gastrins and Arthritis--Rheumatoid

The effects of oral indomethacin on intragastric pH and serum gastrin were investigated in rheumatoid arthritis patients. Nine patients (1 male, 8 female) without a history of peptic ulcer disease and 6 patients with a history of peptic ulcer disease (5 male, 1 female) were studied. To obviate Helicobacter pylori infection as a confounding factor, only patients with positive H. pylori serology were included. After a 5-day period of placebo treatment and after a 5-day period of indomethacin (50 mg t.d.s.; total dose 750 mg), 24-h intragastric pH and basal and meal-stimulated serum gastrin levels were measured in a double-blind placebo controlled cross-over study. There were no differences in the median 24-h pH values between placebo and indomethacin users irrespective of peptic ulcer disease history. Indomethacin resulted in a higher basal and stimulated gastrin response than placebo in patients with a history of peptic ulcer disease. The basal and incremental responses were lower in patients with a history of peptic ulcer disease than in patients without a history of peptic ulcer disease, both during indomethacin and placebo. The same basal and stimulated incremental serum gastrin responses were found during placebo and indomethacin treatment in patients without a history of peptic ulcer disease. No correlation was established between median 2-h post-prandial intragastric pH and post-prandial incremental serum gastrin concentration. We conclude that indomethacin does not influence the intragastric pH of rheumatoid arthritis patients irrespective of history of peptic ulcer disease.

Topics: Administration, Oral; Aged; Arthritis, Rheumatoid; Basal Metabolism; Double-Blind Method; Female; Food; Gastric Acidity Determination; Gastrins; Humans; Hydrogen-Ion Concentration; Indomethacin; Male; Middle Aged; Monitoring, Physiologic; Peptic Ulcer

The effect of continuous versus interrupted high-dose aspirin (ASA) for 14 days was evaluated in a randomized double-blind study in 8 rheumatoid arthritis patients. Acute gastric mucosal injury was measured by serial gastroscopy and gastric biopsy. Significant gross mucosal damage was seen in all patients following 3 days of ASA (P less than 0.01) and persisted without significant change in severity to the end of the study. Histologic gastritis in areas free of hemorrhages and erosions was not increased significantly by ASA. In spite of gross mucosal injury, symptoms occurred infrequently. Serum pepsinogen I, but not serum gastrin, increased significantly following 3 days of ASA, and the elevation persisted to the end of the study. The extent of mucosal injury at 14 days was not significantly different in those receiving ASA continuously from those on an interrupted schedule. Thus, gastric mucosal adaptation to ASA in man was not demonstrated.

Topics: Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Humans; Male; Middle Aged; Pepsinogens; Pyloric Antrum; Time Factors

Apart from the complication of gastrointestinal vasculitis it is not known whether the upper gastrointestinal (UGI) tract has any special disease characteristics in rheumatoid arthritis (RA). However, oesophageal motility disorders have been reported in 30% of RA patients. Hypergastrinaemia has been found in 23-43% of RA patients, usually in combination with a decreased gastric acid output. Another finding suggestive of a decreased secretory state, namely a decreased level of pepsinogen A, was found in RA patients with the sicca syndrome and in patients with active disease. The risk for peptic ulcer disease with regard to nonsteroidal anti-inflammatory drugs (NSAID) is possibly higher in RA patients than in patients with other rheumatic diseases. These findings suggest that in RA patients intrinsic factors play a role in the pathogenesis of the oesophageal motility disorders, in hypergastrinaemia and hypopepsinogenaemia and the related decreased gastric secretory state, and possibly in the increased susceptibility to NSAID-related ulcers. However, there are also indications that oesophageal motility disorders, hypergastrinaemia, and NSAID-related ulcers in RA are the result of extrinsic factors, mainly the use of NSAIDs. The effects of NSAIDs and gold compounds on infection with Helicobacter pylori, a possible pathogenetic factor in ulcer disease, is discussed. It is clear that the discussion about intrinsic and extrinsic factors as a cause of the UGI manifestations in RA remains an intriguing but difficult subject for further studies.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Esophageal Diseases; Esophageal Motility Disorders; Gastric Acid; Gastrins; Helicobacter pylori; Humans; Pepsinogens; Peptic Ulcer; Stomach Diseases

