach, mucosal height, enterochromaffinlike cell density, labeling index of enterochromaffinlike cells, and histamine concentration were elevated after treatment with BY 308. These increases were almost completely abolished by PD 136450. Even in normogastrinemic control rats, PD 136450 significantly decreased mucosal height of the oxyntic part of the stomach and the labeling index of enterochromaffinlike cells. The results show that (a) trophic effects of drug-induced achlorhydria are mediated by gastrin; (b) even in control rats (normogastrinemic), gastrin is a trophic factor for the oxyntic mucosa; and (c) antral gastrin cell hyperplasia in states of chronic achlorhydria is not mediated by gastrin itself.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Achlorhydria; Animals; Enterochromaffin Cells; Gastrins; Histamine; Indoles; Male; Omeprazole; Phenethylamines; Proton Pumps; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Stomach; Time Factors

1. Studies of Helicobacter pylori show that microbes can alter gastrin release. Lack of gastric acid (achlorhydria) causes hypergastrinaemia and allows bacteria to grow within the stomach. We speculated that the bacteria contribute to the rise in gastrin seen after acid inhibition, and tested the idea by comparing plasma gastrin levels during inhibition of acid secretion between germ-free and conventional rats. 2. Matched germ-free and conventional rats (n = 8 per group) received either vehicle (saline) or one of two doses of the histamine-H2-receptor antagonist loxtidine for 1 week. Gastrin was measured in cardiac blood by a specific r.i.a. 3. Plasma gastrin concentrations in germ-free and conventional rats were 59 +/- 11 pmol/l (mean +/- SEM) and 36 +/- 8 pmol/l, respectively, after vehicle, and 153 +/- 30 pmol/l and 181 +/- 27 pmol/l, respectively, after loxtidine at a dose of 10 mg day -1 kg -1, which partially inhibits acid secretion. Administration of loxtidine at a dose of 70 mg day -1 kg-1, which completely inhibits acid secretion, did not produce a significant extra rise in plasma gastrin concentration in germ-free rats (178 +/- 11 pmol/l), but further elevated plasma gastrin concentrations to 278 +/- 26 pmol/l in conventional rats (P less than 0.005 compared with germ-free rats). 4. Loxtidine produced a dose-dependent rise in the number of eosinophils in the gastric mucosa of conventional rats. 5. We conclude that partial inhibition of gastric acid secretion increases gastrin release independently of bacteria, but that bacteria are involved in the further rise in gastrin which occurs on more profound inhibition of gastric acid secretion.

Topics: Achlorhydria; Animals; Dose-Response Relationship, Drug; Eosinophils; Gastric Acid; Gastric Mucosa; Gastrins; Germ-Free Life; Helicobacter pylori; Histamine H2 Antagonists; Leukocyte Count; Rats; Rats, Inbred Strains; Triazoles

Topics: Achlorhydria; Animals; Carcinoid Tumor; Gastrins; Humans; Omeprazole; Rats; Stomach Neoplasms

Time-related changes of serum gastrin levels, gastrin cell, and enterochromaffinlike cell densities, and proliferation kinetics of these cells have been examined in rats during treatment with the substituted benzimidazole BY 308 over a period of 73 days. Serum gastrin levels increased very rapidly from 74 +/- 6 pg/mL (controls) to 438 +/- 31 pg/mL (day 1) and 727 +/- 68 pg/mL (day 4). Thereafter, a steady increase was observed until day 70 (2097 +/- 208 pg/mL). Enterochromaffinlike cell density was unchanged until day 10, but then increased progressively without reaching a plateau (144% above control on day 73). The labeling index of these cells was enhanced shortly after drug application and remained on a constant elevated level from day 14 to day 73 (about 10-fold to 12-fold above controls from day 14 to day 70). The number of gastrin cells increased rapidly within the first week and reached a plateau after 17 days (96% increase above controls). In contrast to enterochromaffinlike cells, the labeling index did not change immediately but increased on day 7 by 37% and returned beneath control values after day 28. The results suggest that in drug-induced achlorhydria, the progressive increase of enterochromaffinlike cells is explained by an enhanced mitosis, whereas other factors in addition to proliferation are responsible for the augmentation of gastrin cells.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Achlorhydria; Animals; Cell Count; Enterochromaffin Cells; Female; Gastric Mucosa; Gastrins; Hyperplasia; Mitotic Index; Omeprazole; Rats; Rats, Inbred Strains; Regression Analysis; Stomach; Time Factors

According to current concepts, it is not feasible to associate achlorhydria with normal gastric mucosa. We have found in a group of high altitude dwellers, that it is possible to associate achlorhydria with normal gastric mucosa verified by endoscopic and histological studies. In this case, basal achlorhydria is associated with resistance to histamine stimulation and with high values of gastrinemia. The possibility of reduced parietal cell mass or the absence of gastrin and histamine receptors and of G-cell hyperfunction or hyperplasia, is discussed.

Topics: Achlorhydria; Adult; Altitude; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Male

Fundic argyrophil cells were studied for a mean period of 68.7 months (range, 11-170) in 18 patients with fundic atrophic gastritis and achlorhydria. Initially, 12 patients had hyperplasia of the argyrophil cells, the severity of which was assessed using a semiquantitative classification based on the number of argyrophil clusters per square millimeter. At the end of the study, the degree of hyperplasia was unchanged in 9 patients, had decreased in 2, and had increased in 1; no significant increase in the number of argyrophil clusters, precarcinoid changes, or carcinoid tumors were observed and the high level of gastrinemia [mean, 4.8 (range, 1.9-8.1) times the upper limit for normal) did not change significantly. Of the 6 patients with no hyperplasia at the outset of the study, 4 continued without hyperplasia and 2 presented a low-grade hyperplasia at the 20th and 130th month. Gastrinemia increased significantly in the last patient and stayed normal in the other 5. This study argues in favor of the stable appearance of fundic argyrophil cells in patients with atrophic gastritis and stable gastrinemia.

Topics: Achlorhydria; Aged; Aged, 80 and over; Anemia, Pernicious; Biopsy; Female; Gastric Fundus; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Humans; Hyperplasia; Male; Middle Aged; Schilling Test

We previously demonstrated that extremely high amounts of N-terminal big gastrin (G-34) fragments are excreted in human urine and three of them are N-terminal octa-, nona-, and decapeptide of G-34. Our subsequent examination revealed that there exists a considerable amount of another N-terminal G-34 fragment in urine, less hydrophobic than the three peptides. We purified this fragment from urine of an achlorhydric patient and determined the structure: less than Glu-Leu-Gly-Pro-Gln-Gly. The purification was carried out by Sep-Pak C18 cartridges, Sephadex G-25, and reverse phase HPLC. The structure was determined by a combination of amino acid analysis, amino acid sequence analysis, and mass spectral analysis. N-terminal hexapeptide of G-34 is the second richest component of urinary N-terminal G-34 fragments next to N-terminal octapeptide of G-34 in normal subjects.

Topics: Achlorhydria; Amino Acid Sequence; Chromatography, Gel; Chromatography, High Pressure Liquid; Gastrins; Humans; Mass Spectrometry; Molecular Sequence Data; Protein Precursors; Solubility

Topics: Achlorhydria; Aged; Carcinoid Tumor; Gastrins; Humans; Male; Stomach; Stomach Neoplasms

We previously demonstrated that there existed extremely abundant NH2-terminal big gastrin immunoreactivity (NT G-34-IR) in human urine. This report describes the purification and sequence of NT G-34-IR from the urine of an achlorhydric patient. The purification was carried out by a combination of Sep-Pak C18 cartridges, Sephadex G-25, and HPLC steps using a radioimmunoassay specific for NH2-terminus of G-34 and ultraviolet absorption at 214 nm as monitors. Three peptides were isolated. The amino acid analysis, mass spectrometry, and sequence analysis confirmed the structures of urinary NT G-34 fragments being less than Glu-Leu-Gly-Pro-Gln-Gly-Pro-Pro, less than Glu-Leu-Gly-Pro-Gln-Gly- Pro-Pro-His, and less than Glu- Leu-Gly-Pro-Gln-Gly-Pro-Pro-His-Leu. NH2-terminal octapeptide of G-34 was the main component of urinary NT G-34-IR.

