Magnesium hydrogen breath test using end expiratory sampling to assess achlorhydria in pernicious anaemia patients.

A modified magnesium hydrogen breath test, using end expiratory breath sampling, is described to investigate achlorhydria. The efficacy of this test in the diagnostic investigation of pernicious anaemia was compared with that of serum pepsinogen I. Twenty one patients with pernicious anaemia--that is, patients with achlorhydria--and 22 with healed duodenal ulcer and normal chlorhydria were studied. Magnesium hydrogen breath test, serum pepsinogen I, serum gastrin, and standard gastric acid secretory tests were performed in all subjects. The mean (SEM) hydrogen peak value was lower in patients with pernicious anaemia than in the duodenal ulcer group (21.7 (1.9) v 71.3 (5.2) ppm; p = 0.00005). The hydrogen peak value had a 95.2% sensitivity and a 100% specificity to detect pentagastrin resistant achlorhydria. Mean serum pepsinogen I concentrations were also significantly lower in patients with pernicious anaemia than in the duodenal ulcer group (10.7 (2.7) v 123.6 (11.8) micrograms/l p = 0.00005). Sensitivity and specificity to detect pernicious anaemia were both 100% for pepsinogen I. It is concluded that this modified magnesium hydrogen breath test is a simple, noninvasive, cost effective, and accurate method to assess achlorhydria and may be useful in the diagnostic investigation of patients with suspected pernicious anaemia.     

Indirect gastric secretory studies

Summary The results of the two simple gastric secretory tests, tubeless gastric analysis and plasma pepsinogen determination, were determined in 217 patients without gastrointestinal disease or azotemia. Patients with pernicious anemia, gastric cancer, duodenal ulcer, azotemia, and diabetes mellitus undergoing depot insulin therapy were also studied. Low pepinsogen in the blood tended to occur with anacidity, while a significantly higher mean pepsinogen level was noted with acid-secreting ability. Similarly, low pepsinogen values were found in the presence of pernicious anemia and gastric cancer, while elevated results were noted with duodenal ulcer, although individual exceptions occurred in most conditions. When positive, tubeless gastric analysis results were shown to be reliable qualitative evidence of ability to secrete acid. A negative resin finding was noted to be strongly suggestive evidence of anacidity or hypochlorhydria, whereas the likelihood that true achlorhydria existed was markedly increased if a second tubeless gastric analysis result was also negative. The two indirect tests of gastric secretory function were shown to complement each other. The effects of various diseases and therapy on gastric pepsin production and plasma pepsinogen values have been discussed. It is felt that these two procedures will find considerable application as screening tests for conditions with altered gastric secretory function, because of their simplicity and accuracy.The azure A ion-exchange resin used in this study was supplied as Diagnex, New Formula, by E. R. Squibb & Sons, New York, N. Y.     

Gastric acid secretion and risk of recurrence of duodenal ulcer within six to eight years after truncal vagotomy and drainage

The value of insulin and augmented histamine tests in predicting recurrence of duodenal ulcer within six to eight years after truncal vagotomy and drainage was assessed in a series of 500 consecutively and electively operated patients. Criteria of recurrence were established by a discriminative analysis of gastric acid secretion parameters. Recurrence was predicted with a probability of about 75% in patients with dyspepsia, the proportion between recurrences and dyspeptic nonrecurrences being 1:1. The discriminatory ability of the insulin test was no better than that of the postoperative histamine test. Men with a preoperative PAO > 46.1 m-equiv/h had a risk of recurrence of 21%, women with a PAO > 41.5 m-equiv/h, 28%. Below these levels the risk was 5 and 1% respectively, demonstrating that recurrence after vagotomy is related to the number of parietal cells before vagotomy. A rationale is provided for antrectomy and vagotomy in duodenal ulcer patients with a high number of parietal cells.     

Prognostic Value of the Augmented Histamine Test in Ulcer Disease and X-ray Negative Dyspepsia

108 patients with duodenal ulcer, gastric ulcer, or X-ray negative dyspepsia, were interviewed 24 to 52 months after an admission to hospital, where an augmented histamine test had been performed. In ulcer patients, who had only received medical treatment, no significant correlation was found between the acid production at the time of the admission and the severity of the symptoms at the follow-up interview. In X-ray negative dyspepsia a negative correlation was found. When those patients who had been treated surgically between admission and interview were taken into account, a positive correlation between PAO and severity of symptoms was found in female gastric ulcer patients, but in duodenal ulcer disease the augmented histamine test was still found to have no prognostic value.     