The relation between the basal and stimulated gastric acid secretion, plasma gastrin, and the gastric microflora was examined in 45 patients with rheumatoid arthritis. Sixteen patients (36%) had basal achlorhydria, and of these, 10 (22%) had achlorhydria or hypochlorhydria after stimulation with pentagastrin. The peak acid output and acidity showed inverse correlation with the disease duration but were not associated with age or with the degree of physical disability. Hypergastrinaemia was found in nine patients (20%), of whom 6 (13%) had significant titres of parietal cell antibody. The acidity of the peak acid output showed negative correlation with plasma gastrin. It was confirmed that the gastric secretory state is a determinant of plasma gastrin levels and in addition influences the growth of micro-organisms in the gastric lumen. The type of microflora in the non-acid stomach was similar to that found in the saliva. A subgroup of eight females was identified who showed low gastric acid secretion rates, positive bacterial cultures, and atlantoaxial subluxation. Gastrin- and insulin-like immunoreactivities were found in joint fluid. The concentrations reflected their plasma levels, suggesting that the peptides are not released at the inflammatory site, but rather that they reach synovial fluid from circulating blood.

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Insulin; Male; Middle Aged; Saliva; Stomach

We examined 51 sera from patients with pernicious anaemia for their capacity to block maximal gastrin stimulation of acid secretion by isolated rodent gastric parietal cells. 14C-aminopyrine accumulation was used as the index of acid secretion in vitro. Sera from patients with pernicious anaemia gave significantly (P less than 0.005) more block of maximal gastrin stimulation of acid secretion (61.7 +/- 37.8%) than sera from 10 patients with systemic lupus erythematosus (19.6 +/- 17.7%), 10 with scleroderma (34.2 +/- 22.3%), five with rheumatoid arthritis (22.4 +/- 15.6%) or 30 from healthy persons (27.4 +/- 12.8%). Maximal histamine stimulation of acid secretion was not inhibited. The blocking factor was present in serum IgG fractions, and serum and IgG fractions gave parallel dose-response and dilution curves. The serum block was abolished by absorption with gastric mucosal cells and correlated with the presence of parietal cell surface autoantibody. We conclude that serum immunoglobulin in pernicious anaemia can block gastrin stimulation of acid secretion and suggest that this block may be mediated by competition with gastrin for surface receptors on parietal cells.

Topics: Adult; Aged; Aminopyrine; Anemia, Pernicious; Animals; Arthritis, Rheumatoid; Autoantibodies; Binding, Competitive; Dose-Response Relationship, Immunologic; Female; Gastric Acid; Gastrins; Humans; Immunoglobulin G; In Vitro Techniques; Intrinsic Factor; Lupus Erythematosus, Systemic; Male; Middle Aged; Parietal Cells, Gastric; Rats; Rats, Inbred Strains; Scleroderma, Systemic

Topics: Arthritis, Rheumatoid; Gastrins; Humans; Sjogren's Syndrome

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Gastrins; Humans; Male; Middle Aged; Sjogren's Syndrome

Since 1973 some Authors reported a high prevalence of raise serum gastrin levels in rheumatoid arthritis. In our study of 37 subjects with classic or defined RA, 29 (78%) had serum gastrin levels significantly higher than controls (mean 156.3% pg/ml versus 58.8 pg/ml) and 8 (22%) had normal levels. Basal acid output (BAO) and maximal acid output (MAO) of all affected patients did not differ from controls. We found no correlation among gastrinaemia, BAO, MAO, inflammation indexes and RA test. According to the normal acid output of our RA patients, hypergastrinaemia should be caused by factors different from hypochlorhydria. It is possible that immunoreactive, but non biologically active, peptides could interfere with RIA of gastrin, or that other factors, such as prostaglandins or antigastrin antibodies, could modify the activity of endogenous hormone.

Topics: Adolescent; Adult; Arthritis, Rheumatoid; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Rheumatoid Factor

Serum gastrin concentrations under basal conditions and following stimulation were assessed in 40 patients suffering from rheumatoid arthritis (RA) and compared with healthy individuals. The RA groups showed no significant differences in comparison with the control population. These conclusions lead the authors to seek the reasons for the rare instances of confirmed hypergastrinaemia in RA.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cortisone; Female; Gastrins; Gold; Humans; Male; Middle Aged

Topics: Adult; Aged; Arthritis, Rheumatoid; Gastrins; Humans; Middle Aged; Osteoarthritis; Sjogren's Syndrome

