gastrins and Gastroesophageal-Reflux

Gastric cancer, a disease with a reduced frequency for decades, now appears to be on the rise again in young Americans. The epidemiology of gastric cancer differs between tumors in the cardia and those of the more distal parts of the stomach. The tumors are divided into the intestinal type showing glandular growth pattern and the diffuse type with a different pattern. The latter often expresses neuroendocrine and more specifically ECL-cell markers suggesting that they originate from the ECL cell, the target cell for the antral hormone, gastrin. Helicobacter pylori gastritis is accepted as the major cause of gastric cancer, but only after having induced oxyntic atrophy which reduces gastric acid secretion and thus induces hypoacidity leading to hypergastrinemia. Long-term hypergastrinemia is known to induce malignant neoplasia in the stomach of animals as well as man. Recently treatment with proton pump inhibitor after Helicobacter pylori eradication in patients with gastroesophageal reflux disease, has been reported to predispose to gastric cancer. Since profound acid inhibition is a well-known cause of gastric neoplasia, it is to be expected that Helicobacter pylori infection and profound acid inhibition has an additive or possibly potentiating effect on the development of gastric cancer.

Topics: Animals; Enterochromaffin-like Cells; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Proton Pump Inhibitors; Stomach Neoplasms

Proton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use.

Topics: Deprescriptions; Enterochromaffin Cells; Gastrins; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Risk Factors; Stomach; Stomach Neoplasms; Withholding Treatment

The manifestations of gastroesophageal reflux disease (GERD) have been recently classified into either esophageal or extra-esophageal syndromes. Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD. Endoscopy had a low sensitivity. Recently, the availability of multichannel intraluminal impedance and pH-monitoring (MII-pH) has modified the diagnostic approach towards atypical manifestations of GERD. There is a rising consensus that this technique should be considered as the gold standard for GERD diagnosis. Gastrin 17 (G-17) has been proposed as a non-invasive marker of GERD, due to the negative feedback between acid and the hormone. G17 levels seem able to identify patients with acid and non-acid reflux.

Topics: Bilirubin; Body Fluids; Chest Pain; Diagnosis, Differential; Electric Impedance; Esophageal pH Monitoring; Gastrins; Gastroesophageal Reflux; Humans; Manometry; Monitoring, Ambulatory; Proton Pump Inhibitors; Symptom Assessment

Helicobacter pylori (Hp) is one of the most common bacteria infecting humans. Recently, certain extragastric manifestations, linked to Hp infection, have been widely investigated, suggesting that Hp infection might be a 'systemic' disease. Accumulating, yet limited, evidence points to a potential association between Hp infection and lung cancer risk. Epidemiologic studies have shown that odds ratios (estimated relative risks) of lung cancer with Hp infection range from 1.24 to 17.78 compared with the controls, suggesting an increased lung cancer risk in the population exposed to Hp infection although far from supporting a causal relationship between Hp and lung cancer. Many studies have demonstrated the existence of Hp in the mucosa of the upper respiratory tract with no direct evidence of Hp-localization in lung tissue in the published literatures, rendering the possible functional mechanism underlying the association an open question. We followed the classic hypothesis-generating path, where we have thoroughly reviewed the publications on lung cancer and Hp infection from serological association to possible mechanisms as: (i) p130cas activated by Src kinase following Hp-host communication and p130cas-related carcinogenesis as in various malignancies; and (ii) gastroesophageal reflux and inhalation of urease or gastrin, which are Hp-related carcinogenic factors and present in lung tissues. We propose rigorous investigations regarding the Hp-lung cancer association and, if confirmed, the mechanisms of Hp infection leading to lung cancer development and progression. Clarification on Hp-lung cancer association is important for the understanding of lung cancer beyond tobacco-smoking-related carcinogenesis.

Topics: Antigens, Bacterial; Bacterial Proteins; Crk-Associated Substrate Protein; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Lung Neoplasms; Odds Ratio; Stomach; Urease

Gastric acid secretion is a complex phenomenon under nervous and hormonal influence. The stimulation of proton pump (H(+), K(+)-ATPase) in the parietal cell represents the final step of acid secretion and this knowledge has led to the development of a class of drugs, the proton pump inhibitors (PPIs), which are targeted at blocking this enzyme. Chemically, all the available PPIs consist of a benzimidazole ring and a pyridine ring, but vary in the specific side ring substitution. As a class, they are the most potent inhibitors of gastric acid secretion available. Although there are differences among PPIs concerning their pharmacokinetics, pharmacodynamics, influence by food and antacids as well as potential for drug interactions, it is not always evident whether these often subtle differences are clinically relevant. A careful evaluation of the available studies reveals that rabeprazole and esomeprazole achieve more rapid acid inhibition than other PPIs. Also, the effect of rabeprazole is less dependent upon genetic make-up than all other PPIs, giving rise to less inter-subject variability and leading to a more predictable effect. Esomeprazole, by inhibiting its own catabolism, makes all patients slow metabolizers, but could expose them to potential drug interactions. PPIs are the mainstay of medical treatment of gastro-oesophageal reflux disease (GORD), in that they are able to provide 80-85% healing rate of oesophageal lesions, including ulcers, and to reduce the incidence of complications like strictures as well as dysplasia and adenocarcinoma in Barrett's oesophagus (BO). Also relief of symptoms can be achieved in about 80% of cases, even though this benefit is reduced by a factor of approximately 20% in patients with non-erosive reflux disease (NERD). Their effect on Barrett's oesophagus and the extra-oesophageal manifestations of GORD is much less consistent. In general, the tolerability profile of PPIs is good in both short- and long-term clinical trials. This safety profile is similar across the various PPIs used in clinical practice and is extended to children and pregnant women, where they do not present any major teratogenic risk.

Topics: Absorption; Drug Interactions; Gastric Acid; Gastrins; Gastroesophageal Reflux; Heart; Hip Fractures; Humans; Pancreatitis; Pneumonia; Proton Pump Inhibitors; Treatment Failure

Topics: Clinical Trials as Topic; Colorectal Neoplasms; Gastrins; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Risk Factors

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

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

Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.

Topics: Animals; Carcinoid Tumor; Cell Transformation, Neoplastic; Drug Tolerance; Enterochromaffin-like Cells; Gastric Acid; Gastric Mucosa; Gastrinoma; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Agents; Helicobacter pylori; Humans; Malabsorption Syndromes; Peptic Ulcer; Proton Pump Inhibitors; Stomach Neoplasms; Time Factors; Zollinger-Ellison Syndrome

To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Endoscopy, Gastrointestinal; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors

Oesophageal adenocarcinoma (OA) remains one of the more deadly forms of gastro-intestinal cancer with a mortality rate exceeding 90%. The incidence of OA remains unabated and has a reported fivefold increase since 1970 [Pera M, Cameron AJ, Trastek VF, Carpenter HA & Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993; 104(2): 510-513]. Gastro-oesophageal reflux disease and its sequelae, Barrett's oesophagus, is one of the principle risk factors in the development of OA, with a 30-fold increased risk in Barrett's patients compared with the general population [Tytgat GNJ. Does endoscopic surveillance in esophageal columnar metaplasia (Barrett's-Esophagus) have any real value. Endoscopy 1995; 27(1): 19-26]. OA is thought to be a microcosm of evolution, developing sequentially along the metaplasia-dysplasia-adenocarcinoma sequence. Progression is attributed to a series of genetic and epigenetic events that ultimately allow for clonal selection of Barrett's cells via subversion of intrinsic control mechanisms regulating cellular proliferation and/or apoptosis. This review will describe the current suppositions of the mechanisms behind the selection and subsequent expansion of Barrett's clones, and focus on some of the principle hallmarks associated with this transition.

Topics: Adenocarcinoma; Animals; Barrett Esophagus; Bile Acids and Salts; Cell Transformation, Neoplastic; Disease Progression; Esophageal Neoplasms; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Inflammation Mediators; Metaplasia; Prevalence

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

Drugs inhibiting gastric acid secretion are widely used because of the high prevalence of acid-related disorders. However, from clinical experience it seems that symptom relapse is common after withdrawal of these drugs. Experimental as well as clinical studies have demonstrated an increased acid secretion after a period of treatment with either histamine 2 receptor antagonists or proton pump inhibitors. Rebound hypersecretion is likely to reflect the following sequence of events: Long-term inhibition of acid output is accompanied by elevated serum gastrin levels, leading to enterochromaffin-like cell activation and proliferation, resulting in increased amounts of histamine being mobilized from these cells to stimulate the parietal cells. The clinical consequences of rebound hypersecretion have not been settled.

Topics: Animals; Biomarkers; Chromogranin A; Enterochromaffin-like Cells; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Histamine; Histamine H2 Antagonists; Humans; Pancreatic Hormones; Parietal Cells, Gastric; Proton Pump Inhibitors; Receptor, Cholecystokinin B; Recurrence; Time Factors

Proton pump inhibitors, which act at the terminal point of acid secretion--the H+, K+-ATPase--are currently the most effective pharmacological treatments available for reflux disease. Despite the efficacy of the proton pump inhibitors, there is still potential for clinical improvement in gastro-oesophageal reflux disease pharmacotherapy. Faster onset of complete acid inhibition and improved duration of efficacy are two potential areas for improvement A number of novel pharmaceutical agents are currently undergoing clinical evaluation for the treatment of gastro-oesophageal reflux disease. These include transient lower oesophageal sphincter relaxation-reducing agents, serotonergic agents/prokinetics, potassium-competitive acid blockers, mucosal protectants, histamine H3 agonists and anti-gastrin agents. One or more of these drug groups may represent the future medical therapy for gastro-oesophageal reflux disease, should they prove effective in the clinical setting. This review summarizes the state of the art with these agents.

Topics: Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gastrointestinal Agents; Histamine Agonists; Humans; Proton Pump Inhibitors; Serotonin Agents; Sodium-Potassium-Exchanging ATPase

The pathogenesis of cancer in Barrett's esophagus is multifactorial. Gastroesophageal reflux seems to be important in the initiation of Barrett's esophagus, but its role in promoting carcinogenesis has yet to be established. Diet, lifestyle and carcinogens, especially the nitrates, may be important in the development of carcinogenesis, and require further investigation. Inhibition of reflux-stimulated inflammatory changes, for example by inhibiting cyclooxygenase, holds promise for decreasing cancer progression. Similarly, dietary and lifestyle modification used in the management of reflux may also help to prevent the development of esophageal cancer. The molecular changes that are associated with the development of cancer in Barrett's esophagus offer several potential areas of intervention to prevent and manage esophageal cancer. Limiting cell growth, increasing apoptosis of damaged cells, limiting cell invasion and angiogenesis factors could be useful to accomplish this goal. Having a greater understanding of the pathogenesis of this condition can only help to develop more management options in the future.

Topics: Barrett Esophagus; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans

The function of the stomach includes initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. The stomach also stores and mechanically disrupts ingested food. Various techniques have been developed to assess gastric physiology, the most important of which is assessment of acid secretion, as well as gastric motility and gastric emptying. The influence of drugs on gastric function and the effect of gastric secretion and mechanical actions on the bioavailability of novel compounds are of critical importance in drug development and hence to clinical pharmacologists. The control of acid secretion is essential in the treatment of peptic ulcer disease as well as gastrooesophageal reflux disease (GORD); pH-metry can be used to determine the necessary dose of an acid suppressant to heal mucosal damage. Disturbed gastric myoelectric activity leading to gastroparesis can cause delayed gastric emptying, often found in patients with diabetes mellitus. Electrogastrography (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition and aid in determining effective therapy.

Topics: Endocrine Glands; Exocrine Glands; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Gastroparesis; Humans; Hydrogen-Ion Concentration; Stomach

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

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

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

Gastroesophageal reflux (GER) occurs in 2 distinct forms that differ in pathophysiology, clinical presentation, natural history, and therapy: mild GER (with no or minimal esophagitis) and classic, severe reflux (at risk for erosive esophagitis). A minority of subjects (< 20%) have the classic, potentially severe pattern of GER caused by reduced lower esophageal sphincter (LES) pressure and prolonged acid reflux, particularly at night, but also during the day. Evaluation and management must be catered to patients with this pattern of reflux. In contrast, symptoms in mild reflux (the majority) often occur during the day after meals in an upright posture (upright reflux); resting LES pressure is usually normal (reflux episodes are related to transient relaxation of the LES) and little reflux occurs at night. Acid reflux, which occurs mostly during the day, overlaps with the normal range and esophagitis is rare; however, symptoms can be distressing. Optimal management is controversial because no outcome trials have been conducted to address management in primary care settings. However, clinical clues can help differentiate mild and severe reflux and guide management decisions. This article provides a detailed approach to current management of GER syndromes.

Topics: Anti-Ulcer Agents; Barrett Esophagus; Cisapride; Endoscopy, Gastrointestinal; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Omeprazole; Predictive Value of Tests; Proton Pump Inhibitors; Risk Factors

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

Gastro-oesophageal reflux (GOR) is common. Nearly all healthy individuals experience occasional or frequent reflux episodes, with or without symptoms, which occur during spontaneous relaxations of the lower oesophageal sphincter, predominantly after meals. It is not known how neural, hormonal and muscular factors contribute to this. A proportion of the patients with reflux disease have normal lower oesophageal sphincter pressures, and their reflux episodes occur during spontaneous sphincter relaxations following the pattern of normals. Nevertheless, most patients with reflux disease have decreased lower oesophageal sphincter pressure, and manoeuvres which increase the intraabdominal pressure provoke "stress" reflux. If the sphincter pressure is very low, "free" reflux occurs; the cause of decreased sphincter pressure is not known. Pharmacological and gastric factors also facilitate GOR. The noxious potency of reflux material on the oesophageal epithelium depends on its components [( H+], pepsin, bile salts, trypsin) and the contact time, which is prolonged during supine and nocturnal reflux episodes, i.e. when clearance function is impaired. In complicated reflux disease it is necessary to consider this multifactorial model of the pathogenesis of reflux disease, and to go on to more sophisticated diagnostic procedures (manometry, scintiscanning, prolonged pH-monitoring) in order to identify an individual patients' predominant pathogenetic factor.

Topics: Cholecystokinin; Esophagitis, Peptic; Esophagogastric Junction; Esophagus; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Histamine H2 Antagonists; Humans; Manometry; Middle Aged; Peristalsis; Pressure

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

Topics: Animals; Bile Acids and Salts; Child; Child, Preschool; Cholera Toxin; Diarrhea; Diarrhea, Infantile; Gastrins; Gastroesophageal Reflux; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Infant; Infant, Newborn; Intestinal Absorption; Intestine, Small; Intestines; Metals; Proteins; Pyloric Stenosis; Syndrome

Topics: Animals; Electric Stimulation; Esophagitis, Peptic; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Mucous Membrane; Pressure; Prostaglandins; Radionuclide Imaging; Stomach

The patient with gastric ulcer (GU) has abnormal reflux of bile-containing duodenal contents into the stomach. Antral gastritis is prominently associated with GU and is more extensive with severe reflux and with ulcer chronicity and probably when bile salts are accompanied by other constituents of duodenal fluids. Smoking is significantly associated with GU, and it produces reflux in normal subjects and in patients with duodenal ulcer, which in turn is commonly associated with GU. Reflux has not been shown to precede either the gastritis or the gastric ulcer and probably persists despite ulcer healing. The pyloric spincter in the patient with GU probably contracts subnormally to endogenous or exogenous secretin or CCK. This can be explained by associated hypergastrinemia since antral acidification improves the response. Because the pylorus may be usually open, abnormal reflux may be related as much or more to disturbances of other gastroduodenal functions known to control the movement of chyme through what may be a relatively passive pyloric zone. Speculation from animal models implicates bile reflux in aspirin-induced and shock-related gastric ulceration and assigns to bile a possible explanation, in part at least, for the apparent therapeutic efficacy of a carbenoxalone derivative and an antipepsin agent. Similar speculation warrants a search in the patient with GU for abnormalities of gastroduodenal peristalsis-related electric activity and for impaired release of secretin, possibly from antral cells of production. Possible abnormal purinergic inhibition of the gastric fundus and pylorus also warrants further study.

Topics: Animals; Bile; Cholecystokinin; Disease Models, Animal; Duodenum; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Humans; Pyloric Antrum; Pylorus; Secretin; Stomach Ulcer

Topics: Atropine; Barium Sulfate; Deglutition; Esophageal Achalasia; Esophageal Diseases; Esophagus; Gastrins; Gastroesophageal Reflux; Humans; Manometry; Muscle Contraction; Nitroglycerin; Peristalsis; Pressure; Pyridostigmine Bromide; Radiography

Topics: Antacids; Asphyxia; Esophagitis; Esophagoscopy; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Hernia, Diaphragmatic; Humans; Methods; Parasympatholytics; Radiography; Stomach Ulcer

Topics: Cineradiography; Deglutition Disorders; Esophageal Achalasia; Esophageal Diseases; Esophageal Stenosis; Esophagogastric Junction; Esophagoscopy; Gastrins; Gastroesophageal Reflux; Heartburn; Hernia, Diaphragmatic; Humans; Manometry

Topics: Animals; Cholecystokinin; Esophageal Achalasia; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Gastrointestinal Motility; Hernia, Diaphragmatic; Humans; Pentagastrin; Pressure; Secretin

Topics: Animals; Esophagus; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Humans; Hydrogen-Ion Concentration; Manometry; Peptides; Radiography

Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H. The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg.. Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg.. Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml.. Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.

Topics: Acetamides; Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Healthy Volunteers; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Piperidines; Proton Pump Inhibitors; Pyridines; Pyrroles; Sulfonamides; Young Adult

Rabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to be highly effective in the treatment of proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) that is refractory to the standard once-daily PPI regimen. We evaluated the efficacy and safety of rabeprazole maintenance therapy at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks.. Patients with RE refractory to standard PPI regimens for at least 8 weeks were enrolled. They were treated with rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive rabeprazole 10 mg q.d. (control) or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52.. In total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%; p < 0.001, χ. In the maintenance treatment of PPI-resistant RE, rabeprazole at 10 mg b.i.d. exerted a stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No particular safety issues were noted during long-term administration. ClinicalTrials.gov number: NCT02135107.

