M. Guslandi

Gastric Mucosal Defences in the Elderly

Background: Elderly subjects are more prone to develop gastric injury, but human data on the state of mucosal protective mechanisms are scarce. The aim of the study was to assess gastric mucus and bicarbonate secretion as well as local microcirculation in elderly patients. Methods: Fasting gastric juice was collected in 45 elderly patients and in 45 control subjects devoid of endoscopic gastric abnormalities. Total mucoproteins, ‘mucoprotective index’ (as qualitative expression of mucus secretion) and gastric bicarbonate (Feldman’s method) were measured. In addition in 24 elderly patients, and in a matching group of younger subjects, gastric mucosal blood flow was measured by laser Doppler flowmetry. Results: Mucus and bicarbonate production was significantly reduced (p < 0.01) in elderly patients, the quality of mucus secretion being unaltered. Gastric mucosal perfusion was also significantly decreased (p < 0.01) in aged subjects. Conclusion: In the elderly gastric mucosal defences are impaired. This is in keeping with a reduced gastric prostaglandin biosynthesis and may account for the higher susceptibility of the mucosa to damaging agents. The possible role of atrophic gastritis and Helicobacter pylori infection as independent confounding factors remains to be determined.

Effects of cimetropium bromide on gastrointestinal transit time in patients with irritable bowel syndrome

Cimetropium bromide is a new antimuscarinic compound with strong antispasmodic activity. The aim of this study was to evaluate the effects of oral cimetropium bromide on total gut transit time in patients with irritable bowel syndrome. Forty patients, divided according to their initial total gastrointestinal transit times and presenting symptoms, were treated with cimetropium bromide 50 mg t.d.s. or placebo for 1 month according to a double‐blind, parallel group design. Before and after treatment all subjects ingested 24 radio‐opaque markers. The total intestinal transit time was determined by evaluating the rate of disappearance of markers from plain X‐ray films of the abdomen taken every 24 h for 4 days. Pain and bowel habits were also monitored. Seven patients did not complete the study. Cimetropium bromide significantly (P < 0.01) shortened the whole gut transit time in patients with prolonged transit time (80.8 ± 4.0 h before vs 60.8 ± 6.7 h after treatment) and improved the global clinical condition significantly compared with placebo (P= 0.029). In patients with a short total intestinal transit time, cimetropium bromide had no effect on whole gut transit time and did not significantly improve symptoms. The results of this study indicate that oral cimetropium bromide is effective both objectively and subjectively in a subgroup of irritable bowel syndrome patients with constipation.

Gastric cancer in chronic atrophic gastritis: Associated gastric ulcer adds no further risk

Atrophic gastritis with intestinal metaplasia is generally considered a precancerous lesion. We followed 261 patients with chronic atrophic gastritis and intestinal metaplasia, with and without gastric ulcer, every 12 months for 9 +/- 2 years by means of endoscopic and histological examination. In the presence of dysplasia, however, studies were carried out every 6 months in moderate cases, or every 3 months in severe cases. Patients with gastric ulcer received medical therapy for 8 weeks; if healing did not occur, treatment was continued. Only subjects with healed ulcers were admitted to the follow-up. To date, 205 subjects have been included in the study. Over a 10-year period, 16 patients with recurrent gastric ulcer and 12 patients with cancer in situ or in an early stage, were subjected to surgery. One case of advanced cancer was observed. Cancer has been found in five of 95 cases of atrophic gastritis with gastric ulcer (5.2%), and in 7 of 166 cases of atrophic gastritis without gastric ulcer (4.2%). The difference was not statistically significant. Our results confirm that gastric ulcer per se is not a high-risk condition, but it must be considered as an epiphenomenon on a background of epithelial atrophy.

Duodenogastric Reflux: Correlations among Bile Acid Pattern, Mucus Secretion, and Mucosal Damage

Forty-five patients with bile reflux at endoscopic examination, confirmed by titration of bile acids in gastric juice, were admitted to the study and divided into three groups in accordance with histologic results: normal findings, chronic superficial gastritis, and chronic atrophic gastritis. Bile acid pattern was determined in duodenal samples by high-performance liquid chromatography titration, and the mucoprotein content of gastric juice was assessed. The results of qualitative analysis of bile acid showed an increase of deoxycholic acid in patients with atrophic gastritis (p less than 0.05) in comparison with controls; determination of taurine and glycine conjugates showed an increase of taurodeoxycholic acid in patients with atrophic gastritis (p less than 0.01) compared with controls. The composition of mucus was altered only in patients with atrophic gastritis. Whether the increase in deoxycholic acid in biliary reflux is a factor in the development of chronic atrophic gastritis or is secondary to the increase of gastric pH, detectable in this condition, is still uncertain. However, the increase of deoxycholic acid and its taurine conjugates may be a factor that leads to persistence of mucosal lesions.

Manometric evaluation of the interdigestive antroduodenal motility in subjects with fasting bile reflux, with and without antral gastritis.

