Effects of chronic therapy with non-steroideal antinflammatory drugs on gastric permeability of sucrose： A study on 71 patients with rheumatoid arthritis

AIM: To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs- induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS: Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and B (group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs). Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS: The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks (P = 0.000). A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION: Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs- induced gastric damage in both acute and chronic therapy. This technique helps to identify patients with clinically silent gastric damages. Pantoprazole (40 mg daily) is effective and well tolerated in chronic NSAID users.     

Gastroduodenal and intestinal permeability in primary biliary cirrhosis

OBJECTIVES: To evaluate gastrointestinal permeability in primary biliary cirrhosis (PBC), using a sensitive method to detect epithelial damage, and to correlate it with the Mayo score, histological stage, ascites, spontaneous bacterial peritonitis, endoscopic signs of portal hypertension and Helicobacter pylori infection. METHODS: Fifty consecutive patients with PBC and 39 patients with cirrhosis of other aetiologies (non-PBC) were enrolled in the study. Coeliac disease was initially ruled out in all participants. Permeability was assessed using sucrose (gastro-duodenum) and lactulose-mannitol (intestine). RESULTS: Sucrose excretion was above the limit in both PBC and non-PBC patients. Twenty-two per cent of PBC patients had an increased result for the lactulose-mannitol test compared to 12.8% of non-PBC cirrhotic patients. PBC patients had high sucrose excretion levels irrespective of the presence of any oesophageal varices, which significantly increased the gastroduodenal permeability in non-PBC patients only when associated with hypertensive gastropathy. Sucrose excretion was significantly enhanced by hypertensive gastropathy in non-PBC patients (P < 0.001) but not in PBC patients. No significant correlation was found in either group between gastrointestinal permeability and the other parameters. CONCLUSIONS: Gastrointestinal permeability is increased in PBC. Portal hypertension contributes to altered gastric mucosal permeability in non-PBC cirrhosis, whereas different epithelial dysfunction can be hypothesized in PBC.     

Effect of acute cigarette smoking, alone or with alcohol, on gastric barrier function in healthy volunteers

BACKGROUND: Smoking is a risk factor for gastroduodenal ulcer and gastric adenocarcinoma. However, the pathophysiological mechanisms induced by acute cigarette smoking in the human gastric mucosa are poorly understood. AIM: To evaluate the effect of acute cigarette smoking, alone or with alcohol, on the gastric permeability to sucrose, a specific marker of mucosal damage in the stomach. SUBJECTS AND METHODS: Twenty healthy volunteers (8 smokers/12 non-smokers) were studied. Each fasted subject ingested 500 ml of a 20% sucrose solution and the amount of sucrose excreted in a 5-hour urine collection was measured by gas chromatography Four sucrose permeability tests were carried out: 1. basal, 2. while smoking 5 cigarettes, 3. after drinking 50 ml of a 40 degrees alcoholic beverage, 4. a combination of 2+3. RESULTS: Sucrose excretion increased after alcohol ingestion (40.5 +/- 6.0 mg vs 143.1 +/- 28.9 mg, p = 0.002), but was not modified by acute cigarette smoking (34.4 +/- 5.9 mg). When alcohol and cigarettes were simultaneously consumed, the increase in alcohol-induced sucrose excretion was significantly reduced (73.1 +/- 16.6 mg, p = 0.03). Basal sucrose excretion was similar in smokers and non-smokers. However, in acute cigarette smoking, a decrease in sucrose excretion was observed in smokers (p = 0.02) but not in non-smokers. CONCLUSIONS: These results indicate that acute cigarette smoking may tighten the gastric mucosa in habitual smokers and this is associated with a smaller increase of gastric permeability induced by alcohol.     

Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation

BACKGROUND: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. METHODS: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. RESULTS: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%; p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%; p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. CONCLUSION: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis.     