An assessment of the augmented histamine test in the diagnosis of peptic ulcer: Correlations between gastric secretion, age and sex of patients, and site and nature of the ulcer

Patients with peptic ulcer, radiologically negative dyspepsia, and gastric carcinoma have been studied with the modified augmented histamine test described in the previous paper. For each disease a range of values is presented and compared with the normal range, taking account of age and sex. The test may be of diagnostic value because comparison of an observed result with the ranges presented may show that a disorder, for example duodenal ulcer, is almost certainly present or almost certainly not present. Thus, in duodenal ulcer about half the values of peak acid output were above the normal range, and there was a threshold figure for peak acid output below which patients with duodenal ulcer were not found. There was a gradient for peak acid output in patients with ulcers at different sites so that ulcers in the body of the stomach < near the angulus < prepyloric < duodenal ulcers. Normal acid output did not exclude carcinoma of the stomach. Abnormally high basal or peak acid output in patients with dyspepsia but negative barium meals may suggest the presence of peptic ulceration.     

Computed normal values for peak acid output based on age,sex and body weight

The value of gastric analysis in the clinical management of patients with duodenal ulcer disease has been limited by lack of information on the expected normal gastric acid production following maximal stimulation. A table of peak acid outputs utilizing the augmented histamine test and based on age, sex and body weight of the individual was devised using the method of least squares.Results of the peak acid output in 64 patients with proven duodenal ulcer and in 38 normal controls, when compared to the computed normal values based on age, sex and body weight, revealed that 90% of patients with duodenal ulcer fell outside the expected normal range, and 92% of the normal subjects fell within the computed normal range. It is felt that these tables are helpful in recognizing individuals with duodenal ulcer or its diathesis.     

Comparative study of the value of the calcium, secretin, and meal stimulated increase in serum gastrin to the diagnosis of the Zollinger-Ellison syndrome.

To evaluate the usefulness of provocation tests in the diagnosis of the Zollinger-Ellison (ZE) syndrome stimulation tests with calcium, 15 mg/kg. 3 h, and secretin GIH, 1 U/kg.30 s, were performed in 15 patients with histologically proven or suspected ZE syndrome. Nine of these 15 patients were without previous gastric surgery and in them meal stimulated serum gastrin levels were measured as well. These tests were also performed in normal subjects and in patients with duodenal ulcer, antrectomy, total gastrectomy, and achlorhydria. All tests were considered to be positive if a more than 50% increase in serum gastrin was found. The results indicate that secretin stimulation is the provocation test of first choice in the diagnosis of this syndrome. This test is most valuable for the following reasons: (1) there were few (two out of 15) false-negative test results in ZE patients; (2) there were no false-positive tests in 69 patients without gastrinoma; (3) it was easy and quick to perform; and (4) there were no adverse reactions. The two ZE patients with negative secretin stimulation tests had negative calcium provocation tests as well, in spite of histologically proven gastrinoma. In 11 patients with suspected or proven ZE syndrome and basal serum gastrin levels of less than 1000 pg/ml a rather good correlation (r = 0-841; P less than 0-01) was found between the percental increase in serum gastrin after stimulation by calcium and secretin. Meal stimulated serum gastrin levels are helpful only in patients without previous gastric surgery.     

The effect of nitrogen mustard and cyclophosphamide on gastric secretion in man

Summary 1. Nitrogen mustard caused achlorhydria, by the criteria of the Diagnex Blue tubeless test, in 7 of 8 patients given the drug for cancer.2. The achlorhydria lasted less than 3 weeks.3. Cyclophosphamide had no demonstrable effect on gastric secretion.4. The mode of action of nitrogen mustard and the reason for the failure of cyclophosphamide to inhibit gastric secretion are discussed.I wish to thank Dr. D. W. Piper, whose advice and criticism helped to make this study possible. I wish to thank E. R. Squibb & Sons, Melbourne, Australia, for the generous supply of Diagnex Blue made available by them for the investigation.     

