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.

99mTc-HMPAO granulocyte scintigraphy in the early detection of postoperative asymptomatic recurrence in Crohn's disease.

The usefulness of 99mTc-HMPAO scintigraphy in the early detection of postoperative recurrence of Crohn's disease was evaluated in 17 patients undergoing ileocecal resection and prospectively followed up for one year. Scintigraphy was performed 6 and 12 months after surgery and recurrence assessed by colonoscopy within two weeks. As controls, four patients with ileocecal resection for cecal carcinoma were studied. To perform scintigraphy, autologous granulocytes were labeled with 99mTc-HMPAO, injected, and tau-camera images acquired after 30 min and 3 hr. Six months after surgery, 4/8 Crohn's disease patients showed endoscopic recurrence, and 30-min scintigraphy was positive only in these four patients (four true positives, four true negatives). At 12 months, endoscopic recurrence was detected in 10/14 Crohn's disease patients, and 30-min scintigraphy was positive in 9/14 patients (eight true positives, three true negatives, two false negatives, one false positive). Scintigraphy at 3 hr showed a lower specificity in detecting CD recurrence both at 6 and 12 months. The endoscopic and 30-min scintigraphic score were significantly correlated both at 6 and 12 months (P = 0.007; P = 0.04). Scintigraphy was negative in 4/4 controls at 30 min (four true negatives) and positive in 1/4 (one false positive) at 3 hr. We conclude that 99mTc-HMPAO scintigraphy at 30 min is a sensitive technique for the early detection of Crohn's disease recurrence in patients under regular follow-up after surgery.

5-Aminosalicylic acid inhibits the impaired epithelial barrier function induced by gamma interferon.

Gamma interferon (IFN gamma) impairs epithelial barrier function and induces HLA-DR expression on colonic cancer cell lines. Salicylates have been shown to reduce IFN gamma induced HLA-DR expression. The effect of 5-aminosalicylic acid (5-ASA) on IFN gamma induced changes in transepithelial resistance and permeability was investigated in HT29 clone 19A and Caco 2 monolayers. Monolayers were incubated with different concentrations of IFN gamma (100, 500, 1000, and 3000 U/ml) and 5-ASA. IFN gamma induced class II expression in a time and dose dependent manner in HT29:19A but not Caco 2 cells. HT29:19A monolayers incubated with both IFN gamma and 5-ASA showed lower HLA-DR expression compared with monolayers incubated with IFN gamma alone. Electrical resistance and 14C-mannitol flux across HT29:19A monolayers were significantly changed by IFN gamma. Addition of both IFN gamma and 5-ASA to the basolateral surface of the monolayers significantly reduced paracellular permeability compared with addition of IFN gamma alone. These data show that IFN gamma is able to induce HLA-DR expression and to impair the barrier function of HT29:19A monolayers, and that 5-ASA reduces IFN gamma induced HLA-DR expression and inhibits the effects of IFN gamma on epithelial barrier function.

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. METHODS: In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study. RESULTS: Fourteen patients on SCFA improved (overall score 11.3 +/- 2.0 vs. 7.4 +/- 3.5) as compared to five in the placebo group (overall score 10.0 +/- 1.9 vs. 8.9 +/- 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pretrial differences between the two groups. CONCLUSION: The present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.

Ileo-rectal anastomosis in ulcerative colitis: results of a long-term follow-up study.

Colectomy with ileo-rectal anastomosis (IRA) was introduced in the 'fifties as an alternative to proctocolectomy with ileostomy in patients with ulcerative colitis (UC). Seventy-four patients affected by UC and submitted to IRA were followed up with clinical, endoscopic and histological controls for a median follow-up period of 9.5 years (range: 3-25 years). The long-term outcome was assessed by evaluating the course of the proctitis, the need for medical therapy, functional results, the need for rectal excision, and mortality during the follow-up. The patients were classified in three groups according to the type of the outcome (success: low-relapsing proctitis, rare or no need for medical therapy, good functional results; partial failure: relapsing proctitis with frequent need for medical therapy and/or poor functional results; failure: necessity of proctectomy). In order to define the prognostic value the clinical characteristics at surgery (age, gender, duration of disease, rectal inflammation, and type of surgery) were compared in the three groups. The long-term outcome was judged as a success in 46 patients (62%), partial failure in 19 patients (26%) and failure in 9 patients (12%). Only one patient developed cancer in the rectal stump (incidence: 1.3%). None of the clinical parameters at surgery except rectal inflammation influenced the outcome: patients showing moderate or severe inflammation in the rectum at surgery had a higher failure rate than those with mild or no inflammation (p < 0.02). These data confirm that colectomy with IRA is a safe surgical procedure with good functional results in most cases and with a low risk of cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized controlled trial of a new PEG-electrolyte solution compared with a standard preparation for colonoscopy.