Effect of stomach motility on measuring stomach permeability with saccharose in vivo]

Determination of the urinary excretion of sucrose after an oral dose has been used as a noninvasive test to measure gastric permeability in several clinical studies. Regarding different contact times of sucrose solution within the gastric mucosa, the present study investigates a possible influence of the gastric emptying rate on the sucrose permeability test. Urinary sucrose excretion and the gastric emptying rate of liquids using 13C-acetate breath test were determined in twelve healthy volunteers. Furthermore, in seven volunteers gastric emptying was accelerated by intravenous erythromycin and prolongated by oral anticholinergic propantheline in nine healthy controls. Breath samples were measured using infrared spectroscopy. The half-emptying time and Lag-phase were correlated with the urinary sucrose excretion. Erythromycin caused a significant (p = 0.02) reduction of the half-emptying time (median 35.0 min) compared with untreated controls (median 59.9 min), whereas propantheline significantly increased the half-emptying time (median 69.4 min, p = 0.01). After pharmacological increase of the half-emptying time the urinary sucrose excretion only slightly differs from the sucrose excretion of controls (median [range] 0.057 [0.034-0.106]% versus 0.031 [0.017-0.162]%), but there was an increase of urinary sucrose excretion in probands following reduction of the half-emptying time with erythromycin (0.077 [0.023-0.221]%. The present study shows that gastric motility has a possible influence on the sucrose permeability test. The sucrose permeability has to be interpreted critically concerning its clinical use especially in patients with altered gastric motility.     

Effect of H. pylori status on gastric ulcer healing in patients continuing nonsteroidal anti-inflammatory therapy and receiving treatment with lansoprazole or ranitidine

OBJECTIVES: The purpose of this research was to determine the impact of pretreatment Helicobacter pylori infection on gastric ulcer healing rates in patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs) and antisecretory medications. METHODS: This was a pooled, prospective analysis of two identical double blind, multicenter, parallel group studies. Six hundred ninety-two patients receiving NSAIDs and with endoscopy-documented gastric ulcers were enrolled from 90 North American sites in primary care and referral centers. Patients were randomized to receive ranitidine (150 mg b.i.d.) or lansoprazole (15 mg or 30 mg once daily) for 8 wk. Ulcer healing was assessed by endoscopy at 4 and 8 wk in an intent-to-treat population. H. pylori status was determined at baseline by histology. RESULTS: Across all three treatment groups, gastric ulcers were more likely to heal and heal faster if the individual was infected with H. pylori. Healing rates at 8 wk were statistically significantly greater among H. pylori positive patients (n = 181) than among negative patients (n = 497) (70% vs 61%, respectively; p < 0.05), especially among those with large ulcers (> 10 mm) and in younger patients (< 60 yr old). Simple healing rates (regardless of H. pylori status) were significantly better in the 15- and 30-mg lansoprazole groups than in the ranitidine group after 4 wk (46%, 54%, and 32%, respectively; p < or = 0.01) and 8 wk (66%, 74%, and 50%, respectively; p < 0.001). CONCLUSIONS: In patients receiving NSAIDs, gastric ulcer healing with an antisecretory agent is significantly enhanced in the presence of H. pylori infection.     

Prevalence of Helicobacter pylori in NSAID users with gastric ulcer

OBJECTIVE: Regarding the interaction of Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs), we cannot accept unanimous conclusions in inducing gastric ulcer. We therefore evaluated the role of Helicobacter pylori and NSAIDs in inducing gastric ulcer. METHODS: Dyspeptic patients receiving NSAIDs underwent endoscopic examination. Gastric ulcer formation and H. pylori status were investigated. Biopsy specimens from the antrum and lower body of the stomach were prepared for the rapid urease test and pathological evaluation. Anti-H. pylori antibody was measured by enzyme-linked immunosorbent assay. RESULTS: Two hundred and twenty-six patients receiving NSAIDs (220 chronic and six on-demand users) underwent gastrofibrescopic examination. There were 110 patients with gastric ulcer and 111 non-ulcer patients with gastritis. The remaining five patients had neither. NSAID users with gastric ulcer showed a low prevalence of H. pylori compared with those without them [55/110 (50.0%) vs 79/111 (71.2%), P < 0.01]. The same tendency was seen when patients receiving low-dose aspirin and those with rheumatoid arthritis were analysed separately [13/29 (44.8%) vs 50/62 (80.6%), P < 0.01, and 11/33 (33.3%) vs 16/26 (61.5%), P < 0.06 with Yates' correction, respectively]. CONCLUSION: Helicobacter pylori infection appeared to be a risk factor for developing gastritis, but we found no evidence that it increases gastric ulcer formation in NSAID users with dyspepsia.     

Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti-inflammatory drugs: a prospective, placebo-controlled, double-blind, parallel-group study

AIM: To evaluate the efficacy of pantoprazole in preventing gastrointestinal lesions in patients with rheumatic diseases receiving continuous, long-term treatment with non-steroidal anti-inflammatory drugs. MATERIAL: This was a prospective, randomised, double-blind, unbalanced, placebo-controlled, parallel group study. Outpatients (n= 104, age range 22-80 years, mean age 59.5) with rheumatoid arthritis or osteoarthritis, requiring chronic intake of NSAIDs (at least 8 weeks prior to the start of the study), were randomised and enrolled to receive either 40 mg pantoprazole (n=70) or placebo (n=34) once daily, for 12 weeks. Patients had endoscopically confirmed gastric and duodenal lesions grade 0, 1 or 2 (Lanza classification grade 0: normal to hyperaemic mucosa; grade 1: 1 to 3 erosions, submucosal haemorrhage or petechiae, grade 2: 4 to 10 erosions, submucosal haemorrhages or petechiae). Clinical and endoscopic evaluations were performed at baseline, after 4, and 12 weeks. The primary end-point of the study was the incidence of gastric or duodenal ulcers after 4 and 12 weeks of treatment. RESULTS: Patients (n=95) were evaluated: 65 in the pantoprazole group and 30 in the placebo group. When considering all patients (those with Lanza score grade 0, 1, 2 at baseline), the overall proportion of patients in remission was 82% and 77% after 4 weeks, and 72% and 59% after 12 weeks in pantoprazole and placebo groups, respectively (cumulative survival analysis according to Kaplan-Meier). The difference between the treatment groups was even more marked when only those patients with normal mucosa at baseline (grade 0) were considered. After 12 weeks, the proportion of patients in remission was 82% (95% confidence limits 70% - 94% in the pantoprazole and 55% (95% confidence limits 33% - 77%) in the placebo treatment group, p=O.036. Adverse events were reported in 4% and 6% of patients in pantoprazole and placebo treatment groups, respectively CONCLUSIONS: Pantoprazole 40 mg once daily was well tolerated and is more effective than placebo in the prevention of peptic ulcers in patients with rheumatic diseases who require continuous, long-term, treatment with NSAIDs.     

Gastric permeability to sucrose is increased in portal hypertensive gastropathy

BACKGROUND: Portal hypertensive gastropathy (PHG) is frequently found among patients with hepatic cirrhosis and at present the only way to detect and follow PHG is via endoscopy. OBJECTIVE: To assess gastric and intestinal permeability and investigate its relationship to endoscopic findings and indices of portal hypertension and hepatic function. DESIGN AND METHODS: Thirty-one non-diabetic patients with hepatic cirrhosis and PHG (PHG+) were studied and compared with 17 cirrhotic patients without PHG (PHG-). All patients underwent endoscopy for the assessment of PHG and Helicobacter pylori status, ultrasound determination of the diameters of spleen and portal vein, and, subsequently, an oral load of sucrose, lactulose, and mannitol. Sugar concentrations were determined in 6-h urine specimens and expressed as a percentage of the orally administered dose or as lactulose/mannitol ratio. RESULTS: The urinary sucrose excretion was significantly elevated in patients with PHG compared to those without (PHG+, 0.20% +/- 0.03; PHG-, 0.07% +/- 0.01; P< 0.001). No difference was found for the small intestinal probes lactulose and mannitol. Gastric sucrose permeability correlated positively with the endoscopic lesion score (P < 0.001), but not with other parameters of portal hypertension or hepatic function. H. pylori status did not influence gastric permeability. The sensitivity of this test reached 100% for PHG scores > 2. CONCLUSIONS: Gastric permeability to sucrose is increased in patients with PHG, independently of the presence of H. pylori. Sucrose permeability may be useful for the follow-up of patients with PHG.     