Topics: Achlorhydria; Amino Acid Sequence; Amino Acids; Chromatography, Gel; Chromatography, High Pressure Liquid; Gastrins; Humans; Mass Spectrometry; Molecular Sequence Data; Peptide Fragments; Protein Precursors; Radioimmunoassay

We report a case of chronic diarrhea due to hypergastrinemia with achlorhydria but without gastritis in a five-year-old boy. Symptoms responded promptly to oral administration of hydrochloric acid and resolved completely after one year of treatment. The pathophysiologic situation in this patient closely resembled that normally seen in neonates, suggesting prolonged but nevertheless transient immaturity of gastric secretions.

Topics: Achlorhydria; Child, Preschool; Chronic Disease; Diarrhea; Gastrins; Humans; Male

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

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

Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells.

Topics: Achlorhydria; Animals; Gastrins; Gene Expression Regulation; Male; Omeprazole; Pyloric Antrum; Rats; Rats, Inbred Strains; RNA, Messenger; Somatostatin

We investigated whether a new long-acting somatostatin analogue (SMS 201-995) could antagonize the trophic effect induced by hypergastrinaemia, resulting from chronic omeprazole treatment, on the rat gastric mucosa and particularly on endocrine cell growth. SMS was administered concomitantly with omeprazole for 70 days. Gastric morphometric and cell proliferative parameters, gastric acid secretion and plasma gastrin levels were examined. New findings with omeprazole pointed out: (i) a trophic effect on the antral mucosa and (ii) that the increase observed in gastrin cell number was not due to stimulation of gastrin cell production by omeprazole but more likely to a prolongation of the gastrin cells' life span. As compared to omeprazole alone, simultaneous SMS administration significantly decreased the parietal cell (P less than 0.05) and gastrin cell (P less than 0.01) labelling indices, mucosal height of total glandular stomach (P less than 0.05) and antral mucosal height (P less than 0.05). It tended to lower fundic mucosal height and fundic argyrophil cell density (P less than 0.2 and P less than 0.1, respectively). SMS, in our conditions, did not accentuate the inhibitory effect of omeprazole on gastric acid secretion nor reduce high plasma gastrin levels. We conclude that SMS modestly counteracts the growth-promoting effect observed in rat gastric mucosa after prolonged omeprazole treatment.

Topics: Achlorhydria; Animals; Endocrine Glands; Female; Gastric Acid; Gastric Mucosa; Gastrins; Octreotide; Omeprazole; Rats; Rats, Inbred Strains

Topics: Achlorhydria; False Positive Reactions; Gastrins; Humans; Secretin

Topics: Achlorhydria; Gastrins; Humans; Secretin

Two patients with chronic abdominal pain and fasting hypergastrinemia had increases in serum gastrin of 440 and 300 pg/ml after injection of 2 U/kg Secretin-KABI. Both subsequently proved to have pentagastrin-fast achlorhydria. Intragastric instillation of 0.1 N HCl suppressed serum gastrin concentration by greater than 60%. In both, the pancreas was normal by sonography or computed tomography (CT) scan and at laparotomy in one. Both are currently asymptomatic 12 and 18 months later. We conclude that achlorhydria may be associated after injection of Secretin-KABI with a false-positive rise in fasting serum gastrin concentration of greater than 200 pg/ml and that gastric analysis for hypochlorhydria should be performed before secretin provocation testing.

Topics: Achlorhydria; Adult; Chronic Disease; False Positive Reactions; Female; Gastric Acidity Determination; Gastrins; Gastritis; Humans; Middle Aged; Pentagastrin; Secretin

The release of gastric somatostatinlike immunoreactivity and gastrin was studied in rats with chronic achlorhydria induced by the substituted benzimidazole BY 308. In vitro, stimulation of gastrin release by acetylcholine was slightly enhanced after 1 day of treatment but no further effects were observed compared to placebo controls. Four weeks of treatment evoked marked gastrin hypersecretion, which was atropine-resistant. Stimulation of gastrin release was inversely correlated to enhancement of basal gastrin levels. Chronic achlorhydria distinctly reduced somatostatin responses to isoproterenol, whereas potent stimulation was observed in controls. Treatment with BY 308 for 1 wk was associated with fully developed gastrin hypersecretion but isoproterenol-stimulated somatostatin release was still unaffected. Hypergastrinemia accompanied by increased antral gastrin and reduced antral and fundic somatostatin concentrations was also found in vivo after 4 wk of treatment with BY 308. It is concluded that chronic achlorhydria not only enhances storage and secretion of gastrin but also diminishes the secretion and tissue stores of somatostatin; adaptive changes of the somatostatin cell occur, however, with a much longer delay.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Achlorhydria; Animals; Benzimidazoles; Female; Gastric Acid; Gastric Mucosa; Gastrins; Omeprazole; Rats; Rats, Inbred Strains; Somatostatin; Time Factors

Topics: Achlorhydria; Antacids; Carcinoid Tumor; Enterochromaffin Cells; Gastrins; Gastritis, Atrophic; Histamine H2 Antagonists; Humans; Hyperplasia; Peptic Ulcer; Risk; Somatostatin; Stomach Neoplasms; Vagotomy, Proximal Gastric

The intravenous secretin test is widely used to distinguish gastrinoma (Zollinger-Ellison syndrome) from other causes of fasting hypergastrinemia. We report 2 patients with fasting hypergastrinemia and a rise of greater than 200 pg/ml in serum gastrin concentration after intravenous injection of 2 CU/kg body wt of pure natural secretin. Both patients had pentagastrin-fast achlorhydria. Thus, the intravenous secretin test may be positive in patients with achlorhydria-related hypergastrinemia. Gastric acid secretion should be measured in hypergastrinemic patients before embarking on a secretin test.

Topics: Achlorhydria; Cross Reactions; False Positive Reactions; Female; Gastrins; Humans; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Animals; Carcinoid Tumor; Cell Division; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Humans; Stomach Neoplasms

Topics: Achlorhydria; Gastrins; Humans; Somatostatin; Stomach Neoplasms

In 40 patients with insulin-dependent diabetes mellitus, the number of gastrin cells in the mucous membrane of the antrum of the stomach was measured by immunohistochemistry according to the method of L. Sternberger. The number of the cells depended on the gravity of antral gastritis, namely their number decreased as the lesion was aggravated. The basal level of serum gastrin was determined by radioimmunoassay in 144 patients with insulin-dependent diabetes mellitus. The high basal level of gastrin was recorded in patients with achlorhydria. However, no correlation was established between the gravity of antral gastritis and the basal level of serum gastrin. If the basal gastrin level is too high, the possibility of asymptomatic paresis of the stomach should be taken into account together with the other factors.

Topics: Achlorhydria; Adult; Biopsy; Cell Count; Diabetes Mellitus, Type 1; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Immunoenzyme Techniques; Male; Middle Aged

Acid and gastrin production after pyloric-preserving pancreaticoduodenectomy was evaluated in six patients. Five patients had low-normal basal and stimulated acid output; the sixth patient was achlorhydric. Fasting gastrin levels were less than 90 to 105 pg/mL (normal range) in five patients, three of whom had stimulated gastrin levels that remained below this range. Two patients had stimulated gastrin levels of 510 pg/mL and 205 pg/mL, respectively, within 15 minutes of eating; however, both levels returned to normal by 120 minutes' time. The sixth patient had mildly elevated fasting (105 pg/mL) and stimulated gastrin levels (160 to 200 pg/mL) throughout the test period. The results suggest that pyloric-preserving pancreaticoduodenectomy does not lead to either gastric hyperacidity or persistent hypergastrinemia.

