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Background: Steroids are highly effective in active Crohn's 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 Crohn's 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. Results: Steroid therapy induced remission within 3 weeks in 91 % of the whole group of patients: at the end of each protocol remission rates were 85% of patients in the group treated for the shorter period and 87% of those treated for the longer period (difference 2%. CI = ‐ 14 to 18, P = NS); remission rates within 6 months after stopping steroids were 53% and 37% respectively (difference 16%, CI = ‐9 to 41, P = NS). Conclusions: No significant differences were found between the two regimens. Multiple courses of steroid treatment in the previous 3 years and a short time interval following previous steroid treatment seem to be risk factors for relapse. Copyright © 1994, Wiley Blackwell. All rights reserved

The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO4) could restore thymic endocrine function in patients with Crohn's 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 Crohn's disease patients were restored by the administration of high doses of zinc.

OBJECTIVE In Crohn's disease (CD), the relationship between genetic predisposition and smoking has not been well defined. The aim of this study was to compare the smoking habits at the time of the diagnosis of CD patients having familial occurrence of inflammatory bowel disease (IBD) with those of some control groups. METHODS In a multicenter study, 136 CD patients with a relative with IBD, 272 healthy controls matched for sex and age, 500 CD patients without familial occurrence of IBD, and 84 ulcerative colitis patients (UC) with familial occurrence of IBD were personally interviewed about their smoking habits. In addition, data for 35 healthy siblings of patients with familial CD were collected by interviewing the patients' relatives. RESULTS The prevalence of smokers was found significantly higher in CD patients with a family history for IBD than in healthy controls and in familial UC patients (OR 2.28 CI 1.5-3.48 and OR 5.81 CI 3.15-10.75, respectively). No significant difference was found either in the percentage of smokers or in the number of cigarettes smoked per day between familial and sporadic CD patients. Among all siblings of CD patients, 72% of affected siblings and 34% of healthy siblings were smokers, concordant with their relatives. CONCLUSIONS In CD patients with familial occurrence of IBD, the percentage of smokers is elevated. It is possible that in a genetically predisposed population, smoking could be an important environmental factor in determining CD or expressing this disease instead of UC.

PURPOSE: The aim of our study was to compare the efficacy and safety of oral mesalazine with mesalazine suppositories in patients with active ulcerative proctitis. PATIENTS AND METHODS: A four-week, randomized, single- blind trial was performed in 58 patients with active, histologically confirmed ulcerative proctitis (≤ 15 cm) to evaluate the efficacy and safety of oral 800-mg mesalazine tablets taken three times per day (n = 29) compared with 400 mg of mesalazine suppositories administered three times per day (n = 29). Patients were evaluated at study entry and after two and four weeks. Efficacy evaluations included a disease activity index, which represents a score with four variables: stools frequency, rectal bleeding, mucosal appearance, and physician's assessment of disease severity. Histologic activity was also assessed at study entry and after two and four weeks in accordance with the criteria by Truelove and Richard. Safety assessment included clinical laboratory parameters and adverse event reports. RESULTS: There were no significant differences with regard to baseline comparisons of demographics and severity between the two treatment groups. Improvement in mean disease activity index score was significantly greater with suppositories compared with oral mesalazine, both at two-week and four-week visits (mean disease activity index scores at baseline, two, and four weeks: suppositories = 7.7, 2.59, and 1.48; tablets = 7.42, 5.72, and 3.48, respectively (P < 0.001)). The rate of histologic remission was significantly greater with suppositories compared with tablets both at two and four weeks (P < 0.01). There were no significant differences in adverse events or clinical laboratory results between treatment groups. CONCLUSIONS: Results of this study indicate that treatment with mesalazine suppositories produces earlier and significantly better results than oral mesalazine in the treatment of active ulcerative proctitis.