The interdigestive antroduodenal motor activity was studied in 15 patients with bile reflux without gastritis (group A), 17 with bile reflux and chronic antral superficial gastritis (group B) and in nine healthy controls (group C), by manometric recording of phases of the interdigestive motility complex (IDMC) over 240 minutes, or until two consecutive migrating motor complexes (MMCs) had been recorded, whichever the shorter. In the patients with bile reflux the occurrence of MMCs was decreased and median duration of the IDMC was significantly prolonged (group A = 162.5 min; group B = 185.0 min), compared with controls (group C = 92.0 min; p less than 0.01 v groups A and B). There were no differences in motility pattern between patients with and without gastritis, suggesting that motor abnormalities are not caused by gastritis, but may precede its occurrence. Delayed occurrence of motor activity fronts increases duodenogastric reflux, but correlation with gastric mucosal lesions was not shown, suggesting that other mechanisms are involved.

Treatment of Chronic Liver Disease with Ursodeoxycholic Acid

Evidence is accumulating that ursodeoxycholic acid (UDCA), an agent widely employed for gallstone dissolution, exerts therapeutic effects in chronic liver disease. UDCA is thought to act mainly by reducing the detergent properties of bile, making it less toxic for the liver cells. Confirming the results of preliminary observations double-blind, placebo-controlled trials have shown that UDCA significantly decreased serum concentrations of liver enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transferase in primary biliary cirrhosis and other cholestatic conditions, as well as in chronic active hepatitis. A substantial improvement in liver histology has also been detected in UDCA-treated patients with primary biliary cirrhosis. The effect of UDCA in chronic hepatitis is currently a matter of investigation.

Mucosal blood flow in erosive duodenitis

Erosive duodenitis is a clinical entity whose pathogenesis is still obscure. Acid secretion is mostly normal, while the possible role of vascular factors has been suggested. We measured mucosal blood flow by means of laser Doppler velocimetry during endoscopy in the duodenal bulb of 10 subjects with erosive duodenitis, 10 duodenal ulcer patients, and 10 healthy controls. Duodenal blood flow in erosive duodenitis was significantly reduced (p < 0.001) compared with controls, whereas no changes were detected in duodenal ulcer. Reassessment of mucosal blood flow after a 6-week treatment with ranitidine failed to show any increase in the perfusion values even in patients with endoscopic healing. Our results suggest that impaired mucosal blood flow is a primary factor in the pathogenesis of chronic duodenal erosions.

Interdigestive Motility Pattern in Subjects with Duodenogastric Bile Reflux

The role of antroduodenal motility in the pathogenesis of duodenogastric biliary reflux is widely accepted, but few and conflicting data are available on the possible motor abnormalities related to this phenomenon in the fed and in the fasting state. In an attempt to define the motility pattern of the antroduodenal region associated with bile reflux in the fasting state, 20 subjects with proven duodenogastric reflux and without disorders of the upper gastrointestinal tract have been studied, and the results have been compared with those observed in 6 control subjects without evidence of reflux. The interdigestive motility complex (IDMC) has been evaluated (mean duration of IDMC and frequency and site of onset of migrating motor complexes). In subjects with duodenogastric reflux a significant increase (p less than 0.01) in the mean duration of IDMCs (179 +/- 22.19 min) was observed, in comparison with controls (108.5 +/- 37 min). A considerable reduction in the frequency of migrating motor complexes (MMC) was also observed, while no differences in the site of onset and the propagation of MMCs and in the percentage of time recorded occupied by the single phases of IDMC were found. This evidence suggests a strict relationship between duodenogastric reflux and the occurrence of phase III of IDMC and supports the hypothesis that the IDMC abnormalities are the cause and not the consequence of biliary reflux. The reduced incidence of MMC may also account for the high incidence of chronic gastritis due to prolonged contact in the fasting state between the gastric mucosa and the duodenal content.

The clinical use of levosulpiride

Several clinical trials of levosulpiride (the levo-rotatory enantiomer of sulpiride) are reviewed in order to assess the effectiveness and tolerability of this agent in various conditions. Overall symptoms in patients with reflux esophagitis were improved by levosulpiride, which increases lower esophageal sphincter pressure more rapidly and effectively than other therapeutic agents. In dyspeptic patients, levosulpiride was found to increase interdigestive migrating motor complexes in the gastric antrum, promoting propagation of motor waves from the stomach into the duodenum. This resulted in symptom relief in significantly more levosulpiride-treated patients than those receiving either domperidone or metoclopramide. Gallbladder and gastric emptying time as well as intestinal transit time were shortened. The antiemetic properties of levosulpiride have been investigated in several clinical situations, in particular in postoperative vomiting and vomiting during cancer chemotherapy. In both cases this agent proved to be effective and well-tolerated.

Brief communication: smoking and duodenal blood flow.

Smoking promotes an increase in both the incidence and the recurrence of duodenal ulcers, but the mechanisms responsible for its adverse effects on the duodenal mucosa are still poorly understood. The aim of the present study was to investigate the effect of chronic cigarette smoking on duodenal blood flow. In 20 dyspeptic patients (10 non‐smokers and 10 smokers) with endoscopically normal duodenum, mucosal blood flow was measured in the duodenal bulb by laser Doppler flowmetry during endoscopy. Basal bulbar perfusion was found to be significantly lower (P < 0.05) in smokers. Our results suggest that duodenal blood flow is reduced in heavy smokers. This may promote duodenal damage because of both local ischaemia and the reduced secretion of protective bicarbonate.