Topics: Aged; Anti-Ulcer Agents; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Endoscopy; Esophagitis, Peptic; Female; Gastrins; Gastroesophageal Reflux; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Polyps; Proton Pump Inhibitors; Rabeprazole; Recurrence; Secondary Prevention; Treatment Outcome

To determine the proportion of patients with gastroesophageal reflux disease who are on proton pump inhibitors (PPIs) who could reduce their prior dosage by half, and identify predictors of successful step-down.. Appropriate hypergastrinemia results from gastric acid inhibition. A gender difference in fasting gastrin with higher levels among women than among men on long-term PPI therapy has been demonstrated.. Patients with endoscopically verified erosive esophagitis on long-term PPI therapy were randomized double blindly to step down their dose by half or continue with the same dose for 8 weeks. Fasting gastrin levels were measured before and after treatment. The primary endpoint was successful step-down throughout the study period.. Overall, 100 patients were randomized, 49 (24 females) to continue with the same dose as before and 51 (25 females) to step down. Female patients had higher gastrin levels compared with male patients: 78 pg/mL (IQR, 50 to 99) versus 50 pg/mL (IQR, 36 to 74) (P=0.007). Among those randomized to the step-down intervention only 3/25 (12%) women failed to complete the 2 months of lower-dose therapy versus 9/25 (36%) men (P=0.09). Female gender (P=0.048) was the strongest predictor for successful step-down (odds ratio=1.27; 95% CI, 1.01-1.60). The chance of failing to maintain symptom control was twice as high in the reduction group (24%) as compared with the control group (13%) (P=0.2).. Female patients on long-term PPI therapy were 3 times more likely to tolerate half of their prior dose. Female gender had higher probability for successful step-down. These results indicate that women with gastroesophageal reflux disease might manage with lower doses of PPIs as compared with men.European Clinical Trial Database (https://eudract.ema.europa.eu/), number 2013-002067-26.

Topics: Aged; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Sex Factors; Time Factors; Treatment Outcome

Gastroesophageal reflux disease lowers the quality of life and increases medical costs. Electroacupuncture has been used to ease symptoms and improve gastrointestinal motility in patients with gastroesophageal reflux disease. The main purposes of this study are to evaluate the efficacy and safety of this procedure.. This is a protocol for a randomized, patient-blinded, assessor-blinded, sham-controlled trial. Sixty participants with symptoms of gastroesophageal reflux disease, who have previously undergone standard treatment, will be recruited from August 2015 at Kyung Hee University Korean Medicine Hospital. The participants will be allocated to either the electroacupuncture (n = 30) or the sham electroacupuncture group (n = 30); the allocation will be concealed from both the participants and the assessors. The EA group will undergo penetrating acupuncture at 18 fixed points and two optional points chosen using the pattern identification for gastroesophageal reflux disease. Electrical stimulation will be applied at some of the acupoints. The sham electroacupuncture group will undergo nonpenetrating acupuncture without electrical stimulation at 18 nonspecific points, each of which will be only 2 cm away from the true acupoints used in the electroacupuncture group. In both groups, the procedure will be performed using the Park device. The treatment will last for 6 weeks (with two sessions each week), and the outcome will be evaluated at baseline, 3 weeks, and 6 weeks. The primary outcome will be the proportion of responders with adequate symptom relief, whereas the secondary outcomes will comprise the results of the Nepean dyspepsia index; the Korean gastrointestinal symptom rating scale; the EQ-5D™; levels of gastrin, motilin, and inflammatory cytokines; the perceived stress scale; the qi-stagnation questionnaire; the patient global impression of change; and the spleen qi deficiency questionnaire.. The results of this trial will provide information about the efficacy and safety of electroacupuncture in the treatment of gastroesophageal reflux disease symptoms, as well as evidence regarding the use of electroacupuncture to treat gastroesophageal reflux disease in real clinical practice.. Clinical Research Information Service Identifier, KCT0001653 . Registered on 12 October 2015.

Topics: Acupuncture Points; Adult; Aged; Biomarkers; Clinical Protocols; Cytokines; Double-Blind Method; Electroacupuncture; Female; Gastrins; Gastroesophageal Reflux; Humans; Inflammation Mediators; Male; Middle Aged; Motilin; Patient Satisfaction; Qi; Recovery of Function; Republic of Korea; Research Design; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

Scant data exist on the normal range of serum gastrin in infants. In phase I and III trials of rabeprazole in gastroesophageal reflux disease, we studied serum gastrin levels in infants 1 to 11 months old, and assessed normal ranges and the effect of acid-suppressive drugs.. Overall, 349 treatment-naïve or treatment-experienced (previously exposed to proton pump inhibitors and/or H2-receptor antagonists) infants with gastroesophageal reflux disease were screened for baseline serum gastrin. Repeat gastrin was monitored at early termination or end of study, allowing assessment of 1 to 8 week daily rabeprazole (5- or 10-mg) treatment on gastrin levels.. Median (5%-95% range) baseline gastrin was 118 ng/L (39-315) in the treatment-naïve group (n = 251), driven mostly by high levels (121.5 [48-326] ng/L) in the 1- to <4-month-old subgroup. Treatment-experienced infants (n = 98) had elevated baseline gastrin levels (152 [48-487] ng/L; P = 0.0011) with no clear difference between previously proton pump inhibitor-exposed and H2-receptor antagonist-exposed groups. At the end of study, mean (standard deviation) levels were unchanged from baseline in infants withdrawn from rabeprazole to placebo (124 [94] ng/L), but elevated from baseline in those continuing treatment with 5-mg (245 [151] ng/L) and 10-mg (332 [222] ng/L) rabeprazole during the study.. Gastrin levels in treatment-naïve infants were elevated through 8 months of age. Between 8 and 12 months of age, they declined so that the median level was within the upper limit of the normal adult range (<100 ng/L). Previous exposure to acid-suppressive medications and short-term exposure to rabeprazole significantly increased gastrin levels in infants younger than 1 year.

Topics: Gastrins; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Infant; Infant, Newborn; Proton Pump Inhibitors; Rabeprazole; Reference Values

Proton pump inhibitors (PPIs) are used primarily to treat gastroesophageal reflux disease. Proton pump inhibitor-induced achlorhydria increases circulating gastrin and chromogranin A (CGA). Chromogranin is a widely used biomarker for the diagnosis and follow-up for gut-based neuroendocrine tumors (NETs). Proton pump inhibitor-induced increases in CGA or gastrin may falsely suggest the presence of a NET when none exists. Pancreastatin, a fragment of CGA, is also commonly used to diagnose and follow NETs. We hypothesized that chronic PPI use would increase circulating plasma gastrin, CGA, and pancreastatin levels.. Thirty patients who used PPIs for 6 months or more (mean ± SD duration, 3.1 ± 2.5 years) and a separate control group of 30 patients who never used antacid medications were prospectively evaluated with plasma gastrin, CGA, and pancreastatin determinations.. Chronic PPI use resulted in significant increases in CGA (15.1 ± 11 vs 131 ± 207 ng/mL; P = 0.005) and significant increases in gastrin (34.8 ± 22.3 vs 167.8 ± 136.2 pg/mL; P = 0.001) compared to controls. In contrast, pancreastatin level in nonusers and chronic PPI users were identical (81.6 ± 36.4 vs 89.4 ± 43.4 pg/mL; P = 0.46).. Pancreastatin levels do not change with chronic PPI use and normal pancreastatin levels may be used to distinguish between drug-induced changes in biomarkers and tumor-related increases in circulating biomarkers.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chromogranin A; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pancreas; Pancreatic Hormones; Pancreatic Neoplasms; Prospective Studies; Proton Pump Inhibitors

Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals.. To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266).. Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy.. Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P < 0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P < 0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin.. Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Chromogranin A; Enterochromaffin-like Cells; Esomeprazole; Female; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Laparoscopy; Male; Middle Aged; Proton Pump Inhibitors; Time Factors; Treatment Outcome; Young Adult

The aim of this prospective clinical study was to evaluate the efficacy and safety of long-term proton pump inhibitor (PPI) treatment for two years in Japanese patients with reflux esophagitis (RE).. The efficacy and safety of two-year (104-week) treatment with rabeprazole (RPZ) 10 mg were studied in patients confirmed to have been cured of RE by PPI and who required long-term maintenance therapy with PPI. We performed serial endoscopy, checked gastroesophageal reflux disease (GERD) symptoms, adverse events, laboratory values and serum gastrin. We also monitored gastric mucosal histology, atrophy and polyps.. The endoscopic non-relapse rate for RE was 87.3% for the 104-week period. GERD symptoms improved based on the fact that the mean change from baseline in GERD symptom score after treatment was a negative value. Treatment was safe; and atrophy was found to have developed in virtually no cases. A few new benign fundic gland or hyperplastic polyps developed throughout the study, but no ECL carcinoids were found to have developed. Serum gastrin levels tended to increase up to 24 weeks, but there were no subsequent changes thereafter up to 104 weeks.. The results confirmed oral RPZ 10 mg to be effective for maintenance therapy in Japanese patients with RE. Although effects on the gastric mucosa were not ruled out, long-term use of RPZ was confirmed to be safe overall.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Aged; Dose-Response Relationship, Drug; Esophagitis, Peptic; Female; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Humans; Japan; Longitudinal Studies; Male; Middle Aged; Prevalence; Prospective Studies; Proton Pump Inhibitors; Rabeprazole; Treatment Outcome

Gastro-Esophageal Reflux Disease (GERD) defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Many drugs are used for the treatment of GERD such as omeprazole (a proton pump inhibitor) which is a widely used antiulcer drug demonstrated to protect against esophageal mucosal injury. Melatonin has been found to protect the gastrointestinal mucosa from oxidative damage caused by reactive oxygen species in different experimental ulcer models. The aim of this study is to evaluate the role of exogenous melatonin in the treatment of reflux disease in humans either alone or in combination with omeprazole therapy.. 36 persons were divided into 4 groups (control subjects, patients with reflux disease treated with melatonin alone, omeprazole alone and a combination of melatonin and omeprazole for 4 and 8 weeks) Each group consisted of 9 persons. Persons were subjected to thorough history taking, clinical examination, and investigations including laboratory, endoscopic, record of esophageal motility, pH-metry, basal acid output and serum gastrin.. Melatonin has a role in the improvement of Gastro-esophageal reflux disease when used alone or in combination with omeprazole. Meanwhile, omeprazole alone is better used in the treatment of GERD than melatonin alone.. The present study showed that oral melatonin is a promising therapeutic agent for the treatment of GERD. It is an effective line of treatment in relieving epigastric pain and heartburn. However, further studies are required to confirm the efficacy and long-term safety of melatonin before being recommended for routine clinical use.. QA13NCT00915616.

Topics: Drug Therapy, Combination; Gastrins; Gastroesophageal Reflux; Humans; Melatonin; Omeprazole; Treatment Outcome

Gastroesophageal reflux disease (GERD) impairs the patient's quality of life (QOL), but the effect of long-term maintenance therapy in elderly patients is unknown.. We conducted a long-term prospective study. Forty-four GERD patients (11 males; mean age 74 years; QUEST score of at least 6 points) were enrolled in this study. Step-down therapy was selected (proton-pump inhibitor [PPI], histamine-2 receptor antagonist and prokinetic agents for 1 month, respectively). Optimal medication for each patient was continued for 5 years. The efficacy, safety of treatment and reflux symptoms were analyzed. The profiles of the patients who had to continue PPI maintenance therapy were also analyzed.. Reflux symptoms were reduced by the PPI based step-down therapy (baseline 13.8 times/month, after 3.2 times/month, P < 0.001). Reflux symptoms improved in 34 patients (77%). None of the 44 patients had to cease treatment because of side-effects and none experienced any complications during the 5-year period. The prevalence of Helicobacter pylori (Hp) infection in the PPI group (29%, 4/14) was significantly lower (P < 0.01) than in the other treatment group (72%, 21/29). The serum pepsinogen I/II ratio in the PPI treatment group (5.7 +/- 0.5) was significantly higher (P < 0.01) than in the others (4.0 +/- 0.3). The predictive factors for PPI maintenance therapy were Hp-negative status and serum pepsinogen I/II ratio >6.0 (odds ratio 12.0, 95% confidence interval 2.7-54.2).. Long-term medication for GERD selected on the basis of the patient's profile (i.e. Hp status and gastric atrophy) improved reflux symptoms.

Topics: Aged; Atrophy; Community Health Services; Drug Administration Schedule; Drug Therapy, Combination; Enzyme Inhibitors; Female; Follow-Up Studies; Gastric Emptying; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gastrointestinal Agents; Heartburn; Helicobacter pylori; Histamine H2 Antagonists; Humans; Japan; Long-Term Care; Male; Pepsinogen A; Pepsinogen C; Prospective Studies; Proton Pump Inhibitors; Proton Pumps; Quality of Life; Time Factors; Treatment Outcome

Adding pectin to an elemental formula increases its viscosity through gelatinization, thus presumably preventing gastro-oesophageal reflux and aspiration pneumonia. We investigated the influence of the viscosity of an elemental formula on gastric emptying. Eleven healthy volunteers underwent three tests at intervals of >1 week. After fasting for >8 h, each subject received a test meal (enteral nutrition solution, enteral solution plus pectin, or water). Then gastric emptying (continuous (13)C breath test), gastro-oesophageal intraluminal pressures, oesophageal pH, and blood levels of glucose, insulin and gastrin were all measured simultaneously. The gastric emptying coefficient was significantly increased by adding pectin to enteral nutrition (3.01 +/- 0.10 vs 2.78 +/- 0.10, mean +/- SE, P < 0.05). The antral motility index was also significantly higher with pectin than without at 45-60 min and 60-75 min after the test meal (526 +/- 237 vs 6.5 +/- 4.6 mmHg s(-1) and 448 +/- 173 vs 2.3 +/- 2.3 mmHg s(-1) respectively; P < 0.05). Plasma glucose was significantly higher with pectin than without it at 60 min after ingestion (141.5 +/- 6.03 vs 125.8 +/- 4.69 microM mL(-1), P < 0.05). In healthy individuals, pectin increased the viscosity of enteral nutrition and accelerated gastric emptying.

Topics: Adult; Blood Glucose; Breath Tests; Enteral Nutrition; Female; Food, Formulated; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Insulin; Male; Pectins; Viscosity

The proportion of proton pump inhibitor users on long-term therapy who can discontinue proton pump inhibitor (PPI) medication without developing symptoms is unknown.. To determine the proportion of patients on long-term PPI therapy who are able to discontinue PPIs without developing symptoms.. Patients on long-term PPIs, without a history of peptic ulcer or esophagitis underwent upper endoscopy. Patients were randomized double-blindly to taper down or continue a constant dosage of omeprazole for three weeks. Thereafter, all patients discontinued PPIs.. Of the 97 patients enrolled, had used PPIs for 48 months, 78% had GERD. A total of 27% did not use PPIs during the year after discontinuation, 31% of the patients randomized to tapering discontinued PPIs and 22% of those who did not could discontinue therapy (NS). Gastro-oesophageal reflux disease (GERD) patients were more prone to continue PPIs than non-GERD patients. Only 16 (21%) of GERD patients were off PPIs vs. 48% of patients without GERD (p < 0.05). Serum gastrin was higher at baseline in GERD patients who resumed PPIs versus non-resumers (p < 0.05). GERD and serum gastrin were independent predictors of PPI requirement.. Discontinuation of PPI was successful in 27% of long-term PPI users. GERD patients had more difficulty discontinuing PPIs than non-GERD patients.

Topics: Aged; Double-Blind Method; Drug Administration Schedule; Dyspepsia; Enzyme Inhibitors; Female; Gastrins; Gastroesophageal Reflux; Humans; Long-Term Care; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Quality of Life; Treatment Outcome; Withholding Treatment

Prolonged gastric acid suppression leads to hypergastrinaemia, which promotes hyperplasia of the enterochromaffin-like (ECL) cells of the oxyntic mucosa. The objective was to determine the effects of 5 years of treatment with rabeprazole or omeprazole on the gastric mucosa.. Two hundred and forty-three patients received rabeprazole (20 mg or 10 mg) or omeprazole (20 mg) once daily for up to 5 years, for gastro-oesophageal reflux disease and 51% completed the whole 5 year period. Gastric biopsy specimens were taken and examined for gastritis, Helicobacter pylori infection, and ECL cell status.. H. pylori infection in the gastric corpus was more common than in the antrum, and remained constant, whereas antral H. pylori infection became less common as the study progressed. H. pylori infection was a highly significant predictor of higher gastritis scores, which were similar among the three treatment groups. ECL cell hyperplasia occurred in a minority of patients, and was associated with serum gastrin concentrations. No ECL cell dysplasia or tumours were observed. There were no significant differences among the treatment groups in gastritis or ECL cell hyperplasia grades.. This study has confirmed the link between ECL cell hyperplasia and elevated serum gastrin concentrations, but has found no evidence that this progresses to high grades of hyperplasia during 5 years of treatment with rabeprazole or omeprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Biopsy; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Metaplasia; Middle Aged; Omeprazole; Prospective Studies; Proton Pump Inhibitors; Rabeprazole; Severity of Illness Index

The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis.. To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment.. A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored.. The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups.. Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.