Background: Mucosal inflammation of the ileal pouch (pouchitis) is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment-resistant disease. Aim: To determine the safety and efficacy of bismuth carbomer enemas in achieving and maintaining remission in treatment-resistant chronic pouchitis. Methods: Twelve patients with treatment-resistant chronic pouchitis were treated nightly for 45 days with enemas containing elemental bismuth complexed with carbomer. Diagnosis of pouchitis and response to treatment were evaluated with the Pouchitis Disease Activity Index (PDAI), which includes clinical, sigmoidoscopic and histological criteria. Serum bismuth concentrations were determined by atomic absorption. Results: Ten of 12 patients (83%) went into remission, with a significant decrease of mean total PDAI score from 12 (range 9–15) to 6 (4–15) (P

Concordance in the extent of disease among the family members of patients with Crohn's disease has not been widely investigated. Furthermore, the relationship between the site of the disease and familial occurrence has never been studied. Our aim was to evaluate the familial occurrence of Crohn's disease in the various sites. Nine hundred thirty-four patients with Crohn's disease, observed consecutively in two gastrointestinal departments, were investigated to determine first-degree familial incidence (in both Crohn's disease and ulcerative colitis). Whenever two or more members were attending the same clinic, only one was regarded as a propositus. The analysis, therefore, was carried out on 882 patients. The exact site of the disease was determined in all patients either at diagnosis or during the follow-up by colonoscopy and by small bowel enema. The rate of concordance in the extent of disease and familial occurrence in the various sites was evaluated and the difference was calculated by chi-square test. Sixty-one propositi were identified among all the patients. Forty-nine had familial occurrence for the same disease (concordant patients), whereas 12 had at least one relative with ulcerative colitis (discordant patients). In 44 propositi with only one relative affected, the rates of concordance in the extent of the disease were 84, 68, 18, and 0% respectively, for the ileum, the ileum-right colon, the ileum-total colon, and the colon. The number of propositi in the various sites was as follows: 4 of 162 (2.4%) patients with the disease located in the colon, 1 of 9 (11%) with the jejunum site, 24 of 380 (6.3%) with the ileum site, 16 of 165 (9.7%) with the ileum and right colon site, and 16 of 164 (9.7%) with the ileum and total colon site. The chi-square values of propositi distribution among other sites and the colon was, respectively, as follows: jejunum, 2.2 (N.S.); ileum, 3.4 (P = 0.06); ileum and right colon, 7.4 (P = 0.006); and ileum and total colon, 7.4 (P = 0.006). This study shows a pronounced concordance in the site of the disease for family members with Crohn's disease and suggests that familial occurrence in Crohn's disease is less frequent when the disease is located in the colon rather than elsewhere.

It has been suggested that certain clinical and morphological features can modify the outcome of Crohn's disease, particularly regarding recurrence after surgery. A series of 233 patiens was followed prospectively. They underwent a resectional surgical procedure for both primary and recurrent Crohn's disease during a fifteen-year period with a minimum follow-up of eighteen months. Possible risk factors for recurrence were studied. They included duration of disease before primary surgery, the type of clinical presentation at onset (whether ``Perforating'' or ``Non-perforating''), the initial anatomical location, the presence of microscopic disease at the resection edges, the type of surgical procedure (anastomosis vs stoma), post-operative surgical complications and the age of the patient. The duration of the disease before the initial operation was the only significant factor related to the recurrence rate.

Background~Aims: Recurrence of lesions of Crohn's disease of the ileum within i year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery. Methods: In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a fivepoint score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed. Results: Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (Z 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (Z 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1. Conclusions: This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.

Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 × 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods. © 1994 Plenum Publishing Corporation.

Concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by solid-phase ELISA in tissue homogenates of mucosal biopsy specimens obtained from pelvic ileal pouches in 13 patients with pouchitis (reservoir ileitis) and 17 with pouches without pouchitis. Normal ileal mucosa was used as a control. IL-1β was detected in all tissue homogenates from patients with pouchitis compared with only 29% from pouches without pouchitis and none from controls. IL-6 and IL-8 were present in all pouchitis specimens, in 70% of the specimens from nonpouchitis and only 30% of specimens from controls. TNF-α was undetectable in all specimens examined. The concentrations of IL-1β, IL-6, and IL-8 were significantly greater (P

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 Crohn's disease. Thirty-one patients previously studied with x-ray underwent abdominal 111In scans and ultrasonography (US). Sensitivity and specificity of US in detecting lesions seen with 111In scan were 77% and 92.8%, respectively. Sensitivity and specificity of 111In 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 P0.01). Our experience suggests that US provided information about the location and inflammatory activity of lesions similar to that obtained from 111In scan.

The in 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 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 (>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. © 1991 Plenum Publishing Corporation.

