P. Paoluzi

Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report.

Colon cells from patients with ulcerative colitis utilize short-chain fatty acids inefficiently and may be exposed to decreased concentrations of these compounds. To test whether irrigation of the inflamed mucosa with short-chain fatty acids is useful, we conducted a six-week preliminary trial in 12 patients with distal colitis. Each patient used twice daily rectal irrigations with 100 ml of a solution containing acetate (80 mM), propionate (30 mM), and butyrate (40 mM). Two patients stopped at three weeks, one because of no improvement and the other because of complete resolution of symptoms. Of the 10 who completed the trial, nine were judged to be at least much improved and showed a change in a mean disease activity index score from 7.9±0.3 (se) to 1.8±0.6 (se) (P≤0.002) and in a mucosal histology score from 7.7±0.7 (se) to 2.6±0.7 (se) (P≤0.002). Thus, ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates.

Short-chain fatty acid topical treatment in distal ulcerative colitis

Background: Some evidence indicates that short‐chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis.

Azathioprine or methotrexate in the treatment of patients with steroid‐dependent or steroid‐resistant ulcerative colitis: results of an open‐label study on efficacy and tolerability in inducing and maintaining remission

Background : The role of azathioprine and methotrexate in inducing and maintaining remission in patients with ulcerative colitis is still controversial.

Anti-tissue transglutaminase antibodies in inflammatory bowel disease: new evidence

Abstract Anti-tissue transglutaminase, previously held to be identical to anti-endomysial antibodies in celiac sprue, has been reported in inflammatory bowel disease patients. To investigate these data further, we evaluated serum and intestinal anti-tissue transglutaminase in inflammatory bowel disease patients, with respect to the Crohn’s disease activity index and the integrated disease activity index. Study population comprised: 49 patients with Crohn’s disease and 29 patients with ulcerative colitis; 45 patients with celiac sprue and 85 autoimmune patients as disease controls; and 58 volunteers as healthy controls. Immunoglobulin A (IgA) anti-recombinant human tissue transglutaminase and anti-endomysial antibody detection in sera and fecal supernatants were performed. Adsorption of positive sera with recombinant human tissue transglutaminase were also performed. Marked increased anti-tissue transglutaminase concentrations were found in celiac sprue, while low-positive values were also found in Crohn’s disease and ulcerative colitis. Anti-endomysial antibodies were detectable only in celiac sprue. Antigen adsorption resulted in a significant reduction of the anti-tissue transglutaminase either in celiac sprue or inflammatory bowel disease sera. A significant correlation between anti-tissue transglutaminase and Crohn’s disease activity index or integrated disease activity index scores was found. Anti-tissue transglutaminase was also detectable in fecal supernatants from inflammatory bowel disease patients. Data highlight that both circulating and intestinal anti-tissue transglutaminases are detectable in inflammatory bowel disease, and that they are related to disease activity. These features underline that, in addition to anti-tissue transglutaminase, an anti-endomysial antibody test is necessary in the diagnostic work-up of celiac sprue, especially in patients with known inflammatory bowel disease.

2-Week Triple Therapy for Helicobacter pylori Infection is Better Than 1-Week in Clinical Practice: a Large Prospective Single-Center Randomized Study

Background:  Proton pump inhibitor (PPI)‐based triple therapies are considered the standard regimens for Helicobacter pylori eradication, but the optimal duration of these regimens is still controversial. The aim of this study was to compare the efficacy of 1‐week versus 2‐week triple therapies in H. pylori‐positive patients.

Comparison of two different daily dosages (2.4 vs. 1.2 g) of oral mesalazine in maintenance of remission in ulcerative colitis patients: 1-year follow-up study

Background : Mesalazine as maintenance therapy in ulcerative colitis is used worldwide and has been proven to be effective. However, the optimal dosage remains to be defined.

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial

Objectives: A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis. Methods: From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (≤ 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features. Results: The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0–21) in the mesalazine b.i.d. group, 32% (95% CI: 16–49) in the mesalazine u.i.d. group, and 47% (95% CI: 29–65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up. Conclusions: The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.