Sucrose permeability as a meas of detecting diseases of the upper digestive tract

The healthy gastric epithelium will not allow easy permeation of a disaccharide-sized molecule such as sucrose. However, during gastric damage, intact sucrose can pass the gastric epithelium and ultimately appear in the urine. We examined the relationship between total urinary sucrose excretion and various diseases. We used 149 patients (105 had upper gastrointestinal disease, 12 had gastric cancer and 32 were normal). Subjects were given a solution containing 100g sucrose in 450 c.c. water. All urine was collected for 7.5 h. The urinary sucrose concentration was determined by anion exchange high-performance liquid chromatography. Total urinary sucrose excretion was significantly higher in patients with gastric ulcer and those with gastric cancer than in endoscopically normal controls. In the 34 patients with gastric ulcer, the total sucrose excretion was closely correlated with ulcer size. Ulcer location did not affect urinary sucrose excretion. A strong correlation was also observed between sucrose excretion and lesion size in the 12 patients with gastric cancer. The sucrose permeability test may be a relatively sensitive method to detect gastric disease.     

Effects of aspirin and Helicobacter pylori on the gastroduodenal mucosal permeability to sucrose.

BACKGROUND: A non-invasive marker is needed to identify patients with significant gastrointestinal injury due to non-steroidal anti-inflammatory drugs. Gastrointestinal permeability to sucrose has been suggested as such a test. AIMS: To assess the utility of sucrose permeability as a marker of gastroduodenal mucosal injury after single and multiple doses of aspirin, to identify the site of increased sucrose permeability, to explore the relation between sucrose permeability and endoscopic findings, and to evaluate whether Helicobacter pylori infection influenced gastroduodenal sucrose permeability. METHODS: After a fasting urine was obtained, 500 ml of a solution containing 100 g of sucrose was ingested. Urine was collected for five hours and assayed for sucrose by high performance liquid chromatography. Sucrose permeability was also assessed 20 minutes after ingestion of 650 mg of aspirin and eight to 12 hours after a 72 hour course of 650 mg aspirin four times a day. The site of increased permeability was identified after pyloric occlusion with a double balloon tube. RESULTS: Thirty seven healthy volunteers participated. Sucrose permeability (mean (SEM)) increased after both single (195.2 (27) mg and multiple (196.4 (31) mg) doses of aspirin compared with baseline (53.7 (10) mg; p < 0.0005). Balloon pyloric occlusion confirmed that the site of increased sucrose permeability was the stomach. The effect of aspirin on sucrose permeability was similar in those with and without H pylori infection. CONCLUSION: These results confirm the use of sucrose permeability as a marker of aspirin induced gastroduodenal mucosal injury and identify the stomach as the major site of increased permeability. H pylori infection does not seem to change gastric mucosal sucrose permeability either at baseline or after ingestion of aspirin.     

Effects of selective COX-2 inhibitors on the gastric permeability of sucrose: a controlled study with placebo and ibuprofen