Background - Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. Aims - To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. Patients - Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. Methods - A positive ANCA serology was determined with a standard indirect immunofluroescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-. generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. Results - There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-6. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). Conclusions - p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

Steroids are very useful drugs in the treatment of active Crohn's disease (CD), but clinical relapses after steroid withdrawal may be very high.

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-1β release from fresh and cultured colonic biopsies and IL-1β 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-1β activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1β were detected only in 3 plasma samples, all from active patients. Significantly more IL-1β was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p

Barium enema and colonoscopy are contraindicated in severe attacks of ulcerative colitis because of the possibility of toxic megacolon and perforation. The authors have assessed abdominal ultrasound in 38 patients with severe ulcerative colitis. Ultrasound revealed bowel wall thicknesses ranging from 3.9 to 9.2 mm (mean 7.7) extending the whole length of the colon, to the transverse colon, and to the descending colon, respectively, in 18, 10 and eight patients. The degree of bowel thickening was related to the severity of inflammation based on clinical, sigmoidoscopic and histological evaluation. In two patients, ultrasound showed a thin bowel wall distended without motility, suggesting the diagnosis of toxic megacolon (confirmed radiologically). An excellent correlation (95%) was found between ultrasound and technetium-99 scanning. Ultrasound might be a reasonable first investigation in the assessment of patients with severe ulcerative colitis.

Background Recent data indicate that 5-aminosalicylic acid (5-ASA) is most effective in preventing relapse of Crohn's disease in patients with a short duration of remission before enrolment. Aim To evaluate the efficacy of oral 5-ASA treatment, started immediately after achieving steroid-induced remission, in preventing clinical relapses of Crohn's disease. Methods Patients with active Crohn's disease, achieving remission on steroids, were randomized to oral 5-ASA 3 g/day or placebo, while steroids were tapered over 6 weeks. The trial was terminated after interim analysis showed a slightly higher relapse rate in the 5-ASA group, and the calculated probability of seeing a statistically significant difference by completing the study was minimal. Results Final analysis included 117 patients (58 taking 5-ASA and 59 taking placebo; follow-up 9.2 ± 6.5 months). Cumulative relapse rates at 6 and 12 months were 34% and 58% in 5-ASA patients and 31% and 52% in placebo patients, respectively (rate difference + 0.095; 95% CI = −0.085– + 0.274). Subgroups analysis showed that 5-ASA was equally ineffective in patients with ileal, colonic or ileocolonic disease. Conclusions Contrary to previous results, in our study early introduction of treatment with oral 5-ASA did not prevent relapse in Crohn's disease patients treated with steroids to induce remission.

Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects.We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn's disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes.Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7).In patients with Crohn's disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse.

We describe two families in which some members are affected by familial polyposis syndrome: in one family a case of ulcerative colitis and in the other a case of Crohn's disease were found. This is the first report about this family association, but in our opinion the fact that two cases have been found in one series suggests that this association could be more frequent than reported so far. The research for a genetic pattern of inflammatory bowel disease could be addressed towards chromosome 5.

The activation of circulating polymorphonuclear leukocytes was determined in terms of superoxide radical generation and granulocyte elastase release in untreated patients with ulcerative colitis (N=10) and Crohn's disease (N=9) in remission and in control subjects (N=10). Superoxide radical generation was determined by monitoring spectro-photometrically the reduction of ferricytochrome, after stimulation of cells with phorbol myristate acetate. Plasma elastase concentration was measured by a solid-phase enzyme immunoassay technique as the complex with alpha-1-proteinase inhibitor. Superoxide formation by polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease was significantly lower compared with controls [median (range) nmol/min/mg protein: Crohn's disease 7.8 (7.1-9.6); ulcerative colitis 8.25 (7.4-10.3); controls 14.7 (13.6-15.8)] (P < 0.001), while no difference was found between the two groups of patients. In contrast plasma elastase levels in patients with ulcerative colitis and Crohn's disease were similar to that of controls. This defective respiratory burst of polymorphonuclear leukocytes in patients with inflammatory bowel disease in remission, in absence of an altered degranulation, could represent an important factor for the pathogenesis of these diseases. © 1994 Plenum Publishing Corporation.

