Incidence of inflammatory bowel disease in Italy: a nationwide population-based study. Gruppo Italiano per lo Studio del Colon e del Retto (GISC)

BACKGROUND: The epidemiology of inflammatory bowel disease (IBD) in Southern Europe is still unclear. Sporadic reports suggest a lower incidence of IBD in Italy than in other Western Countries and the USA. METHODS: A nationwide population-based study was carried out to estimate IBD incidence rates in eight Italian cities. All new cases of IBD diagnosed over 4 years in the target populations were collected from multiple information sources. RESULTS: From 1989 to 1992, 509 ulcerative colitis (UC), 222 Crohn's disease (CD) and 10 undefined IBD cases were collected, giving age-adjusted incidence rates (per 100,000 per year) of 5.2 for UC and 2.3 for CD. Using the capture-recapture method, an estimated completeness of 0.81 was obtained for case archives, without appreciable and significant differences between areas. The rates computed after correcting underestimation were 6.8 for UC and 2.8 for CD. The sex ratio M/F was 1.7 for UC and 1.0 for CD. The highest age-specific incidence rates were between 30 and 39 years for UC and between 20 and 29 years for CD. CONCLUSIONS: The incidence rate of CD in italy is homogeneous between the cities investigated and lower than those reported for other Mediterranean countries. In contrast, the UC incidence rate is within the range of those reported in European studies. A wide variability in the UC rates between the cities was also observed. These results could be related to different environmental factors or the genetic background of the populations, or both.

Acute pancreatitis after azathioprine treatment for ulcerative colitis.

Inflammatory bowel disease, in addition to intestinal involvement, may be complicated also by other extra-intestinal manifestations. Moreover, drugs commonly employed in the treatment of ulcerative colitis and Crohn's disease may induce iatrogenic pancreatitis. Acute pancreatitis is described in two ulcerative colitis patients following azathioprine treatment.

Dietary habits as risk factors for inflammatory bowel disease.

OBJECTIVE: To examine the influence of dietary factors in Italian patients with ulcerative colitis and Crohn's disease. DESIGN: We studied dietary habits immediately prior to the onset of disease in 104 patients enrolled in a prospective, epidemiological study of the incidence of inflammatory bowel disease in Italy. METHODS: Each patient was interviewed using a recall questionnaire to provide information on the daily intake of nutrients. The differences in diet between patients and healthy subjects matched for age, sex and city of residence were determined. RESULTS: Our data confirm that patients with Crohn's disease and ulcerative colitis have a high intake of total carbohydrate, starch and refined sugar. This resulted in a significantly higher relative risk (P < 0.001) in both ulcerative colitis and Crohn's disease patients. Total protein intake was significantly higher in ulcerative colitis, but not in Crohn's disease patients, than in controls. Fibre consumption did not differ between patients and controls. CONCLUSIONS: Our results confirm that carbohydrate consumption is significantly higher in IBD patients than in healthy controls. Ulcerative colitis patients also consumed more total protein than controls. The pathogenetic significance of these findings, however, remains unclear.

Electromechanical activities of human uteri during extra-corporeal perfusion with ovarian steroids.

A new experimental system was designed to study human uterine activities based on the extra-corporeal perfusion of isolated human uteri. Electromechanical activities in the uterine wall were recorded using bipolar silver-silver electrodes, endoluminal pressure catheters and a dedicated acquisition, storage and analytical system. The electrical signals recorded were isolated spikes and rhythmic activities; the last being primarily associated with organized mechanical events. Perfusion media containing 17 beta-oestradiol alone or with progesterone were used for those uteri obtained during proliferative (n = 5) or secretory (n = 5) phases of the menstrual cycle, respectively. Progesterone caused a reduction of frequency (P < 0.001) and duration (P < 0.001) of the rhythmic electrical activity, and decreased the endoluminal pressure at both detection sites (P < 0.01). 17 beta-Oestradiol increased both frequency (P < 0.001) and duration (P < 0.001) of the rhythmic electrical activity as well as the endoluminal pressure at two different detection sites (3 and 5 cm from the fundus) (P < 0.05). Significant differences between the fundus and cervix sites in the uterine wall were detected. In conclusion, uterine perfusion would be useful to examine the effects of uterotonic and tocolytic drugs before administration to humans, at no risk to the patients. Oestrogens increase and progesterone decreases both electrical and mechanical uterine activities.

Epidemiological characteristics of inflammatory bowel disease in Bologna, Italy--incidence and risk factors.