OBJECTIVE: Acute and chronic use of non-steroidal anti-inflammatory drugs can increase gastrointestinal permeability. Celecoxib, which selectively inhibits the enzyme cyclooxygenase-2, is a novel anti-inflammatory drug with minimal gastrointestinal toxic effects while retaining anti-inflammatory efficacy. Our aim was to assess the potential effects of celecoxib on gastric permeability in comparison with placebo and ibuprofen. DESIGN: We conducted a prospective, double-blind, cross-over study. SETTING: This study is carried out at Marmara University Hospital. PARTICIPANTS: Twenty-five healthy subjects entered the study but 19 subjects completed the treatment. INTERVENTION: Subjects were randomized to celecoxib 100 mg twice daily, ibuprofen 600 mg twice daily or placebo for 7 days in pre-defined sequences. Treatments were separated by a 7 day washout period.MAIN OUTCOME MEASURE: Gastric permeability was assessed by measuring urinary excretion of sucrose spectrophotometrically. RESULTS: Ibuprofen 600 mg twice daily produced greater increases in gastric permeability compared with placebo or celecoxib (geometric mean of urinary sucrose recovery was 59.15, 32.65 and 33.11 mg/h for ibuprofen, placebo and celecoxib, respectively) (P < 0.001). Celecoxib was generally better tolerated than ibuprofen. CONCLUSIONS: When compared with ibuprofen, celecoxib 100 mg twice daily has no significant effect on gastric mucosa in healthy subjects.     

Significance of a novel sucrose permeability test using serum in the diagnosis of early gastric cancer

AIM: To investigate the usefulness of sucrose permeability test using serum in the diagnosis of gastric diseases, with special reference to early gastric cancer (EGC). METHODS: A total of 63 subjects, including 11 patients with gastric ulcer, 20 patients with gastric cancer (13, early; 7, advanced) and 32 healthy controls, were studied. Blood and urine samples were collected repeatedly for 5 h before and after the sucrose loading. Sucrose levels were measured by a newly developed enzymatic method. RESULTS: Serum sucrose levels started to increase 15 min after loading, and peaked at 60 min in the gastric disease groups. The levels for gastric ulcer, EGC and advanced gastric cancer (AGC) at 60 min were significantly higher than that in the healthy controls (26.9±2.4, 34.4±5.0, and 71.8±15.6 vs 7.9±0.7 mol/L, respectively, p<0.01). The cut-off level set at 15.4 mol/L (60 min) offered the best distinction between EGC patients and healthy controls; and the sensitivity and specificity were 92.3% and 93.8%, respectively, while those of the urine method were 76.9% and 93.8%, respectively. CONCLUSIONS: The gastric permeability test using serum is reliable for the detection of EGC, and this test can provide results much earlier than the conventional urine method. This test may offer a useful alternative to more invasive tests for EGC.     

Nonsteroidal anti-inflammatory drug use does not affect short-term endoscopic and histologic outcomes after Helicobacter pylori eradication in patients with rheumatoid arthritis

We evaluated the effects of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on endoscopic and histological findings in patients with rheumatoid arthritis (RA) before and after the eradication of Helicobacter pylori infection. Helicobacter pylori (H. pylori) eradication using lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 mg twice daily for 1 week was conducted in 44 patients (mean age: 56.5 years) with RA. Using the updated Sydney system, endoscopic and histological findings of the greater curvature of the antrum, the greater curvature of the upper corpus, and the lesser curvature of the lower corpus were compared before and after eradication, for a mean follow-up period of 3.5 months. Overall, H. pylori eradication was successful in 32 patients (72.7%). Of these 32 patients, 23 were NSAID users. In the successful eradication group, (1) there was no significant change on endoscopic findings, including gastric erythema and erosion in all three regions irrespective of NSAIDs use; (2) of 17 active ulcers before eradication in NSAIDs users, all healed except for one duodenal ulcer that persisted, where one patient newly developed a gastric ulcer, one developed erosive duodenitis, and two developed reflux esophagitis, all in NSAID users; (3) neutrophil infiltration and chronic inflammation were significantly improved in all three regions after H. pylori eradication irrespective of use of NSAIDs, while atrophic change and intestinal metaplasia did not change. In the eradication failure group; (1) there was no significant change on endoscopic and histological findings in the three regions; (2) two of three ulcers present before eradication on NSAID users persisted even after eradication, and no new cases of gastric ulcer or erosive duodenitis occurred. In conclusion, over a mean follow-up period of 3.5 months, use of NSAIDs in Japanese patients with RA did not impair the healing process of gastric and duodenal ulcers nor did it affect the endoscopic and histological improvements associated with H. pylori eradication.     

