Search

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.

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.

In Crohn's disease, prednisone is believed to be ineffective for relapse prevention. Because all patients with Crohn's 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.

A controlled trial has been carried out in order to compare the efficacy of enemas containing a high dosage of 5-ASA (4 g) 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.

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.

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.

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 exact role of 111In leukocyte scanning in the assessment of clinical activity of Crohn's disease (CD) is still a matter of controversy. In our center we studied 22 patients with CD (8 with active disease) with standard 111In labelled mixed leukocyte scans. We determined the extent of the lesion measured as lesion-occupied cells on scanned area and the degree of inflammatory activity assessed as count ratio between the involved region and the iliac crest. Particularly in delayed scans, these scintigraphic parameters showed good correlation with clinical and laboratory indices of disease activity. In our series, only 6 patients had completely negative scans. They were in clinical and laboratory remission, and 5 of them had undergone surgery for CD during the previous year, with no radiological and/or endoscopic findings of recurrence. Among the other 8 patients in clinical remission, 5 had positive early scans, while the rest showed persistent delayed images. Moreover both early and delayed leukocyte scans were positive in 8 cases in which disease was undoubtedly active. A 1-year follow-up was available for 14 patients in clinical remission when 111In-scan was performed. During this period, 3 patients, all of whom had had early and delayed positive 111In-scan, suffered from clinical relapse; no clinical relapses were documented in patients with only 4th hour positive scans. In conclusion, in our series, 111In-scan was also frequently positive in patients in clinical remission; in this patient subset persistent images on delayed scans might suggest the risk of clinical relapse.

Malnutrition is frequently reported in chronic diseases with involvement of gastrointestinal tract, such as Crohn's disease; however, information about this problem is scarce, and available only for hospitalized patients with severe disease. The aim of this study was to evaluate the nutritional status of 44 consecutive outpatients with Crohn's disease in remission or in a stage of low activity (CDAI less than 250). Eighteen of the patients weighed less than 90% of ideal weight and 5 of these weighed less than 80%. Triceps skinfold, a measure of fat store, was less than or equal to 15th percentile in 30%; arm muscle circumference, indicative of muscle mass, was less than or equal to 15th percentile in 59%. The alteration of weight and arm muscle circumference was greater in patients with midly active disease (p less than 0.005) and in those with ileal and ileocolic involvement. Caloric intake, assessed by a seven day questionnaire, was generally good (35.9 +/- 11 Kcal/kg ideal weight/day) and sufficient to maintain weight. Creatinine height index was elevated in 55% of the whole group. Serum albumin was decreased in only 2 cases, and haemoglobin in only 4. Our results show that malnutrition is a serious problem also in outpatients with Crohn's disease. Anthropometric parameters are more sensitive indicators than conventional laboratory studies.

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.

The role of allergic responses to dietary antigens in the pathogenesis of inflammatory Bowel Disease (IBD) remains speculative. We studied 50 patients with Ulcerative Colitis (UC), 50 patients with Crohn's Disease (CD) and 100 healthy controls (HC) matched for sex and age. In these patients total serum IgE and specific IgE to ten selected foods were estimated using Phadebas PRIST and RAST. There was no significant difference in the total serum IgE level between UC, CD and HC. The percentage of positive reaction to specific IgE was significantly lower in HC (score 1-2: 7%; score 2: 3%) compared with UC (score 1-2: 24%, p less than 0.004; score 2: 8%, n.s.) and CD (score 1-2: 16%, n.s.; score 2: 12%, p less than 0.03). In CD with colic or ileocolic involvement, the percentage of patients with a positive response to RAST was significantly greater (score 1-2: 26%; score 2: 21%) than in CD with ileal involvement. The considerable increase in positive results to RAST in IBD may be due to a greater absorption of antigens through the diseased wall.

The prognosis of ulcerative colitis has been studied in 122 patients with this disease who had been referred to Bolgna 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.

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).

Production of leucocyte migration inhibition factor by peripheral blood leucocytes in response to challenge with gluten fractions has been proposed as a reliable in vitro test for the diagnosis of coeliac disease. We have performed the leucocyte migration inhibition test with two different gluten fractions, GFIII and B2, in untreated and treated coeliac patients, patients with other intestinal diseases (abnormal controls) and healthy controls, and evaluated the sensitivity, specificity and positive and negative predictability of the test for the diagnosis of coeliac disease. Using GFIII as antigen leucocyte migration was significantly inhibited, compared to healthy controls, not only in treated and untreated coeliacs but also in abnormal controls. Using B2 gluten subfraction as antigen only treated coeliacs and abnormal controls differed significantly from healthy controls. The elevated number of abnormal controls showing migration inhibition consistently affected the diagnostic value of the test, which did not vary using B2 subfraction instead of GFIII as antigen. Our study confirms previous observations of gluten sensitization, as detected by leucocyte migration inhibition, in coeliac patients but strongly questions the claim that coeliac disease can be diagnosed on the basis of a positive leucocyte migration inhibition test without the need for intestinal biopsy.

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.

Plasma levels of total 5-aminosalicylic acid (5-ASA) were determined after a single administration of 2 g and 4 g 5-ASA enemas to 6 patients with ulcerative colitis. The mean plasma levels and AUC values confirmed that the active substance is poorly absorbed by rectal route.

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 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.

Currently there are no completely reliable methods for predicting an impending relapse in Crohn's disease. As approximately 50% of patients in remission [Crohn's disease activity index (CDAI) less than 150] show some laboratory abnormalities, we inquired whether these alterations might be of value for predicting relapse. We prospectively studied 41 patients with Crohn's disease who had been showing CDAI less than 150 for at least 6 mo before entering the study and who were not receiving any long-term treatment. The 41 patients were studied at the ninth and at the 18th month after inclusion in the study. Disease activity was monitored by CDAI calculation and by measurement of erythrocyte sedimentation rate, white blood cell count, hemoglobin, albumin, alpha 2-globulin, serum iron, C-reactive protein, alpha 1-glycoprotein, and alpha 2-antitrypsin. Seventeen of the 41 patients had a clinical relapse during follow-up. At the beginning of the study the patients who later relapsed showed a remarkable alteration of acid alpha 1-glycoprotein (p less than 0.0001), alpha 2-globulin (p less than 0.0003), and erythrocyte sedimentation rate (p less than 0.0006), in comparison with the patients who remained in remission. by discriminant analysis a prognostic index with these laboratory investigations provided a high percentage (88%) of accuracy according to the outcome at the 18th month.

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).

In 34 consecutive patients in whom the diagnosis of Hirschsprung's disease (HD) was suspected, the reliability of clinical symptoms, radiological parameters, and anorectal manometry was retrospectively and blindly evaluated by three independent investigators. In 19 patients the diagnosis of HD was histologically proved, while in the remaining 15 cases the diagnosis of idiopathic constipation was justified by persistent success of medical treatment at regular follow-up. Anorectal manometry was correctly diagnostic in all the patients who were examined. The recto and inhibitory reflex, recorded in all the patients with idiopathic constipation was absent in patients suffering from HD. Moreover, other manometric parameters, peculiar to HD were found: a significant lower anal resting pressure and pain threshold, as well as a decreased frequency of spontaneous rhythmic oscillations. The reliability of radiological and clinical data for these diagnoses appeared to be inadequate. Therefore, the diagnosis of HD can be confidently stated only on the basis of manometric investigations.

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.