Topics: Adult; Aged; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Esophagitis, Peptic; Female; Gastrins; Gastroesophageal Reflux; Genotype; Heterozygote; Homozygote; Humans; Male; Middle Aged; Mixed Function Oxygenases; Omeprazole; Polymorphism, Genetic; Recurrence; Treatment Outcome

Erosive gastro-oesophageal reflux disease (GERD) is a chronic condition requiring long-term maintenance treatment. However, few trials of proton pump inhibitors in maintaining healing of erosive or ulcerative GERD are conducted for longer than 1 year.. To compare the efficacy and safety of 10- and 20-mg rabeprazole with placebo in the 5-year maintenance of healing in patients previously diagnosed with erosive/ulcerative GERD healed in an acute efficacy trial.. Patients (N = 497) were randomized to receive once-daily doses of 10- or 20-mg rabeprazole or placebo. The primary efficacy measure was endoscopically documented absence of oesophageal erosions or ulcerations.. After 5 years, relapse rates in both rabeprazole groups were significantly lower than with placebo (rabeprazole 20 mg, 11%; 10 mg, 23%; placebo, 63%; P < 0.001 for rabeprazole vs. placebo; P = 0.005 for rabeprazole 20 mg vs. 10 mg). Both rabeprazole doses were significantly superior to placebo in preventing relapse of heartburn frequency and improving patient quality of life. Analyses of adverse events, biopsy findings and laboratory values showed no evidence of clinically significant effects.. Five-year maintenance therapy with rabeprazole is effective in preventing relapse of erosive or ulcerative GERD and is well tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Dose-Response Relationship, Drug; Double-Blind Method; Esophagitis, Peptic; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Patient Compliance; Proton Pump Inhibitors; Rabeprazole; Secondary Prevention; Treatment Outcome

Gastro-oesophageal reflux disease has a chronic course, and often requires long-term treatment. Proton pump inhibitors are the treatment of choice for both acute and maintenance treatment, but little is known from randomized controlled trials of their effects beyond 1 year.. To compare the efficacy and safety of two doses of rabeprazole with 20 mg omeprazole in the maintenance treatment of erosive gastro-oesophageal reflux disease over 5 years.. Two hundred and forty-three patients who had previously responded to acute treatment for erosive gastro-oesophageal reflux disease were prospectively randomized to receive 5 years of treatment with rabeprazole (10 or 20 mg daily) or omeprazole (20 mg daily). The primary outcome measure was endoscopically confirmed relapse of erosive gastro-oesophageal reflux disease.. One hundred and twenty-three patients (51%) completed all 5 years of the study, with similar completion rates in the three groups. Relapses occurred in nine of 78 (11.5%), eight of 82 (9.8%) and 11 of 83 (13.3%) patients in the rabeprazole 20 mg, rabeprazole 10 mg and omeprazole 20 mg groups, respectively. Gastric biopsy showed no evidence of any harmful effects. All treatments were well tolerated.. Rabeprazole 10 mg, rabeprazole 20 mg and omeprazole 20 mg all had similar efficacy in the maintenance treatment of gastro-oesophageal reflux disease. All three were safe and well tolerated during 5 years of treatment.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Prospective Studies; Rabeprazole; Recurrence; Treatment Outcome

To evaluate the safety of lansoprazole in children between 1 and 11 years of age.. In a phase I/II, open-label, multicenter (11 sites) study, children with symptomatic gastroesophageal reflux disease (GERD), erosive esophagitis (> or = grade 2), and/or esophageal pH < 4 for > 4.2% of the 24-hour period were assigned, on the basis of body weight, to lansoprazole 15 mg (< or = 30 kg) or 30 mg (> 30 kg) once daily for 8 to 12 weeks. At the discretion of the investigator, the dosage of lansoprazole was increased up to 60 mg daily in children who continued to be symptomatic after 2 weeks of treatment. Safety for all study participants was monitored by adverse event reports and laboratory evaluations.. Sixty-six children were enrolled in the study and were included in the safety analysis. Throughout the treatment period, no child discontinued therapy because of an adverse event and no clinically significant changes in laboratory values were observed. Three of the 32 children (9%) who received lansoprazole 15 mg once daily (mean exposure 50.3 days) and 6 of the 34 children (18%) who received the 30 mg once-daily dose (mean exposure 49.4 days) experienced one or more treatment-related adverse events before any dose increase. The three children in the lansoprazole 15 mg treatment group were treated with doses of 0.6 mg to 1.2 mg/kg/day; those in the lansoprazole 30 mg treatment group were treated with doses of 0.7 mg to 0.9 mg/kg/day. Only one child experienced a new treatment-related adverse event after an increase in lansoprazole dose to 1.3 mg/kg/day. Treatment-related events experienced by two or more children were: constipation (lansoprazole 15 mg QD, two children; lansoprazole 30 mg QD, one child), and headache (lansoprazole 30 mg QD, two children). Mean fasting serum gastrin levels were significantly increased from 58.0 pg/mL at baseline to 112.4 pg/mL at week 2 and 121.9 pg/mL at the final visit (P < or = 0.001 for each comparison). However, the median fasting serum gastrin levels at the week 2 and the final visit were within the normal range (25-111 pg/mL).. Lansoprazole, when administered on the basis of body weight in children between 1 and 11 years of age, is safe and well-tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Esophagitis; Female; Gastrins; Gastroesophageal Reflux; Humans; Infant; Lansoprazole; Male; Omeprazole; Proton Pump Inhibitors; Safety

The objective of this study was to compare the efficacy and safety of the proton pump inhibitor rabeprazole to that of the histamine-2 (H2)-receptor antagonist ranitidine in the treatment of erosive gastroesophageal reflux disease. The primary indicator of efficacy was the absence of esophageal erosions or ulcerations as determined by posttreatment endoscopy. Secondary indicators of efficacy included improvement in frequency and severity of daytime and nighttime heartburn.. A total of 338 patients were enrolled and randomly assigned to therapy with rabeprazole 20 mg once daily in the morning or to ranitidine 150 mg four times daily. At baseline and at 4 wk, patients underwent endoscopy for evaluation of esophageal lesions. Patients whose lesions healed by wk 4 had therapy discontinued; others remained on therapy and had repeat endoscopy at 8 wk. Also recorded at study visits were patients' ratings of heartburn symptoms and overall sense of well being, patients' reports of time lost from daily activities, antacid use, and adverse events. Serum gastrin levels were measured and argyrophil enterochromaffin-like cell histology evaluated at baseline and when the patient ended therapy.. At wk 4, healing was observed in 59% (98/167) of patients assigned to rabeprazole therapy, compared with 36% (60/169) of those receiving ranitidine (p < 0.001). By 8 wk, healing was seen in 87% (146/167) and 66% (112/169) of patients in the rabeprazole and ranitidine groups, respectively (p < 0.001). There were also significant differences between the two groups favoring rabeprazole with respect to resolution or improvement of heartburn symptoms and improvement in sense of well-being. No drug-related serious adverse events were seen with either therapy; fewer patients assigned to rabeprazole had treatment-emergent signs and symptoms. Serum gastrin levels increased over baseline in the rabeprazole group, but the mean value remained within normal limits.. Rabeprazole was superior to ranitidine in esophageal healing and symptom relief in patients with erosive gastroesophageal reflux disease, and was equally well tolerated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Antacids; Benzimidazoles; Double-Blind Method; Female; Gastrins; Gastroesophageal Reflux; Heartburn; Histamine H2 Antagonists; Humans; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Rabeprazole; Ranitidine; Treatment Outcome

A hypothesis suggesting that profound acid inhibition therapy facilitates and hastens the development of gastric glandular atrophy in patients infected with Helicobacter pylori was investigated in this randomized study comparing omeprazole therapy with antireflux surgery (ARS) for chronic gastroesophageal reflux disease (GERD).. Patients with esophagitis and/or chronic GERD were enrolled; 155 patients were randomized to ARS and 155 to long-term omeprazole therapy. Baseline data were obtained and repeated after 3 years in 131 ARS patients and in 139 omeprazole-treated patients. Histopathologic status of the oxyntic mucosa was assessed according to the Sydney system.. Forty omeprazole-treated patients were infected with H. pylori compared with 53 in the ARS group. Basal gastrin levels were significantly higher in H. pylori-infected patients, particularly in the omeprazole group. No further increases in serum gastrin levels were observed during 3 years. Despite 3 years of therapy, only slight changes were found in the prevalence of inflammation in the corpus mucosa of H. pylori-infected subjects. A slow progression of gastric glandular atrophy was observed in these patients irrespective of therapy with no obvious difference between treatment regimens. Intestinal metaplasia (all of type I) was only exceptionally observed with no difference between the treatment arms.. Acid-suppressive therapy in the form of omeprazole maintained for 3 years facilitates neither the development of gastric glandular atrophy of the corpus mucosa nor the occurrence of intestinal metaplasia in H. pylori-infected GERD patients.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Atrophy; Esophagitis; Female; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Prospective Studies

Gastric acid secretion, gastrin release, gastric emptying, and gastroesophageal acid reflux were measured in asymptomatic individuals before and after elimination of Helicobacter pylori gastritis. After basal gastric acid secretion and serum gastrin concentrations were measured, meal-stimulated gastric acid secretion and gastrin release were assessed during in vivo intragastric titration to pH 3. Experiments were repeated 4 wk after treatment with lansoprazole, amoxicillin, and clarithromycin. Esophageal pH was also monitored for 24 h before and after therapy. Basal gastric acidity increased approximately 20 mmol/l in subjects whose infection was eradicated (P < 0.05) but not in those with persistent infection. Basal and meal-stimulated gastric acid secretion did not change after H. pylori eradication, despite a 41% reduction in meal-stimulated gastrin release (P < 0.05). Gastroesophageal acid reflux increased two- to threefold after successful treatment (P < 0. 05) but did not change in subjects with persistent infection. Thus elimination of H. pylori gastritis increases gastric acidity, probably by reducing nonparietal alkaline secretion, and this may facilitate gastroesophageal acid reflux.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Esophagitis; Female; Food; Gastric Acid; Gastric Emptying; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Monitoring, Physiologic; Omeprazole; Penicillins; Polyethylene Glycols; Postprandial Period; Solvents

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

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

elucidate the mechanisms that lead to severe hypergastrinaemia during long-term omeprazole therapy for gastro-oesophageal reflux disease (GERD).. A total of 26 GERD patients were studied during omeprazole maintenance therapy. Twelve patients with severe hypergastrinaemia (gastrin > 400 ng/L) were compared with 14 control patients (gastrin < 300 ng/L). Helicobacter pylori serology and a laboratory screen were obtained in all patients. Gastric emptying was scored by the evidence of food remnants upon endoscopy 12 h after a standardized meal. Gastric antrum and corpus biopsies were analysed for histological parameters, as well as somatostatin and gastrin concentrations. All patients underwent a meal-stimulated gastrin test and the hypergastrinaemia patients also underwent a vagal nerve integrity assessment by pancreatic polypeptide testing (PPT).. Severe hypergastrinaemia patients had a longer duration of treatment (80 vs. 55 months; P = 0.047) and were characterized by a higher prevalence of H. pylori infection (9/12 vs. 2/14, P = 0.004), corpus mucosal inflammation and atrophic gastritis (P < 0.04). This was reflected in lower serum pepsinogen A concentrations (mean +/- S.E.M. 53.6 +/- 17.9 vs. 137 +/- 16.0 mg/L, P = 0.03), pepsinogen A/C ratio (1.8 +/- 0.3 vs. 4.1 +/- 0.6, P = 0.005) and mucosal somatostatin concentrations (2.75 +/- 0.60 vs. 4.48 +/- 1.08 mg/g protein, P = 0.038). Two patients in the hypergastrinaemia group had signs of delayed gastric emptying, but none in the normogastrinaemia group did (P = N.S.). In addition, both groups had a normal meal-stimulated gastrin response.. Severe hypergastrinaemia during omeprazole maintenance therapy for GERD is associated with the duration of therapy and H. pylori infection, but not with abnormalities of gastric emptying or vagal nerve integrity.

Topics: Aged; Anti-Ulcer Agents; Area Under Curve; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Omeprazole; Pancreatic Polypeptide; Vagus Nerve

Treatment with H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) induces hypergastrinemia and causes rebound hypersecretion of gastric acid after treatment, and during treatment with H2RAs tolerance develops. In the present study we investigated whether a treatment period with a PPI induced tolerance to an H2RA.. Thirteen patients with esophagitis were given omeprazole for 90 days. Twenty-four-hour pH monitorings without and with ranitidine were performed before and after treatment with omeprazole. Blood samples and biopsy specimens from the oxyntic mucosa were analyzed for gastrin, histamine, and chromogranin A.. An increase in mucosal histamine and a reduction in the effect of ranitidine on gastric pH was found 14 days after discontinuing omeprazole compared with before treatment in Helicobacter pylori-negative but not in H. pylori-positive patients.. Treatment with omeprazole reduces the effect of ranitidine in H. pylori-negative patients. This is caused by an increase in histamine released by the enterochromaffin-like cell secondarily to hypergastrinemia, corresponding to the tolerance towards H2RAs seen in patients with Zollinger-Ellison syndrome.

Topics: Adult; Aged; Chromogranin A; Chromogranins; Drug Tolerance; Esophagitis; Female; Gastric Acid; Gastrins; Gastroesophageal Reflux; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Histamine Release; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Ranitidine

To determine the results of a new surgical procedure for patients with Barrett's esophagus.. In addition to pathologic acid reflux into the esophagus in patients with severe gastroesophageal reflux and Barrett's esophagus, increased duodenoesophegeal reflux has been implicated. The purpose of this study was to establish the effect of a new bile diversion procedure in these patients.. Sixty-five patients with Barrett's esophagus were included in this study. A complete clinical, radiologic, endoscopic, and bioptic evaluation was performed before and after surgery. Besides esophageal manometry, 24-hour pH studies and a Bilitec test were performed. After surgery, gastric emptying of solids, gastric acid secretion, and serum gastrin were determined. All patients underwent highly selective vagotomy, antireflux procedure (posterior gastropexy with cardial calibration or fundoplication), and duodenal switch procedure, with a Roux-en-Y anastomosis 60 cm in length.. No deaths occurred. Morbidity occurred in 14% of the patients. A significant improvement in symptoms, endoscopic findings, and radiologic evaluation was achieved. Lower esophageal sphincter pressure increased significantly (p < 0.0001), as did abdominal length and total length of the sphincter (p < 0.0001). The presence of an incompetent sphincter decreased from 87.3% to 20.9% (p < 0.0001). Three of seven patients with dysplasia showed disappearance of this dysplasia. Serum gastrin and gastric emptying of solids after surgery remained normal. Basal and peak acid output values were low. Twenty-four hour pH studies showed a mean value of 24.8% before surgery, which decreased to 4.8% after surgery (p < 0.0001). The determination of the percentage time with bilirubin in the esophagus was 23% before surgery; this decreased to 0.7% after surgery (p < 0.0001). Late results showed Visick I and II gradation in 90% of the patients and grade III and IV in 10% of the patients.. This physiologic approach to the surgical treatment of patients with Barrett's esophagus produces a permanent decrease of acid secretion (and avoids anastomotic ulcer), decreases significantly acid reflux into the esophagus, and abolishes duodenoesophageal reflux permanently. Significant clinical improvement occurs, and dysplastic changes at Barrett's epithelium disappear in almost 50% of the patients.

Topics: Adult; Aged; Barrett Esophagus; Bile Reflux; Duodenum; Female; Follow-Up Studies; Fundoplication; Gastric Acid; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Postoperative Complications; Prospective Studies; Vagotomy

We studied the effect of gastrin-17 on lower esophageal sphincter (LES) characteristics in man. Nine healthy volunteers participated in two experiments performed in random order during continuous infusion of saline (control) or gastrin-17 (15 pmol/kg/hr). LES pressure (LESP) and transient lower esophageal sphincter relaxations (TLESR), as most the important reflux mechanism, were measured with intraesophageal sleeve manometry combined with pH metry. Infusion of gastrin-17 resulted in plasma gastrin levels comparable to those reached after a mixed meal. During continuous gastrin infusion, LESP decreased significantly (P < 0.05) compared to control. The rate and duration of TLESR was not influenced by gastrin-17. Gastroesophageal reflux and the number of TLESR associated with reflux were significantly (P < 0.05) increased during gastrin infusion. These results suggest that in humans gastrin at physiological postprandial plasma concentrations decreases LESP, does not influence TLESR, but increases the percentage of TLESR associated with reflux.

Topics: Adult; Esophagogastric Junction; Female; Gastrins; Gastroesophageal Reflux; Hormones; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Manometry; Muscle Relaxation

To clarify the lower esophageal sphincter (LES) pressure response to alkali ingestion, normal subjects and postantrectomy patients with either a gastroduodenostomy or gastrojejunostomy were studied in a double-blind controlled fashion. LES pressure and serum gastrin concentrations were measured after ingestion of a 100 ml bolus of either 0.4 M NaHCO3 or 0.4 M NaCl. In addition, the effect of a therapeutic dose (30 ml) of a commercial antacid preparation was studied in a double-blind fashion in 14 patients with gastroesophageal reflux disease. Peak increases in LES pressure above basal were significantly higher (p less than 0.05) after NaHCO3 than after NaCl in normal subjects and in patients with vagotomy and Billroth I antrectomy, but not in patients with vagotomy and Billroth II antrectomy. Serum gastrin concentrations were unaffected by alkali. Thirty milliliters of liquid antacid containing aluminum and magnesium hydroxide resulted in a small sustained rise in LES pressure over the first 50 min after ingestion, but this was not statistically different than the placebo response. It is suggested that: 1) neither the antrum nor intact vagi nor gastrin were required for NaHCO3 ingestion to increase LES pressure; 2) the increase in LES pressure with NaHCO3 ingestion appears to rely upon an intact duodenum and may relate to volume and osmolarity of the alkali load; and 3) therapeutic doses of a liquid commercial antacid does not significantly increase LES pressure in the presence of an intact stomach.

Topics: Adult; Antacids; Bicarbonates; Double-Blind Method; Esophagogastric Junction; Gastrectomy; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pressure; Sodium; Sodium Bicarbonate; Sodium Chloride

Twenty-four-hour intragastric pH and serum gastrin profiles were monitored in six male asymptomatic patients who previously were found to have esophagitis on endoscopy and biopsy. They received cimetidine 300 mg qid (C), ranitidine 150 mg bid (R), or placebo (P) for one week each, utilizing the Latin-square design. The mean BAO was 0.4 +/- 0.2 mmol/hr, and the pentagastrin-stimulated MAO was 21.2 +/- 3.2 mmol/hr. In the P-treated patients, the pH fluctuated between 1.8 and 3.5 and over 90% of the readings were less than pH 4. As compared to P, both C and R significantly suppressed H+ after breakfast, overnight, and over the 24-hr period. The mean pH after lunch was significantly higher in R than in P, but not in C. Over the 24-hr period, a higher percentage of the readings were above pH 4.0 in R as compared to C. During the night, 50% of the pH readings were above pH 4.0 in C and R, whereas in P 50% of the pH readings were less than pH 2.0. The integrated gastrin responses after each meal were similar in C and R and were greater than in P. The biphasic response of the ratio of H+ and gastrin (H+/G) following each meal was suppressed by both H2-receptor antagonists, with numerically lower values obtained in R than in C. This study suggests that ranitidine 150 mg bid is superior to cimetidine 300 mg qid in suppressing the 24-hr intragastric acidity.

Topics: Adult; Aged; Cimetidine; Double-Blind Method; Eating; Esophagitis; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Radioimmunoassay; Ranitidine; Time Factors

In a double-blind study comparing ranitidine to placebo in the treatment of symptomatic gastroesophageal reflux disease (GERD), we assessed gastric emptying time, gastroesophageal reflux, and gastrin response to food. Mean half-time for gastric emptying, measured using 99mTc-sulfur colloid, was 109 minutes in GERD and 102 minutes in nine healthy asymptomatic controls. This difference was not significant, but one-third of GERD had emptying times of 2 S.D.s beyond the mean for the normal controls. The patients with GERD refluxed an average of 2.3% (0.1-10%) of the isotope in 120 minutes compared with only 0.2% (0.0-0.5%) in control subjects. Reflux scans and gastric emptying times did not change with healing of esophagitis or with symptomatic improvement from ranitidine and antacids. There was no relationship between the percentage of the test dose refluxed into the esophagus and the rate of gastric emptying. The mean fasting gastrin concentration in GERD, 133 +/- 12 pg/ml, was higher than in healthy controls, 93 +/- 10 pg/ml (p less than 0.01). After stimulation with a standard meal, the integrated gastrin response (IGR) was similar in controls and GERD patients, but IGR was significantly higher after 6 weeks therapy with ranitidine. These results suggest that: 1) gastric emptying time may be prolonged in some patients with GERD, 2) basal but not food-stimulated gastrin concentrations may be abnormal in GERD, 3) reflux scans have limited use in the investigation of GERD, and 4) ranitidine therapy is associated with an increase in food-stimulated gastrin concentrations.