Nonsteroidal anti-inflammatory drug use does not affect short-term endoscopic and histologic outcomes after Helicobacter pylori eradication in patients with rheumatoid arthritis

Abstract

We evaluated the effects of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on endoscopic and histological findings in patients with rheumatoid arthritis (RA) before and after the eradication of Helicobacter pylori infection. Helicobacter pylori (H. pylori) eradication using lansoprazole 30?mg, amoxicillin 750?mg, and clarithromycin 200?mg twice daily for 1 week was conducted in 44 patients (mean age: 56.5 years) with RA. Using the updated Sydney system, endoscopic and histological findings of the greater curvature of the antrum, the greater curvature of the upper corpus, and the lesser curvature of the lower corpus were compared before and after eradication, for a mean follow-up period of 3.5 months. Overall, H. pylori eradication was successful in 32 patients (72.7%). Of these 32 patients, 23 were NSAID users. In the successful eradication group, (1) there was no significant change on endoscopic findings, including gastric erythema and erosion in all three regions irrespective of NSAIDs use; (2) of 17 active ulcers before eradication in NSAIDs users, all healed except for one duodenal ulcer that persisted, where one patient newly developed a gastric ulcer, one developed erosive duodenitis, and two developed reflux esophagitis, all in NSAID users; (3) neutrophil infiltration and chronic inflammation were significantly improved in all three regions after H. pylori eradication irrespective of use of NSAIDs, while atrophic change and intestinal metaplasia did not change. In the eradication failure group; (1) there was no significant change on endoscopic and histological findings in the three regions; (2) two of three ulcers present before eradication on NSAID users persisted even after eradication, and no new cases of gastric ulcer or erosive duodenitis occurred. In conclusion, over a mean follow-up period of 3.5 months, use of NSAIDs in Japanese patients with RA did not impair the healing process of gastric and duodenal ulcers nor did it affect the endoscopic and histological improvements associated with H. pylori eradication.     

Intestinal permeability and postheparin plasma diamine oxidase activity in the prediction of Crohn's disease relapse.

A method of detecting presymptomatic relapse of Crohn's disease could allow for the selective use of maintenance or intensified medical therapy in those with an increased risk of relapse. The aim of this study was to evaluate three potential laboratory markers of relapse: intestinal and gastroduodenal permeability and plasma diamine oxidase activity. Intestinal permeability (lactulose/mannitol test), gastroduodenal permeability (urinary sucrose excretion), and postheparin plasma diamine oxidase activity were serially measured in 61 adults with Crohn's disease in remission (CDAI <150) for at least 30 days. Subjects were followed periodically for clinical relapse (CDAI >150 and increased by at least 100 points or the need for steroids or surgery). Fourteen patients (23%) relapsed. A cut-off of 0.030 for the lactulose/mannitol ratio was defined. Those with ratios above the cutoff had a 7.0 times greater risk of relapse (p<0.001). Three subjects who went from a normal ratio to an abnormal ratio relapsed, whereas none of 32 subjects with a repeatedly normal ratio relapsed. Sucrose excretion and plasma diamine oxidase activity did not predict relapse. Serial testing of intestinal permeability, but not of gastroduodenal permeability or plasma diamine oxidase activity, was useful in predicting relapse in asymptomatic patients.     

Effect of longterm misoprostol coadministration with non-steroidal anti-inflammatory drugs: a histological study.

