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 less than 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.

Enhancement of gastric mucosal blood flow with sulglycotide.

Twelve patients with dyspepsia whose gastric abnormalities ranged from diffuse reddening of the mucosa to multiple erosions were treated for 4 weeks with oral sulglycotide, a sulphated glycopeptide with known gastroprotective and ulcer-healing properties. Before and after treatment, gastric mucosal blood flow was assessed by means of laser Doppler flowmetry. A significant (P < 0.01) increase in mucosal perfusion was observed after sulglycotide treatment, suggesting that enhancement of mucosal blood flow may contribute to the therapeutic properties of the drug.

Gastric effects of a prostaglandin E1-derivate (rioprostil) on acid, alkaline, and mucus secretion.

In a double-blind crossover study, the gastric effects of a single oral dose of rioprostil (150 and 300 micrograms) or placebo were compared in basal conditions and during a 120-minute pentagastrin infusion. A slight decrease in basal acid output and a nonsignificant rise in basal bicarbonate secretion were observed with the 300-micrograms dose. Pentagastrin-stimulated acid secretion was reduced by the prostaglandin derivate, especially with the 300-micrograms dose. Compared with placebo, 300 micrograms of rioprostil significantly stimulated basal mucoprotein secretion and bicarbonate and mucus output during pentagastrin infusion. The results suggest that 300 micrograms of rioprostil exerts both a moderate antisecretory activity and a strengthening effect on the gastric mucus-bicarbonate barrier.

Effect of carbenoxolone and cimetidine on gastric mucin.

To determine whether the addition of carbenoxolone to a cimetidine regimen would prevent mucus deficiency in patients with duodenal ulcer, we compared the effect of combined therapy with the effects of treatment with cimetidine alone and carbenoxolone alone. Carbenoxolone proved to be ineffective on gastric mucus induced by cimetidine, the behavior of gastric mucin fractions being similar to that observed in patients treated with cimetidine alone. When used alone, however, carbenoxolone demonstrated mucus-stimulating action.

Accuracy of the plasma amino acid-consumption test in detecting pancreatic diseases is due to different methods.

The aim of this study was to evaluate the controversial specificity of the plasma amino acid (AA)-consumption test in detecting pancreatic diseases by using two different quantitative methods. A total of 55 subjects: 13 healthy subjects, 13 patients with chronic pancreatitis (three mild/moderate, eight severe), 13 patients with pancreatectomy and complete suppression of the exocrine pancreatic secretion, eight patients with chronic liver disease (five with impaired synthetic function), and eight patients with chronic renal failure. Total plasma AAs were quantified by a colorimetric method (p-benzoquinone) in all subjects, at 0, 30, 45, and 60 min during and 30 min after minute 60 of i.v. cerulein infusion (50 ng/kg/h). Either total and individual AAs were quantified by chromatography (high-performance liquid chromatography; HPLC) in 10 healthy subjects, 10 patients with pancreatectomy, and 10 with chronic pancreatitis at 0 and 60 min after the start of the cerulein infusion. For the colorimetric method, healthy subjects had maximal percentage decreases of total AA concentrations not significantly different from those of patients with pancreatectomy and significantly higher than those of patients with chronic pancreatitis (p < 0.0001) or chronic liver disease (p < 0.001). Pancreatic function, as assessed by fecal elastase-1 test, was not significantly correlated to the maximal percentage decrease in total plasma AAs. For the chromatographic method, total AA concentrations were not significantly correlated to those determined by colorimetry. The concentration of each of the individual plasma AAs varied considerably in each group. Fecal elastase-1 values were normal (> or = 200 microg/g) in all patients without pancreatic disease and in only one of 11 patients with chronic pancreatitis and exocrine insufficiency. The type of method used can explain the different results of the AA-consumption test. This test is not very specific for the pancreas.

Pilot trial of nicotine patches as an alternative to corticosteroids in ulcerative colitis.