Rectal treatment with enemas, foams, and suppositories is the most efficient method of delivering an adequate quantity of locally active drugs to the distal colon. In a pilot study carried out by colonoscopy in four patients, it was observed that 4 g 5-ASA in 20 ml foam spread up or beyond the splenic flexure and more extensively than 2 g 5-ASA in 10 ml foam. Therefore we have undertaken a study in order to compare by scintigraphy the colonic distribution of 4 g 5-ASA foam versus 4 g 5-ASA in 100 ml liquid enemas in 10 patients with ulcerative colitis using a crossover randomized design. Both preparations were labeled with 100 MBq [99mTc] sulfur colloid before administration. Anterior scans were taken at intervals for 4 hr. Activity, expressed as a percentage of total radioactivity, was measured in the rectum, sigmoid, descending, transverse, and ascending colon. Six patients had the same extent of spread with the two formulations; in three patients with foam and in one patient with enema a greater spread was observed. the foam reached the upper limit of disease in all cases, while enema failed in two cases. The maximum spread with foam was observed within 30 min in nine of 10 patients compared with seven of 10 after enema. Compared to enema, foam distributes more uniformly and seems to persist longer in the descending and sigmoid colon. The 5-ASA colonic foam shows some more favorable characteristics than enema for the local treatment of left-sided ulcerative colitis. © 1992 Plenum Publishing Corporation.

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 < 0.001) and patients with inactive disease (p < 0.001). The RI of the SMA was significantly lower in active disease than in controls (p < 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 < 0.01) and patients with inactive disease (p < 0.05). The RI of the SMA was significantly lower in active disease than in controls (p < 0.005) and in patients with inactive disease (p < 0.005). Doppler follow-up studies were carried out in 10 patients after initiation of treatment. A normalization of hemodynamic variables occurred in 7 of 10 patients in whom clinical and laboratory remission was noted (p < 0.01 for Vmean and p < 0.05 for RI). This preliminary study suggests the utility of Doppler US in the non-invasive evaluation of hemodynamic changes in IBD. Whether this can translate into a helpful tool for the assessment of disease activity and patient management requires further investigation. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

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

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.

not available

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

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 4g 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. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

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. © 1990 Raven Press, Ltd., New York.

The clinical course of Crohn's disease in 131 patients was studied for a mean period of 4.2 +/- 3.2 years. The clinical activity of the disease, expressed as percentage of patients per year in an active phase, is high in the first year (70.2 percent) and progressively decreases during subsequent years (25 percent after seven years). The percentage of patients who needed steroid treatment is high during the first year (68 percent) and falls to 19 percent after seven years. An operative risk rate of 54 percent was registered, with a probability of reoperation equal to 34 percent. Clinical relapse after the first surgery occurred in 70 percent of cases. The registered mortality was 6.9 percent, with a ratio of 6 to 1 between observed and expected mortality. In conclusion, the disease, while showing a tendency to reduce its activity over the years, is burdened by a risk of surgery and mortality which progressively increases with time.

The effect of domperidone, a peripheral antidopaminergic drug, on sigmoid motor activity in the irritable bowel syndrome, has been evaluated by measuring pressures in 3 opentipped tubes perfused with distilled water at a constant flow rate of 0.636 ml/min and inserted into the sigmoid colon. Domperidone 20 mg i.v. in 10 patients, did not induce any significant change in basal motility, but prevented the increase in motor activity produced by the infusion of dopamine 5 micrograms/kg/min for 10 min. It appears that domperidone had no effect on sigmoid motor activity, although the inhibition of dopamine-induced motility confirms the presence of specific dopaminergic receptors in the colon and the antidopaminergic action of domperidone.

Sulpiride, a benzamide derivative, selectively antagonizes dopaminergic receptors within and outside the central nervous system. Dopamine has previously been shown to increase colonic motility. In the present investigation the motor response of the pelvic colon to a standard 1000 calorie meal was studied in 12 patients with the irritable bowel syndrome. The meal induced a significant increase in motor activity, lasting for 1 h and greatest in the first 30 min. In 6 cases the administration of sulpiride 100 mg i.m. significantly reduced the postprandial increase in colonic motor activity. Thus dopaminergic receptors may be involved in the colonic motor response to food.