Evaluation of a new immunochromatographic based whole blood near patient test for the diagnosis of Helicobacter pylori infection

BACKGROUND: Infection with H pylori is very common and may cause chronic gastritis, predisposes to gastric and duodenal ulcers, leads in some cases to gastric lymphoma and has been recognised as a class I gastric carcinogen. Rapid, inexpensive, reliable tests are needed to facilitate the diagnosis. METHODS: This prospective clinical study was undertaken to evaluate a new whole blood antibody test (helicoCare) in correlation to three tests for diagnosis of H pylori infection (histology, ELISA and rapid urease test). 304 patients (mean age 56.5 years, range of 11-93 years) referred for esophagogastroduodenoscopy were included in this uni-centric study over a nine-month period. According to the guidelines for clinical trials in H pylori infection, patients with at least two positive tests were classified as positive for H pylori. RESULTS: 132 patients (43.4 %) were positive for H pylori, of which helicoCare identified 118 missing one gastric and one duodenal ulcer. 172 patients (56.6 %) were H pylori negative, of which helicoCare identified 163. Sensitivity was proven to be 89.4 % and specificity 94.8 %. In a special subgroup of 75 patients younger or equal to 45 years, 28 patients were positive for H pylori (37.3 %). In this group a sensitivity of 85.7 % and a specificity of 97.9 % was found for the helicoCare. CONCLUSIONS: The helicoCare test showed sufficient sensitivity and satisfying specificity for H pylori diagnosis similar to or better than those of rapid urease test or ELISA. The helicoCare whole blood test may be useful for in-office H pylori diagnosis especially in patients under 45 years.     

Is the gastrin response to secretin provocation a function of antral G-cell mass? Results in the hypergastrinemia of acid hyposecretion

Some patients with hypergastrinemic achlorhydria may have false-positive secretin provocation as an exaggeration of the normal gastrin response to secretin, presumably related to an increased, or more responsive, antral G-cell mass. To test this hypothesis, we reviewed our experience with secretin provocation in normogastrinemic subjects with presumed normal antral G-cell mass (normal--17, duodenal ulcer--13) and in patients with hypergastrinemia related to changes in antral G-cells (vagotomy--5, hypochlorhydria--7, achlorhydria--10). Basal serum gastrin (mean +/- SEM) was progressively higher for each group; normal (42 +/- 3 pg/ml), duodenal ulcer (53 +/- 4 pg/ml), vagotomy (226 +/- 54 pg/ml), hypochlorhydria (346 +/- 92 pg/ml), achlorhydria (844 +/- 100 pg/ml). On selective analysis of only those with gastrin rises, significant differences (p less than 0.05) in peak gastrin change were found between achlorhydria (93 +/- 21 pg/ml) compared with all other groups and between hypochlorhydria (40 +/- 12 pg/ml) versus normal (6 +/- 1 pg/ml). Linear regression in these responders showed a significant correlation (p less than 0.001) between basal gastrin and peak gastrin change after secretin. There were no false-positive secretin provocation tests, but four achlorhydric patients had gastrin rises greater than 100 pg/ml, whereas no patient in the other categories had rises above 90 pg/ml. Our results support the concept that patients with hypergastrinemic achlorhydria tend to have greater G-cell responsiveness to secretin provocation, which may account for the false-positive results in some such patients.     

Diagnosis of Helicobacter pylori infection in patients with bleeding ulcer disease: rapid urease test and histology.

INTRODUCTION: The endoscopic diagnosis of Helicobacter pylori infection in patients with bleeding peptic ulcer is limited by a decreased sensitivity in standard invasive tests, rapid urease test and histology. There is controversy about the convenience of using one, neither, or both diagnostic tests. AIMS: To evaluate the results of simultaneously performed rapid urease test and histology in the diagnosis of Helicobacter pylori infection (H. pylori) in patients with bleeding peptic ulcer. PATIENTS AND METHODS: We included 173 patients, 98 male and 75 female, with an average age of 62 years (18-88), with upper gastrointestinal bleeding secondary to duodenal ulcer (115) or gastric ulcer (58), diagnosed within 24 hours after hospital admission. None of the patients had received treatment for H. pylori, proton pump inhibitors or antibiotics in the two weeks prior to the upper gastrointestinal bleeding episode. H. pylori infection was investigated in all patients by two antral biopsy samples for histological study (hematoxilin-eosin) and one or two antral biopsies for rapid urease test (Jatrox-H.p.-test). In cases with a negative urease test and histology, a 13C urea breath test was performed. Infection was considered present when at least one invasive test or the breath test was positive, whereas both invasive tests and the breath test had to be negative to establish an absent infection. RESULTS: 152 patients (88%) showed H. pylori infection, 104 patients (90%) with duodenal ulcer and 48 patients (83%) with gastric ulcer. In all 119 cases (78%) were diagnosed by the urease test and 112 cases (74%) by histology. Both methods were used to diagnose 134 of 152 cases (88%) (p < 0.05), these being positive in 97 cases and negative in 39 cases. In 18 of these 39 cases, the breath test was positive. CONCLUSIONS: Histology and urease test have similar diagnostic values for the identification of H. pylori in patients with bleeding peptic ulcer. Due to its rapid results, the urease test should be the method of choice. However, additional biopsies should be performed, and, when negative, a histological study should be carried out, since a combination of both methods allows a more precise diagnosis.     