Topics: Achlorhydria; Duodenum; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis; Pylorus; Radioimmunoassay

Gastric acid secretion is known to be controlled by a complex system of interacting factors. Amongst these, regulatory peptides make a significant contribution. In the present study, immunocytochemistry and radioimmunoassay were used to investigate gastric regulatory peptides in animals with pharmacologically reduced gastric acid secretion. Increased numbers of densely immunostained antral gastrin-immunoreactive (G) cells were seen in rats which had been rendered virtually achlorhydric by administration of high-dose (400 mumol/kg daily) omeprazole over a 10-week period. These morphological changes were accompanied by increases in the plasma, antral and fundic concentrations of gastrin, as measured by radioimmunoassay. In contrast, antral somatostatin-containing cells were reduced, and there was a corresponding fall in the tissue content of the peptide. Ten weeks after treatment had ceased, the peptide profiles had returned to normal. No other regulatory peptide, whether endocrine or neural, appeared to alter during treatment with high-dose omeprazole. Treatment with high-dose (700 mumol/kg daily) ranitidine also caused an elevation in the G cell population and the antral and plasma content of gastrin, but to a lesser extent than that observed during omeprazole treatment. Somatostatin cells and tissue levels did not alter in these animals, and no other morphological changes could be detected. Radioimmunoassay, however, measured reduced quantities of vasoactive intestinal peptide, peptide histidine isoleucine and calcitonin gene-related peptide. Achlorhydria, induced by omeprazole at a dosage of 250-500 times that required for effective acid inhibition in man and animals, therefore resulted in reciprocal changes in gastrin and somatostatin cells. These changes are support for the postulated roles of these peptides in the control of gastric acid secretion.

Topics: Achlorhydria; Animals; Gastrectomy; Gastric Acid; Gastric Fundus; Gastrins; Gastrointestinal Hormones; Histocytochemistry; Omeprazole; Radioimmunoassay; Ranitidine; Rats

Multiple polypoidal carcinoid tumours of the stomach were found in 5 patients with achlorhydria (4 of whom had pernicious anaemia) as a result of autoimmune atrophic gastritis. The tumours were small (nearly all less than 1 cm diameter) and appeared to grow very slowly, if at all; no significant enlargement or complications were seen during periods of observation of up to 6 years. No extragastric hormonal syndromes were identified. They differed from the carcinoid tumours usually found in the intestinal tract by being composed of argyrophil (not argentaffin) cells of the enterochromaffin-like (ECL) type. Fasting plasma levels of gastrin, which is believed to be trophic to ECL cells, were very high in all patients. Thus, chronic hyperplasia of gastric ECL cells (as a result of hypergastrinaemia) may have been responsible for development of the tumours. Long-term, uninterrupted achlorhydria produced by potent inhibitors of gastric acid secretion might therefore predispose to carcinoid tumours of the stomach.

Topics: Achlorhydria; Aged; Anemia, Pernicious; Carcinoid Tumor; Female; Gastrins; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Stomach Neoplasms

To establish normal values for gastric secretory function in preterm infants, we studied 34 healthy preterm infants once a week during hospitalization. Basal acid output, pentagastrin-stimulated acid output, fasting serum gastrin, and fasting serum pancreatic polypeptide were measured during each study. Basal acid output at 1 week of age was 12 mumol/kg/hr, increasing over the first 4 weeks to 30 mumol/kg/hr. Administration of pentagastrin 6 micrograms/kg subcutaneously increased acid output in all age groups. Pentagastrin-stimulated acid output at 1 week was 21 mumol/kg/hr, increasing over the first 4 weeks to 44 mumol/kg/hr. Acid secretion did not change significantly over the next 4 to 6 weeks. Fasting serum gastrin concentration was stable over the first 6 weeks of life, but doubled during the end of the second month. Pancreatic polypeptide was found at low levels throughout the study. These studies confirm that the majority of healthy preterm infants secrete acid in quantity sufficient to maintain the gastric pH less than or equal to 4, providing a barrier to bacteria and protein antigens.

Topics: Achlorhydria; Age Factors; Enteral Nutrition; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Infant, Premature; Pancreatic Polypeptide; Pentagastrin

In 68 patients with chronic renal failure (CRF), 15 patients with duodenal ulcer and 15 normal subjects, basal plasma gastrin levels and basal and stimulated gastric acid secretion were measured. Two antisera were used: antiserum R2702 with specificity for human G34 and its N-terminal fragments [G34] and antiserum 2604 with specificity for the four main components of gastrin (total gastrin). Basal gastrin concentrations of both total gastrin and G34-like immunoreactivity (G34LI) were significantly higher in the CRF patients than in the other two groups, irrespective of dialysis. Total gastrin levels were not correlated with serum creatinine levels. Total gastrin levels were significantly decreased during hemodialysis, but G34LI levels showed no significant change. A small amount of total gastrin was detected in the dialysate by antiserum 2604. As to the postprandial gastrin release, in the first 30 min, the pattern of response in the patients with CRF was similar to that of the normal subjects, but the peak value was attained later, and the response was more rather prolonged. Gastric analysis showed a low basal acid out put and impaired acid secretion in response to secretagogue. It is concluded that (1) one of the predominant circulating forms of gastrin in CRF is G34LI, and (2) the hypergastrinemia in the CRF patients is probably due to reduced removal of gastrin by kidneys, increased gastrin production by impairment of the negative acid feedback mechanism induced by parietal cell dysfunction or reduced parietal cell sensitivity to gastrin by atrophic gastritis.

Topics: Achlorhydria; Adult; Endoscopy; Female; Food; Gastric Acid; Gastrins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Protein Precursors; Renal Dialysis

We determined total gastrin and pepsinogen I in frozen serum samples from 175 overnight-fasted women 54 years old, and from 81 overnight-fasted women 60 years old, who took part in a population study in 1968-69. We also assayed samples from some of these women, who participated in clinical follow-up studies in 1974-75 and 1980-81: all of the women in the initial group whose serum gastrin concentration exceeded the 85th centile value and, as a reference group, a randomized subsample of women whose initial serum gastrin concentration was less than the 80th centile. Samples with total gastrin concentration greater than 400 ng/L were also assayed for gastrin-17 and gastrin-34. We found that: a pronounced increase of serum gastrin persisted throughout the study period for most of these postmenopausal women, indicating that conversion of type A gastritis (antrum-sparing) to pan-gastritis is uncommon; unexplained high concentrations of pepsinogen I in relation to the reference interval for young and middle-aged adults, as well as in relation to serum gastrin, were common; and the gastrin-17/gastrin-34 ratio is not correlated with the outcome of pronounced hypergastrinemia.

Topics: Achlorhydria; Fasting; Female; Follow-Up Studies; Food; Gastrins; Gastritis; Humans; Longitudinal Studies; Middle Aged; Pepsinogens; Sweden

Clinical, histological, histochemical and ultrastructural characteristics of eight cases of carcinoid tumors of the non-antral portion of the stomach are presented. Four cases with multiple polypoid lesions are accompanied by an increased level of gastrin. A normal level of gastrin was present in the other four cases with isolated tumor and a normal component of endocrine cells in the uninvolved mucosa. In the first group with multiple lesions, the histological and histochemical analysis of the endocrine cells revealed a wide range of appearances: a) "simple hyperplasia", b) "nodular hyperplasia", and c) carcinoid tumor. These aspects suggested a different pathogenesis for the carcinoid tumors of the non-antral portion of the stomach with possible therapeutical implications.

