Genetic determinants of alcohol addiction and metabolism: a survey in Italy.

BACKGROUND: Although multiple genes are involved in alcoholism and can contribute differently to the risk of dependence and liver damage, no studies have investigated susceptibility to addiction in combination with susceptibility to liver damage due to differences in ethanol metabolism. METHODS: We evaluated the role of three polymorphic genes related to alcohol metabolism (CYP2E1) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in Florence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control series of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: No difference was found in the frequency of the CYP2E1 Rsal c2 allele (2.5% among alcoholics and 4.7% among controls) and the DraI C allele (6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1 genotype (B1/B1 or B1/B2) was significantly associated with smoking (p = 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant association, however, emerged in the group of alcoholics, with a five times higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus positive alcoholics. CONCLUSIONS: Overall, our results provided no evidence of an increased susceptibility to develop alcoholism that was associated with the three genotypes investigated, either alone or in combination. An increased risk of developing liver cirrhosis for S/S homozygous carriers among alcohol-dependent patients was observed for the first time.

A capture-recapture estimate of inflammatory bowel disease prevalence: the Florence population-based study.

BACKGROUND: A recent population-based epidemiological study identified the patients with a diagnosis of ulcerative colitis or Crohn's disease resident in the metropolitan Florence area in the period 1978-1992 and defined their vital status on 31 December, 1992. AIMS: To estimate the completeness of Inflammatory Bowel Disease prevalent case ascertainment in the study area. SUBJECTS AND METHODS: In a Registry, specifically developed during the study, 767 patients fulfilled the criteria for the definition of prevalent cases as of 31 December, 1992. At the same time, we had access to an independent source of potential patients: the Regional Health Department kept a list of all Inflammatory Bowel Disease patients allowed free access to specific health care provided only to selected diagnostic categories. We then compared the two different sources and used a capture recapture analysis to estimate the number of cases missed by both sources. RESULTS: A total of 331 patients were reported by both sources, 436 were found only in the Registry while a large group of potential cases not present in our Registry was found only in the List. After careful confirmation of the diagnosis for each individual patient and contact with his/her physician, we identified an additional 102 cases that were included in the final population series of 869 prevalent cases. This capture-recapture analysis led to a revised estimate of 1,003 prevalent cases, suggesting that 134 patients had been missed by both sources, resulting in an Inflammatory Bowel Disease prevalence rate of 186 per 100,000. CONCLUSIONS: According to this method our previous study underestimated the true prevalence of 13.4% (95% confidence interval: 9.8-16.6%). On account of some degree of negative dependence between the two sources the loss was probably in the lower range of this interval. Completeness of case ascertainment should be evaluated and discussed in all studies designed to provide population-based estimates for health care planning.

Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study.

OBJECTIVES: To assess the efficacy of a combination of oral and topical 5-aminosalicylic acid (5-ASA) for the maintenance treatment of ulcerative colitis, we undertook a double-blind randomized clinical trial. METHODS: Patients aged 18 to 65 yr (with disease extent greater than proctitis only) were eligible for inclusion in the study if they met the following criteria: (a) history of two or more relapses in the last year; (b) achievement of remission in the last 3 months (with maintenance of remission for at least 1 month). Patients enrolled in the study were randomly assigned to one of the two following 1-yr treatments: (1) combined therapy with 5-ASA tablets 1.6 g/day and 5-ASA enemas 4 g/100 ml twice weekly; (2) oral therapy with 5-ASA tablets 1.6 g/day and placebo enemas/twice weekly. The main end point of the study was the maintenance of remission at 12 months. RESULTS: Upon completion of the study, relapse occurred in 13 of 33 patients in the combined treatment group versus 23 of 36 patients in the oral treatment group (39 vs 69%; p = 0.036). No significant side effects related to treatment were observed in either group. A simplified pharmacoeconomic analysis shows that this form of combined treatment can have a favorable cost-effectiveness ratio. CONCLUSIONS: Our results indicate that 5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. This form of combination treatment can be appropriate for patients at high risk of relapse.

Spondyloarthritis in patients with ulcerative colitis.