The Augmented Histamine Test with Special Reference to Achlorhydria

The Kay augmented histamine test has been used in a special study of 30 patients with pernicious anaemia and 136 other subjects suspected of having achlorhydria. The findings have been correlated with uropepsinogen excretion, serum levels of vitamin B₁₂, and gastric biopsy. The definition of achlorhydria is specially considered.     

Observations on gastric acid output by a three-hour histamine infusion test using maximal doses on patients with duodenal ulcer and in normal controls

The results of a series of histamine infusion tests extended over a period of three hours in 100 patients with duodenal ulcer and in 30 normal controls showed that while in the former group acid secretion continued to rise hourly both quantitatively and qualitatively throughout each of the three-hour periods of the tests, this did not occur in the normal controls in whom acid secretion levelled off during the second hour. Assay of 30-minute aspirates in the duodenal ulcer group showed that the 90-120 minute specimen (doubled) gave a close approximation to the values obtained during the third hour and represents maximal acid secretion of the gastric mucosa.     

14C-urea breath test for assessment of gastric Helicobacter pylori colonization and eradication.

BACKGROUND AND OBJECTIVE: Urea breath test (UBT) is a reliable noninvasive technique for detecting gastric Helicobacter pylori colonization. 14C isotope-based test requires simple equipment and is inexpensive. We studied the utility of 14C-UBT in diagnosis of gastric H. pylori infection. METHODS: Presence of H. pylori was studied using antral histology and culture in patients with rapid urease test (RUT)-positive peptic ulcer. 14C-UBT was performed using a 185-kBq dose. Radioactivity in 15-min breath samples was measured using a beta-scintillation counter and result expressed as % dose recovered/mmol CO2. H. pylori was considered positive when any two tests were positive. All tests were repeated one month after completion of H. pylori eradication therapy. RESULTS: Among 41 patients (duodenal ulcer 36, gastric ulcer 5), H. pylori was detected by histology in 23 (56%) and by culture in 27 (66%). Overall, H. pylori was detected in 28 (68%) patients. Follow-up assessment was possible in 28 patients: 26 cleared the infection (all three tests negative). Mean 14C recovery values at 15 minutes associated with H. pylori-positive status were significantly higher (12.3 [SD 6.8] x 10(-3); n=30; p<0.001) than those associated with H. pylori-negative status (2.1 [0.9] x 10(-3); n=26). Using receiver-operating-characteristic analysis of 15-minute 14C recovery values, a cut-off of 6.5x10(-3) gave the best separation of H. pylori-positive and -negative cases. 14C-UBT had 93% sensitivity, 96% specificity and 95% accuracy. CONCLUSION: 14C-UBT appears to be a reliable noninvasive test for diagnosis of H. pylori infection.     

Sample taking problems in measuring actual histamine levels of human gastroduodenal mucosa: specific and general relevance in clinical trials on peptic ulcer pathogenesis and selective proximal vagotomy.

Changes in histamine storage in the oxyntic mucosa of duodenal ulcer patients and their reversal by vagotomy and the histamine H2-antagonist cimetidine supported the hypothesis that histamine could be a causal factor in peptic ulcer pathogenesis. The specificity of these findings was impaired by problems in biopsy taking, however, and in the preparative steps before measuring the actual histamine contents in all parts of the gastric mucosa and in the duodenum. A prospective trial was carried out in 190 patients to identify these sources of bias and to overcome them by appropriate study designs. Usually a direct correlation was found between weight of biopsy and mucosal histamine content. This problem was solved by selecting a biopsy forceps producing smaller variations in sample size, by limiting the time of cold ischaemia to four to five minutes only and by taking three biopsy specimens for each single histamine value. The actual histamine content of mucosal biopsies remained constant for about four to five minutes only. The 'disappearance' rate was faster in control subjects than in duodenal ulcer patients. Hence by variation of the cold ischaemia time any artefacts of differences between mucosal histamine levels in controls and duodenal ulcer patients could be produced. Using the optimised sample taking procedure mucosal histamine contents of several gastric regions and the duodenal bulb were measured in 24 patients with duodenal ulcer, after selective proximal vagotomy without drainage and in control subjects without any stomach disease (randomised controlled trial). The histamine content was lower in all parts of the upper gastrointestinal tract in duodenal ulcer patients than in controls and was raised again in all regions after selective proximal vagotomy. As the most likely hypothesis it is suggested that vagal reflexes with afferent fibres coming from the oxyntic mucosa stimulate histamine release in duodenal ulcer patients by efferent peptidergic neurones to all parts of the stomach and the duodenum where the ulcer lesion is situated.     