Topics: Adult; Aged; Anti-Ulcer Agents; Clinical Trials as Topic; Double-Blind Method; Female; Furans; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Random Allocation; Ranitidine

A new pH capsule telemetry technique was used to measure the pH fluxes in the upper part of the gastrointestinal tract in normal volunteers, symptomatic patients and in those with hiatal herniorrhaphy during the preoperative and postoperative period. The Darvon-sized pH capsule is swallowed with ease and with minimal discomfort by a fasting patient. The pH of the surrounding media activates an FM radio transmitter within the capsule to emit a continuous radio signal which is converted by a receiver to a linear graph on a strip chart recorder. This pH capsule telemetry test is easy to perform on an ambulatory basis and allows an accurate and reproducible determination of the presence or absence of esophageal reflux in patients with and without a hiatal hernia. Its correlation with symptomatic reflux is higher than that found with a conventional gastrointestinal series examination. The technique allows a much clearer distinction to be made between those patients with real symptomatic esophagitis secondary to actual reflux and those with other esophageal, cardiac or pulmonary symptoms existing withour reflux. This study also reveals a consistently lower fasting gastric pH in patients with signs and symptoms of reflux than in normal individuals without reflux. The technique enabled a more accurate assessment of the efficacy of hiatal hernia repair and revealed a reduced degree of esophageal reflux in those patients who had undergone successful repair with fundic plication.

Topics: Clinical Trials as Topic; Esophagitis; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Hydrogen-Ion Concentration; Radiography; Telemetry

The effects of oral metoclopramide, 10 and 20 mg, bethanechol, 25 mg, and placebo on lower esophageal sphincter pressure (LESP) were studied in 15 men with symptoms of gastroesophageal reflux and basal LESP less than 11 mm Hg. Each drug produced a significant increase in LESP when compared to placebo. Metoclopramide, 20 mg, produced a greater increase than either metoclopramide, 10 mg, or bethanechol, 25 mg. Serum gastrin concentrations were not altered by any of the drugs. Side effects were unremarkable. The LESP increasing effect of metoclopramide might be useful in treatment of gastro-esophageal reflux.

Topics: Administration, Oral; Adult; Aged; Bethanechol Compounds; Clinical Trials as Topic; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Male; Metoclopramide; Middle Aged; Placebos; Pressure

A few studies suggest that hormones play a role in the motility of the lower esophagus, but data is rare. In this prospective study we evaluated the correlation between hormones (TSH, fT3, fT4, calcitonin, gastrin, and VIP) and gastroesophageal reflux disease (GERD), esophageal motility disorders, and gastrointestinal symptoms.. 100 consecutive patients with reflux symptoms and dysphagia were hospitalized for diagnostic evaluation. Self-reporting questionnaires were handed out and patients routinely underwent serum analysis (TSH, fT3, fT4, calcitonin, gastrin, and VIP), 24-hour-pH-impendance monitoring, and high-resolution manometry.. Motility disorders were found in 38 out of 86 patients. There were no correlations between hormones, the DeMeester Score, and the lower esophageal sphincter pressure. A strong inverse relation between calcitonin and the Integrated Relaxation Pressure of the esophagogastric junction was found (r=-0.492; p<0.001). No correlations were found between hormone levels and the responses given in the questionnaires. Positive correlations, however, were found between VIP and gastrointestinal symptoms, as well as correlations between fT3 and dysphagia. Within the group with minor motility disorders, TSH and fT4 correlated with outcomes of the SCL-questionnaire. fT4 correlated with the typical symptoms, as well as the gastrointestinal symptoms (diarrhea, constipation, flatulence). TSH correlated with the typical symptoms. Moreover, a correlation between VIP and gas-bloat-symptoms was found within group II CONCLUSIONS: No correlation between TSH, fT3, fT4, gastrin, VIP, calcitonin, and GERD in the sense of acid reflux was found, although calcitonin seems to have an effect on the lower esophageal sphincter.. Ein Zusammenhang zwischen Hormonen und Motilität des Ösophagus wird in einzelnen Studien beschrieben, jedoch gibt es hierfür kaum Daten. In unserer prospektiven Untersuchung wollten wir den Zusammenhang zwischen Hormonen (TSH, fT3, fT4, Calcitonin, Gastrin und VIP) und der gastroösophagealen Refluxkrankheit (GERD), Motilitätsstörungen und gastrointestinalen Symptomen untersuchen.. 100 Patienten mit Refluxsymptomen und/oder Dysphagie wurden zur stationären Abklärung aufgenommen. Validierte Fragebögen wurden ausgehändigt, 24-Stunden-pH-Impendanz-Monitoring und hochauflösende Manometrie wurden durchgeführt. Des Weiteren erfolgte eine Serumanalyse von TSH, fT3, fT4, Calcitonin, Gastrin und VIP.. Motilitätsstörungen fanden sich in 38 von 86 Patienten. Es zeigte sich kein Zusammenhang zwischen Hormonen, dem DeMeester-Score und dem Druck des unteren Ösophagussphinkters, jedoch eine starke inverse Korrelation zwischen Calcitonin und der Integrated Relaxation Pressure (IRP) des gastroösophagealen Übergangs (r=–0,492; p<0,001). Des Weiteren zeigten sich keine Zusammenhänge zwischen Hormonwerten und den Ergebnissen von Symptom-Fragebögen. Positive Korrelation zeigte sich bei VIP und gastrointestinalen Symptomen sowie bei fT3 und Dysphagie. In der Gruppe mit „minor motility disorders“ korrelierten TSH und fT4 mit typischen Symptomen und fT4 mit gastrointestinalen Symptomen (Durchfall, Obstipation, Flatulenz) sowie VIP mit „gas-bloat“-Symptomen.. Wir konnten keinen Zusammenhang zwischen TSH, fT3, fT4, Gastrin, VIP und Calcitonin mit der gastroösophagealen Refluxkrankheit im Sinne einer Säureexposition zeigen, jedoch scheint Calcitonin einen Effekt auf den unteren Ösophagussphinkter zu haben.

Topics: Calcitonin; Deglutition Disorders; Esophageal Motility Disorders; Esophageal pH Monitoring; Esophageal Sphincter, Lower; Gastrins; Gastroesophageal Reflux; Humans; Manometry; Prospective Studies; Thyrotropin

The aim: To study of changes in the level of serum gastrin (GN) and somatostatin (SST) in patients with GERD after ChECT and determined their characteristics from clinical forms of GERD.. Materials and methods: 64 patients with different clinical forms of GERD were examined. The patients with GERD were divide into 2 clinical groups. Group 1 included 34 patients with GERD after ChECT, among them there were 14 males (41.2 %) and 20 females (58.8 %), with the average age of 40.2 ± 3.2 years. Group 2 consisted of 30 patients with GERD without ChECT. Among them there were 18 males (60.0 %) and 12 females (40.0%), with the average age of 38.9 ± 4.7 years. All patients were tested for serum SST and GN level by enzyme-linked immunosorbent assay (ELISA).. Results: In all patients with GERD of both group there was a significant increase in the level of serum SST. At the same time, a more higher indicators have been established in 2 Group of patients (increase up to 0.702 ± 0.029 pg / ml - p <0.01). Noteworthy is the change in the level of SST in the serum in both groups of the examined patients depending on the clinical form of GERD, with the maximum increase in patients with atypical manifestation of GERD. The analysis of the level of GN in blood serum indicates its decrease in the examined patients. In this case, the most pronounced changes were found in patients with extraesophageal clinical signs of GERD.. Conclusions: 1. In patients after ChECT gastroesophageal reflux disease often has atypical symptoms (mostly cardiac and bronchopulmonary forms in 45.0% and 25.0 % of examend patients). 2. There was detected an increase in the level of blood SST of patients with GERD while there was observed a decrease in the GN indicator in the serum, especially in its atypical forms. 3. Duodenogastric reflux is often diagnosed during endoscopic examination of patients with GERD after cholecystectomy. At the same time, its severity correlates with the level of SST in blood serum (r=0.76; p<0.01 in the typical form and r= 0.72; p<0.05 in the atypical clinical form of GERD).

Topics: Adult; Cholecystectomy; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Serum; Somatostatin

Topics: Gastrins; Gastroesophageal Reflux; Humans; Zollinger-Ellison Syndrome

Gastrinoma may cause refractory esophageal stricture due to gastro-esophageal reflux disease (GERD), but imaging technologies have limited power in its diagnosis. A 74-year-old female with a history of peptic ulcers suffered from repeated epigastralgia, and she visited a local hospital. An esophago-gastro-duodenoscopy (EGD) demonstrated severe reflux esophagitis and multiple peptic ulcers. Blood examination revealed a high value of fasting serum gastrin. Multi-detector computed tomography showed a hypervascular and tiny nodule in duodenal bulb, although other imaging technologies did not. Short-term medication with a proton pump inhibitor or potassium-competitive acid blocker was intermittently provided, but dysphagia was repeatedly worsened, and she was referred to our division. Serum hypergastrinemia was retained, and EGD reexamination depicted esophageal stricture, treated by multiple sessions of endoscopic balloon dilatation. Primary tumor was not identified by the morphological imaging technologies, but a selective arterial secretagogue injection test suggested its existence in the duodenum or pancreatic head. Pancreaticoduodenectomy was performed, and histological study identified 2 mm-sized microgastrinoma buried in Brunner`s glands on the posterior wall of the duodenum bulb. We reported a case with difficulty in diagnosis of the smallest sporadic gastrinoma of the duodenum, which might cause refractory GERD-associated stricture.

Topics: Aged; Duodenum; Esophageal Stenosis; Female; Gastrinoma; Gastrins; Gastroesophageal Reflux; Humans; Pancreatic Neoplasms; Peptic Ulcer; Potassium; Proton Pump Inhibitors; Secretagogues

Depending on etiology, prognosis and malignant potential, recent S2k guideline differentiates gastric neuroendocrine tumors (gNET) in 4 types with different treatment implications.We report on a 55-year-old patient with the accidental finding of a 15 mm gNET. Apart from a prolonged use of proton pump inhibitors (PPI) for 20 years as a treatment for gastroesophageal reflux disease, there were no other associations or risk factors for gNETs. Formally, this patient would have been classified as a type III gNET, implicating gastric surgery. From a pathophysiological point of view, however, the assumed prolonged gastrin hypersecretion would have justified an assignment as a type I gNET. The gNET was resected by ESD, but histology showed an R1 situation. After cessation of PPIs, there is no recurrence so far. Besides, the initially documented numerous and large gland polyps showed an impressive regression only a few weeks after cessation of PPI.This case points to a probably underestimated gap in the present gNET classification. On the basis of present literature, the therapeutic dilemma of PPI-associated gNETs is discussed. A new assignment of PPI associated gNETs as type Ib could help to overcome this dilemma.. Die aktuelle S2k Leitlinie unterteilt neuroendokrine Tumore des Magens (gNETs) abhängig von der Genese, Prognose und dem Malignitätsgrad in therapeutisch unterschiedlich anzugehende 4 Typen.Wir berichten über einen 55-jährigen Patienten, bei dem sich als Zufallsbefund ein 15 mm großer gNET fand; einziger Risikofaktor war eine zwanzigjährige Therapie mit Protonenpumpenblockern (PPI) aufgrund einer gastroösophagealen Refluxerkrankung. Rein formal hätte dieser Fall als ein Typ III NET gewertet und operiert werden müssen, pathophysiologisch entsprach er durch die anzunehmende langjährige Gastrinüberstimulation aber eher einem Typ I NET. Der gNET konnte via ESD entfernt werden, allerdings mit einer R1 Situation. Nach Absetzen der PPIs zeigte sich bislang kein Tumorrezidiv; darüber hinaus bildeten sich die zuvor bestehenden großen Drüsenkörpercysten wenige Wochen nach Absetzen der PPI eindrucksvoll zurück.Der Fall demonstriert eine vermutlich unterschätzte Lücke in der aktuellen gNET Klassifikation. Anhand der aktuellen Literatur wird das therapeutische Dilemma bei PPI-assoziierten gNETs diskutiert, dem durch eine Benennung von PPI-assoziierten gNETs als Typ I b Rechnung getragen werden könnte.

Topics: Gastrins; Gastroesophageal Reflux; Humans; Middle Aged; Neuroendocrine Tumors; Proton Pump Inhibitors; Stomach Neoplasms

In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms.. We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD.. At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett's esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p<0.0001). Similarly, in the primary care setting, 163 GERD patients had statistically significant low levels of G-17 as compared with 132 dyspeptic patients (0.5±0.2 pg/L vs. 4.0±2.6 pg/L, p<0.0001). Moreover, in the primary care setting, no statistically significant differences were found for G-17 levels between patients with erosive and non-erosive reflux pattern (0.4±0.2 vs 0.7±0.3; p=0.08). In primary care, the accuracy of G-17 less than 1 pg/L to diagnose non-invasively GERD was 94.3%.. Low levels of G-17 were detected in patients with erosive esophagitis and Barrett's esophagus in a referral center and in patients with typical GERD symptoms in a sample of patients from a primary care setting.

Topics: Adult; Aged; Esophagitis, Peptic; Esophagoscopy; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged

Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG.. Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared.. Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit.. Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated.

Topics: Aged; Antibodies, Bacterial; Autoimmune Diseases; Biomarkers; Endoscopy, Digestive System; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter pylori; Humans; Italy; Male; Middle Aged; Pepsinogens; Prospective Studies; Proton Pump Inhibitors

To evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease.. On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 8 weeks by 30 patients (11 men, mean age: 67.8) with non-erosive reflux disease who responded well to maintenance therapy using proton pump inhibitor and answered "very satisfied" or "satisfied" to an overall satisfaction survey (5-grade scale). The degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin levels before breakfast was examined before and after on-demand therapy. The number of vonoprazan tablets taken and the frequency (regular, temporary, rare) of its administration were also investigated.. All patients completed 8-week on-demand therapy with 20-mg vonoprazan. Comparisons of patient satisfaction levels before and after therapy revealed no significant differences in the number of patients who were very satisfied and satisfied with the therapy. Furthermore, there were no significant differences in score of symptoms or gastrin levels before and after therapy. During 8-week on-demand therapy, patients took 11 tablets (median) (7.0-18.0 tablets: 25-75 percentiles), and 30.0% of patients (n = 9) took vonoprazan on a regular basis (at least 2 tablets a week).. On-demand therapy with 20-mg vonoprazan exerted equivalent effects to continuous PPI maintenance therapy for patients with non-erosive reflux disease.

Topics: Aged; Drug Administration Schedule; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Treatment Outcome

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

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

Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety.. To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies.. Safety data were collected from patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and changes in laboratory variables were analysed.. Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12 , folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the first year.. No major safety concerns arose during 5-12 years of continuous PPI therapy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

Topics: Aged; Chromogranin A; Esomeprazole; Female; Gastrins; Gastroesophageal Reflux; Humans; Laparoscopy; Male; Middle Aged; Omeprazole; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Young Adult

Reporting on three cases of gastric neuroendocrine tumors (g-NETs) in patients taking long-term proton pump inhibitors (PPIs). These tumors are not classifiable considering current criteria. g-NETs are currently grouped as: types 1 and 2, related to hypergastrinemia due to chronic atrophic gastritis and Zollinger-Ellison syndrome respectively, and type 3, normogastrinemic and more aggressive. Although the g-NETs onset in patients taking PPIs is biologically plausible, only a few cases have been reported so far.. From January 2005 to July 2014, 31 g-NETs were referred to our Unit: 24 (77%), one (3%) and three (10%) resulted types 1, 2 and 3, respectively. Three cases (10%) did not meet the current classification criteria.. The three patients were administered long-term PPIs for gastro-esophageal reflux disease. Patient 1: a 78-year-old man, with a 4-mm well-differentiated g-NET (Ki-67<1%) and marked hypergastrinemia. Patient 2: a 58-year-old man affected by a 6-mm well-differentiated (Ki-67 = 4%) g-NET, with normal gastrin levels. Patients 3: a 67-year-old woman with an 18-mm well-differentiated g-NET (Ki-67 <2%), with mild hypergastrinemia. In the three patients, histology and pertinent blood tests excluded chronic atrophic gastritis, Helicobacter pylori infection or Zollinger-Ellison syndrome. The first two patients underwent endoscopic polypectomy; in the third case total gastrectomy was performed. Further clinical, endoscopic and imaging follow-up did not show any g-NET recurrence.. The present data point to the existence and epidemiological relevance of g-NETs associated with PPIs intake. These neoplasms are not included in the current classification, thus their treatment and follow-up have not been established.

Topics: Aged; Endoscopy; Female; Gastrectomy; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Neuroendocrine Tumors; Proton Pump Inhibitors; Stomach Neoplasms

To evaluate the occurrence of gastroesophageal reflux and possible mechanisms in Helicobacter pylori infection.. Symptoms of H. pylori-infected children, their total gastroesophageal reflux episodes, acid exposure percentage, gastrin, ghrelin, and motilin levels were evaluated before and after H. pylori eradication.. Forty-two H. pylori-infected children were eligible for this study. Acid exposure % and total reflux episodes before and after H. pylori eradication were 10.2%±14.8% vs. 7.71%±5.0% and 94.7%±102.1% vs. 64.6%±55.0%, respectively (p=0.28, p=0.082). There was an insignificant change in the serum gastrin (93.4±153.8 pmol/L vs. 1.28±149.4 pmol/L, p=0.67), ghrelin (7.69±197.5 pg/mL vs. 8.36±299.5 pg/mL, p=0.274), and motilin (75.1±81.2 pg/mL vs. 97.2±80.5 pg/mL, p=0.206) levels after eradication. Gastrin and ghrelin levels were negatively correlated after H. pylori eradication (r=-0.38, p=0.031). There was no association between gastroesophageal reflux episodes and gastrin, ghrelin, and motilin levels (r=0.25 and p=0.11; r= 0.24 and p=0.13; r=-0.23 and p=0.14, respectively).. H. pylori infection is neither protective nor harmful in the gastroesophageal reflux. Neither ghrelin nor motilin levels was associated with gastroesophageal reflux. None of gastrin, ghrelin, and motilin levels was affected by H. pylori infection. There is an inverse association between gastrin and ghrelin levels after H. pylori eradication.

