P. Iannone

Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis.

5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.

Placebo-controlled trial of oral 5-ASA in relapse prevention of Crohn's disease

Treatment of Crohns disease (CD) in clinical remission is still a debated issue. Previous studies have shown a high risk of relapse for patients with CD in clinical remission (CDAI<150) but with some abnormally high laboratory parameters as well as a possible beneficial role of low-dosage steroid treatment in this group of patients. Furthermore, good results have been reported on the efficacy of 5-aminosalicylic acid (5-ASA) in moderately active CD. In our study we verified the efficacy of a slow-release oral 5-ASA preparation in preventing relapses in a group of patients in clinical remission but with raised laboratory parameters. Forty-four patients were randomized in a double-blind manner to receive either 5-ASA (2 g/day) or placebo for four months. Location of disease and previous steroid treatment were similar in both groups. One patient in the 5-ASA group discontinued the drug because of uterine bleeding. During the study period, 13 of 22 placebo-treated patients and 11 of 21 5-ASA-treated patients relapsed (corrected chi square=NS). Considering the location of disease, three of 10 patients in the 5-ASA group and six of nine patients in the placebo group with ileal CD relapsed (therapeutic gain with 5-ASA: 36.6%; 95% allowance for error from −6% to 79.2%). Moreover, in seven patients with ileal CD who remained in remission, we found a statistically significant decrease in α1 acid glycoprotein and C-reactive protein from the second month of the study. In conclusion, although results with 5-ASA in CD seem disappointing, the possible benefit of higher dosages of 5-ASA in selected subgroups of CD patients is discussed.

Scavenger effect of sulfasalazine, 5-aminosalicylic acid, and olsalazine on superoxide radical generation

Thein vitro antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-SSA), and olsalazine (OAZ), was studied by evaluating their effects on superoxide (O2−•) production. Assay systems were the xanthine-xanthine oxidase (X/XOD) reaction and phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), using the cytochromec (cyt-c) reduction assay and a luminol-dependent chemiluminescence method. 5-ASA, SASP, and OAZ showed a dose-dependent scavenger effect in both O2−• generating systems, 5-ASA being the most powerful (>50% of inhibition in the PMNs system and >70% in the X/XOD system at 10 μM concentration). SP had an inhibitory effect only in the PMNs system but did not modify the activity of xanthine oxidase, thus excluding a scavenger action. These data suggest that the scavenger effect of 5-ASA, SASP, and OAZ may be an important mechanism of action.

Steroid treatment in active Crohn's disease: a comparison between two regimens of different duration

Background: Steroids are highly effective in active Crohns disease; clinical relapse following steroid withdrawal, however, is frequent. We used two steroid regimens of different duration in order to compare their efficacy in inducing and maintaining clinical remission. Methods: Seventy patients with active Crohns disease were treated with methylprednisolone 40 mg/day i.m. for 3 weeks and then with two different regimens of tapering dosage: one for a further 4 weeks and another for a further 12 weeks.

The possible utility of steroids in the prevention of relapses of Crohn's disease in remission. A preliminary study.

In Crohns disease, prednisone is believed to be ineffective for relapse prevention. Because all patients with Crohns Disease Activity Index lower than 150 and with some altered lab tests (erythrocyte sedimentation rate, C-reactive protein, alpha-1-acid glycoprotein, alpha-1-acid antitrypsin, and white blood cell count) had a clinical relapse in 18 months of follow-up, we tried to ascertain whether methylprednisolone could reduce the risk of clinical relapse in such patients. Eighteen patients were included in a controlled study against placebo. Nine patients were treated with methylprednisolone at a dosage of 0.25 mg/kg daily for a period of 6 months; treatment was discontinued if disease relapsed or if lab tests were normalized. During the steroid treatment, 1 of 9 patients showed a clinical relapse; in 7, the normalization of lab tests was obtained; in 5 of these 7 patients a relapse occurred within 1 month after the suspension of the treatment; in 1 patient, lab tests remained altered. In those 9 patients on placebo, relapses occurred in 7. We conclude that methylprednisolone was effective in the prevention of relapses for patients in clinical remission but with altered lab tests.

Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation

Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (<20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p<0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.

Comparison of scintigraphy with indium-111 leukocyte scan and ultrasonography in assessment of x-ray-demonstrated lesions of crohn's disease

The aim of this study was to compare the results obtained with an indium-111 scan with those obtained with less expensive and harmless ultrasonography to evaluate the location and inflammatory activity of Crohns disease. Thirty-one patients previously studied with x-ray underwent abdominal111In scans and ultrasonography (US). Sensitivity and specificity of US in detecting lesions seen with111In scan were 77% and 92.8%, respectively. Sensitivity and specificity of111In scan in detecting x-ray-defined lesions were 69.2% and 92.7%; the figures for US were 73% and 93.3%, respectively. Considering the evaluation of disease activity, ultrasonographic bowel wall thickness was significantly related to scintigraphic intensity of emission (r=0.75 P<0.01). Our experience suggests that US provided information about the location and inflammatory activity of lesions similar to that obtained from111In scan.

Bronchopulmonary Involvement in Ulcerative Colitis

We report two cases of pulmonary involvement in ulcerative colitis. The first patient, a 37-year-old woman, had bilateral basal bronchiectasis full of mucopurulent secretion, with a marked improvement of pulmonary function and roentgenographic appearance after a conservative approach. The second patient had severe pulmonary fibrosis of autoimmune nature and died owing to a pulmonary infection. In the second patient, a sulfasalazine reaction as an etiologic factor was excluded, while in the first this possibility seemed unlikely. Therefore, we take these two cases as examples of the extraintestinal manifestations of ulcerative colitis.

5-aminosalicylic acid suppositories in the management of ulcerative colitis

Abstract5-aminosalicylic acid (5-ASA) suppositories have been used in the authors out-patient clinic in Bologna for the treatment of distal ulcerative colitis (UC). One hundred fifty-six patients with mild or moderate attacks of UC were treated using different protocols for controlling active disease. Improvement was observed in 88.5 percent of the therapeutic cycles after one month. A small preliminary maintenance study using only 400-mg suppositories of 5-ASA twice a day for 6 or 12 months showed a remission percentage similar to salicylazosulfapyridine (SASP).

Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease

The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO4) could restore thymic endocrine function in patients with Crohns disease who showed decreased plasma concentrations of zinc and active thymulin, a zinc‐dependent thymic hormone. Twenty‐seven patients in clinical remission were randomly assigned to receive, for 3 months, one of the following treatments: 60 mg/day ZnSO4; 200 mg/day ZnSO4 or placebo. Plasma thymulin activity and zinc concentrations significantly increased only in patients treated with 200 mg/day ZnSO4. Lymphocyte subpopulations, within the range of normality before zinc supplementation, were unaffected by any of the administered treatments. In conclusion, low plasma concentrations of zinc and thymulin in Crohns disease patients were restored by the administration of high doses of zinc.