Recently, in Bologna, an inflammatory bowel disease incidence of 7.7/10(5)/year has been calculated, about one third of that reported in Northern Europe, confirming the existence of a 'North-South gradient'. A first peak of incidence was observed at 20-29 years of age and a second peak at 60-69 years of age for ulcerative colitis (UC) alone. A prevalence of UC males, mainly after the 7th decade, and of Crohn's disease (CD) females in the first peak was found. A greater frequency of ex-smokers in UC, with a relative risk (RR) significantly higher in males for all age groups (RR = 6.1; p < 0.01) and of smokers in CD with a RR significantly higher in 20- to 29-year-old females (RR = 11.6; p < 0.05) was observed. A different pattern for the two diseases exists: male ex-smokers and young female smokers are at risk of developing UC and CD, respectively.

[Methods of analyzing gastrointestinal motor activity]. / Metodi di analisi dell'attività motoria gastrointestinale.

In an attempt to computerize the measurements of various analytical features of gastrointestinal motility signals, a brief description of these signals, particularly for myoelectric and contractile activities, is given. The study of myoelectrical activity includes frequency and coupling based on period (1/T) and Fast Fourier Transform (FFT) based correlation and spectral analysis techniques. The contractile signals are studied for motility index as an indication of the amount of activity, waveform features, propagational characteristics, and the frequency of contractions. To deal with situations where only electrical activities are recorded, a methodology for the analysis of spike bursts as per contractile activities is given.

Levels of zinc and thymulin in plasma from patients with Crohn's disease.

Levels of zinc in plasma from patients with Crohn's disease were significantly lower than those of sex and age matched controls. We also measured the level of plasmic thymulin, a hormone released by the thymus gland, which in its active form binds one zinc molecule. The zinc unbound form of thymulin is biologically inactive and its level in the blood is a very sensitive marker of even marginal zinc deficiency. Levels of active thymulin were significantly reduced in plasma from patients with Crohn's disease, whereas plasma concentrations of the inactive form was higher than in controls. The in vitro addition of zinc ions restored thymulin activity in plasma from patients with Crohn's disease, and induced the disappearance of the inactive form. These findings suggest the existence of a zinc dependent alteration regarding the biological function of thymic hormones in patients with Crohn's disease. Such a defect might explain some of the immunological abnormalities observed in these pathological conditions.

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

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.

Reduction by cimetropium bromide of the colonic motor response to eating in patients with the irritable bowel syndrome.

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.

Clinical course of Crohn's disease in Italy.

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.

A laboratory index for predicting relapse in asymptomatic patients with Crohn's disease.

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.

Importance of laboratory parameters in the evaluation of Crohn's disease activity.

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.

Dietary allergy evaluated by PRIST and RAST in inflammatory bowel disease.

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.

Dopamine-induced migrating myoelectrical complex-like activity in human duodenum.

The effect of dopamine on human gastric and small intestinal interdigestive motility was investigated in 12 subjects. Intestinal motility was recorded by means of a four-lumen polyvinyl probe with four open tips located 15 cm apart, continuously perfused with distilled water. In each subject during the same study, after recording two consecutive spontaneous phase III of migrating myoelectrical complexes and when a phase II appeared, dopamine was infused intravenously twice in a dose of 5 micrograms/kg/min for 15 min with an interval of 20 min between each infusion. In six subjects, the second dopamine infusion was preceded by a treatment with sulpiride (10 mg, intravenously, as bolus) or domperidone (10 mg, intravenously, as bolus), each considered a highly selective dopamine antagonist. The results show that dopamine stimulates duodenal motility producing a pattern similar to that observed in phase III of spontaneously occurring migrating myoelectrical complexes. The second dopamine infusion reproduced in all cases the same pattern of motility as observed during the first infusion. Sulpiride and domperidone prevented the effect of dopamine in all cases. It is therefore suggested that dopamine-induced duodenal motility may involve specific dopaminergic receptors.

Retrograde spread of 5-aminosalicylic acid enemas in patients with active ulcerative colitis.

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.

Anorectal motility and rectal sensitivity in chronic idiopathic constipation: effect of high-fiber diet.

The rectoanal inhibitory reflex and rectal sensitivity were evaluated in 13 patients with idiopathic chronic constipation and in 13 control subjects. A double balloon probe was used to stimulate and record the rectoanal inhibitory reflex and rectal sensitivity. The results showed a linear relationship between relaxation amplitude and the logarithm of rectal distending volume, and between relaxation duration and the logarithm of rectal distending volume, with a significant reduction of relaxation amplitude in the patient group. The rectal sensitivity thresholds were significantly increased in patients compared with controls. In 10 additional patients with chronic constipation, motility and sensitivity parameters were evaluated before and after 28 days of high-fiber diet. After diet, the values of relaxation amplitude were significantly increased, returning within normal range, but sensitivity parameters did not change. In conclusion, it appears that in adult chronic idiopathic constipation, anorectal motility and rectal sensitivity are altered, and that only motor abnormalities are corrected by a high-fiber diet.