Topics: Achlorhydria; Adult; Aged; Carcinogens; Carcinoid Tumor; Chromaffin System; Enterochromaffin Cells; Female; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Precancerous Conditions; Stomach; Stomach Neoplasms

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

The individual daily intake of gluten was calculated in 45 patients with dermatitis herpetiformis (DH) on the basis of a depth interview about food habits. Gastric and small intestinal morphology and function were studied concurrently. Mean daily gluten intake was estimated to be 15 g, a figure which corresponds well to the average gluten intake in Sweden. There was a significant correlation between the degree of morphological mucosal changes of the small intestine and the quantity of gluten ingested. All patients with jejunal villous atrophy consumed more than 10 g gluten daily and all but one patient with normal jejunal villous structure had a gluten intake of less than 10 g/d. The findings suggest a dose-dependent effect of gluten on the intestinal mucosa. Conversely, the daily gluten intake was not correlated to gastric morphology, gastric acid secretion, serum gastrin levels or serum parietal cell antibodies. Patients with reduced ability to secrete gastric acid did not differ from the remaining patients in this respect. Whereas the coeliac-like enteropathy in DH seems to be caused by ingested gluten, the frequently occurring achlorhydric atrophic gastritis must be assumed to be of different immunopathogenesis.

Topics: Achlorhydria; Adolescent; Adult; Aged; Celiac Disease; Dermatitis Herpetiformis; Duodenum; Feeding Behavior; Female; Gastric Acid; Gastric Mucosa; Gastrins; Glutens; Humans; Intestinal Mucosa; Jejunum; Male; Middle Aged

A 24-month-old female child experienced watery diarrhea, growth failure, and abdominal pain from age 3 months. Hypergastrinemia, hypochlorhydria, and fundic gastritis were documented. A secretin stimulation test was normal but protein meal stimulation revealed an abnormal serum gastrin response. Antral biopsies revealed G cell hyperplasia. Chronic treatment with antacids and an anticholinergic agent was unsuccessful. Spontaneous recovery occurred at age 29 months. Gastrin stimulation tests, gastric acid secretory tests, antral mucosal biopsies, and multiple basal serum gastrin levels were repeated. All were normal. Follow-up of greater than 3 years has documented a completely normal clinical and laboratory course.

Topics: Achlorhydria; Biopsy; Chromaffin System; Diarrhea, Infantile; Enterochromaffin Cells; Female; Follow-Up Studies; Gastrins; Humans; Hyperplasia; Infant; Pyloric Antrum; Time Factors

This report presents a case of multicentric gastric carcinoid (gastrin containing) tumors of the fundus associated with achlorhydria and pernicious anemia. It is suggested that stimulation of the antral G cells and possibly fundic argyrophilic cells by achlorhydria associated with atrophic gastritis may lead to hyperplasia, and eventually to neoplasia in the latter, in the form of gastric carcinoid with gastrin production.

Topics: Achlorhydria; Anemia, Pernicious; Carcinoid Tumor; Gastric Fundus; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pyloric Antrum; Staining and Labeling; Stomach Neoplasms

In order to evaluate whether gastric inhibitory polypeptide (GIP) could be responsible for the postprandial fall in serum gastrin previously observed in patients with achlorhydria, 7 achlorhydric patients were given 100 ml Lipomul (66 g triglycerides) on one occasion, and 5 of these patients were later given a 30-min intravenous infusion of porcine GIP in a dose of 1 microgram/kg. Following the Lipomul ingestion, serum gastrin fell significantly, whereas no effect on serum gastrin was seen during the intravenous GIP infusion. A small, but significant release of serum insulin was seen shortly after starting the GIP infusion, together with a significant and more sustained release of plasma pancreatic polypeptide (PP). It is concluded that GIP does not lower the serum gastrin levels in achlorhydric patients, but that GIP might participate in the intestinal phase of the PP release.

Topics: Achlorhydria; Adult; Aged; Corn Oil; Dietary Fats; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Male; Middle Aged; Oils; Pancreatic Polypeptide

We tested the validity of the concept that chronic atrophic gastritis can be subdivided into type A and B in hospital patients and normal subjects with proven pentagastrin-refractory achlorhydria. Classification was based on the determination of the basal serum gastrin and parietal cell antibodies. Of 59 hospital patients with achlorhydria, 71% could be classified as belonging to either type A or B; for 29% the criteria for neither type were fulfilled. Of 14 asymptomatic persons with achlorhydria found in 564 normal persons, five could be classified as having type A gastritis, and one as type B gastritis. In eight (53%) persons, an elevated serum gastrin was found in the absence of parietal cell antibodies, representing an intermediate type of atrophic gastritis. Because one-third of the hospital patients and more than half the persons with achlorhydria in a normal population had to be classified as belonging to an intermediate type, the discrimination between type A and B atrophic gastritis in achlorhydria seems to be of limited practical value.

Topics: Achlorhydria; Antibodies; Gastric Mucosa; Gastrins; Gastritis; Gastritis, Atrophic; Humans

Fasting gastrointestinal motor and hormone patterns were studied in 11 healthy volunteers. Cyclic motor activity was present in all subjects during fasting, but the duration and site of onset of each cycle were variable, even in the same subject. Fasting gastrin, GIP, and glucagon levels remained low and constant during the 8-hr study, while plasma motilin levels exhibited cyclic variation in 7 of the 11 subjects. Achlorhydria (induced with cimetidine in 5 of the 11 subjects) did not alter the pattern of fasting motor activity or plasma motilin. In the remaining six subjects, the effect of liquid nutrient meals was examined. Ingestion of a sodium chloride bolus failed to disrupt fasting cyclic activity, while all nutrient-containing solutions inhibited gastric phase-2 motor activity, the duration of inhibition being longest for the mixed and lipid meals. All nutrient meals released GIP, while only protein and mixed meals released gastrin, and the lipid meal released motilin. Our study confirms the rhythmicity of interdigestive motor cycles in man and demonstrates their lack of dependence on gastric acid secretion and some relationship to motilin cycles in certain individuals as determined by radioimmunoassay. Transition from fasting to fed pattern (after liquid meals) is characterized by the inhibition of phasic gastric pressure changes in the antrum and the development of irregular activity in the intestine, similar in pattern to fasting phase 2. Because the duration of interruption of the gastric interdigestive pattern by meals depends on their nutrient content, we conclude that dietary composition may be a major determinant of the fasting-fed motor balance in man.

Topics: Achlorhydria; Adult; Aged; Duodenum; Fasting; Food, Formulated; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Jejunum; Male; Middle Aged; Motilin; Pyloric Antrum

9 patients with achlorhydria and hypergastrinemia and 8 control patients with normal gastric H+ secretion and normal serum gastrin level were studied before and after a mixed liquid test meal. Mean plasma gastric inhibitory polypeptide increased to significantly higher values in the achlorhydric group than in the control group 30, 60 and 90 min after the meal. In the achlorhydric group mean serum gastrin fell significantly below the basal level 60 and 90 min after the meal, whereas a significant increase was observed in the control group.