Topics: Adolescent; Biomarkers; Child; Female; Follow-Up Studies; Gastrins; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Humans; Incidence; Male; Motilin; Prognosis; Prospective Studies; Turkey

The natural immunomodulator lactoferrin is known to possess anti-inflammatory effects. However, there have been no studies examining the mode of action of lactoferrin in protecting the esophageal mucosa against damage. We investigated the effect of lactoferrin on gastric acid secretion and in protecting against acute acid reflux-induced esophagitis in rats.. Male Wistar rats aged 8 weeks, weighing 210-240 g, were used for all the experiments. A gastric perfusion system was installed using the method of Ghosh et al. Lactoferrin was administered once via the caudate vein, starting 24 hours before an acute acid reflux (treatment mode), or saline (control). Statistical comparison of the parameters between the two test conditions was performed.. No significant differences in basal or stimulated gastric acid secretion, or in the serum gastrin level were observed between the two test conditions. Esophageal damage was attenuated by lactoferrin in a dose-dependent manner, as reflected by the improvement in the esophageal tissue weight and macroscopic scores. Significant reductions in the histological scores, myeloperoxidase activity and the levels of proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β were also observed following lactoferrin administration.. We concluded that lactoferrin exerts a protective effect against acute acid reflux-induced esophageal damage in rats.

Topics: Animals; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Esophagus; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Inflammation Mediators; Injections, Intravenous; Lactoferrin; Male; Mucous Membrane; Protective Agents; Rats, Wistar

We present a case of a gastric neuroendocrine carcinoma in a patient with a history of long-term proton pump inhibitor (PPI) use. A 49-year-old man using PPI for the last 15 years due to gastroesophageal reflux disease developed progressive dysphagia, dyspepsia and weight loss. Upper gastrointestinal endoscopy, endoscopic ultrasonography and abdominal CT diagnosed a malignant tumor localized to a hiatal hernia. Fasting serum chromogranin A and gastrin concentrations were elevated (32 nmol/l and 159 pmol/l, respectively). Helicobacter pylori PCR analysis of antral biopsies was negative. Biopsies from endoscopically normal oxyntic mucosa showed enterochromaffin-like (ECL) cell hyperplasia. Tumor biopsies revealed a poorly differentiated neuroendocrine carcinoma. Sevier-Munger staining, immunohistochemistry and electron microscopy indicated ECL cell as origin of the tumor cells. Concerns have previously been raised about the safety of long-term PPI use due to a possible increased risk of cancer. This case illustrates a patient with a poorly differentiated neuroendocrine carcinoma with ECL cell characteristics probably induced by hypergastrinemia secondary to long-term PPI use.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Carcinoma, Neuroendocrine; Chromogranin A; Gastrins; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Stomach Neoplasms; Time Factors

Proton pump inhibitors (PPI) remain the leading therapy for acid-related disorders. Long-term PPI use increases the risk of pneumonia and enteric bacterial infections and of nosocomial Clostridium difficile-associated diarrhoea. PPIs do not lead to vitamin B12 or iron deficiencies and do not induce malignancies or increase the risk of major birth defects. Prolonged PPI use may be a weak risk factor for certain fractures and results in hypergastrinaemia and parietal cell hyperplasia leading to rebound acid hypersecretion, which may induce symptoms on withdrawal of therapy.

Topics: Anti-Ulcer Agents; Bacterial Infections; Congenital Abnormalities; Dyspepsia; Fractures, Bone; Gastrins; Gastroenteritis; Gastroesophageal Reflux; Heartburn; Humans; Neoplasms; Omeprazole; Pneumonia; Proton Pump Inhibitors; Risk Factors; Time Factors; Vitamin B 12 Deficiency

An algorithm (GastroPanel) for the non-invasive diagnosis of atrophic gastritis has been previously proposed, based on serum pepsinogen-I, gastrin-17, and Helicobacter pylori (H. pylori) antibodies. The aim of the present study was to evaluate whether serum markers correlate with and predict gastric atrophy in gastroesophageal reflux disease (GERD) patients.. The baseline data of the prospective ProGERD study, a study on the long-term course of GERD (n=6215 patients), served to select patients with atrophic gastritis diagnosed in biopsies from gastric antrum and corpus, and control cases without atrophy. A total of 208 pairs were matched for age, sex, GERD status (erosive vs non-erosive), presence of Barrett's esophagus, and histological H. pylori status were retrieved. Serum pepsinogen-I, gastrin-17, and H. pylori antibodies were determined using specific enzyme immunoassays.. A significant negative correlation was found between the degree of corpus atrophy and the level of serum pepsinogen-I. A previously-reported negative correlation between the degree of antral atrophy and serum gastrin-17 could not be confirmed. The low sensitivity (0.32) and specificity (0.70) of the GastroPanel algorithm were mainly due to over diagnosis and under diagnosis of advanced atrophy in the antrum.. The diagnostic validity of the GastroPanel algorithm to diagnose gastric atrophy non-invasively is not sufficient for general use in GERD patients.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Barrett Esophagus; Biomarkers; Biopsy; Case-Control Studies; Endoscopy, Gastrointestinal; Europe; Female; Gastrins; Gastritis, Atrophic; Gastroesophageal Reflux; Helicobacter pylori; Humans; Immunoenzyme Techniques; Male; Matched-Pair Analysis; Middle Aged; Pepsinogen A; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Young Adult

The relationship between gastroesophageal reflux disease (GERD) and Helicobacter pylori is controversial. We evaluated endoscopic, 24-h gastric and esophageal acid profile among patients with GERD in relation to H. pylori, as the latter might alter gastric acid secretion.. Patients with GERD (n = 123), who were not on acid-suppressive drugs, and had not received anti-H. pylori therapy, underwent gastroduodenoscopy and tests for H. pylori detection. Esophageal manometry, 24-h pH metry, serum pepsinogen-I (PG-I), PG-II and gastrin-17 ELISA were done in all these patients. Univariate and multivariate analyses were performed to assess independent predictors for erosive esophagitis (EE).. Of 123 patients (mean age 40.5 [13.1] years, 85 [69.1%] men), 59 (47.9%) had H. pylori infection. EE was more common in H. pylori non-infected than infected (49 vs. 32, p < 0.001). Among patients older than 40 years, absence of H. pylori was associated with lower esophageal pH and longer reflux (p = 0.02 and p < 0.001, respectively). PG-I/PG-II ratio was lower in H. pylori infected subjects (p < 0.001). In patients with higher LA grade of esophagitis, elevated PG-I levels and PG-I/PG-II ratio were associated with more acidic stomach (p = 0.04 and p = 0.01, respectively). Multivariate analyses showed low gastrin-17 (p = 0.016), higher age (p = 0.013), hiatus hernia (p = 0.004) and absence of H. pylori (p = 0.03) were independent predictors for risk of EE.. H. pylori infection is associated with less acidic stomach and less severe GERD. Low gastrin-17, higher age, hiatus hernia and absence of H. pylori were the best predictors for EE risk.

Topics: Adult; Age Factors; Endoscopy, Digestive System; Esophagitis, Peptic; Esophagus; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Prospective Studies; Severity of Illness Index; Sex Factors

The neuroendocrine marker, chromogranin A (CgA) increases during medium- or long-term proton-pump inhibitor (PPI) treatment.. To analyze the effect of ultra-short-term and diverse dose of PPI therapy on serum CgA and gastrin levels and evaluate the effect of PPI treatment cessation.. Fasting serum CgA and gastrin were determined in newly diagnosed gastroesophageal reflux disease (GERD) patients (n = 54) treated with diverse doses of PPI during a 28-day period, in patients treated with PPIs for at least 6 months (n = 42), and in subjects where PPI treatment could be stopped (n = 11).. A significant stepwise increase of CgA levels was observed after 5 days during the 28-day period treatment with all PPI doses. Gastrin increased significantly also in the standard and high-dose PPI subgroups. The most prominent increase of CgA was observed in the high-dose PPI subgroup. Serum CgA and gastrin were markedly elevated after 6 months of PPI treatment, and decreased significantly after 5 days of PPI discontinuation.. Serum CgA increases significantly even after ultra-short-term (5 days) PPI therapy. After long-term treatment, 5-day cessation of PPI therapy is sufficient to decrease significantly both CgA and gastrin levels.

Topics: Adult; Aged; Aged, 80 and over; Chromogranin A; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Time Factors; Young Adult

Gastrin, acting through peripheral cholecystokinin (CCK) 2 receptors, is a major hormonal regulator of gastric acid secretion. The effects of gastrin on acid secretion occur both acutely and chronically because gastrin directly stimulates gastric acid secretion and also exerts trophic effects on the enterochromaffin-like and parietal cells that together constitute the acid secretory apparatus of the stomach. Several antagonists that target the CCK2 receptor have been identified and investigated for the treatment of gastroesophageal reflux disease and pancreatic cancer. In this paper, we discuss the contribution of gastrin to these disease pathologies and the data generated to date from clinical studies investigating CCK2 receptor antagonists.

Topics: Animals; Drug Delivery Systems; Enterochromaffin-like Cells; Gastric Acid; Gastrins; Gastroesophageal Reflux; Humans; Pancreatic Neoplasms; Parietal Cells, Gastric; Receptor, Cholecystokinin B

The assessment of the serum gastrin concentrations and the role of enterohormone in children with primary acid gastroesophageal reflux (GER) and GER secondary to cow's milk allergy (CMA).. 138 children were diagnosed with pathological acid GER on the basis of pH-metric examination. 76 (28.8%) patients had primary GER and 62 (23.5%) patients had GER secondary to CMA.Serum gastrin concentration (fasting and postprandial) was assessed before treatment and 1 and 2 years after initiation of the therapy.. The children with primary GER had the fasting gastrin concentration 69.46 ± 11.87 μU/ml before treatment, 77.86 ± 26.35 μU/ml after 1 year and 83.78 ± 25.21 μU/ml after 2 years of treatment. The children with GER secondary to CMA had gastrin concentrations 89.61 ± 26.75, 73.17 ± 19.49 and 73.90 ± 20.31 μU/ml respectively. The mean postprandial gastrin concentration after treatment was higher than before treatment in children with both primary and secondary GER. The primary GER group had postprandial gastrin concentration 96.07 ± 33.51 μU/ml before treatment and 116.06 ± 33.95 μU/ml and 118.48 ± 33.96 μU/ml after 1st and 2nd year of therapy respectively. The secondary GER group had postprandial gastrin concentration 85.33 ± 14.12 μU/ml before treatment and 106.55 ± 24.51 μU/ml and 110.36 ± 24.67 μU/ml after 1st and 2nd year of therapy respectively.. The mean fasting serum gastrin concentrations in patients with primary and secondary GER were similar and mean postprandial concentrations were higher than fasting concentrations in both study groups.

Topics: Animals; Cattle; Child, Preschool; Esophageal pH Monitoring; Female; Food Hypersensitivity; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Infant; Male; Milk; Milk Hypersensitivity; Postprandial Period; Time Factors

Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett's esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE.. We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia.. A total of 95 patients were enrolled. The mean age was 64.7 (+/-10.0) years, and 70.5% were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P=0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95% confidence interval (CI): 1.20-24.8).. In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression.

Topics: Adenocarcinoma; Aged; Barrett Esophagus; Biomarkers, Tumor; Biopsy, Needle; Cell Transformation, Neoplastic; Confidence Intervals; Cross-Sectional Studies; Esophageal Neoplasms; Esophagoscopy; Female; Gastrins; Gastroesophageal Reflux; Humans; Immunohistochemistry; Incidence; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Precancerous Conditions; Probability; Prognosis; Proton Pump Inhibitors; Regression Analysis; Risk Assessment

A 37-year-old female, who had a neuroendocrine pancreatic neoplasm, underwent duodeno-cephalo-pancreatectomy. In the 2 years following surgery, she had normal levels of serum chromogranin A (CgA), gastrin and other tumor markers. About 3 years after surgery, owing to the onset of reflux-like dyspeptic symptoms, the patient started treatment with the PPI esomeprazole. During PPI treatment, the patient's serum CgA level rose to more than three times the upper limit of normal, although her gastrin levels remained in the normal range. These findings were interpreted as being suggestive of neuroendocrine tumor relapse.. Thoraco-abdominal CT, In¹¹¹-octreotide total body scan, CT of sella turcica, Tc(99m)-sestamibi neck scan, mutational analysis of chromosome 11q13 (site of multiple endocrine neoplasia type 1 [MEN1] gene). Discontinuation of, and rechallenge with, esomeprazole.. Esomeprazole-induced hyperchromograninemia in the absence of elevated levels of fasting serum gastrin.. Discontinuation of acid-suppressive treatment and continuation of oncologic follow-up.

Topics: Adult; Anti-Ulcer Agents; Chromogranin A; Education, Medical, Continuing; Esomeprazole; Female; Gastrins; Gastroesophageal Reflux; Humans; Neuroendocrine Tumors

Gastrin and pepsinogens reflect the functional state of the gastric mucosa.. To evaluate whether serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease (GERD).. In all, 388 patients with heartburn not taking any form of acid suppressive therapy were matched-controlled for age and gender and sub-classified into four groups: group 1 non-erosive reflux disease (NERD); group 2, erosive reflux disease (ERD) Los Angeles (LA) A and B, group 3, ERD LA C and D; group 4 Barrett's oesophagus (BO). Fasting serum was analysed for gastrin 17, pepsinogen I, pepsinogen II und Helicobacter pylori using specific EIA tests (GastroPanel; Biohit, Plc).. Kruskal-Wallis test and analysis of variance.. There was a significant difference among the four groups with respect for pepsinogen I, but not for pepsinogen II, the pepsinogen I pepsinogen II ratio, H. pylori serology and gastrin levels. Pepsinogen I was the lowest in NERD and the highest in BO (median 91.6, mean +/- standard deviation 106.2 +/- 51.6 vs. median 114.7, mean +/- standard deviation 130.4 +/- 70.6; P = 0.046). Pepsinogen I levels were higher in H. pylori positive subjects. After adjusting for H. pylori status, the differences in pepsinogen I across patient groups were no longer statistically significant (P = 0.298).. Serum gastrin and pepsinogen I and II do not correlate with the different grades of severity of GERD. The non-invasive GastroPanel is not useful for the differentiation of the various forms of GERD.

Topics: Antibodies, Bacterial; Biomarkers; Case-Control Studies; Endoscopy, Gastrointestinal; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogens; Prospective Studies

Long-term therapy with potent acid inhibitors is a common treatment for gastro-esophageal reflux disease. Administration of proton pump inhibitors (PPIs) causes profound and continuous hypochlorhydria by inhibition of the proton pump in gastric parietal cells. Long-term hypergastrinaemia increases mucosal thickness and enterochromaffin-like cell density in oxyntic mucosa.. The aim of this study was to see whether this very common clinical intervention induces significant changes in the gastric mucosal gene expression pattern.. Seven patients suffering from gastro-esophageal reflux disease were included in this study. Endoscopic biopsies were taken from the corpus mucosa before and toward the end of a 3-month treatment with the PPI esomeprazole.. Microarray analysis identified 186 differentially expressed genes. A high proportion of genes with changed gene expression levels during PPI treatment are involved in proliferation, apoptosis, and stress response.. This study identified many genes that were not previously known to be affected by inhibition of gastric acid secretion. Further characterization of the functional roles of genes whose expression is modulated by potent acid inhibition may give new insight into the biological responses to potent acid inhibition, including the mucosal response to the moderately increased gastrin levels encountered in clinical practice.

Topics: Adult; Aged; Anti-Ulcer Agents; Apoptosis; Biopsy; Cell Proliferation; Esomeprazole; Esophagoscopy; Female; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gene Expression Profiling; Gene Expression Regulation; Humans; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Proton Pump Inhibitors

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; bcl-Associated Death Protein; Cyclooxygenase 2; Disease Progression; Esophageal Neoplasms; Gastrins; Gastroesophageal Reflux; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Inhibitor of Apoptosis Proteins; Microtubule-Associated Proteins; Models, Biological; Neoplasm Proteins; NF-kappa B; Prevalence; Survivin

To explore the incidence of acid and bile reflux in children with gastroesophageal reflux disease (GERD) and to study the roles of bile and gastrin in the pathogenesis of childhood GERD.. Forty-two cases of GERD were divided into two groups according to endoscopic findings: reflux esophagitis (RE) and non-erosive reflux disease (NERD). The patients underwent 24-hr ambulatory esophageal pH and bilirubin monitoring. The serum concentration of gastrin was detected by radioimmunoassay. Thirteen children without gastroesophageal reflux symptoms, digestive tract disease and severe systemic organic disease served as the Control group.. Of the 42 cases of GERD, 24 cases were confirmed with RE, with esophageal mucosal lesions, and 18 were NERD without esophageal mucosal lesions by endoscopy. Both acid and bile reflux parameters, including the percentage of total time with pH < 4 and bilirubin absorbance >/= 0.14, the total number of reflux episodes and the number of bile reflux episodes lasting longer than 5 minutes, were significantly higher in the GERD patients than those in the Control group (P < 0.05). The time of esophageal acid exposure (pH < 4) and the percentage of total time with bilirubin absorbance >/= 0.14 increased significantly in the RE group compared with in the NERD group (P < 0.05). Sixteen RE patients had a mixed reflux of bile and acid (66.7%) but only 6 NERD patients (33.3%) had (P < 0.01). The serum concentration of gastrin in the RE group (125.12 +/- 45.06 pg/mL) and the NERD group (98.22 +/- 27.92 pg/mL) was significantly higher than that of the Control group (74.22 +/- 20.34 pg/mL) (P < 0.01, P < 0.05 respectively). A significant difference was noted in the serum concentration of gastrin between the RE and the NERD groups (P < 0.05).. Mixed reflux of bile and acid are common in children with GERD. Bile reflux may play a role in the development of GERD. Gastrin parasecretion may participate in the development of GERD. Gastrin and bile reflux may have synergistic effects on the development of childhood GERD.