Prostaglandins are widely used in the prevention and healing of non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers, but their longterm effect on the human gastric mucosa is unknown. This study assessed the effect of coadministration of prostaglandins with NSAIDs on the histology of the gastroduodenal mucosa. Histological appearances (using the Sydney system) of gastric biopsy specimens from 180 patients receiving longterm NSAID treatment of whom 90 had been receiving misoprostol (400-800 micrograms/day) for one to two years were studied. Both groups of patients were comparable with regard to clinical and demographic details. There was no significant difference (p > 0.1) in the prevalence of chronic gastritis (total, corpus or antrum only) between patients receiving (36 of 90 (40%)) or not receiving misoprostol (35 of 90 (39%)). Chronic gastritis was equally associated with the presence of Helicobacter pylori, 86% and 73% (p > 0.1), respectively, in the two groups. Significantly fewer patients receiving misoprostol had reactive gastritis than those receiving only NSAIDs (8 (9%) versus 27 (30%), p < 0.01). Reactive gastritis was not associated with H pylori. Thirty nine (43%) of the misoprostol treated patients had normal histology compared with 16 (18%) receiving only NSAIDs (p < 0.01). These results show two different patterns of gastric damage in patients receiving NSAIDs, namely chronic and reactive gastritis. Misoprostol treatment was associated with a significantly reduced prevalence of reactive gastritis and it is suggested that this, along with its antisecretory action, may explain the reduced prevalence of gastroduodenal lesions when coadministered with NSAIDs.     

Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon： An open-label pilot study

AIM： To investigate the use of high dose consensusinterferon in combination with ribavirin in former iv drug users infected with hepatitis C.
METHODS： We started, before pegylated （PEG）interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon （CIFN） and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 μg of CIFN daily for 8 wk, followed by 9 μg daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72.
RESULTS： More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively, showing a negative qualitative PCR [genotype 1 fourteen patients （56%）, genotype 2 five （50%）, genotype 3 thirteen （87%）, genotype 4 four （50%）]. Forty-eight percent of genotype 1 patients showed sustained virological response （SVR） six months after the treatment. CONCLUSION： CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy （EOT） rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GTI and high viral load or for non-responders after failure of standard therapy.     

Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon: An open-label pilot study

AIM: To investigate the use of high dose consensusinterferon in combination with ribavirin in former iv drug users infected with hepatitis C.METHODS: We started, before pegylated (PEG)interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon (CIFN) and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 μg of CIFN daily for 8 wk, followed by 9 μg daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72.RESULTS: More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively,showing a negative qualitative PCR [genotype 1 fourteen patients (56%), genotype 2 five (50%),genotype 3 thirteen (87%), genotype 4 four (50%)].Forty-eight percent of genotype 1 patients showed sustained virological response (SVR) six months after the treatment.CONCLUSION: CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy (EOT) rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GT1 and high viral load or for non-responders after failure of standard therapy.     

Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs

BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile. Our objective was to compare the effect on gastrointestinal permeability of acute equieffective doses of four different NSAIDs; three were designed to reduce gastrointestinal mucosal injury. MATERIALS: Healthy volunteers underwent sugar tests in a randomised fashion, 15 days apart, at: (1) baseline; (2) after two days of 75 mg slow release (microspheres) indomethacin; (3) after two days of 7.5 mg oral meloxicam which preferentially inhibits cyclooxygenase 2; and (4) after two days of 750 mg naproxen. A subgroup of subjects was tested after two days of 200 mg celecoxib. In each test, subjects ingested a solution containing sucrose, lactulose, and mannitol and sucralose, to evaluate gastroduodenal, intestinal, and colonic permeability, respectively. RESULTS: Gastric permeability was significantly affected by naproxen (p<0.05) but not by slow release indomethacin, meloxicam, or celecoxib. Intestinal permeability was significantly increased by the first three NSAIDs (p<0.05) but not by celecoxib. Abnormal lactulose/mannitol ratios were observed in 42% of meloxicam treatments, in 62% during indomethacin, and in 75% of subjects treated with naproxen. Finally, colonic permeability, as measured by sucralose, was not significantly increased by any of the four drugs. CONCLUSION: Our study provides evidence that the newly developed NSAIDs reduce gastric mucosal permeability significantly. However, most produced significant alteration of small intestinal permeability. In contrast, our results suggest that celecoxib seems to exhibit the most desirable gastrointestinal side effect profile.