Cornelius P. Dooley

Prevalence of Helicobacter pylori Infection and Histologic Gastritis in Asymptomatic Persons

We estimated the prevalences of Helicobacter pylori (formerly called Campylobacter pylori) infection and histologic gastritis in 113 asymptomatic persons, using endoscopic biopsy of the gastric antrum and corpus. Unsuspected lesions, mainly mucosal erosions, were revealed at endoscopy in 16 subjects (14 percent). Gastritis was found in 42 subjects (37 percent), of whom 36 (32 percent of the total) were found to be infected with H. pylori on the basis of hematoxylin-eosin staining. H. pylori was not found in any of the 71 subjects with normal histologic features. Gastritis and H. pylori were noted in both the antrum and corpus in 75 percent of those infected (n = 27). The prevalence of H. pylori infection increased from 10 percent (2 of 20 subjects) in those between the ages of 18 and 29, to 47 percent (7 of 15) in those between the ages of 60 and 69, but the effect of age did not reach statistical significance. The prevalence of gastritis increased significantly with advancing age. Stepwise logistic regression analysis revealed that the relative risk for H. pylori infection associated with recent (within six months) antibiotic use was 5.8 (95 percent confidence interval, 1.5 to 22.1), whereas the relative risk was 6.5 (95 percent confidence interval, 1.4 to 29.2) for those who had never used bismuth compounds. We conclude that histologic gastritis and H. pylori infection commonly occur in the stomach of apparently normal persons and increase in prevalence with advancing age. All the subjects with H. pylori infection had gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion.

The Clinical Significance of Campylobacter pylori

Campylobacter pylori has recently been isolated from gastric mucosal biopsy specimens. Campylobacter pylori has many attributes in common with other campylobacters but it may represent a new genus. It produces abundant quantities of urease, and this property has been used to develop a rapid diagnostic test. The organism is found predominantly beneath the gastric mucus layer that lines the surface epithelium of the stomach. Infection with C. pylori causes an acute histologic gastritis which may become chronic. The bacterium is the etiologic agent in type-B gastritis. Prevalence of the organism in asymptomatic persons appears to be age related. Campylobacter pylori is found commonly in patients with peptic ulcer disease, always in association with chronic gastritis. Eradication of the organism is associated with healing of the gastritis and a lower relapse rate in duodenal ulcer disease. A role for the organism in other upper gastrointestinal diseases is unproven.

Double-contrast barium meal and upper gastrointestinal endoscopy. A comparative study.

One hundred randomly selected inpatients were examined with both double-contrast barium meal and endoscopy in a blinded prospective fashion. All studies were done by staff personnel, with equal clinical information available to both the radiologist and endoscopist. The final diagnosis was made by a review committee of participating radiologists and endoscopists. Endoscopy was more sensitive (92% versus 54%, p less than 0.001) and specific (100% versus 91%, p less than 0.05) than the double-contrast barium meal. Both procedures significantly affected the clinical outcome of the patient, the effect of endoscopy being significantly greater than that of the double-contrast barium meal. Although errors with the barium study related predominantly to an inability to show subtle lesions, poor patient cooperation and perceptual and technical failures were additional significant factors. Endoscopy is recommended for certain groups of patients.

Helicobacter pylori infection in pernicious anemia: A prospective controlled study

Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process.

Variability of migrating motor complex in humans

Fasting gastrointestinal motility in the human is characterized by the regular cycling activity of the migrating motor complex (MMC). Our purpose was to define the variability of the MMC within and between a group of six healthy subjects studied for 6–9 hr over six separate days with a perfused catheter system. A total of 88 phase III events was observed during 255 hr of recording in this group. The mean MMC cycling time varied significantly between subjects (range 113–230 min,P<0.001), and variation within subjects also was wide (sd range 58–70 min). Seventy-one percent of phase III events commenced in the gastric antrum, 18% in the proximal duodenum, 10% in the distal duodenum, and 1% in the proximal jejunum. For each subject, the velocity of propagation of phase III decreased significantly (P<0.001), and phase III duration increased significantly (P<0.001), with increasing distance from the os. In the antrum, phase I was predominant, and significant (P<0.006) variation between subjects was noted for percentage of MMC cycle occupied by phase I (overall mean ±sd 55±23%). Phase II was predominant in both duodenum and jejunum (mean range 70–80%), and no significant variation was noted between subjects for percentage of MMC occupied by phase II. We conclude that human MMC activity varies widely between individuals and within the same individual when studied on separate days.

Abnormalities of the Migrating Motor Complex in Diabetics with Autonomic Neuropathy and Diarrhea

Diarrhea is a common symptom in long-standing diabetes. The pathogenesis of this diarrhea remains obscure, although it appears to be related to the development of autonomic neuropathy, which may cause several abnormalities including altered gut motility. We studied fasting gastrointestinal motility for a mean of 210 min in a group of 12 type-II diabetics with diarrhea. All patients had peripheral neuropathy and symptoms of autonomic neuropathy. Their motor activity was compared with that of a group of six normal volunteers. In addition, gastrointestinal transit time was assessed by the hydrogen breath test. The presence of bacterial overgrowth was assessed by the hydrogen breath test and culture of jejunal secretions. The diabetics showed grossly disordered motor activity. There was a complete absence of phase-III activity in two patients. Most phase IIIs commenced in the distal duodenum or jejunum. The phase-III component was often of short duration at each recording site. There was increased velocity of propagation between sites. Continuous phase-II activity was noted in some patients. Antral activity was absent or reduced during phase II. Gastrointestinal transit time was significantly prolonged in the diabetics. Bacterial overgrowth was demonstrated in three diabetic subjects. These motility abnormalities are nonspecific and are unlikely to play a major role in the pathogenesis of diabetic diarrhea.

Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia

Nonulcer dyspepsia is a common clinical syndrome whose etiology is unknown. The sensitivity of the gastric mucosa to acid and duodenal contents in 18 patients with nonulcer dyspepsia was studied. The patients had a normal upper gastrointestinal endoscopy and biopsy specimens were obtained for determination of Helicobacter pylori status. Fifteen of the 18 patients were infected with H. pylori. All patients underwent intubation with double-lumen tube and collection of cholecystokinin-stimulated pancretico-biliary secretions. Subsequently, normal saline, 0.1N hydrochloric acid, and autologous duodenal secretions were infused into the stomach in a randomized blinded fashion. A positive response was defined as the production of epigastric pain by acid and/or bile but not by saline. By this definition, only 6 patients (33%) had a positive response and none had reproduction of their usual symptoms. In patients with a negative response, only 4 remained asymptomatic during all infusions. The remaining 8 had symptoms during infusion of saline, 7 of whom also had symptoms during infusion of acid and/or duodenal secretions. Two of these patients had reproduction of their usual symptoms. In conclusion, the gastric mucosa in patients with nonulcer dyspepsia is not abnormally sensitive to acid or duodenal contents.

Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy

Exocrine pancreatic insufficiency has been observed in some diabetics with peripheral neuropathy and diarrhea. Several mechanisms may be responsible for this insufficiency: (1) pancreatic atrophy, (2) disruption of the cholinergic enteropancreatic reflexes, or (3) elevated serum levels of peptides such as glucagon and pancreatic polypeptide which are known to inhibit pancreatic exocrine secretion. To clarify the mechanism(s) involved in this exocrine pancreatic impairment, we studied 10 diabetics with diarrhea and peripheral neuropathy. Their results were compared to those of eight normal volunteers. Each subject underwent a standardized pancreatic function study which assessed nonstimulated secretion, the response to intrajejunal infusion of a mixture of amino acids, and the output following intravenous administration of secretin and cholecystokinin (CCK). In separate studies, the effect of a background infusion of bethanechol and secretin on the pancreatic response to CCK was assessed in six patients and six normal controls. Compared to normals, all diabetics exhibited a significant reduction in both enzyme and bicarbonate secretion to all stimuli. This reduction was not corrected by administering bethanechol. Plasma glucagon and pancreatic polypeptide levels in diabetics were not significantly higher than those in controls. We conclude that diabetics with diarrhea and peripheral neuropathy exhibit impairment of their exocrine pancreatic secretion and possible mechanisms for this are discussed.

Variations in Gastric and Duodenal Motility During Gastric Emptying of Liquid Meals in Humans

The gastric emptying of liquids is determined by the pressure gradient between the stomach and the duodenum. This study monitored intragastric and intraduodenal pressures of 7 healthy volunteers during the gastric emptying of an acid meal (pH 2) and an oleate meal (50 mM) in comparison with the gastric emptying of a 154 mM saline meal (pH 7) in order to elucidate the mechanisms of delayed gastric emptying seen with the acid and the fatty meals. Antroduodenal motility was measured by means of a continuously perfused catheter system, and fundic pressure was monitored by means of a water-filled balloon. Gastric emptying was measured with the double sampling dye dilution technique. As expected, the gastric emptying of the pH 7 meal (t 1/2 = 2.2 +/- 0.7 min) was significantly faster than that of the acid (t 1/2 = 11 +/- 2.1 min) and the oleate (t 1/2 = 18 +/- 2 min) meals. The rapid gastric emptying of the neutral meal was consistently associated with a significant increase in tonic fundic pressure (p less than 0.05), a feature never seen with the acid and the oleate meals. There was no change in duodenal motility with the gastric emptying of the neutral meal, whereas duodenal activity did tend to increase with the acid and oleate meals. Thus the proximal stomach appears to be the main determinant of variations in the gastric emptying of liquids, whereas the duodenum appears to have a less prominent role.

Role of fasting gastrointestinal motility in the variability of gastrointestinal transit time assessed by hydrogen breath test.

Gastrointestinal motility and transit time, measured by the hydrogen breath test, were simultaneously assessed in six healthy volunteers. Each subject underwent six studies on separate days. On each day motility was measured in the gastric antrum, duodenum, and proximal jejunum and 15 g of lactulose was given either by mouth during gastric phases I, II, III of the motor migrating complex or infused duodenally during duodenal phases I, II, III, one phase being studied each day in random order. Fasting activity was not interrupted by the lactulose. The lactulose transit time decreased significantly from a peak with phase I through phase II to a minimum with phase III (mean (SD) 155 (26) min v 120 (10) min v 94 (14) min, p less than 0.001). Similar results were noted when the lactulose was instilled intraduodenally (156 (23) min v 125 (19) min v 100 (17) min, p less than 0.001). No correlation was found between motility index and transit. These results suggest that different phases of fasting gastrointestinal motility are major determinants of the transit time estimated by the hydrogen breath test and explain the variability of this test in practice.