Sulphasalazine and 5-aminosalicylic acid in long-term treatment of ulcerative colitis: report on tolerance and side-effects.

BACKGROUND Use of sulphasalazine in ulcerative colitis patients is hampered by a variety of side-effects, including male infertility. 5-aminosalicylic acid is better tolerated and has been increasingly used to treat patients intolerant/allergic to sulphasalazine but it may also be associated with side-effects. AIM To evaluate tolerance of long-term treatment with sulphasalazine and 5-aminosalicylic acid in ulcerative colitis. METHODS Side-effects to sulphasalazine (2-3 g/day) and 5-aminosalicylic acid (1.2-2.4 g/day) were recorded in 685 patients: 410 patients received only sulphasalazine, 130 only 5-aminosalicylic acid, and 145 both drugs. In patients with side-effects to sulphasalazine, a desensitisation protocol (rechallenge) was attempted to improve tolerance, and patients still presenting side-effects after desensitisation were switched to 5-aminosalicylic acid. Male fertility was also assessed in 42 males on sulphasalazine and on 5-aminosalicylic acid. RESULTS Side-effects were observed in 110/555 patients (20%) on sulphasalazine and in 18/275 patients (6.5%) on 5-aminosalicylic acid during a median period of follow-up of 7 and 5 years, respectively. Desensitisation was achieved in 40% of patients intolerant to sulphasalazine. 5-aminosalicylic acid intake induced side-effects in 2/130 patients (1.5%) who had not taken sulphasalazine before versus 4/91 patients (4%) tolerating sulphasalazine and 12/54 patients (22%) intolerant/allergic to sulphasalazine, the difference in incidence of side-effects in the two latter groups being statistically significant (4.4% vs 20.8%, p=0. 001). Fertility was found to be affected in all patients on sulphasalazine but improved when put onto 5-aminosalicylic acid. CONCLUSIONS 5-aminosalicylic acid should be considered the drug of choice in the treatment of ulcerative colitis bearing in mind that intolerance or allergy may occur in a few patients also on this drug.

Production of immunoglobulin G and G1 antibodies to cytoskeletal protein by lamina propria cells in ulcerative colitis

BACKGROUND & AIMS Recent studies suggest an autoantigenic role for tropomyosin-related protein(s) in ulcerative colitis (UC). This study examined whether immunoglobulin G and G1 subclass antibodies against tropomyosins are produced spontaneously by the lamina propria mononuclear cells (LPMCs) that infiltrate the inflamed UC tissue. METHODS LPMCs were isolated from colonic biopsy specimens from 29 patients with UC, 15 with colonic Crohns disease (CD), and 13 with non-inflammatory bowel disease (IBD). The autologous peripheral blood mononuclear cells (PBMCs) were obtained. Cells were cultured in vitro and unstimulated for 10 days. Spontaneous production of immunoglobulin G and G1 antibodies against tropomyosins was measured by enzyme-linked immunosorbent assays using highly enriched tropomyosins from skeletal muscle and colonic mucosa. RESULTS The total immunoglobulin G produced by LPMCs from both patients with UC and CD was comparable but higher than from patients with non-IBD (P < 0.05). However, immunoglobulin G antibodies to tropomyosins were higher in patients with UC than in patients with CD (P < 0.04) and non-IBD (P < 0.02). LPMCs from patients with symptomatic UC produced higher immunoglobulin G antibodies to tropomyosins than patients with UC in remission (P < 0.03), symptomatic CD (P < 0.04), and non-IBD (P < 0.02). Immunoglobulin G antibodies to tropomyosins predominantly belonged to immunoglobulin G1 subclass. The autologous PBMCs showed comparable results. CONCLUSIONS Immunoglobulin G antibodies predominantly belonging to immunoglobulin G1 subclass and reactive against tropomyosin-related protein(s) are spontaneously produced by LPMCs from the colonic mucosa in patients with UC.

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group.

Objectives:A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis.Methods:From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (≤ 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features.Results:The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0–21) in the mesalazine b.i.d. group, 32% (95% CI: 16–49) in the mesalazine u.i.d. group, and 47% (95% CI: 29–65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p= 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up.Conclusions:The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.