Topics: Achlorhydria; Adult; Dietary Carbohydrates; Dietary Proteins; Female; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Time Factors

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

Three patients with the watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome were studied. All had watery diarrhea, hypokalemia and hypercalcemia. Plasma vasoactive intestinal polypeptide (VIP) levels determined by radioimmunoassay were markedly elevated in these patients, indicating that they had VIP-producing tumors. Plasma VIP levels determined serially after the operation indicate that its determination is useful in estimating the effect of a treatment. As for multiple endocrine neoplasia type 1 (MEN1), two out of the three cases belonged to this category. Patient 1 had a brother with insulinoma, and in case 2, even though there was no family history, the autopsy revealed not only multiple tumors of the pancreas but also pituitary adenomas, chief cell hyperplasia of the parathyroid glands, thyroid adenomas and adrenocortical adenomas. VIP and other hormones in the tumors as well as in the plasma were examined extensively in these cases. In case 1, VIP, gastrin and calcitonin were produced in the tumor and only plasma VIP levels were elevated. In case 2, with multiple tumors, tumor 1 produced VIP, glucagon pancreatic polypeptide, gastrin and calcitonin, and tumor 2, VIP, pancreatic polypeptide, gastrin and beta-melanocyte stimulating hormone. In this case, plasma VIP, pancreatic polypeptide and glucagon levels were elevated. In case 3, VIP and calcitonin were produced in the tumor, and plasma VIP and calcitonin levels were elevated. These results indicate that (1) VIP is a good tumor marker for the WDHA syndrome due to VIP-producing tumors; (2) patients with the WDHA syndrome are sometimes associated with MEN1; and (3) VIP-producing tumors are multiple hormone-producing tumors, and VIP predominantly elevated in the plasma results in the WDHA syndrome, although other hormones such as pancreatic polypeptide, glucagon and calcitonin are sometimes found to be elevated in plasma without contributing to the clinical features.

Topics: Achlorhydria; Adult; Calcitonin; Diarrhea; Female; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypokalemia; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Parathyroid Hormone; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Calcium; Gastrins; Humans; Molecular Weight; Pentagastrin; Peptic Ulcer; Pyloric Antrum; Zollinger-Ellison Syndrome

Thirteen persons with normal pentagastrin-stimulated gastric H+ secretion and 17 with achlorhydria were studied with a liquid test meal after an overnight fast. Blood was drawn before and every 30 min for 180 min after start of the meal. Serum gastrin, serum PG I, and serum vitamin B12 were determined by radioassay methods. Serum PG I was significantly lower in the achlorhydric subjects than in the normal secretors. The meal induced a slight and late rise in serum PG I in the control group. In contrast, the meal caused a slight fall in the achlorhydric persons. Basal serum gastrin was significantly higher in the achlorhydric group, in whom the meal also caused a significant fall in serum gastrin, which contrasts sharply with the rise in the control group. Although serum gastrin fell significantly in the achlorhydric group, a meal-induced rise in serum gastrin was observed in some of the achlorhydric subjects with basal serum gastrin below 100 pmol/l. Serum vitamin B12 was reduced in 8 of the 17 persons with achlorhydria, and in these 8 subjects serum PG I was significantly lower than in those with achlorhydria and normal serum vitamin B12.

Topics: Achlorhydria; Female; Food; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pepsinogens; Vitamin B 12

We have measured the serum gastrin response to feeding in 3 groups of achlorhydric patients, and have compared the results with those of 12 normal controls. An increased postprandial serum gastrin response was found in 6 of 8 patients with hypergastrinemia and pernicious anemia, in all 10 patients with hypergastrinemia and normal absorption of vitamin B12, and in 2 of 7 achlorhydric patients with normal fasting serum gastrin levels. A reduced serum gastrin response to feeding was found in 2 patients with pernicious anemia and very high basal serum gastrin levels of 3,010 and 3,800 pg/ml, and in one achlorhydric patient with normogastrinemia. The remaining 4 patients with achlorhydria and normogastrinemia had normal postprandial serum gastrin responses. It is concluded that the serum gastrin response to feeding in patients with achlorhydria is heterogeneous.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Fasting; Female; Food; Gastrins; Humans; Male; Middle Aged

Parietal cell autoantibody (PCA), basal gastrin, and calcium-stimulated gastrin were measured in twenty patients with achlorhydria, in eight patients with the Zollinger-Ellison syndrome, and in fifty control subjects. In twelve patients with achlorhydria with a spared antrum, PCA was positive and basal gastrin was elevated. In contrast, eight achlorhydric patients with antral gastritis had negative PCA and significantly lower basal gastrin levels. Patients with the Zollinger-Ellison syndrome did not demonstrate positive PCA despite elevated levels of basal gastrin, nor was PCA present in normal controls. This study suggests that certain achlorhydric states are caused by an autoimmune response, particularly if antral function is spared.

Topics: Achlorhydria; Anemia, Pernicious; Autoantibodies; Calcium; Gastrins; Gastritis; Humans; Stomach; Zollinger-Ellison Syndrome

Seventeen of 37 healthy volunteers participating in studies of acid secretion and 1 patient with Zollinger-Ellison syndrome became rapidly and profoundly hypochlorhydric. A mild illness with epigastric pain occurred in 9 subjects, usually several days before detection of hypochlorhydria. Gastric mucosal biopsy specimens taken from subjects during hypochlorhydria revealed severe fundal and antral gastritis; however, even when acid secretion was severely depressed, parietal cells were abundant and appeared normal histologically. During hypochlorhydria, gastric permeability to hydrogen, sodium, and lithium was normal in 4 subjects. Serum gastrin concentrations were usually normal, whereas serum pepsinogen concentrations were invariably elevated. Serum parietal cell antibodies were not present. Acid secretion returned to near baseline levels in 14 of 17 subjects after a mean of 126 days (range 53--235); severity of gastritis diminished concurrently in 7 of 10 subjects on whom biopsies were serially performed. An infectious etiology is suspected, although serologic studies and bacterial and conventional viral cultures of stool and gastric juice have not identified a candidate agent.

Topics: Achlorhydria; Adult; Aged; Dietary Proteins; Disease Outbreaks; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pepsinogens; Pyloric Antrum; Zollinger-Ellison Syndrome

Forty eight patients were evaluated to ascertain a correlation (if any) between gastric acid secretion, fasting and post prandial serum gastrin levels, gastric biopsy (antrum and fundus) and gastric emptying time after a standard test meal. The following conclusions were obtained: a) 57.8% of patients with atrophic gastritis and achlorhydria had evaluated serum gastrin levels; b) most patients with high gastrin levels had normal antrum on biopsy or showed only minimal inflamatory changes, while those with normal gastrin levels disclosed more pronounced histological changes; c) patients with achlorhydria had slower gastric emptying rates, and this was more evident among those with higher gastrin levels (though differences were not statistically significant). Further studies are required for a better understanding of the relationship between gastric emptying rate and gastrin levels in patients with chronic gastritis.

Topics: Achlorhydria; Adult; Aged; Chronic Disease; Female; Gastric Emptying; Gastric Juice; Gastrins; Gastritis; Humans; Indium; Male; Middle Aged; Pyloric Antrum; Radioisotopes

Topics: Achlorhydria; Fasting; Gastrins; Humans; Vitiligo

Gastrin release was studied in 5 hypergastrinemic patients, both during calcium infusion and EDTA infusion. In each patient, gastrin decreased in conjunction with the fall in plasma calcium, and increased during calcium infusion. Plasma gastrin and calcium levels were strongly correlated.

Topics: Achlorhydria; Adolescent; Adult; Calcium; Edetic Acid; Female; Gastrins; Humans; Hyperplasia; Infusions, Parenteral; Male; Middle Aged; Pyloric Antrum; Secretory Rate; Zollinger-Ellison Syndrome

In 32 subjects, the HCl secretion, the histological state of the antral and fundic mucosa and the gastrin response to a liquid meal extract were studied. Atrophy of the antrum was associated with normal gastrin concentration in the fasting state and after the test meal, in the presence of normal fundic mucosa and HCl secretion. In achlorhydria and atrophic gastritis, fasting gastrinemia was significantly elevated in subjects with a normal antrum, and only moderately increased in subjects with an atrophic antrum. The gastrin response to feeding was correlated to the fasting gastrin concentration in achlorhydric subjects with normal antral mucosa, in contrast to a uniformly reduced output in achlorhydric subjects with atrophic lesions of the antral mucosa.