In ten patients with mild to moderate clinical relapses of ulcerative colitis during treatment with mesalazine (1 g t.i.d.) and with a previous history of poorly tolerated steroid courses, transdermal nicotine (15 mg daily) was added for 4 weeks. Clinical findings were assessed by employing Rachmilewitz's activity index. In 7 of the patients, clinical remission was achieved, the results persisting for up to 3 months after nicotine withdrawal. Endoscopic and histological examination, when performed, confirmed the clinical findings. Nicotine patches may represent a good alternative to steroids in selected patients with mild to moderate relapses of ulcerative colitis. The precise mechanism of action remains unknown.

Colloid bismuth versus famotidine in the treatment and prevention of duodenal ulcer relapse: results of a double-blind, double dummy randomized study.

Fifty-three consecutive patients with active duodenal ulcer (DU) were randomly included in a double-blind, double-dummy study to test the healing and relapsing rate of two treatment regimens: famotidine 40 mg nocte for 4-8 weeks, followed by 20 mg for 12 months after healing of the ulcer and colloidal bismuth (CBS) (240 mg bid) for 4-8 weeks, followed by placebo maintenance treatment. The results of the short term period confirmed the efficacy of CBS in healing DU (24/25 in CBS group and 19/23 in famotidine group). However, the relapse rate in the CBS-treated group was higher (77.8% at 12 months) than in the famotidine group (35.7%) (p = 0.041). Only 7 patients (41.2%) were cleared from Helicobacter pylori (HP) after CBS treatment. In conclusion, the high relapse rate observed in CBS treated patients may be related to the high percentage of patients with HP infection in the tested group and support the hypothesis that lack of efficacy of CBS in preventing DU recurrence is related to its poor eradication of HP.

Outcome of ulcerative colitis after treatment with transdermal nicotine.

OBJECTIVE: Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects. DESIGN: A randomized, comparative study. PATIENTS AND METHODS: Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopic signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment. RESULTS: Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group. CONCLUSION: Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids.

Gastric microcirculation and bicarbonate production in heavy smokers.

OBJECTIVE: To determine the effect of chronic cigarette smoking on gastric mucosal blood flow and bicarbonate secretion. METHODS: Three groups, each consisting of eight dyspeptic patients with normal endoscopic features, were studied: group A contained non-smokers, group B light smokers (< 10 cigarettes/day) and group C heavy smokers (> 10 cigarettes/day). Blood flow was measured in the gastric antrum by laser-Doppler flowmetry, and basal bicarbonate secretion was determined in fasting gastric juice by the method of Feldman. RESULTS: Both mucosal blood flow and bicarbonate secretion were significantly reduced (P < 0.01) in group C. CONCLUSION: In heavy smokers, gastric mucosal perfusion and alkali production are impaired. This can contribute to the noxious effects of smoking on the gastric mucosa. It remains to be determined whether these effects of smoking are causally related.

Selection criteria for pre-operative endoscopic retrograde cholangiography and endoscopic-laparoscopic treatment of biliary stones.

OBJECTIVE: Pre-operative endoscopic retrograde cholangiography (ERCP) prior to laparoscopic cholecystectomy (LC) is the most common treatment of gallbladder and common bile duct (CBD) stones. In this study we evaluate our selection criteria for pre-operative ERCP and the results of endoscopic-laparoscopic treatment in patients with CBD stones. DESIGN: Consecutive adult patients admitted to the department of surgery because of symptomatic cholelithiasis were included in a prospective open trial. PARTICIPANTS: Between January 1996 and December 1996, 841 patients underwent LC at our hospital. ERCP pre-LC was performed in 95 of the 841 patients, on the basis of our selection criteria. INTERVENTIONS: The indication to perform ERCP was suggested by a dilatated CBD (> 10 mm) or ductal stones, abnormal serum liver tests, persisting for more than 3 days, jaundice, cholangitis or pancreatitis. Twelve months after surgery, all patients were contacted by telephone to exclude symptoms related to residual stones. RESULTS: Cannulation of the CBD was successful in 94 of 95 patients submitted to pre-LC ERCP. CBD stones were found in 87 patients (95.6%) in 22 of whom (25.2%) they were in the form of small stones or sludge. In only three of 94 patients (3.2%) no alterations of the CBD or papilla were found. Complications occurred in eight of 98 patients (in five after endoscopic sphincterotomy (ES), and in three after LC). CONCLUSIONS: Pre-operative ES in selected patients with coexisting gallbladder and CBD stones has been a good approach and the criteria that we used for selection of patients to be submitted to pre-operative ERCP/ES seem to be effective.