Topics: Adolescent; Bile; Child; Child, Preschool; Female; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male

In the Western world, the incidence of oesophageal adenocarcinoma has increased over the last 30 years coinciding with a decrease in the prevalence of Helicobacter pylori. Trends of increasing oesophageal adenocarcinoma can be linked causally to increasing gastro-oesophageal reflux disease (GORD) which can be linked to an increasingly obese population. However, there is no plausible biological mechanism of association between H. pylori, obesity, and GORD. Ghrelin, a peptide produced in the stomach, which regulates appetite, food intake, and body composition, was studied in H. pylori positive asymptomatic subjects.. Plasma ghrelin, leptin, and gastrin were measured for six hours after an overnight fast, before and after cure of H. pylori in 10 subjects. Twenty four hour intragastric acidity was also assessed.. After cure, median (95% confidence intervals) integrated plasma ghrelin increased from 1160.5 (765.5-1451) pg/ml x h to 1910.4 (1675.6-2395.6) pg/ml x h (p=0.002, Wilcoxon's rank sum test), a 75% increase. This was associated with a 14% increase in 24 hour intragastric acidity (p=0.006) and non-significant changes in leptin and gastrin. There was a significant positive correlation between plasma ghrelin and intragastric acidity (r(s) 0.44, p=0.05, Spearman's rank correlation).. After H. pylori cure, plasma ghrelin increased profoundly in asymptomatic subjects. This could lead to increased appetite and weight gain, and contribute to the increasing obesity seen in Western populations where H. pylori prevalence is low. This plausible biological mechanism links H pylori, through increasing obesity and GORD, to the increase in oesophageal adenocarcinoma observed in the West.

Topics: Adenocarcinoma; Adult; Esophageal Neoplasms; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Peptide Hormones; Radioimmunoassay

To study the relationship of Helicobacter pylori, lower esophageal sphincter pressure and gastrin in gastroesophageal reflux disease, to evaluate the effect of Helicobacter pylori on gastroesophageal reflux disease.. 20 patients were underwent 24-hour ambulatory esophageal pH monitoring to confirm the diagnosis of gastroesophageal reflux disease, and their lower esophageal sphincter pressure was measured by esophageal manometry. The patients were diagnosed endoscope negative GERD and endoscope positive GERD by endoscopy, and 3 biopsy specimens obtained from the gastric antrum at the same time were used for Helicobacter pylori culture, rapid urease test and Warthin-Starry stain. Hp infection was affirmed when at least two of the three tests were positive, then the patients were divided into Hp-negative group and Hp-positive group. Fasting serum gastrin concentration was determined by radioimmunoassay in 13 patients.. Hp-positive patients were 8 (male 4, endoscope negative GERD 2, mean age 55 +/- 9), Hp-negative patients were 12 (male 10, endoscope negative GERD 3, mean age 55 +/- 10). 13 of these patients were performed fasting serum gastrin measurement. The mean lower esophageal sphincter pressure, gastrin concentration and 24-hour pH monitoring DeMeester score in Hp-positive patients group were 11.25 mm Hg, 87.437 pg/ml and 72.30 respectively, and those in Hp-negative patients group were 13.75 mm Hg, 88.725 pg/ml and 55.64. Between the two groups, there was no significant difference in LESP, gastrin and DeMeester score (P = 0.193, P = 0.932 and P = 0.479); There was no correlation between LESP and gastrin, while serum gastrin level is associated strongly with DeMeester score (r = 0.902, P < 0.01).. The study showed that Helicobacter pylori had no effect on LESP by gastrin, however serum fasting gastrin concentration and DeMeester score were associated with each other.

Topics: Adult; Aged; Esophagogastric Junction; Female; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged

Topics: Barrett Esophagus; Esophageal Neoplasms; Gastrins; Gastroesophageal Reflux; Humans

The association between gastroesophageal reflux disease and end-stage renal disease remains unclear. We aimed to assess the prevalence of gastroesophageal reflux disease and also to identify possible pathogenetic factors in the development of reflux in symptomatic end-stage renal disease patients.. The study involved 42 end-stage renal disease patients with upper GI symptoms (group I) and 46 age- and sex-matched controls who did not have renal disease but had the same symptoms (group II). Endoscopy, endoscopic biopsies, and 24-h esophageal pH studies were used to diagnose gastroesophageal reflux disease. Subjects were also investigated for Helicobacter pylori gastritis and GI amyloidosis.. The prevalences of gastroesophageal reflux disease in the two groups were similar (81% vs 84.8%, p = 0.423). The prevalence of H. pylori infection was significantly lower in group I than in group II (38.1% vs 67.4%, p = 0.01). There were II cases of GI amyloidosis in group I. Multivariate logistic regression analysis in group I showed that GI amyloidosis (OR = 7.28, 95% CI = 1.13-46.93), chronic ambulatory peritoneal dialysis treatment (OR = 5.54, 95% CI = 1.01-30.43), and absence of H. pylori infection (OR = 3.75, 95% CI = 1.01-13.9) were significantly associated with reflux esophagitis.. Upper GI symptoms are important in predicting gastroesophageal reflux disease in end-stage renal disease patients. Chronic ambulatory peritoneal dialysis, GI amyloidosis, and absence of H. pylori infection seem to be risk factors for the development of gastroesophageal reflux disease in end-stage renal disease patients.

Topics: Adult; Amyloidosis; Esophagitis; Esophagus; Female; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Male; Middle Aged; Monitoring, Physiologic; Multivariate Analysis; Prevalence; Risk Factors

Serum chromogranin A (CgA), a marker of neuroendocrine neoplasia, increases during profound gastric acid inhibition, possibly reflecting the trophic effect of gastrin on the enterochromaffin-like (ECL) cells.. This study investigated the clinical value of serum CgA as a screening test for gastric fundic enterochromaffin-like (ECL) cell hyperplasia during acid-suppressive therapy.. A consecutive series of 230 dyspeptic patients referred for upper gastrointestinal endoscopy was investigated in a cross-sectional design. They were 154 patients on continuous medium-term (6 weeks to one year) or long-term (longer than one year) acid inhibition with either proton pump inhibitors (PPIs, n = 117) or histamine2-receptor antagonists (H2RAs, n = 37) for gastro-oesophageal reflux disease, and 76 nontreated subjects, with normal endoscopic findings (control group). Fasting blood samples were analysed for gastrin and CgA. Gastric biopsy specimens (oxyntic mucosa) were examined for histological evaluation of gastritis (Sydney classification) and of ECL cell hyperplasia (Solcia classification).. Serum CgA levels correlated positively with serum gastrin, following a quadratic function (r = 0.78, P < 0.0001). Elevated serum CgA values during long-term acid inhibition correlated with the presence and severity of fundic ECL cell hyperplasia. Multivariate analysis identified hypergastrinaemia (P < 0.0001), duration of acid inhibition (P < 0.0001), H. pylori infection (P = 0.008), ECL cell hyperplasia (P = 0.012), and body gland atrophy (P = 0.043) as independent predictors of elevated serum CgA. In subjects on long-term acid inhibition (n = 123), serum CgA was equally sensitive but more specific than serum gastrin for the detection of ECL cell hyperplasia (sensitivity, 91.3% for both; specificity, 73% vs. 43%, P < 0.0001).. During long-term gastric acid inhibition, serum CgA levels reflect the presence and severity of fundic ECL cell hyperplasia. Serum CgA is therefore a useful screening test for gastric ECL cell proliferative changes within this context.

Topics: Adult; Aged; Anti-Ulcer Agents; Chromogranin A; Chromogranins; Cross-Sectional Studies; Enterochromaffin-like Cells; Female; Gastric Acid; Gastric Fundus; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Male; Mass Screening; Middle Aged; Multivariate Analysis; Sensitivity and Specificity

Recent studies have clarified a close association between H. pylori infection and gastritis, peptic ulcer disease, and gastric cancer, but there is little information concerning the relationship between H. pylori infection and reflux esophagitis (RE). We investigated the relationship between H. pylori, RE, and corpus gastritis.. Ninety-five patients with RE and 190 sex- and age-matched asymptomatic healthy controls demonstrating no localized lesions in the upper GI tract were studied and evaluated for H. pylori infection, histologic gastritis, serum gastrin, and pepsinogens (PGs).. H. pylori infection was significantly lower in RE patients than in asymptomatic controls (41% vs. 76%, p <.01). Histologic gastritis of both the antrum and corpus was significantly less frequent (antrum; p <.01, corpus; p <. 01), and serum levels of PGI and the PG I/II ratio were significantly higher in RE patients than in controls (PGI; p <.05, PG I/II ratio; p <.01). When the subjects were divided into two age groups (59 years of age and younger and 60 years of age and older), a significant difference was found only among patients over 60 years of age (29% vs. 85%, p <.01). Among subjects in this age group, gastritis in both the antrum and corpus were significantly milder in RE patients than in controls. Although the prevalence of H. pylori infection was similar between the two groups of patients under 59 years of age, corpus gastritis was significantly milder in patients than in controls (p <.05).. A significantly low prevalence of H. pylori infection was found in RE patients over 60 years of age but not in those under 59 in comparison with sex- and age-matched controls. The relative lack of corpus gastritis might play a role in the pathogenesis of RE in our population through preservation of the acid secretion area.

Topics: Age Factors; Aged; Case-Control Studies; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Female; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Pepsinogens; Prevalence; Pyloric Antrum; Stomach

Proton pump inhibitors (PPIs) block gastric acid secretion and may increase serum gastrin concentration. The aim of this study was to determine whether fasting serum gastrin concentration predicts gastric acid suppression in patients on PPI therapy. Ambulatory pH monitoring with one pH probe in the distal esophagus and a second probe in the stomach was performed in patients with persistent symptoms of GERD despite PPI treatment. Upon completion of pH monitoring, blood was drawn for measurement of fasting serum gastrin concentration. In all, 51 patients were studied: 26 on PPIs, 1 on H2-receptor antagonists, and 24 off acid suppression. Fasting serum gastrin correlated inversely with percent time of gastric pH < 4 for all patients (r = -0.553; P<0.001) and for the subgroup of 26 patients on PPIs (r = -0.435; P = 0.027). In patients on PPIs, an elevated gastrin (> or =100 pg/ml) was associated with gastric pH < 4 for 25+/-7% of the time compared to 54+/-5% when the gastrin was normal (P = 0.004). Therapeutic gastric acid suppression (gastric pH < 4 for <50% of time) was present in 6 of 7 (86%) patients with an elevated fasting serum gastrin, compared with only 8 of 19 (42%) patients with a normal serum gastrin (P<0.05). In conclusion, there is a significant inverse correlation between the fasting serum gastrin concentration and gastric acid profile in patients with GERD. An elevated fasting serum gastrin concentration while on PPI therapy suggests that gastric acid secretion is adequately suppressed.

Topics: Fasting; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Helicobacter pylori; Humans; Male; Middle Aged; Monitoring, Ambulatory; Proton Pump Inhibitors

The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years).. Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus.. In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients.. Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Barrett Esophagus; Child; Drug Resistance; Esophagitis; Female; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Humans; Hyperplasia; Male; Middle Aged; Omeprazole; Time Factors; Treatment Outcome

Topics: Anti-Ulcer Agents; Barrett Esophagus; Drug Administration Schedule; Esophageal Neoplasms; Esophagitis, Peptic; Fundoplication; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Proton Pump Inhibitors; Time

The polymorphic enzyme CYP2C19 is of importance for the metabolism and effects of omeprazole during short-term treatment.. To investigate the relationship between CYP2C19 genotype and the effects of long-term omeprazole treatment.. A total of 180 patients with acid related disorders were genotyped for wild type and mutated CYP2C19 alleles by allele-specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoassays, and pepsinogen I and H. pylori serology were assessed by ELISA methods.. In 108 of the patients, who received a single dose of 20 mg omeprazole, there was no difference in gastrin and chromogranin A concentrations between the three CYP2C19 genotypes. In 72 patients on long-term treatment (> 1 year) with 20 mg omeprazole daily, serum gastrin as well as plasma chromogranin A concentrations (mean +/- s.e.) were both about threefold higher in the wild type/mutated (52.1 +/- 7.6 pM and 7.3 +/- 1.3 nM (n=19), respectively) compared to wild type/wild type (14. 7 +/- 0.9 pM and 2.5 +/- 0.1 nM (n=52), respectively; both comparisons P=0.0001). In a single mutated/mutated patient on long-term treatment, both gastrin and chromogranin A were high (88 pM and 13.7 nM, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n=19) patients on long-term treatment, compared with the corresponding wild type/wild type (n=49) group (147 +/- 19 microg/L vs. 193 +/- 12 microg/L, P=0. 04).. Patients with one (and probably also with two) mutated CYP2C19 allele(s) on long-term treatment with omeprazole had significantly affected serum gastrin and pepsinogen I and plasma chromogranin A concentrations compared with patients with two normal alleles. This indicates that changes in gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual's capacity to metabolize omeprazole.

Topics: Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Biomarkers, Tumor; Chromogranin A; Chromogranins; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Genotype; Helicobacter pylori; Humans; Male; Middle Aged; Mixed Function Oxygenases; Omeprazole; Pepsinogen A; Peptic Ulcer; Polymorphism, Genetic; Radioimmunoassay

Topics: Cysts; Gastric Fundus; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Humans; Omeprazole; Parietal Cells, Gastric; Polyps; Stomach Diseases

Topics: Barium Sulfate; Esophageal Motility Disorders; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Hydrochloric Acid; Manometry; Monitoring, Physiologic; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Aggregated Albumin

After Nissen fundoplication, dyspeptic symptoms such as fullness and early satiety develop in >30% of patients. These symptoms may result from alterations in proximal gastric motor and sensory function.. We have evaluated proximal gastric motor and sensory function using an electronic barostat in 12 patients after successful laparoscopic Nissen fundoplications (median follow-up; 12 months). Twelve age- and gender-matched patients with severe gastroesophageal reflux disease (GERD) and 12 healthy volunteers served as controls. Studies were performed in the fasting state and after meal ingestion. Gastric emptying tests were performed in all patients. Vagus nerve integrity was measured by the response of pancreatic polypeptide (PP) to insulin hypoglycemia.. Minimal distending pressure and proximal gastric compliance were not significantly different between post-Nissen patients, GERD patients, and healthy controls. Postprandial relaxation of the stomach, however, was significantly (p < 0.05) reduced post-Nissen (267 +/- 34 ml), compared with controls (400 +/- 30 ml) and GERD (448 +/- 30 ml). Postprandial relaxation was significantly (p < 0.01) prolonged in GERD patients. Postprandial relaxation of the stomach correlated with gastric emptying of solids (r = 0.62; p = 0.01). Gastric emptying of solids became significantly (p < 0.05) faster after fundoplication. Postprandial fullness was significantly (p < 0.05) increased in the operated patients.. Post-Nissen patients have a significantly reduced postprandial gastric relaxation and significantly accelerated gastric emptying, which may explain postoperative dyspeptic symptoms. The abnormalities result from fundoplication and not from vagus nerve injury or reflux per se, because in reflux patients gastric relaxation and gastric emptying are prolonged.

Topics: Adult; Cholecystokinin; Eating; Fasting; Female; Fundoplication; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Laparoscopy; Male; Middle Aged; Postoperative Period; Pressure; Sensation; Stomach; Vagus Nerve

Gastric mucosal histamine content, enterochromaffin-like cell density, and mast cell density were studied in 13 subjects under omeprazole therapy, 13 partially gastrectomized subjects with a Billroth II reconstruction, 10 partially gastrectomized subjects with a Roux-en-Y reconstruction, and 9 control subjects. Histamine content was significantly greater both in the subjects with higher gastrinemic levels (omeprazole-treated subjects) and those with more abundant enterogastric reflux (Billroth II subjects) than in controls. Enterochromaffin-like cell density was significantly greater in the omeprazole subjects than in each of the other groups. Mast cell density was significantly greater in Billroth II subjects than in controls. Serum gastrin levels, mucosal histamine content, and enterochromaffin-like cell density were positively correlated. Gastrin was not correlated to mast cell density. These results support the existence of different control pathways for enterochromaffin-like and mast cells. Moreover, they suggest that enterochromaffin-like cells and mast cells are involved in the regulation of gastric secretion and in gastric mucosal injury-repair mechanisms, respectively, due to histamine release.

Topics: Aged; Biopsy; Enterochromaffin Cells; Female; Gastrectomy; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Histamine; Humans; Immunohistochemistry; Male; Mast Cells; Middle Aged; Omeprazole

Topics: Adult; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Omeprazole; Time Factors

Topics: Gastric Acid; Gastrins; Gastroesophageal Reflux; Humans; Omeprazole

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

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

We usually use the stomach to hung up into the chest and to the neck for esophago-gastrostomy in the patients of esophageal cancer. We had studied the intrathoracic stomach function in patients after esophagectomy with isotope 99m Tc labelled 717-resin semisolid meal for scintigram. We measured the gastric emptying time (GET) and fund the GET1/2 was no difference between the preoperative group and contrast group (P > 0.05). The study indicated that GET1/2 was faster obviously in postoperative patients with pyloroplasty than without pyloroplasty (P < 0.01). It was proved that to perform pyloroplasty with esophagostomy should be used routinely for preventing the pylorospasm, dilatation of the intrathoracic stomach and gastroesophageal reflux. At the same time, we found fasting serum gastrin (FSG) was increased (P < 0.01) in patients after esophagectomy than before, but basal acid output (BAO) decreased. It indicated that vagotomy caused the BAO decreasing and PH increasing. There were some relations between high level of FSG and postoperative diarrhea.

Topics: Esophageal Neoplasms; Esophagectomy; Female; Gastrectomy; Gastric Acid; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Stomach

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

We evaluated the effect of graded exercise on esophageal motility and gastroesophageal reflux. We studied eight trained cyclists using a catheter with three strain-gauge transducers connected to a solid-state datalogger and an ambulatory intraesophageal pH monitor. Each study lasted 4 hr during which subjects exercised on a stationary bike for 1 hr at 60% of peak O2 uptake (O2 max), 45 min at 75% of O2 max, and for 10 min at 90% of O2 max. Subjects rested 1 hr before exercise (control period) and for 30 min between exercise sessions. Studies were performed after an overnight fast and subjects received only intravenous infusion of 5% glucose solution during the study. Plasma concentrations of gastrin, motilin, glucagon, pancreatic polypeptide (PP), and vasoactive intestinal peptide (VIP) were determined at rest and before and after each exercise session. The duration, amplitude, and frequency of esophageal contractions declined with increasing exercise intensity, and the differences were significant (P < or = 0.05) for all three variables at 90% O2 max. The number of gastroesophageal reflux episodes and the duration of esophageal acid exposure were significantly (P < or = 0.05) increased during exercise at 90% O2 max. Plasma hormone concentrations showed no significant changes between rest and the various exercise sessions. Thus, exercise has profound effects on esophageal contractions and gastroesophageal reflux which are intensity dependent. These effects are not mediated by the hormones measured.