Topics: Achlorhydria; Adult; Aged; Atrophy; Dyspepsia; Fasting; Female; Food; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged

Topics: Achlorhydria; Anemia, Pernicious; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum; Somatostatin

Topics: Achlorhydria; Adult; Aged; Atrophy; Chronic Disease; Gastric Mucosa; Gastrins; Gastritis; Humans; Middle Aged

Topics: Achlorhydria; Aged; Female; Gastrins; Humans; Hyperparathyroidism; Middle Aged

Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis the mean number of gastrin cells per field of vision was 52 +/- 6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin levels was 324 +/- 56 pmol/l and the number of gastrin cells was 79.6 +/- 7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361 +/- 186 pmol/l and 88.0 +/- 14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0 +/- 3.3 pmol/l, and the number of gastrin cells was 6.2 +/- 3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.

Topics: Achlorhydria; Adult; Aged; Atrophy; Chronic Disease; Female; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pyloric Antrum

The serum concentrations of immunoreactive gastrin and immunoreactive calcitonin were measured in 13 fasting patients with achlorhydria and pernicious anaemia and in 10 age- and sex-matched fasting control subjects. All patients had highly elevated concentrations of gastrin in serum (1468 +/- 336 pg/ml, mean "/- SEM). The mean concentration in the controls was 35.2 +/- 6.4 pg/ml. No difference in the concentration of calcitonin was found between the pernicious anaemia patients and the controls, the levels being 0.93 +/- 0.08 and 0.89 +/- 0.03 ng/ml, respectively. Suppression of endogenous gastrin secretion in 5 of the patients by intragastric acid administration was not accompanined by any decrease in calcitonin concentration in serum. The findings suggest that chronically elevated endogenous gastrin is without influence on calcitonin secretion.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Calcitonin; Fasting; Female; Gastrins; Humans; Male; Middle Aged

The morphological changes of gastric mucosa taken from different areas has been studied in patients of approximately the same age with achlorhydria, extreme hypochlorhydria and normochlorhydria. The serum gastrin level and parietal cell antibodies were determined in the achlorhydric parietal cell antibodies were determined in the achlorhydric patients. In the latter the diffuse gastritis was localized in the corpus-fundic area, while the changes in the antral region were few and occurred mostly in the superficial zone. In normochlorhydric patients however, the diffuse gastritis was localized in the antral region, with only few changes at the corpus-fundic area. In patients with extreme hypochlorhydira either the fundic or the antral region was involved. Besides the diffuse gastritis intestinal metaplasia, pseudopyloric metaplasia, and atrophy of mucosa were also observed, although much less commonly. The increase of gastrin level could not be related to a definite morphological pattern in the gastric mucosa. It can be assumed that each of the two types of gastritis has a different natural history; the antral site of gastrititis cannot be transformed into the fundic site, nor can the fundic site be transformed into the antral site.

Topics: Achlorhydria; Aged; Atrophy; Biopsy; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Metaplasia; Middle Aged; Pyloric Antrum

Topics: Achlorhydria; Anemia, Pernicious; Diet; Esophagogastric Junction; Gastrectomy; Gastrins; Gastritis; Humans; Lymphatic Metastasis; Methods; Stomach Neoplasms

Several haematological findings (especially the values of serum LDH and its isoenzymes) were compared with changes in the gastrin level in pernicious anaemia. While vitamin B12 substitution therapy led to normalization of the anaemia and of the enzyme levels, gastric atrophy and, hence, the elevation in serum gastrin levels remained unchanged. Determination of serum gastrin, therefore, provides a valuable tool for the verification of the diagnosis of pernicious anaemia in treated cases.

Topics: Achlorhydria; Anemia, Pernicious; Animals; Clinical Enzyme Tests; Gastrins; Humans; Isoenzymes; L-Lactate Dehydrogenase; Rabbits; Radioimmunoassay; Vitamin B 12

Forty-two patients with pernicious anemia (PA) and 35 patients with achlorhydria but without PA were investigated by means of serum gastrin determination and estimation of circulating parietal cell and thyroidal autoantibodies. In 38 of the 77 patients, gastroscopic and histopathological examinations of the antral and corpus mucosa were performed. The patient groups were similar with regard to distribution of high and normal serum gastrin levels, the frequencey of autoantibodies and antrum-sparing atrophic gastritis. In the present selection of patients, therefore, the achlorhydria group was supposed to represent a precursor state of the group with PA. A minor proportion of patients with severe atrophic gastritis of the antrum as well as of the corpus mucosa was found in the two groups.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Autoantibodies; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Vitamin B 12

Elevation in fasting serum gastrin levels was found in three patients being evaluated for persistent upper abdominal pain without radiographic evidence of peptic ulcer disease. Fiberoptic endoscopy of the upper gastrointestinal tract in each patient revealed characteristic changes of chronic atrophic gastritis. Gastric biopsies showed diffuse chronic inflammation in the lamina propria, a decrease in the number of parietal cells, and "intestinalization" of gastric mucosa. Total achlorhydria was demonstrated after a maximal histalog stimulus; however, serum levels of vitamin B12 and Schilling test values were normal in all three patients. Parietal cell antibodies were found in the serum in all patients in a dilution of 1:20 to 1:80. These cases represent autoimmune (type A) chronic atrophic gastritis and should be distinguished from chronic simple (type B) gastritis, in which serum gastrin levels are normal and no parietal cell antibodies are found in the serum. Patients with autoimmune gastritis should be observed at frequent intervals for the occurrence of pernicious anemia or gastric carcinoma.

Topics: Achlorhydria; Adult; Antacids; Atrophy; Autoantibodies; Autoimmune Diseases; Chronic Disease; Female; Gastrectomy; Gastrins; Gastritis; Humans; Middle Aged

Topics: Achlorhydria; Animals; Autoantibodies; Gastric Mucosa; Gastrins; Humans; Rats

Topics: Achlorhydria; Aged; Biopsy; Female; Gastrins; Gastritis; Humans; Male; Middle Aged; Stomach

Gastric bypass as a 90 per cent gastric exclusion operation was used in 393 patients with massive obesity to limit food intake. Stomal ulcer has occurred in 1.8 per cent of such patients or one ulcer per 140 man years of observation. The studies of indwelling fundic pH and of gastric acid secretion from the excluded stomach indicate that acid secretion is reduced after gastric bypass but that the acid, unbuffered by food in the excluded stomach, results in a lowered gastrin secretion after a meal. Thus, gastric bypass in inhibitory to acid secretion in most morbidly obese patients who do not have known acid peptic disease.

Topics: Achlorhydria; Analysis of Variance; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastroenterostomy; Humans; Obesity; Peptic Ulcer; Stomach Ulcer

Hypergastrinemia occurs in achlorhydric states if the antrum is not diseased, and evidence has been presented that suggests that antral gastritis diminishes gastrin levels in achlorhydric patients. There is a dramatic gastrin response to calcium challenge in patients with pernicious anemia. Only minimal response was observed in patients with atrophic gastritis. Unlike the response observed in the Zollinger-Ellison syndrome, secretin challenge suppresses gastrin in achlorhydric states. These findings add a new dimension to the utility of serum gastrin determinations.