Effect of sulglycotide on gastric bicarbonate secretion in humans.

The effect of sulglycotide, a cytoprotective agent with a healing effect on ulcers, on gastric bicarbonate secretion in humans was evaluated. Fifteen healthy volunteers were treated with sulglycotide 400 mg t.i.d. for 10 days. Before and after treatment the bicarbonate content of basal gastric juice was determined by Feldman and Barnett's method. Sulglycotide was found to increase significantly (p less than 0.0001) basal HCO3- production from the human stomach, thus strengthening the gastric mucosal defences. It was concluded that the cytoprotective and therapeutic properties of the drug are partially related to stimulation of gastric alkaline secretion.

Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel disease.

BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors in inflammatory bowel disease, particularly Crohn's disease. The aim of our study was to assess rectal blood flow in patients with active inflammatory bowel disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood flow was performed by laser Doppler flowmetry in 45 subjects divided into three groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS: Rectal perfusion was found to be significantly impaired in patients with ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our results confirm the role of local ischemia in ulcerative colitis, but do not support the theory that vascular factors play a key role in the pathogenesis of Crohn's disease.

Precancerous gastric lesions and Helicobacter pylori.

BACKGROUND/AIMS: Previous publications in the literature have reported an association between incidence of Helicobacter pylori (HP) infection and gastric cancer. The role of HP in precancerous gastric lesions or in their evolution towards neoplastic disease is not so clear. MATERIALS AND METHODS: We studied 174 patients with atrophic gastritis. RESULTS: Intestinal metaplasia (IM) was detected in 165 subjects of the patients and different grades of dysplasia were observed in 32 subjects. HP was found in 75 (52.8%) of 165 subjects with IM, in 7 (34.7%) with both IM and dysplasia and in 3 with dysplasia alone. There was no significant difference in the prevalence of HP infection in the three IM types, type I (47.7%), type II (54.7%) and type III (48.4%) (p = n.s.). In contrast, the prevalence of HP positive patients was significantly lower in dysplasia (10/32 vs 22/32; p < 0.005). At the same time, the frequency of HP was significantly lower for subjects with IM and dysplasia than for those with type I IM (41/83 vs 7/32; p = 0.01). CONCLUSIONS: At present, in our experience, HP infection is rather infrequent in type III IM and it is found less often in cases of dysplasia. We have taken these results to suggest that the modified gastric mucosa becomes inhospitable for HP and, consequently, that other factor are probably responsible for promoting gastric carcinogenesis.

Comparison of ranitidine, domperidone maleate and ranitidine + domperidone maleate in the short-term treatment of reflux oesophagitis.

In the treatment of reflux oesophagitis, either drugs preventing regurgitation of gastric juice in the lower oesophagus or pharmacological agents increasing the pH of the refluxing material are employed. In the present study 45 outpatients with reflux oesophagitis were randomly treated with either ranitidine (150 mg b.i.d.) or domperidone maleate (20 mg t.i.d.) or both drugs for six weeks. Before and after treatment the severity of dyspeptic symptoms and the grade of endoscopic and histological changes were assessed. The three therapeutic regimens were significantly and equally effective in inducing symptomatic relief and promoting endoscopic and histological disappearance or improvement of oesophagitis. The combined use of ranitidine and domperidone maleate failed to show any additional benefit compared with treatment with either drug alone.

Weakening effect of famotidine but not of nizatidine on the mucus-bicarbonate barrier of the human stomach.

Twenty outpatients with various duodenal disorders but endoscopically normal gastric mucosa were randomly treated for 4 weeks with either nizatidine (300 mg h.s.) or famotidine (40 mg h.s.). Before and after treatment quantitative and qualitative evaluations of gastric mucus secretion as well as measurement of gastric bicarbonate output were performed. No changes in the mucus-bicarbonate barrier were observed after nizatidine treatment. In contrast, famotidine was found to impair the quality of mucus, thus weakening the mucosal defences against re-ulceration after treatment withdrawal.