Topics: Adult; Analysis of Variance; Bicycling; Esophagus; Exercise; Exercise Test; Gastrins; Gastroesophageal Reflux; Glucagon; Humans; Hydrogen-Ion Concentration; Male; Manometry; Motilin; Pancreatic Polypeptide; Peristalsis; Reference Values; Vasoactive Intestinal Peptide

The plasma gastrin levels in fasted horses (21.1 +/- 15.6 pg/ml), in horses with spasmodic colic (7.3 +/- 5.4 pg/ml) and in horses with impaction of the left ventral large colon and/or pelvic flexure (11.4 +/- 3.1 pg/ml) were not significantly different. The plasma gastrin concentrations of horses with strangulation obstruction of the small intestine, large colon displacement or adynamic ileus, and which had no gastric reflux, were 12.9 +/- 8.7 pg/ml and did not differ from fasted gastrin levels. Horses which had 5-10 litres of stomach content reflux had a higher mean gastrin level (32.2 +/- 22.6 pg/ml) (range 8.7-83.0) than the fasted horses. The mean plasma gastrin level (69.0 +/- 32.2 pg/ml) (range 27.0-122.0 pg/ml) in horses which had gastric reflux and 11-20 litres of stomach content outflow through the nasogastric tube were significantly higher (P less than 0.0004) than in fasted horses or in horses with spasmodic colic, impaction of the left ventral large colon or in horses from which no gastric reflux could be obtained.

Topics: Animals; Colic; Fasting; Gastrins; Gastroesophageal Reflux; Horse Diseases; Horses; Intestinal Obstruction; Radioimmunoassay

Combined oesophageal and gastric 24-hour pH monitoring and oesophageal manometry were performed in 19 patients with resistant reflux oesophagitis after short-term therapy with omeprazole (40 to 60 mg daily) or during maintenance treatment with omeprazole (20 to 80 mg daily). Omeprazole's effects on acidity were analysed as well as any possible influence on oesophageal motility. A pH in the stomach of below 4 was present during considerable periods of time (in 27 of 29 measurements), particularly during the night. As a consequence, pathological gastro-oesophageal reflux occurred, particularly in the supine period. Insufficiency of the lower oesophageal sphincter was present in all but one patient; decreased or virtually absent motility of the oesophagus was found in 63% of the patients. Combined intragastric and intra-oesophageal pH monitoring, with oesophageal manometry, may contribute to the management of patients with reflux disease resistant to treatment with omeprazole. The present study emphasizes the need to individualize therapy in patients with refractory gastrooesophageal reflux disease.

Topics: Adult; Aged; Aged, 80 and over; Drug Resistance; Esophagus; Female; Gastric Acid; Gastrins; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Muscle, Smooth; Omeprazole

Topics: Adult; Asthma; Cholecystokinin; Eating; Esophagus; Female; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hormones; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Motilin; Neurotensin; Peristalsis; Somatostatin

Gastric acid secretion in response to a protein meal and to exogenously administered synthetic human gastrin 17-I was measured in patients with Barrett's esophagus, patients with uncomplicated gastroesophageal reflux, and normal age- and sex-matched controls. Acid secretion, both basally and in response to gastrin 17-I, was significantly greater in patients with Barrett's esophagus compared to normal individuals without reflux. Basal gastrin levels and meal-stimulated levels of the hormone were similar among all three groups. Sensitivity to gastrin, expressed as the concentration causing half-maximal acid secretion, was also similar among the study groups. It is speculated that elevated basal acid production in Barrett's esophagus may contribute to the pathogenesis of the disorder.

Topics: Barrett Esophagus; Chronic Disease; Cimetidine; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Monitoring, Physiologic; N-Methylscopolamine; Parasympatholytics; Scopolamine Derivatives

Twenty patients with gastroesophageal reflux disease (10 with compensated and 10 with decompensated gastroesophageal incompetence) were examined to determine if there was a correlation between the ability of physiological stimuli to tonicize the lower esophageal sphincter (LES) and the response to pentagastrin stimulation (Gastrodiagnost). The pressure of the lower esophageal sphincter as well as blood levels of the hormones/neurotransmitters gastrin, PP and VIP were determined after giving a 300 ml intragastral bolus of either 0.9% NaCl or 20% peptone solution. All patients exhibited per definitionem a positive common-cavity phenomenon on abdominal compression. Intravenous pentagastrin stimulated the LES in patients with compensated gastroesophageal incompetence (GI) but not in those with decompensated GI (p less than or equal to 0.0005). Esophagoscopy revealed a severe esophagitis in 80% of the patients with decompensated GI but in only 10% of the patients with compensated GI. Peptone stimulated the LES in patients with compensated GI (p less than or equal to 0.005) at 5, 10 and 15 minutes, pepton vs. NaCl). Neither NaCl nor peptone increased the tone of the LES in patients with decompensated GI. Peptone but not NaCl caused a significant increase of serum gastrin in all patients: there was no difference between the two groups. Neither NaCl nor peptone influenced VIP levels in peripheral blood. PP levels increased significantly in both groups following peptone. Physiological responsiveness of the LES can be inferred from the manometric data and the results of the pentagastrin test. A negative reaction to pentagastrin is associated with a loss of response to physiological stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Esophagitis, Peptic; Esophagogastric Junction; Esophagoscopy; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged; Pancreatic Polypeptide; Peptones; Vasoactive Intestinal Peptide

The oesophageal pH was recorded for 3 h after a test-meal in 27 healthy control subjects (group I), 40 patients with alcoholic cirrhosis (group II), and 22 patients with a normal liver and symptoms of gastro-oesophageal reflux (control refluxers). Gastro-oesophageal reflux was observed in 10 of the cirrhotic patients. Marked reflux episodes lasted longer in cirrhotic refluxers than in control refluxers (P less than 0.05). The frequency of ascites, bleeding from ruptured oesophageal varices, peripheral neuropathy and hepatic encephalopathy were not significantly different according to presence or absence of reflux. Plasma concentrations of gastrin, somatostatin, motilin and vasoactive intestinal peptide (VIP) were measured in groups I and II. Fasting plasma motilin levels, and the release of motilin and of VIP after the meal were higher in group II than in group I. Basal levels and post-prandial profiles of the four peptides tested did not differ between cirrhotics with or without gastro-oesophageal reflux. We conclude that in patients with alcoholic cirrhosis: gastro-oesophageal reflux is frequent (25%) and characterized by prolonged reflux episodes; reflux is not correlated with the degree of liver failure and plays no significant role in the rupture of oesophageal varices; and raised plasma motilin and VIP levels cannot account for the high incidence of reflux in cirrhotics.

Topics: Adult; Aged; Aged, 80 and over; Female; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Motilin; Somatostatin; Vasoactive Intestinal Peptide

Topics: Esophagogastric Junction; Female; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged

Surgical approach to short bowel syndrome has been dealing with two major problems: lack in absorptive surface and dysfunction of the peristalsis of the widely distended loop above the anastomosis. In those children having a very short intestine, one is reluctant to either resect or reduce the diameter of this loop. Bianchi, followed by Boeckman and Traylor, described a procedure of loop lengthening by dividing it longitudinally. Their procedure has the advantage of restoring normal peristalsis without losing any absorptive surface. A modification of the original procedure of Bianchi is described. We report on its application in a child born with laparoschisis and intestinal atresia; she had in fact 25 centimetres of duodenum and proximal jejunum anastomosed with left colonic angle. This child was referred to us with functional occlusion related to distension above an intact and unobstructed anastomosis. She was operated on at six weeks of age. Postoperatively oral feeding could be started after one month. Broviak's catheter for parenteral nutrition was removed at six months. In conclusion we believe that this technique offers a chance of better and faster adaptation to children born with short bowel syndrome.

Topics: Dietary Fats; Enteral Nutrition; Feces; Female; Gastrins; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Intestinal Absorption; Intestine, Small; Malabsorption Syndromes; Nitrogen; Parenteral Nutrition; Pneumoperitoneum; Postoperative Complications; Short Bowel Syndrome

Topics: Adolescent; Diagnosis, Differential; Duodenal Diseases; Duodenal Ulcer; False Positive Reactions; Female; Gastrins; Gastroesophageal Reflux; Humans; Pain; Stomach Diseases; Zollinger-Ellison Syndrome

Jordan and Herrington have both advocated the addition of a proximal gastric vagotomy [PGV] to fundoplication to improve exposure and decrease the likelihood of vagal entrapment which might lead to delayed gastric emptying. This study documents the effect of fundoplication with or without PGV on gastric emptying and postprandial gastrin values. Twelve dogs had measurement of gastric emptying of an isotopically labeled solid meal. Plasma gastrin was also measured at 15-min intervals for 1 hr postprandially following a 60 g beef meal. Six of the animals then had a standard fundoplication with incorporation of vagi in the wrap; the other six underwent fundoplication combined with PGV, excluding the vagi. All studies were repeated after 8 weeks. Gastric emptying was unchanged by fundoplication alone. PGV resulted in a slight but significant slowing of gastric emptying (P = 0.04), values by paired t test. Fundoplication alone had no effect on serum gastrin levels, but there was a slight, statistically insignificant increase in serum gastrin when PGV was added (P greater than 0.1). This delay could aggravate pre-existing emptying problems in patients with esophagitis. These data do not support inclusion of proximal gastric vagotomy as a routine part of the fundoplication.

Topics: Animals; Dogs; Gastric Emptying; Gastric Fundus; Gastrins; Gastroesophageal Reflux; Vagotomy

The antireflux mechanism of the Nissen fundoplication was investigated in 15 mongrel dogs by esophageal manometry. Nissen fundoplication increased the lower esophageal resting pressure for 2 weeks after operation; however, by 4 weeks it had decreased to a level which did not differ significantly from the preoperative value. Thus, lower esophageal sphincter (LES) length, unlike LES pressure, was maintained for a long period. These results suggest that restoration of competence at the gastroesophageal junction after Nissen fundoplication depends on an adequate length of LES as well as increased LES pressure. The gastrin-stimulated LES pressure 1, 2 and 4 weeks after operation was significantly higher than the preoperative stimulation pressure. Therefore, it seems that the antireflux mechanism is associated not only with the mechanical aspect of the wrapping but also with creation of a new muscular sphincter substitute that reacts sufficiently to gastrin stimulation.

Topics: Animals; Dogs; Esophagogastric Junction; Esophagus; Gastric Fundus; Gastrins; Gastroesophageal Reflux; Manometry; Pressure

In this study we compared both endogenous gastrin release to a known gastrin stimulant, phenylalanine, and fasting antral mucosal gastrin concentration in normal subjects and patients with documented gastroesophageal reflux. Resting lower esophageal sphincter pressure in the reflux patients (14.7 +/- 1.5 mm Hg) was significantly less (p less than 0.01) than in the normal subjects (27.5 +/- 2.7 mm Hg). Basal serum gastrin concentrations were similar in the two groups. There were significant (p less than 0.05) increases in peak serum gastrin in response to intragastric administration of phenylalanine in both normal subjects (20.6 +/- 6.7 pg/ml, p less than 0.05) and refluxers (22.4 +/- 3.0 pg/ml, p less than 0.01) but there were no significant differences in these responses between normals and refluxers. Mean integrated gastrin response to phenylalanine in the reflux patients (812 +/- 116 pg ml-1 h-1) was slightly higher than that in normals (609 +/- 328 pg ml-1 h-1) although the difference was not significant. Antral gastrin concentration was slightly higher in reflux patients (15.7 +/- 2.2 ng/mg tissue) than in normals (10.4 +/- 4.2 ng/mg tissue), although this difference was not significant. There was no correlation between antral gastrin concentration and either integrated serum gastrin response or gastric acid output. We conclude that there is no difference between patients with gastroesophageal reflux and normal subjects with regard to serum gastrin levels, endogenous gastrin release, or antral gastrin concentration. These observations suggest no role for gastrin in the mediation of lower esophageal sphincter incompetence or the pathophysiology of gastroesophageal reflux.

Topics: Adult; Aged; Esophagogastric Junction; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Humans; Middle Aged; Phenylalanine; Pressure; Pyloric Antrum

The effects of truncal vagotomy on the functional and morphological changes produced by duodenogastric reflux have been studied in the dog. Duodenogastric reflux caused progressive damage to gastric mucosa, hypersecretion of acid to pentagastrin, and a hypergastrinemic response to a standard meal. Truncal vagotomy barely altered the mucosal changes produced by reflux, but it did prevent antral gland hyperplasia and reduced the acid and gastrin secretory responses. These findings are clinically reassuring in that vagotomy effectively prevented the hypersecretory state produced by duodenogastric reflux.

Topics: Animals; Dogs; Duodenal Diseases; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Histamine; Hyperplasia; Pentagastrin; Vagotomy

Under basal conditions serum gastrin concentration was compared with lower oesophageal sphincter pressure (pull-through perfusion manometry) and gastrooesophageal reflux (continuous pH measurements) in 72 patients. Between patients with low, middle and high basal gastrin level no differences were obtained for mean sphincter pressure. Mean reflux frequency and total reflux duration were increased significantly in patients with high gastrin level compared with patients with low gastrin level. Mean basal gastrin level was found to be higher in patients with symptoms of reflux than in patients without symptoms.

Topics: Esophagitis, Peptic; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Male; Manometry; Pentagastrin

Topics: Female; Gastrins; Gastroenteritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Hypertrophy; Infant; Infant, Newborn; Male; Pyloric Stenosis; Secretin

Gastroesophageal reflux has rarely been reported in the Zollinger-Ellison syndrome, presumably due to elevation in the lower esophageal sphincter pressure. We have evaluated 15 patients with the Zollinger-Ellison syndrome for evidence of esophageal disease. Five presented initially with esophageal disease: one, reflux symptoms; two, severe esophagitis; and two, strictures. Six of 15 had heartburn and nine of 15, objective evidence for reflux disease. Mean lower esophageal sphincter pressure was higher in the Zollinger-Ellison syndrome than in controls but was unrelated to serum gastrin levels. Zollinger-Ellison syndrome patients without heartburn had a higher mean sphincter pressure than did patients with heartburn (who had a mean sphincter pressure similar to that of controls but greater than that in patients with idiopathic gastroesophageal reflux). Four patients had biopsy evidence of esophagitis, one in association with Barrett's epithelium. Gastroesophageal reflux and its complications appear to be common in the Zollinger-Ellison syndrome.

Topics: Adult; Esophagogastric Junction; Esophagoscopy; Female; Gastrins; Gastroesophageal Reflux; Heartburn; Humans; Male; Manometry; Middle Aged; Prospective Studies; Zollinger-Ellison Syndrome

Topics: Bed Rest; Brain Stem; Diabetes Complications; Duodenal Ulcer; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Hernia, Hiatal; Humans; Scleroderma, Systemic

The gastroplasty tube has been used in the control of reflux since it was originally described by Collis in 1961. Several variations of the procedure have been reported indicating a low frequency of anatomic recurrence but a high frequency of reflux. Two forms of gastroplasty procedure are used: partial fundoplication in which gastric fundus incompletely wraps the gastroplasty and high pressure zone, and total fundoplication in which a circumferential wrap is constructed. The authors conducted a clinical review, using the patient's history, radiology and manometry, of 135 patients with partial fundoplication gastroplasty (PFG) and 250 patients with total fundoplication gastroplasty (TFG). In both groups the anatomic recurrence rate was low; however, with PFG the frequency of reflux was 44.6% and 25.7% of patients had notable symptoms. With TFG no patient had reflux. The response of the gastroplasty tube to meal-induced gastrin release and to neurogenic stimulation was tested. Basal tube pressure was low and showed no response to gastrin release and no augmented neurogenic response. It was concluded that the gastroplasty tube did not have intrinsic properties of value in controlling reflux and that reflux control depended upon the method of fundoplication. The role of the gastroplasty tube is in preventing anatomic recurrence.

Topics: Eating; Esophagus; Gastrins; Gastroesophageal Reflux; Humans; Manometry; Methods; Motilin; Pancreatic Polypeptide; Recurrence; Stomach

Topics: Adult; Esophagogastric Junction; Female; Gastrectomy; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pressure; Vagotomy; Zollinger-Ellison Syndrome

Gastrin has a regulating effect on the complicated closing mechanism of the lower oesophageal sphincter. This hormone produced in G-cells of the pyloric antrum and carried by the blood stream has its greatest effect on the anterior fundus wall, cardias and the lower oesophageal sphincter. Thus, when there is a failure in the closing mechanism of the lower oesophageal sphincter produced by lacking maturity of the oesophageal fibers and the cardias zone, only those surgical procedures using the gastric fundus in order to correct the failure can guarantee a good result, if medical treatment has not been successful. The authors comment on the physiological basis of the treatment, the medical as well as the surgical one, of the gastro-oesophageal reflux.

Topics: Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Pyloric Antrum

Topics: Adolescent; Adult; Female; Gastrins; Gastroesophageal Reflux; Heartburn; Humans; Postpartum Period; Pregnancy

Topics: Animal Feed; Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Esophageal Achalasia; Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Prognosis; Secretin

In summary, the recent understanding of the pathogenesis of gastroesophageal reflux disease as owing to LES incompetence has led to improvement in both the diagnosis and the treatment of this disorder. Diagnosis now dependent on demonstrating the presence of reflux, an incompetent sphincter mechanism, or some complication of reflux. Treatment is focused on reducing the endogenous factors that contribute to reflux, or actually restoring the sphincteral barrier to reflux by pharmacologic or surgical means.

Topics: Bethanechol Compounds; Cimetidine; Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Humans; Metoclopramide; Pressure

New manometric techniques in for examining the lower oesophageal sphincter (LOS) were applied an investigation of the oesophago-gastric junction after partial gastric resection. Pressure and blood gastrin data are reported for eight cases examined before and after surgery, under basal conditions and after stimulation with a protein meal. It was found that gastric resection leads to a decrease in LOS performance (43.6% fall in maximum pressure) and length (-33.3%). There is also a 93.5% decrease in the pressure response to a protein meal, and hence a predisposition to gastroesophageal reflux.

Topics: Adult; Aged; Esophagitis, Peptic; Esophagogastric Junction; Gastrectomy; Gastrins; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged; Pressure

Topics: Adult; Animals; Dogs; Esophagogastric Junction; Female; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hormones; Humans; Male; Manometry; Motilin; Peptides; Peristalsis

The author sets out a comprehensive review of gastro-oesophageal reflux in pregnancy. Comment is offered on the fairly limited means of treating this troublesome condition and some of the problems in future research are discussed.