Topics: Achlorhydria; Anemia, Pernicious; Atrophy; Calcium; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Infusions, Parenteral; Male; Middle Aged; Pyloric Antrum; Secretin

The effect of protein-rich food, intravenous calcitonin injections, and intragastric instillation of hydrochloric acid on serum gastrin concentrations and gastrin component pattern was studied in hypergastrinemic patients (pernicious anemia) and matched control subjects. Moreover, plasma secretin concentrations were measured during intragastric acidification. The intragastric acidification resulted in rapid fall in serum gastrin concentrations, although not below the upper limit of normal range. The small components, III (gastrin-17-like) and IV (gastrin-13-like), almost disappeared, whereas the concentrations of component I and component II (gastrin-34-like) were less affected. The increase in secretin concentrations after intragastric acidification was smaller in patients with pernicious anemia than in normal subjects, although the difference was not significant. In contrast to the results in normal control subjects, neither food nor calcitonin produced significant variations in serum gastrin concentrations and gastrin component pattern of pernicious anemia patients. The failure of food to stimulate and of calcitonin to inhibit release of gastrin in the majority of pernicious anemia patients might suggest that gastrin secretion in these patients is autonomous. However, considering the recently recognized slow metabolic clearance rate of big gastrins, the effect of intragastric acidification suggests that the mechanism for acid inhibition of the antral gastrin secretion is intact in patients with achlorhydria.

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Calcitonin; Dietary Proteins; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Secretin

Topics: Achlorhydria; Anemia, Pernicious; Atrophy; Fasting; Gastrins; Gastritis; Humans; Intrinsic Factor; Radioimmunoassay

38 patients were found to have achlorhydria after maximal stimulation with pentagastrin and on multiple biopsies (atrophy of gastric mucosa). It was demonstrated that the sequence pH-antroreceptors-G cells-parietal cells-pH antroreceptors was interrupted already in mild or moderately severe superficial gastritis of the antral mucosa involving more than half of the antral surface. Reduction of specific functional epithelium is unlikely in this form of inflammation so that it is probably an effect of the pH receptors.

Topics: Achlorhydria; Adult; Aged; Atrophy; Biopsy; Female; Gastric Juice; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pentagastrin; Pyloric Antrum

A women had hypergastrinaemia associated with the variety of gastritis (Type A) that is associated usually with pernicious anaemia, together with recurring bouts of severe abdominal pain. Fasting serum gastrin levels ranged between 600 and 2750 pg/ml. There was a rise in serum gastrin levels after a standard protein meal, indicative of a large G cell mass, and a fall after intragastric HCI, which led to a trial of treatment with HCI; this gave some symptomatic relief. After surgical antrectomy there was a profound fall of serum gastrin from a pre-operative level of 2500 pg/ml to constant values of 16--25 pg/ml, and complete and lasting relief from the bouts of abdominal pain.

Topics: Achlorhydria; Female; Gastrins; Gastritis; Humans; Hydrochloric Acid; Middle Aged; Pyloric Antrum

Due to recent reports claiming that gastrin is present in the gastric juice, the method for gastrin determination has been evaluated. Separate experiments showed that gastrin added to gastric juice disappears rapidly if the juice is not boiled or neutralized. A total of 82 patients with various abdominal disorders were examined. No or only a trace amount of gastrin was found in untreated, boiled, or boiled and neutralized gastric juice in every patient, including three patients with achlorhydria. Histamine injection (0.04 mg. per kilogram, subcutaneously) did not influence this and was without effect upon serum gastrin concentrations of nine duodenal ulcer patients. Because gastrin apparently is degraded rapidly by gastric juice, this study does not necessarily disprove that gastrin is secreted into the stomach. However, the virtual absence of gastrin in all specimens examined, including some collected directly upon boiling water bath during continuous gastric aspiration lends no support to this speculation. Because gastrin does not survive even a short exposure to gastric juice without degradation, we suggest that earlier reports on the presence of gastrin within the stomach are questionable.

Topics: Achlorhydria; Anemia, Pernicious; Chromatography, Gel; Drug Interactions; Duodenal Ulcer; Dyspepsia; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Histamine; Hot Temperature; Humans; Iodine Radioisotopes; Radioimmunoassay; Resins, Plant; Sodium Isotopes

Topics: Achlorhydria; Calcium; Gastrins; Humans; Pyloric Antrum; Secretin

Topics: Achlorhydria; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum

Topics: Achlorhydria; Adolescent; Adult; Aged; Anemia, Pernicious; Autoantibodies; Female; Fluorescent Antibody Technique; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Radioimmunoassay; Skin Manifestations; Vitiligo

Topics: Achlorhydria; Adolescent; Adult; Age Factors; Aged; Anemia, Pernicious; Antibodies; Gastrins; Gastritis; Humans; Middle Aged; Vitiligo

Topics: Achlorhydria; Diagnosis, Differential; Duodenal Ulcer; Fasting; Gastrectomy; Gastrins; Humans; Hyperplasia; Malabsorption Syndromes; Male; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Stomach Diseases; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Gastrectomy; Gastric Juice; Gastrins; Humans; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Anemia, Pernicious; Atropine; Depression, Chemical; Fasting; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Pentagastrin; Secretory Rate

Topics: Achlorhydria; Animals; Diarrhea; Dogs; Gastric Juice; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypokalemia; Stimulation, Chemical; Water-Electrolyte Balance

Topics: Achlorhydria; Adult; Age Factors; Aged; Anemia, Pernicious; Autoantibodies; Biopsy; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Radioimmunoassay; Stomach

Patients with atrophic gastritis but normal antral mucosa and achlorhydria were divided into three groups according to age-under 40, 40 to 70, and over 70 years. Serum gastrin, both basal and following a standard protein meal, was estimated in all patients by radioimmunoassay. There was a significant correlation between the magnitude of the gastrin response and age, the older the patient the greater the response. These results suggest that with increasing duration of gastritis and continued stimulation of a normal antrum in the absence of inhibition by acid, the functional G (gastrin) cell mass increases. However the possibility exists that each cell may secrete more gastrin in response to the same stimulus with age. This may be resolved by counting the number of G cells in the stomachs of subjects with atrophic gastritis and different ages.

Topics: Achlorhydria; Adult; Age Factors; Aged; Atrophy; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Radioimmunoassay

Topics: Achlorhydria; Adult; Age Factors; Arthritis, Rheumatoid; Gastric Juice; Gastrins; Humans; Sjogren's Syndrome

Topics: Achlorhydria; Depression, Chemical; Fluoroscopy; Gastric Acidity Determination; Gastrins; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Radioimmunoassay; Secretin; Stomach Neoplasms; Time Factors

Topics: Achlorhydria; Atrophy; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum; Stomach Diseases

1. A radio-immunoassay for gastrin has been developed using partially purified porcine gastrin to raise antibodies and highly purified natural porcine gastrin I for radio-iodination with (125)I. The separation of antibody-bound from free hormone was performed by a double-antibody method.2. In this assay highly purified natural porcine gastrin I, synthetic human gastrin I, radio-iodinated porcine gastrin I, gastrin in the plasma of a healthy volunteer, a patient with pernicious anaemia and another patient with the Zollinger-Ellison syndrome were immunologically identical.3. The fasting plasma gastrin concentration of fourteen gastric ulcer patients was significantly higher than that of the 113 hospital controls with no history of gastro-intestinal disease, while twenty-seven duodenal ulcer patients had gastrin levels within the normal range.4. Plasma gastrin concentration was significantly elevated in pernicious anaemia (fifty-one patients), achlorhydria (thirty-three patients), hypochlorhydria (eleven patients) and in nine patients with histologically proven Zollinger-Ellison syndrome.5. In human volunteers a protein meal stimulated endogenous gastrin release while a carbohydrate meal did not. Atropine sulphate I.M., and hydrochloric acid orally, produced a significant fall in the level of circulating gastrin.