Ranitidine vs metoclopramide in the medical treatment of reflux esophagitis.

45 patients with symptomatic reflux esophagitis were randomly treated with either Ranitidine (150 mg b.i.d.) or Metoclopramide (10 mg t.i.d.) for six weeks. The severity of dyspeptic symptoms and the grade of endoscopic and histological esophagitis were assessed before and after treatment. Both drugs proved significantly effective in inducing symptomatic and endoscopic improvement, but Ranitidine appeared significantly superior in promoting disappearance or improvement of endoscopic esophagitis. Moreover Ranitidine was found to significantly reduce the severity of histological changes, whereas Metoclopramide was unable to do so.

Omeprazole-induced changes in gastric mucus secretion.

The influence of omeprazole treatment on gastric mucus secretion in man was examined in two separate studies. 24 outpatients with endoscopic duodenitis but normal gastric mucosa were treated under double-blind conditions with either omeprazole 20 mg o.m. or placebo for four weeks. Omeprazole was found to induce a significant reduction (p less than 0.001) in the amount of neutral and total mucoproteins into the gastric juice and in the viscous and protective properties of mucus as assessed by a Mucoprotective Index. In a subsequent study 12 omeprazole-treated patients were re-examined either 10 days (6 patients) or 15 days (6 patients) after the drug withdrawal. A trend towards normalization of mucus secretion was detectable already after 10 days, but only at 15 days did gastric mucus fully revert to normal. The results suggest that the decrease in the quantity and quality of mucus secretion observed with omeprazole is a transient phenomenon, secondary to the sustained acid suppression induced by the drug and clinically irrelevant.

Effect of a gel formulation of sucralfate on gastric microcirculation.

Dyspeptic patients (n = 12) with endoscopic signs of chronic gastritis were treated orally for 28 days with a new gel formulation of sucralfate at a dose of 1 g twice daily. Before and after treatment, gastric blood flow was assessed during endoscopy by means of laser Doppler flowmetry. The sucralfate gel promoted a significant increase (P < 0.001) in blood perfusion in all patients, restoring normal levels of gastric microcirculation. The results are consistent with observations in animals, suggesting that the mechanisms responsible for the gastroprotective and therapeutic properties of sucralfate include enhancement of mucosal blood flow.

[Effects of the administration of magnesium hydroxide on gastric acidity in health volunteers]. / Effetto della somministrazione di idrossido in magnesio sulla acidità gastrica in volontari sani.

Antacids are often the first therapeutic approach in patients with pyrosis. We carried-out a study on 8 healthy volunteers who underwent a 24 hour gastric pH-metry to assess the real efficacy of magnesium hydroxide administration on gastric acidity. Magnesium hydroxide was alternatively administered at different dosages (400 mg or 800 mg) in the population studied. Our results showed a mild and non reproducible response to lower dose, but, on the contrary, the 800 mg dose always induced an immediate, effective and prolonged antacid action, reaching a maximum pH value of 5 and lasting up to 40 minutes. Our study confirms, using a modern and reliable technique as the 24-hour gastric pH-metry, the antacid activity of magnesium hydroxide.

[Preliminary results of treatment with Tagamet (cimetidine SK and F) in gastric and duodenal ulcers]. / Primi risultati del trattamento con Tagamet (cimetidina SK & F) nelle ulcere gastriche e duodenali.

Following 3x200 mg Tagament (cymetidine SK & F) tablets at meals and 2 in the evening (5 per day) for an average of 31 days, complete endoscopic cure was obtained after 29 days (duodenal patients) and 35 days (gastric patients) in 26/27 subjects with slow healing histories (17 with duodenal and 10 with gastric ulcer). Rapid regression of pain and dyspepsia was observed form the outset and there was a marked reduction in the consumption of antacid preparation. Its marked efficacy and good tolerance make Tagamet a drug of choice in the treatment of peptic, duodenal and gastric ulcers.