Topics: Esophagogastric Junction; Female; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Metoclopramide; Pregnancy; Pregnancy Complications

Lower esophageal sphincter pressure (LESP) was measured in 10 biopsy-proved cirrhotics with esophageal varices and tense ascites before and after diuresis to evaluate of ascites might play in the development of variceal bleeding. In the 10 cirrhotic men studied, basal LESP was 30.9 +/- 1.7 mm Hg before and 22.7 +/- 1.3 mm Hg (P less than 0.01) after a diuresis which resulted in a mean 12-kg weight loss. LESP responses to abdominal compression were also evaluated. The change in LESP in response to a standard degree of abdominal compression was greater in the presence of ascites (8.5 +/- 0.4) than in its absence (6.3 +/- 0.4) (P less than 0.01). Basal gastric pH and fasting plasma gastrin concentrations did not differ during the two testing periods. Based on these data and the rarity with which cirrhotic patients with ascites complain of heartburn, it is concluded that reflux esophagitis caused by failure of the lower esophageal sphincter to remain competent is unlikely to be a significant etiological factor in the development of variceal bleeding.

Topics: Adult; Esophageal and Gastric Varices; Esophagogastric Junction; Fasting; Gastric Juice; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Humans; Hydrogen-Ion Concentration; Liver Cirrhosis; Male; Middle Aged; Pressure

The lower esophageal high pressure zone (HPZ) was characterized manometrically and reflux status determined in eight male rhesus monkeys. The studies were repeated six weeks and six months after 50 per cent distal small bowel resection. At the same time fasting serum gastrin and gastric inhibitory polypeptide values were assayed. In seven animals precise antrectomy with gastroduodenal anastomosis was performed and the studies repeated. HPZ pressure increased from 6.7 +/-0.67 mm Hg (+/-1 SEM) to 10.3 +/- 0.76 mm Hg at six weeks (p less than 0.005). At six months the pressure was 9.3 +/- 1.02 mm Hg (p less than 0.02) and after antrectomy 15.2 +/- 3.1 (not significant from 6 month value, p less than 0.02 from control). Serum gastrin and GIP values showed significant elevations at six weeks, but six month and postantrectomy results were not statistically different from control. Reflux episodes for the group were reduced at six weeks and six months. After antrectomy increased reflux was noted.

Topics: Animals; Duodenum; Esophagus; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastroesophageal Reflux; Haplorhini; Macaca mulatta; Male; Pressure; Pyloric Antrum

In investigations with various groups of patients there was no correlation between fasting serum IRG levels and LES pressures in individual subjects with undisturbed for disturbed sphincters. After food ingestion a short phase of LES pressure increase (from 13.5 +/- 1.5 to 21.7 +/- 3.8 mm Hg) could be observed. This peak occurs during the phase of rise in gastrin level, but there was no correlation between IRG levels and LES pressure in individual cases. In patients with gastroesophageal reflux we can demonstrate a diminished release of gastrin after a test meal, but there was also a diminished capacity of the LES. In conclusion, in this investigation it has not been possible to show a clear connection in humans between serum IRG and LES function.

Topics: Esophageal Achalasia; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Pressure; Time Factors; Zollinger-Ellison Syndrome

In this study we determined the acute effect of bethanechol (5 mg SC) on gastroesophageal reflux (GER) and lower esophageal sphincter pressure (LESP) in 27 patients with symptomatic esophagitis. The effect of bethanechol on esophageal acid clearance was also determined in 7 of the patients. Intraluminal pH monitoring prior to bethanechol administration demonstrated free or stress-induced reflux episodes in 18 of the 27 patients. Following bethanechol (1) LESP increased significantly, (2) GER diminished or ceased in many of the patients, and (3) acid clearance times decreased significantly. Some individuals, however, continued to reflux despite LESP elevation to 30 mm Hg or more. This latter finding suggests that LESP alone is not the sole factor governing LES competency. Other factors such as improved esophageal emptying may also contribute to the beneficial therapeutic effect of bethanechol in patients with heartburn.

Topics: Bethanechol Compounds; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Middle Aged; Pressure

Lower oesophageal sphincter pressure and fasting plasma gastrin and progesterone were measured in 31 women in the last trimester of pregnancy and in 10 healthy female control subjects. Eighteen of the pregnant women suffered from heartburn but 13 did not. All of the control subjects and 10 women from each of the two pregnant groups were tested for gastro--oesophageal reflux by direct measurement of intraluminal pH. The mean barrier pressure of the lower oesophageal sphincter was lower in both groups of pregnant women than in the controls (P less than 0-05) and the mean barrier pressure of the women with heartburn was lower than that of the pregnant women without heartburn, though this difference did not reach statistical significance. Eight of 10 of the pregnant women with heartburn had moderate or severe reflux, and3 of 10 of the pregnant women without heartburn also had moderate or severe reflux. Most women who reflux have heartburn, nevertheless, some asymptomatic women also reflux, and therefore all pregnant women must be considerered at risk from Mendelson's syndrome if subjected to a general anaesthetic for an emergency obstetric procedure.

Topics: Adolescent; Adult; Anesthesia, Obstetrical; Esophagogastric Junction; Esophagus; Female; Gastrins; Gastroesophageal Reflux; Heartburn; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Pressure; Progesterone; Stomach

Topics: Esophagitis, Peptic; Esophagogastric Junction; Esophagoscopy; Esophagus; Gastric Juice; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Manometry; Muscle, Smooth; Muscles; Reflex

Topics: Esophageal Achalasia; Esophagitis; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hormones; Humans

Findings in this study correlated a low circulating gastrin level with an incompetent lower esophageal sphincter mechanism and abnormal reflux. Such reflux, in amounts causing esophagitis distally, was treated surgically by a mechanically simple method of fundoplication. The success of this reefing method of fundoplication was explained by using physiologically active sling fibers of the gastric fundus to augment the lower esophageal sphincter. Available gastrin was used more effectively in this manner. The high incidence of associated foregut diseases suggested an embryologic factor in the development of gastroesophageal reflux. The dilated hiatus and its attendant hernia had no apparent relationship to the development of reflux esophagitis. The term symptomatic sliding hiatal hernia, therefore, seemed to be a diagnostic and therapeutic misnomer.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Esophagitis, Peptic; Esophagogastric Junction; Female; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Hernia, Hiatal; Humans; Male; Manometry; Middle Aged; Muscle Tonus; Postoperative Complications; Suture Techniques; Vagotomy

Topics: Animals; Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Haplorhini; Intestine, Small; Male; Manometry

Lower esophageal sphincter pressure, basal gastric pH, and fasting plasma gastrin were measured sequentially in female volunteers who were using oral contraceptives. No difference in basal gastric pH or fasting plasma gastrin was observed during any of the three selected periods studied. Lower esophageal sphincter pressure was the same during menses (20.8 +/- 1.7) when the volunteers took no medication during the phase of the cycle when the volunteers were ingesting ethinylestradiol (18.3 +/- 1.7). Lower esophageal sphincter pressure decreased significantly (P less than 0.01) to 9.4 +/- 1.2 during the phase of the cycle when the volunteer took the progestation agent, dimethisterone, as well as ethinylestradiol. It is therefore proposed that the progessive rise in plasma progesterone alone or in combination with estrogens that occurs during the course of pregnancy might be responsible for the increased incidence of symptomatic heartburn in pregnant women.

Topics: Adult; Contraceptives, Oral; Contraceptives, Oral, Sequential; Dimethisterone; Esophagogastric Junction; Ethinyl Estradiol; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Menstruation; Muscle Contraction; Pressure

Fasting and after meals serum gastrin levels were determined in healthy subjects and patients with different gastroenterological diseases (duodenal and gastric ulcer, hiatal hernia with gastroesophageal reflux, Billroth II gastric resection, atrophic gastritis, Zollinger-Ellison, Ménétrier, chronic calcifying pancreatitis, gastric carcinoma and lymphoma). The results pointed to the usefulness of evaluating both fasting levels and "gastrin curve" after meals as an expression of the rapidity of response of hormone-secreting gastric cells. Calculation of the I.G.O. (Integrated Gastrin Output) must also be carried out to provide a parameter from which the overall ability of G cells to secrete in response to feeding can be assessed.

Topics: Duodenal Ulcer; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Hernia, Hiatal; Humans; Pancreatitis; Stomach Neoplasms; Zollinger-Ellison Syndrome

The purpose of this study is to determine whether lower esophageal sphincter (LES) incompetency is a common occurrence in patients with liver cirrhosis and contributes to the development of variceal bleeding. Resting LES pressure (17.8 +/- 1.1 mm Hg) in 35 patients with cirrhosis was similar to that of our control population (17.3 +/- 2.0 mm Hg). No differences were found among patients with ascites, variceal hemorrhage, or with different degrees of hepatic decompensation. In both patients and control subjects the LES responded with a significant pressure increase to gastric alkalinization. Symptoms and radiological evidence of gastroesophageal reflux were extremely uncommon in patients with liver cirrhosis. Based on these data it is unlikely that acid-pepsin regurgitation is a significant factor in the development of variceal hemorrhage.

Topics: Adult; Aged; Ascites; Esophageal and Gastric Varices; Esophagitis, Peptic; Esophagogastric Junction; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Liver Function Tests; Manometry; Middle Aged; Muscle Contraction

Topics: Bile Acids and Salts; Duodenal Ulcer; Duodenum; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Intestinal Secretions; Specimen Handling; Stomach Ulcer

Topics: Animals; Biliary Tract Diseases; Contraceptives, Oral; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Intestine, Small; Liver; Liver Neoplasms; Liver Regeneration; Pancreas Transplantation; Postoperative Complications; Rats; Stomach; Transplantation, Homologous; Vagotomy

Changes in plasma gastrin and lower oesophageal sphincter pressure were measured in 20 subjects after a standard protein meal. Significant increases in both gastrin and sphincter pressure were seen. Peak gastrin response occurred an average of 19-5 minutes and peak lower oesophageal sphincter response 40-0 minutes after the meal. Both gastrin and sphincter pressure showed a wide spectrum of response. In 5 subjects there was no appreciable rise (less than 5 pg/ml) in plasma gastrin after the meal, and 3 of these had symptoms of oesophageal reflux. In this group there was only a small but nervertheless significant rise in lower oesophageal sphincter pressure (mean pressure rise 18-0 per cent of fasting value, p less than 0.05). Greater increases in sphincter pressure (mean rise 54-2 per cent, p less than 0.005) were seen in subjects with a moderate (up to 50 pg/ml) rise in plasma gastrin, and those with the most marked gastrin response (less than 50 pg/ml) showed the greatest rise in pressure (mean rise 80-3 per cent, p less than 0.0025). These results suggest that endogenous plasma gastrin is the main stimulus to the rise in lower oesophageal sphincter pressure after food. Subjects with a poor gastrin response to the meal have only a small increase in sphincter pressure and as a result may be more liable to develop gastro-oesophageal reflux.

Topics: Dietary Proteins; Eating; Esophagogastric Junction; Fasting; Gastrins; Gastroesophageal Reflux; Humans; Pressure; Time Factors

The effects on intraluminal pressure in the oesophagus, the cardiac sphincter, and the gastric fundus of intravenous prostaglandin F2alpha, E2, And of rectal indomethacin were studies in 41 subjects. Intravenous infusion of prostaglandin F2alpha (0-05 to 0-8 mug kg-minus1) produced marked, dose-related and sustained elevation of cardiac sphincter pressure without significantly affecting oesophageal peristalsis or gastric fundal motility. Sphincteric relaxation during swallowing was prolonged. Plasma gastrin levels were unchanged. Intravenous infusion of PGE2 (0-08 mug kg-minus1 min-minus) inhibited sphincter contractions to serial bolus intravenous injections of pentagastrin (0-1 or 0-2 mug kg-minus 1). Rectal indomethacin (200 mg) resulted in a riseof cardiac sphincter pressure, suggesting that endogenous synthesis of an inhibitory (E-type) prostaglandin was suppressed. The results indicate that prostaglandin E2 may be concerned in the regulation of cardiac sphincter tone in man, whilst prostaglandin F2alpha may be useful in the treatment of gastrooesphageal reflux.

Topics: Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Humans; Indomethacin; Injections, Intravenous; Pentagastrin; Pressure; Prostaglandins; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Rectum; Stomach; Suppositories

Resting lower esophageal sphincter pressures and fasting serum gastrin levels were measured in 35 consecutive patients. 28 of these patients were subdivided into Group I, which consisted of 9 patients with symptomatic gastroesophageal reflux and hiatus hernia, and Group II was further subdivided into Group IIA, 5 patients with hiatus hernias, and Group IIB, 14 patients without hiatus hernia. Mean LES pressures for Groups I, IIA, and IIB were 9.7, 36.8, and 25.6 cm H2O, and serum gastrin levels were 129, 74, and 116 pg/ml, respectively. Examination of these data as a whole or as subgroups failed to demonstrate a correlation between these two variables. The remaining 7 patients had abnormal sphincters (3 patients which scleroderma and 2 with achalasia) or abnormal serum gastrin levels (1 patient with pernicious anemia and 1 patient with antrectomy and Billroth II anastomosis). For these patients as well, no correlation between LES pressure and serum gastrin level was found. These results cast doubt on the hypothesis that endogenous gastrin is a major factor in the maintenance of resting LES pressure.

Topics: Adult; Aged; Esophagogastric Junction; Fasting; Female; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Male; Middle Aged; Pressure

Serum gastrin concentration was measured in newborns and infants with no gastrointestinal disorders, in the fasting state and after food stimulation. Mean fasting concentration in 14 newborns aged 1 to 12 days (130 . 4 pg/ml +/- 11 . 4 SE) was significantly higher than the mean value in 23 infants aged 1.5 to 22 months (101.4 +/- 6.6 pg/ml). Ingestion of the usual milk meal resulted in a definite rise of the serum gastrin level in the 5 subjects tested (3 newborns and 2 infants). The mean fasting serum gastrin level in 6 babies with hiatus hernia and gastro-oesophageal reflux was found to be no different from the corresponding value in 8 age-matched controls. However, a conspicuously raised fasting gastrin concentration was observed in one infant with lower oesophageal dyskinesia. The results indicate that the release of gastrin and the reactivity of the hormone-producing sites to food stimulation in early life are similar to those in adult humans. No defect of gastrin release was shown in patients with gastro-oesophageal reflux.

Topics: Animals; Esophageal Diseases; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Infant; Infant, Newborn; Milk

Topics: Adult; Cardia; Contrast Media; Dumping Syndrome; Duodenal Ulcer; Esophagoscopy; Esophagus; Female; Follow-Up Studies; Gastrins; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Male; Manometry; Middle Aged; Peptic Ulcer; Peristalsis; Postgastrectomy Syndromes; Posture; Radiography; Radioimmunoassay; Stomach Neoplasms

Topics: Calcitonin; Cardia; Ceruletide; Gastrins; Gastroesophageal Reflux; Glucagon; Hernia, Hiatal; Humans; Manometry; Secretin

Topics: Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Hydrogen-Ion Concentration; Manometry; Peptides; Prostaglandins

Topics: Antacids; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Receptors, Cholinergic

Topics: Animals; Disease Models, Animal; Dogs; Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Hernia, Hiatal; Manometry; Stimulation, Chemical

Topics: Animals; Dogs; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Glucagon; In Vitro Techniques; Perfusion

Topics: Animals; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Research Design

Topics: Animals; Atropine; Diaphragm; Dogs; Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Gastrointestinal Motility; Manometry; Methods; Pressure; Stomach

Topics: Adult; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Glycine; Humans; Middle Aged; Pressure; Sodium Hydroxide

Topics: Adult; Aged; Dietary Proteins; Dose-Response Relationship, Drug; Esophagus; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pentagastrin; Pressure; Radioimmunoassay

Topics: Bile; Gastric Juice; Gastrins; Gastroesophageal Reflux; Histamine Release; Humans; Pylorus; Stomach Ulcer

Topics: Adult; Aged; Bethanechol Compounds; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Edrophonium; Esophagus; Gastric Juice; Gastrins; Gastroesophageal Reflux; Humans; Injections, Intravenous; Middle Aged; Muscle, Smooth; Pentagastrin; Pressure; Stimulation, Chemical

Topics: Animals; Esophageal Achalasia; Esophagus; Gastric Juice; Gastrins; Gastroesophageal Reflux; Humans; Muscle, Smooth; Opossums; Pressure

Topics: Adult; Aged; Bethanechol Compounds; Edrophonium; Esophagus; Female; Gastrins; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Muscles; Pressure; Stimulation, Chemical; Time Factors

Topics: Antacids; Esophagitis; Esophagoscopy; Esophagus; Gastrins; Gastroesophageal Reflux; Heartburn; Hernia, Diaphragmatic; Humans; Hydrogen-Ion Concentration; Parasympatholytics; Perfusion; Pressure; Radiography

Topics: Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Maxillary Sinus; Muscle, Smooth; Pentagastrin

Topics: Bethanechol Compounds; Esophagogastric Junction; Esophagus; Gastric Juice; Gastrins; Gastroesophageal Reflux; Hormones; Humans; Hydrogen-Ion Concentration; Male; Muscle, Smooth; Parasympathomimetics; Pentagastrin; Secretin

Topics: Antacids; Diet Therapy; Dietary Proteins; Esophagitis; Esophagitis, Peptic; Gastrins; Gastroesophageal Reflux; Humans; Parasympatholytics

Topics: Cardia; Cholecystokinin; Gastrins; Gastroesophageal Reflux; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Manometry

Topics: Esophageal Achalasia; Esophageal Diseases; Esophagogastric Junction; Esophagus; Gastrins; Gastroesophageal Reflux; Humans; Muscle, Smooth

Topics: Adult; Antacids; Cerebral Palsy; Child; Esophageal Diseases; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Humans; Infant; Infant, Newborn; Manometry; Muscle Spasticity

Topics: Esophagogastric Junction; Gastric Juice; Gastrins; Gastroesophageal Reflux; Hernia, Diaphragmatic; Humans; Pressure

Both hog gastrin and synthetic gastrin stimulate the cardiac sphincter to increase tone and augment the resistance to reflux. Endogenous gastrin has a similar effect, and gastrin also stimulates the secretion of acid which has also been found to increase the resistance of the sphincter, but the effect of gastrin appears to be independent of the secretory stimulus.

Topics: Cardia; Esophagogastric Junction; Gastric Juice; Gastrins; Gastroesophageal Reflux; Humans; Injections, Intravenous; Manometry; Peptides; Secretory Rate; Stimulation, Chemical