Topics: Achlorhydria; Anemia, Pernicious; Animals; Atropine; Dietary Proteins; Duodenal Ulcer; Gastrins; Guinea Pigs; Humans; Hydrochloric Acid; Iodine Isotopes; Methods; Rabbits; Radioimmunoassay; Stimulation, Chemical; Stomach Ulcer; Sucrose; Swine; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Circadian Rhythm; Fasting; Gastrins; Gastritis; Humans; Stomach; Time Factors

The serum gastrin response to a standard protein meal has been determined in achlorhydric patients with atrophic gastritis and contrasted with the response in normal subjects whose gastric contents were kept continuously neutral by intragastric bicarbonate instillation. Five normal subjects showed a significant increase in serum gastrin from a mean (+/- SEM) of 17 +/- 3 pg/ml to 119 +/- 10 pg/ml but their response did not approach that of four patients with atrophic gastritis and antral sparing (605 +/- 133 pg/ml to 1418 +/- 186 pg/ml). By contrast, in four patients with antral gastritis, there was no significant change in gastrin levels (24 +/- 13 pg/ml to 55 +/- 19 pg/ml). These studies indicate that the gastrin-secreting cell mass is increased in atrophic gastritis with antral sparing and decreased in atrophic gastritis with antral involvement, as compared to the normal state. They provide further evidence for the existence in man of two distinct forms of atrophic gastritis.

Topics: Achlorhydria; Aged; Bicarbonates; Dietary Proteins; Female; Gastrins; Gastritis; Humans; Male; Middle Aged; Stomach

Topics: Achlorhydria; Adult; Age Factors; Aged; Anemia, Pernicious; Antibody Formation; Female; Fluorescent Antibody Technique; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Sex Factors; Time Factors; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Adult; Digestion; Gastrins; Gastritis; Gelatin; Humans; Proline

The gastric antral mucosa was studied histologically in 22 patients with atrophic gastritis, of whom 11 had high levels and 11 had normal levels of serum gastrin. The antrum was graded histologically from normal to grade 3 gastritis. All patients with hypergastrinaemia (nine seropositive and two seronegative for parietal cell antibody) had either a normal antrum or minimal (grade 1) antral gastritis. In contrast all but one patient without raised serum gastrin (nine seronegative and two seropositive for parietal cell antibody) had severe (grades 2-3) antral gastritis. Thus circulating gastrin levels observed in patients with gastritis and achlorhydria can be directly related to the presence or absence of antral mucosal damage.Comparison of the histological appearances of the antral mucosa with serum gastrin and parietal cell antibody status has provided a basis for the separation of two distinctive forms of atrophic gastritis.

Topics: Achlorhydria; Anemia, Pernicious; Antibodies; Atrophy; Chronic Disease; Gastric Mucosa; Gastrins; Gastritis; Humans; Middle Aged; Postgastrectomy Syndromes; Radioimmunoassay; Stomach

Topics: Achlorhydria; Age Factors; Anemia, Pernicious; Gastrins; Humans; Radioimmunoassay

Fasting gastrin levels in serum were measured in 49 patients with different types of chronic gastritis and in matched controls. In 15 patients with established pernicious anaemia the mean (+/- S.E. of mean) level of gastrin was greatly raised (699 +/- 99 pg/ml). In 17 patients with chronic atrophic gastritis, seropositive for parietal cell antibody but with adequate vitamin-B(12) absorption, the level was also raised (476 +/- 74 pg/ml). By contrast, in "simple" atrophic gastritis seronegative for parietal cell antibody the gastrin levels were significantly lower for both diffuse atrophic gastritis (129 +/- 31 pg/ml) and multifocal gastritis (14 +/- 4 pg/ml). These levels were similar to those in the controls (46 +/- 7 pg/ml).The mechanism of the raised gastrin levels remains uncertain, but neither achlorhydria nor in vivo action of the parietal cell antibody wholly accounted for the hypergastrinaemia.We conclude that hypergastrinaemia is characteristic of gastritis associated with autoimmune reactions to gastric antigens and pernicious anaemia and that a raised serum gastrin is a useful marker of the type of gastritis that tends to progress to the gastric lesion of pernicious anaemia. The findings suggest that this type of gastritis is an essentially different disease from "simple" atrophic gastritis, and the differences in gastrin levels may be due to sparing of the antral mucosa in the autoimmune type but not in "simple" gastritis.

Topics: Achlorhydria; Aged; Anemia, Pernicious; Antibodies; Antigens; Autoimmune Diseases; Chronic Disease; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Vitamin B 12

Topics: Achlorhydria; Chronic Disease; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Humans; Hydrogen-Ion Concentration; Hypertrophy; Insulin; Intubation, Gastrointestinal; Protein-Losing Enteropathies; Stimulation, Chemical; Stomach; Stomach Diseases; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Adult; Blood Glucose; Fatty Acids, Nonesterified; Gastrins; Glucose; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreas; Secretory Rate; Stimulation, Chemical; Time Factors

Topics: Achlorhydria; Antacids; Gastric Juice; Gastrins; Gastritis; Humans; Pepsin A

Topics: Achlorhydria; Adult; Age Factors; Aged; Duodenal Ulcer; Fasting; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Gastrins; Humans; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Adult; Aged; Biopsy; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Stomach Diseases

Topics: Achlorhydria; Adenoma, Islet Cell; Animals; Biological Transport, Active; Cell Membrane Permeability; Cholecystokinin; Diarrhea; Gallbladder; Gastrins; Gastrointestinal Hormones; Hypokalemia; Rabbits; Secretin; Tissue Extracts

Topics: Achlorhydria; Adolescent; Adult; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Hormones; Histamine; Humans; Male; Middle Aged; Radiography; Stomach; Time Factors

Topics: Achlorhydria; Animals; Bile Ducts; Biliary Tract; Cats; Duodenum; Gastric Acidity Determination; Gastric Juice; Gastrins; Pancreatic Ducts; Peptic Ulcer; Perfusion; Secretory Rate; Time Factors

Topics: Achlorhydria; Anemia, Pernicious; Gastric Juice; Gastrins; Gastritis; Histamine; Humans; Intrinsic Factor; Radioimmunoassay; Schilling Test; Vitamin B 12

Topics: Achlorhydria; Anemia, Pernicious; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Histamine; Humans; Peptic Ulcer; Pyrazoles; Stomach Neoplasms; Vagotomy

Topics: Achlorhydria; Animals; Cats; Duodenum; Gastric Acidity Determination; Gastric Juice; Gastrins; Intestinal Mucosa; Peptic Ulcer; Secretin

Topics: Achlorhydria; Anemia, Macrocytic; Gastrins; Histamine; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Radioimmunoassay; Stimulation, Chemical; Time Factors; Vitamin B 12

Topics: Achlorhydria; Anemia, Hypochromic; Anemia, Pernicious; Gastric Mucosa; Gastrins; Humans; Intrinsic Factor; Peptic Ulcer; Peptides; Pylorus; Secretory Rate; Skin Tests; Vagotomy

It is suggested that there are two hormonal syndromes associated with noninsulin-secreting islet cell tumours and this case is an example of the non-gastrin-secreting type with watery diarrhoea and hypokalaemia. The patient had histamine-fast achlorhydria and a normal gastric biopsy and no gastrin was recovered from the tumour tissue. The watery diarrhoea was isosmotic with plasma and was increased by an intravenous saline load. There was a dramatic response to steroids.

Topics: Achlorhydria; Adenoma, Islet Cell; Aldosterone; Cortisone; Dexamethasone; Diarrhea; Feces; Gastrins; Humans; Hypocalcemia; Hypokalemia; Neoplasms; Pancreatic Neoplasms; Potassium; Prednisone; Sodium; Surgical Procedures, Operative; Urine; Water-Electrolyte Balance; Zollinger-Ellison Syndrome