In an attempt to further evaluate the conflicting incidence of hypergastrinemia in patients with rheumatoid arthritis (RA), serum gastrin concentration has been determined in 58 RA patients and in 58 healthy subjects. Mean levels were significantly higher in RA patients than in controls, although clearly high values were only found in 3 subjects with severe hypochloridria. During one year of immunosuppressive treatment in 12 RA patients with cyclophosphamide plus colchicine serum gastrin levels did not change, while a significant decrease was observed in another 12 patients after 2 months' treatment with haloperidol, a dopamine receptor blocker; this decrease was sustained throughout the one year treatment. Indomethacin administration up to 6 months did not change serum levels in a control group of 12 RA patients. Serum gastrin concentration in patients treated with haloperidol was significantly lower than in those treated with indomethacin at 2 and 6 months, while no significant differences were observed between cyclophosphamide- and indomethacin-treated groups. These results confirm and extend previous studies showing inhibition of gastrin secretion by antidopaminergic drugs. No correlations were observed between serum gastrin levels and inflammatory indices, both in basal conditions and during any drug treatment.

Topics: Adult; Aged; Arthritis, Rheumatoid; Colchicine; Cyclophosphamide; Dopamine Antagonists; Fasting; Female; Gastrins; Haloperidol; Humans; Immunosuppressive Agents; Indomethacin; Male; Middle Aged

In order to evaluate the incidence and aetiology of hypergastrinaemia 53 patients with seropositive rheumatoid arthritis were examined for gastric acid secretion, fasting serum gastrin concentration, circulating parietal cell antibodies, and some parameters of the activity of inflammation of rheumatoid arthritis. The basal and maximum acid output was found to be subnormal in this group (P less than 0.01), and in 11 of these patients (23%) the fasting serum gastrin levels were raised (P less than 0.05). This hypergastrinaemia correlated strongly with maximum acid output. Only in cases of achlorhydria or hypochlorhydria (maximum acid output less than 2 mmol/l) was the serum gastrin level markedly raised. Two out of 5 patients with achlorhydria were found to have circulating parietal cell antibodies, and 1 had decreased absorption of vitamin B12. No relationship was found between serum gastrin and duration or activity of rheumatoid arthritis; nor was there a relationship between basal serum gastrin and the various antirheumatic drugs administered.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Fasting; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Secretory Rate; Time Factors

Topics: Arthritis, Rheumatoid; Gastrins; Humans; Indomethacin; Male

In an attempt to confirm the reported high incidence of raised serum gastrin levels in patients with rheumatoid arthritis (RA), gastrin concentrations were estimated in 54 patients. Only three patients (6%) had basal hypergastrinaemia. The heptadecapeptide (G17) and total carboxyl-terminal immunoreactive gastrin responses to a standard protein meal were measured by specific radioimmunoassay in these three patients and in nine normogastrinaemic RA patients displaying the same age range. The three hypergastrinaemic patients showed significantly greater and more prolonged G17 and total carboxylterminal immunoreactive gastrin responses to the meal compared with the normogastrinaemic RA patients (P less than 0.02). Two of these three patients agreed to have an acid output study (pentagastrin 6 microg/kg subcutaneously) and gastric mucosal biopsies taken for histology. Both were found to be achlorhydric and to have atrophic gastritis. This study suggests that basal hypergastrinaemia in RA patients is considerably less common than previously reported and, when present, is associated with achlorhydria. In addition, the incidence of achlorhydria in rheumatoid arthritis is similar to that found in a normal age-matched population.

Topics: Adult; Arthritis, Rheumatoid; Dietary Proteins; Female; Gastric Juice; Gastrins; Gastritis; Humans; Male; Middle Aged

Topics: Adult; Aged; Arthritis, Rheumatoid; Dietary Proteins; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Rheumatoid Factor

To elucidate further the pathogenesis of steroid-induced ulceration, plasma gastrin levels, both basal and after a test meal, were studied in normal volunteers and patients treated with glucocorticoids or corticotropin. In normal subjects the acute intravenous administration of 100 mg prednisolone had no effect on plasma gastrin levels. After oral administration of prednisolone (40 mg daily, for four days) a significant increase of the basal, the reactive, and the over 90-min integrated gastrin release was observed. In this group, the glucocorticoid treatment had a slight, but significant influence on gastric acid and pepsin secretion, while acidity and pepsin output stimulated by pentagastrin was not affected. In patients treated with prednisolone for more than 24 weeks, the oral administration of this hormone failed to alter basal gastrin values but affected significantly secretion after the test meal. In patients with multiple sclerosis, after intramuscular administration of corticotropin (60 IU daily, for 12 days), an increase of the basal, the reactive, and the integrated gastrin release also was found. Glucocorticoid-induced hypergastrinemia provides information on the pathogenesis of steroid-induced ulceration.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Arthritis, Rheumatoid; Gastrins; Glucocorticoids; Humans; Middle Aged; Multiple Sclerosis; Prednisolone; Radioimmunoassay

