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Biomedical subjects

P Gionchetti

Publications and source records attributed to P Gionchetti.

At least 91 records · Page 5Linked to original sources

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

Treatment of Crohn's 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 less than 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 alpha 1 acid glycoprotein and C-reactive protein from the second month of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Changes in splanchnic hemodynamics in inflammatory bowel disease. Non-invasive assessment by Doppler ultrasound flowmetry.

An increase in splanchnic blood flow in both arterial and venous beds has been demonstrated in inflammatory bowel disease (IBD) by means of angiographic and scintigraphic studies. Doppler ultrasound (US) enables a non-invasive evaluation of splanchnic arterial inflow in the superior mesenteric artery (SMA) and of venous outflow in the portal vein. The aim of this study was to assess the role of Doppler US in detecting changes in the hemodynamic variables measured in patients with IBD. Forty-five patients with IBD were studied, including 22 with Crohn's disease (CD) and 23 with ulcerative colitis (UC), and compared with 45 matched normal subjects. The mean velocity of portal flow (Vmean) and the resistance index (RI) of the SMA were evaluated by Doppler US. In CD the Vmean of portal flow was significantly higher in patients with active disease than in controls (p less than 0.001) and patients with inactive disease (p less than 0.001). The RI of the SMA was significantly lower in active disease than in controls (p less than 0.005), but no significant difference was noted between active and inactive CD. Also in UC, the Vmean of portal flow was significantly higher in patients with active disease than in controls (p less than 0.01) and patients with inactive disease (p less than 0.05). The RI of the SMA was significantly lower in active disease than in controls (p less than 0.005) and in patients with inactive disease (p less than 0.005). Doppler follow-up studies were carried out in 10 patients after initiation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Interleukin 1 beta (IL-1 beta) release from fresh and cultured colonic mucosa in patients with ulcerative colitis (UC).

Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohn's disease (CD) and ulcerative colitis (UC). IL-1 beta release from fresh and cultured colonic biopsies and IL-1 beta plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1 beta activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1 beta were detected only in 3 plasma samples, all from active patients. Significantly more IL-1 beta was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p less than 0.01). Furthermore, specimens from active UC released significantly more IL-1 beta than those from patients in remission (p less than 0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

Adult↗

Influence of steroid treatment's duration in patients with active Crohn's disease.

Steroids are very useful drugs in the treatment of active Crohn's disease (CD), but clinical relapses after steroid withdrawal may be very high. We investigated the efficacy of two steroid regimens of different duration in inducing remission and in maintaining it after drug suspension. Patients with active CD were randomly assigned to scheme A, lasting 7 weeks (27 patients), or to scheme B, lasting 15 weeks (27 patients). Remission rates at the end of the treatment were 81% for scheme A and 85% for scheme B. Relapse rates at 6 months after stopping the treatment were 50% (11 patients) and 52% (12 patients), respectively. Remission rates seem not to be influenced by the duration of the treatment, but patients recently treated with steroids showed a higher relapse rate if they received the short-duration treatment.

Adult↗

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

The in vitro antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-ASA), 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 cytochrome c (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 (greater than 50% of inhibition in the PMNs system and greater than 70% in the X/XOD system at 10 microM 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.

Aminosalicylic Acids↗

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.

Adult↗

Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial.

Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 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 less than 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.

Adult↗

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.

Adolescent↗

Role of rectal formulations: enemas.

Clinical experience with mesalazine enemas in the treatment of ulcerative colitis is reviewed. After rectal administration, plasma mesalazine levels remain low, and 15% of the administered dose is recovered in the urine. Enemas containing 2 and 4 g of mesalazine have been shown to be effective, safe, and well tolerated by patients with mild and moderate ulcerative colitis. Patients who cannot tolerate sulfasalazine and patients who do not respond to other treatments have been successfully treated with mesalazine enemas. Suppositories of mesalazine are more suitable for patients with disease confined to the distal region of the colon, whereas mesalazine enemas should be used in patients with more extensive disease. Mesalazine enemas have also been used for maintenance therapy in ulcerative colitis.

Aminosalicylic Acids↗

5-Aminosalicylic acid suppositories in the management of ulcerative colitis.

5-aminosalicylic acid (5-ASA) suppositories have been used in the author's 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).

Adult↗

Macrophage subpopulations in lamina propria of normal and inflamed colon and terminal ileum.

The aim of this study was to characterise human intestinal macrophages in normal and inflamed ileum and colon. Immunoperoxidase staining with a panel of monoclonal antibodies and histochemical staining for acid phosphatase and non-specific esterase was performed. In the superficial lamina propria, normal colonic macrophages were larger and more strongly positive for acid phosphatase and non-specific esterase than those in normal terminal ileum. There were more macrophages staining with monoclonal antibody RFD1 in the superficial lamina propria of the latter. Studies in inflammatory bowel disease tissue showed the presence of macrophages staining with monoclonal antibodies RFD9 and 3G8 which were rarely present in normal tissue and represented a different pattern from that seen in infectious colitis. Studies on isolated intestinal macrophages confirmed the findings in tissue sections. Subpopulations of intestinal macrophages are likely to have different functional roles. Phenotypic changes during inflammation may be induced by mediators of inflammation or may represent a recently recruited population of cells.

Adolescent↗

5-Aminosalicylic acid as enemas or suppositories in distal ulcerative colitis?

Thirty-nine patients with documented active distal proctitis (less than 20 cm) received either 5-aminosalicylic acid (5-ASA) enemas (2 g in 100 ml) or suppositories 1 g b.i.d., in a controlled study. Twenty patients received enemas, while 19 patients received suppositories, for 30 days. No difference could be observed in terms of efficacy; however, it was the patients' opinion that treatment with suppositories was easier than that with enemas (p less than 0.01).

Administration, Rectal↗

Macrophage and lymphocyte subpopulations in magnifying endoscopic lesions of Crohn's disease.

Using dye staining and a magnifying colonoscope, small lesions in the rectum of patients with Crohn's disease (which had otherwise appeared normal on sigmoidoscopy) can be detected. Subpopulations of macrophages and lymphocytes in the abnormal and adjacent normal areas of the rectum were studied using a panel of monoclonal antibodies. There was a distinct increase in RFD9+ and 3G8+ macrophages in the abnormal areas compared with the normal. The CD4:CD8 ratio of lymphocytes in the two areas remained unchanged.

Antibodies, Monoclonal↗