The prognosis of ulcerative colitis has been studied in 122 patients with this disease who had been referred to Bologna from various parts of Italy and were then followed up. The overall mortality rate was 4.9% and the percentage of patients who were treated by total colectomy was 15.5%. Postoperative mortality was 10.5%, and the percentage of patients who developed carcinoma of the colon was 0.8%. All these figures fall within the range of values for the relevant variables quoted by previous authors from different countries. It is concluded that the prognosis of ulcerative colitis in the 122 Italian patients in the present study was similar to that reported previously in patients of other nationalities.

Cimetropium bromide is an antimuscarinic compound with antispasmodic properties. Its effect on meal-stimulated sigmoid motor activity in 30 patients with the irritable bowel syndrome, mainly with pain and constipation, has been evaluated. The mechanical activity of the sigmoid colon was recorded with a probe with three open-tipped tubes ending 45, 30, and 15 cm from the anal margin. After a recording period of 60 min, 5 mg cimetropium bromide or saline was given i.v., according to a randomized, double-blind design 5 min before a 1000 calorie meal, and motility was then recorded for 2 h. The meal caused a significant increase in motor activity for 90 min in the saline-treated group. Cimetropium bromide abolished the peak of motor activity 10-20 min after the meal and significantly inhibited postprandial colonic motility for at least 2 h (p less than 0.01). This effect provides a rationale for the use of cimetropium bromide in treatment of the irritable bowel syndrome.

The purpose of this work was to evaluate the efficacy of adding a caloric supplement to the daily diet of malnourished outpatients with Crohn's disease in remission. Seven underweight patients following a one month period of weight-maintenance diet took 10 KCal/kg Ideal body weight/day of a nutritionally complete preparation (carbohydrates 82%, proteins 10%) as supplement for 2 months. At the end of this period, a significant increase in body weight (mean 3 ± 0.3%) as well as a sum of 10 skinfolds (mean 13.1 ± 4.0%) were observed. No significant change in arm muscle circumference was recorded. All the patients then continued with their weight-maintenance diet alone for a further 2 months and during this period a mean decrease of 0.65 ± 0.7% of body weight occurred. A caloric supplement may be a means of increasing body weight and anthromometric variables in underweight patients with Crohn's disease.

In an attempt to know the exact retrograde spread of high-dosage 5-aminosalicylic acid enemas, we have studied eight patients with active left-sided colitis, by adding a small amount of barium sulfate to the enemas and by checking the spread radiologically after 15 minutes, 1 hour, and 6 hours. Four grams of 5-aminosalicylic acid in 100-ml enemas and 4 gm in 200-ml enemas were used. The same experiment was repeated in a subsequent attack, with enemas labeled with technetium-99m and checked by scintiscans in five of these patients. We always have observed a volume-dependent spread of enemas but, interestingly, in the patients studied with technetium-99m there was always a wider spread than that which was detected with barium enemas. In all five patients, 100-ml enemas reached the splenic flexure. In two patients with total colitis, a progression of 100-ml technetium-99m enemas was performed in the transverse colon, but the maximum opacity remained in the left side. We can conclude that 4 gm of 5-aminosalicylic acid in 100-ml enemas can be suitable for treating patients with left-sided colitis, and will represent a valid addition for patients with more extensive colitis.

Some laboratory investigations are abnormal during the course of Crohn's disease (CD). We investigated the trend of some of these laboratory tests in a group of patients with CD to study the relationships between an activity index made up of such laboratory parameters only (LCDAI) and the usual Crohn's disease activity index (CDAI). One hundred thirty-one examinations of 63 patients were evaluated. At each investigation, besides calculation of the CDAI, 10 laboratory investigations were carried out. Three gastroenterologists independently gave an overall evaluation of the laboratory activity for each of the 131 examinations on the basis of the results of the blood tests alone. The sum of the evaluations was used as an independent variable on which a laboratory index was developed by multiple regression analysis. C reactive protein, red cell sedimentation rate, acid alpha 1-glycoprotein, alpha 1-antitrypsin, and white blood cells had an important share in the development of this laboratory index. The evaluation of the relationships existing between LCDAI and CDAI showed that in patients with moderate to severe clinical disease activity, LCDAI was constantly altered. The same happened in 55% of cases in clinical remission, which suggests an inflammatory activity that is not clinically evident. These results point to the advisability of supplementing a predominantly clinical index, such as CDAI, with a laboratory index such as LCDAI in the evaluation of CD.