Anterior seromyotomy with posterior truncal vagotomy in chronic duodenal ulcer

Anterior seromyotomy with posterior truncal vagotomy was carried out on 25 patients with chronic duodenal ulcer to evaluate its effectiveness as an acid reducing procedure. There was a 76.7% and 76.8% reduction in basal and maximal acid output respectively (augmented histamine test). Twenty-three patients were asymptomatic at 4-6 years' follow-up, while two patients had delayed gastric emptying not necessitating reoperation. There was no mortality. This procedure is a reasonable alternative to highly selective vagotomy.     

The augmented histamine test in the differential diagnosis between ulcer and cancer of the stomach

The maximum gastric acidity has been studied using the augmented histamine test in patients with gastric ulcer, with ulcers in the body of the stomach, with pre-pyloric ulcers, and in patients with gastric carcinoma. The results have not enabled a clear distinction to be made between simple and malignant ulcers.     

Correlation of salivary and gastric acid secretions in duodenal ulcer patients in tropics

Salivary flow rates on mechanical stimulation by forced spitting method and by chemical stimulation with 10% citric acid and gastric acidity using an augmented histamine test were determined in 20 adult patients suffering from duodenal ulcer and in 20 adult control subjects matched with respect to age, sex, and body weight. Salivary flow rates were found to be much higher in response to chemical than to mechanical stimulus in both the groups. Duodenal ulcer patients exhibited an unexplained exaggerated response to chemical stimulation. Salivary pH, amylase, sodium, and potassium levels showed no significant differences between the two groups. The flow rates by either method generally showed a positive correlation with body weight in both the groups. Histamine stimulated gastric acid secretion was higher in duodenal ulcer patients than in controls. Acid secretion did not appear to be related to weight and also showed no consistent correlation with the salivary flow rates. It was concluded that (1) the salivary flow was dependent on body weight in duodenal ulcer patients as well as in controls, and (2) although salivary gland hyperplasia could be postulated in duodenal ulcer patients on the basis of increased salivary flow, the latter was poorly related to maximal acid secretion and therefore, if a combination of parietal cell and salivary gland hyperplasia did exist, it should be considered as incidental.     

Histamine and duodenal ulceration in renal transplant recipients.

Six of 25 renal transplant recipients had a duodenal ulcer at endoscopy. Histamine concentration and the activity of histamine methyltransferase, the degrading enzyme of histamine, were measured in gastric mucosal biopsies obtained at endoscopy and compared with patients with duodenal ulcer but not undergoing transplant and with patients with an apparently normal stomach and duodenum. Histamine concentrations in the corpus (no ulcer, median: 151 nmol/g; DU, median: 122 nmol/g) and in the antrum (no ulcer, median: 118 nmol/g; with DU, median: 113 nmol/g) of renal transplant patients, irrespective of ulcer diagnosis, and in patients with a chronic duodenal ulcer (median corpus histamine: 137 nmol/g and median antral histamine: 126 nmol/g) were not different from one another but significantly lower than the corresponding values in normal subjects (median corpus histamine: 241 nmol/g, p less than 0.01, and median antral histamine: 178 nmol/g, p less than 0.05). Histamine concentration in the corpus was significantly higher than in the antrum in all three groups of patients (p less than 0.05). There were no significant differences in histamine methyltransferase activity in any of the groups studied. Mucosal histamine and histamine methyltransferase activity were significantly correlated in the corpus (p less than 0.05) and antrum (p less than 0.02). Plasma concentration of histamine after transplant was higher in the patients who subsequently were discovered to have a duodenal ulcer (p less than 0.05). The occurrence of ulcer after transplantation was not related to the serum creatinine level. The uniform depletion of gastric histamine and increase in circulatory histamine after renal transplantation may be a factor in the pathogenesis of duodenal ulcer disease in this clinical situation.     

Postbulbar duodenal ulcer in a patient with pentagastrin-fast achlorhydria

This report describes the clinicopathologic features of a 55-yr-old man found to have a bleeding, postbulbar duodenal ulcer and fasting hypergastrinemia. Gastric analysis revealed pentagastrin-fast achlorhydria. Healing of the ulcer was documented 8 wk after vagotomy, antrectomy, gastrojejunostomy, and a course of sucralfate therapy. The etiology of the postbulbar ulcer was uncertain. This is the first documented case of a duodenal ulcer with pentagastrin-fast achlorhydria.