The efficacy, tolerability and patient acceptance of a new flavoured PEG solution for gut lavage was compared with a standard preparation for bowel cleansing in a randomized controlled trial of patients undergoing colonoscopy. One hundred and sixty patients were randomly allocated either to a standard preparation (2-day semi-liquid diet, laxatives and cleansing enemas) or to gut lavage (fractionalized ingestion of lavage solution, two litres in the afternoon before and a third litre the morning of the examination). Adequacy of colon cleansing was scored evaluating residual stool in each colonic segment and overall mucosal visibility. Tolerability of methods was assessed by evaluating the incidence and severity of side-effects. Patient acceptance was graded (good, fair to good, poor) according to the patient's judgement about the ease of execution and interference with sleep and working activity. Less residual stool (p < 0.05) and better visualization of colonic mucosa (p < 0.05) were obtained with gut lavage than with standard preparation. Both methods were well-tolerated and a low incidence of side effects was recorded in both groups. Patient acceptance was good in more than 80% of patients in both groups. We conclude that gut lavage is a rapid, effective and well-tolerated method for bowel cleansing. The use of a flavoured solution in a fractionalized schedule seems to improve the tolerability and the patient acceptance of this method.

Absence of circulating interferon in patients with inflammatory bowel disease. Suggestion against an autoimmune etiology.

Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-alpha) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN. No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN.

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 less than or equal to 0.002) and in a mucosal histology score from 7.7 +/- 0.7 (SE) to 2.6 +/- 0.7 (SE) (P less than or equal to 0.002). Thus, ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates.

Phenotypes and spontaneous immunoglobulin production in mononuclear cells suspensions isolated from colonic biopsies of patients with mild active and quiescent ulcerative colitis.

Lamina propria mononuclear cells can be isolated from mucosal specimens of human colon. In the present study, we have explored whether both the phenotypes and functional properties can be studied in lamina propria mononuclear cell suspensions isolated from the same set of endoscopic biopsies in patients with ulcerative colitis. The counts of CD11b+ lamina propria mononuclear cells in mild active ulcerative colitis were significantly higher than those of both quiescent ulcerative colitis and controls. Similarly, the CD16+ and the CD19+ lamina propria mononuclear cells were significantly increased in mild ulcerative colitis patients in comparison to both quiescent ulcerative colitis and control lamina propria mononuclear cells. Lamina propria mononuclear cells from all the biopsy samples appeared to produce detectable amounts of immunoglobulins of the three classes. The production of IgG in mild ulcerative colitis cultures was significantly higher than that observed in quiescent ulcerative colitis and controls. In contrast, the production of IgA in active ulcerative colitis lamina propria mononuclear cell cultures appeared to be significantly lower than that of both quiescent ulcerative colitis and controls. This study shows that morphology, phenotypes, and functional properties can be assessed in lamina propria mononuclear cell suspensions obtained from the same set of endoscopic biopsy samples. We have also shown that changes in phenotypes and functional status of lamina propria mononuclear cells occurred in mild active ulcerative colitis while no significant abnormality of these parameters was found in quiescent ulcerative colitis. This indicates that a normalization of mucosal immune functions occurs in ulcerative colitis patients when complete clinical and histological remission is achieved.

A constitutional 5q23 deletion.

A 14 month old girl was found to have a deletion of the whole of band 5q23. By comparing 19 other cases monosomic for a part of the 5q13-q31 segment, the constitutional 5q interstitial deletions fall into two groups: adult patients with Gardner-like symptoms and mental retardation associated with deletion 5q21-q22, and patients (mostly children) with unspecific signs and symptoms and different deletions.