Serum immunoreactive gastrin is raised in some patients with rheumatoid arthritis (RA). In this paper paired samples taken within 30 minutes of each other show that this phenomenon is reproducible. Dilution curves show identity between gastrin from RA patients and from patients with no RA, and the raised immunoreactive gastrin concentration is demonstrable in patients who do not have chronic atrophic gastritis and in whom both basal and stimulated acid output concentrations are normal. Samples of gastric mucous membrane obtained from the body of the stomach and gastroscopy under direct vision in 18 patients with raised serum immunoreactive gastrin concentrations were normal.

Topics: Arthritis, Rheumatoid; Female; Gastric Juice; Gastrins; Histamine; Humans; Male; Pentagastrin; Radioimmunoassay

A significant rise in immunoreactive gastrin in a proportion of patients with rheumatoid arthritis is confirmed. Such a rise does not seem to occur in other inflammatory or tissue destructive diseases. The patients with raised immunoreactive gastrin appear to form a separate population but the factors determining this separation remain obscure. Anti-inflammatory drugs, at least during short-term administration have no influence on immunoreactive gastrin concentrations.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antigens; Arthritis; Arthritis, Rheumatoid; Female; Gastrins; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Myocardial Infarction; Osteoarthritis; Psoriasis; Radioimmunoassay; Spondylitis, Ankylosing; Tuberculosis, Pulmonary

Serum gastrin radioimmunoassay (RIA) is a sensitive and specific method suitable for measurement of circulating concentrations of this peptide hormone, which is a major regulator of gastric acid secretion. When performed under optimal conditions this RIA permits measurement of low and normal serum gastrin levels and changes that occur after physiologic stimulation. Hypergastrinemia may be secondary to atrophy of the acid-secreting gastric mucosa. This form of pypergastrinemia is appropriate and leads to no seriousequences. Hypergastrinemia associated with gastric acid hypersecretion is inappropriate. The major cause is a gastrinsecreting tumor (gastrinoma) that produces the clinical picture of the Aollinger-Ellison syndrome. The differential diagnosis of inappropraite hypergastrinemia includes antral G-cell hyperplasia and ISOLATED RETAINED ANTRUM. Accurate diagnosis of these conditions may be aided by ancillary studies including feeding, secretin, and calcium stimulation tests. Distinction among these conditions is important in planning appropriate surgical tratment.

Topics: Antibody Specificity; Arthritis, Rheumatoid; Catecholamines; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Kidney Failure, Chronic; Pentagastrin; Pheochromocytoma; Pyloric Antrum; Radioimmunoassay; Stimulation, Chemical; Stomach Neoplasms; Vagotomy; Zollinger-Ellison Syndrome

Topics: Administration, Oral; Adult; Aged; Antibodies; Antigens; Arthritis, Rheumatoid; Carbon Dioxide; Chlorides; Female; Gastrins; Glycyrrhiza; Humans; Male; Middle Aged; Peptic Ulcer; Plants, Medicinal; Potassium; Radioimmunoassay; Secretin; Sodium; Succinates; Triterpenes

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cosyntropin; Gastrins; Glycyrrhiza; Humans; Indomethacin; Male; Phytotherapy; Plants, Medicinal; Radioimmunoassay; Rats; Secretin; Succinates; Terpenes; Time Factors

Topics: Adrenocorticotropic Hormone; Adult; Aged; Arthritis, Rheumatoid; Blood Glucose; Carbohydrate Metabolism; Cholesterol; Female; Gastrins; Glucagon; Humans; Hydrocortisone; Injections, Intramuscular; Insulin; Lipid Metabolism; Male; Middle Aged; Osteoarthritis; Spondylitis, Ankylosing; Triglycerides

Topics: Adult; Aged; Antibodies; Arthritis, Rheumatoid; Blood Sedimentation; Drug-Related Side Effects and Adverse Reactions; Female; Gastrins; Humans; Iatrogenic Disease; Male; Middle Aged; Radioimmunoassay; Stomach

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

Topics: Animals; Arthritis, Rheumatoid; Gastrins; Humans; Rats