Anorectal motility and gastrointestinal transit time were studied in 25 patients complaining of non-organic constipation. Colonic pain was reported by 14 patients, it was absent in the remaining 11. The group with painful constipation was composed of four men and 10 women and age onset of the symptom was 22.1 +/- 5.1 years. The other group was composed only of women and painless constipation was reported to have begun at 7.9 +/- 2.2 years previously. In the group presenting painful constipation higher values of the anal maximum resting pressure, of the amplitude of the rectoanal inhibitory reflex, lower values of sensation threshold, need to evacuate, maximum tolerable volume were recorded, in comparison with those registered in the painless constipation group. All these differences were significant. In the latter group the total transit time was always very slow (186.0 +/- 4.7 h), while it was quite variable in the other group, so that the mean was in the normal range (79.0 +/- 10.0 h). The data show that two different patterns of motor abnormalities can be recognised in constipated patients. The presence of colonic pain can suggest the characteristics of the underlying motor abnormality.

This study is a double-blind controlled trial in 86 patients of the efficacy of retention enemas containing 4 g 5-aminosalicylic acid (5-ASA), believed to be the active metabolite of sulphasalazine, compared with retention enemas of 100 mg of hydrocortisone for the topical treatment of mild or moderate ulcerative colitis. 5-ASA enemas given to 44 patients were significantly more effective than hydrocortisone enemas given to 42 patients, and produced 93, 93, and 77% remission in clinical, sigmoidoscopic, and histological terms, respectively, compared with corresponding remission rates of 57, 54, and 33% in the hydrocortisone treated patients.

Thirty-nine patients with documented active distal proctitis (

5-Aminosalicylic acid (5-ASA) is the active component of Salazopyrin and induces a prompt and excellent improvement, when administered as high dosage enema, in patients suffering from active ulcerative colitis. However, the high instability of this metabolite makes its large use difficult. We aimed at finding a more stable preparation and therefore wondered whether another similar molecule, i.e. 4-aminosalicylic acid (4-ASA, generally known as p-aminosalicylic acid, PAS), which differs from 5-ASA only for the position of the amino group, might be a valid alternative. Therefore, 4-ASA at 2 g dosage, administered as rectal enema, was compared to an equivalent preparation of 5-ASA. We carried out a double-blind therapeutical trial, in which 63 patients, similarly matched for age, sex and extent of disease, took part. The analysis of the final results showed that in the 5-ASA group, 26 (81%) out of 32 patients improved clinically, 25 (78%) sigmoidoscopically and 15 (46%) histologically. In the group of the 31 patients treated with 4-ASA, 24 (77%) improved clinically, 24 (77%) sigmoidoscopically and 13 (41%) histologically. Since no difference was registered between the two types of treatment (p = 0.141, X2 test), 4-ASA could be a possible form of treatment for active ulcerative colitis.

A controlled trial has been carried out in order to compare the efficacy of enemas containing a high dosage of 5-ASA (4g) versus enemas containing hydrocortisone 100 mg. The trial was conducted on 86 patients, 44 of whom received 5-ASA and 42 received hydrocortisone. The results were favorable in terms of clinical, sigmoidoscopic, and histologic criteria for 5-ASA treatment. Other aspects have been investigated, such as retrograde spread of enemas which have been shown to reach the left colon. No nephrotoxicity was detected. The long term experience confirmed the preliminary positive results. © 1987 Plenum Publishing Corporation.

5-aminosalicylic acid (5-ASA) is a new treatment for patients suffering from ulcerative colitis but only limited information is available about its rectal absorption. We therefore studied seven patients with ulcerative colitis in remission, and five with active disease to determine acetylated and free 5-ASA plasma concentrations and urinary acetyl 5-ASA after the administration of three different types of enemas: (2 g 5-ASA/100 ml, 4 g/100 ml, and 200 ml). In patients in remission urinary acetyl 5-ASA excretion was dose and volume dependent (p less than 0.01; p less than 0.05) but this correlation was absent in active disease. Because aminosalicylates are usually eliminated through the kidney, these low values (10% in active disease and 19% in those in remission) suggest that the beneficial action may be local. Urinary recovery was significantly lower in patients with active disease (p less than 0.01; p less than 0.02). No accumulation of 5-ASA was found in plasma after repeated daily administration.