BACKGROUND: Extraintestinal manifestations can complicate the course of ulcerative colitis and can influence the prognosis. AIMS: Sixty-eight patients of the metropolitan area of Florence with ulcerative colitis in clinical and endoscopic remission were evaluated to establish the presence of spondyloarthritis. PATIENTS AND METHODS: Each patient was studied through clinical and radiological evaluations to assess the presence of joint involvement. RESULTS: We found signs of spondyloarthritis in 19 patients (27.9%). Four of them had a classic ankylosing spondylitis (5.8%) and in 3 of them the aplotype HLA B27 was present. Sacroileitis was found in 9 (13.2%) patients (monolateral in 5 cases and bilateral in 4). Six patients (8.8%) showed an unclassifiable form of arthritis, fulfilling the Amor criteria. In 13 of 19 patients with spondyloarthritis, we found a pancolic extension of disease (68.4%). CONCLUSIONS: The results obtained from our series of ulcerative colitis patients reveal a lower proportion of cases of spondyloarthritis than that found in other Italian studies. We are planning further investigations on a larger population to better assess the prevalence of spondyloarthritis in ulcerative colitis patients.

A population-based study of inflammatory bowel disease in Florence over 15 years (1978-92).

BACKGROUND: In the group of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are considered to be more frequent in Western countries and in areas with a high socioeconomic development but relatively infrequent in southern Europe. Sporadic reports have indicated a lower incidence and a milder course of the disease in Mediterranean countries. Although conclusive data on this point are still lacking, recent reports suggest an increase in both incidence and prevalence rates. METHODS: The incidence of UC and CD during the period January 1978 to December 1992 and their prevalence on 31 December 1992 were estimated in the 15-year-old population of the metropolitan area of Florence. Clinical, demographic, and follow-up information was collected for all identified IBD patients. RESULTS: A total of 796 residents (345 females and 454 males) were newly diagnosed as having IBD during the study period. Of these 593 had UC and 203 CD. The age-standardized incidence rates, calculated for each of five 3-year consecutive periods, rose from 3.8 (in 1978-80) to 9.6 per 100,000 person-years (in 1990-92) for UC and from 1.9 (in 1978-80) to 3.4 (in 1990-92) for CD. Both trends were statistically significant. The prevalence estimated on 31 December 1992 was 121.0 and 40.0 per 100,000 inhabitants for UC and CD, respectively. CONCLUSIONS: Our results confirm that IBD incidence rates and prevalence in this area of central Italy are currently comparable with those reported in northern Europe. These data are necessary for planning adequate health care services for IBD patients.

Intermittent versus continuous 5-aminosalicylic acid treatment for maintaining remission in ulcerative colitis.

We performed a 12-month clinical trial to compare the relative effectiveness of an intermittent 5-ASA regimen and a continuous 5-ASA regimen for the maintenance treatment of patients with ulcerative colitis in remission. Fifty patients with ulcerative colitis in remission for a minimum period of 1 month participated in the study. Twenty five patients received an intermittent treatment with 5-ASA tablets (2.4 g for the first week of each month) and 25 received a continuous treatment with tablets (1.6 g each day). Patients were assessed clinically every two months and endoscopically every 6 months. Our results show that the two treatments were equally effective. The relapse-free rates at 12 months were 71% in patients receiving the intermittent treatment and 66% in patients given the continuous treatment. This difference is not statically significant. Further studies are needed to assess whether the intermittent regimen can be an alternative to life-long treatment in patients who have maintained remission for a long period of time.

Effectiveness of 5-aminosalicylic acid for maintaining remission in patients with Crohn's disease: a meta-analysis.

OBJECTIVES: We conducted a meta-analysis of the published randomized clinical trials to evaluate the effectiveness of 5-aminosalicylic acid (5-ASA) for maintaining remission in inactive Crohn's disease. METHODS: The trials were identified by standard computerized techniques for literature search. All studies included in the meta-analysis were aimed at evaluating the effectiveness of 5-ASA in comparison with a control group receiving either no treatment or placebo. RESULTS: Our meta-analysis of five clinical trials published as full-length articles indicates that 5-ASA significantly reduces the relapse frequency in patients with inactive Crohn's disease [odds-ratios (95% CI): 0.56 (0.37-0.84) at 6 months, 0.47 (0.33-0.67) at 12 months, 0.53 (0.38-0.73) at 24 months]. The pooled relapse-free rates in the treatment group were 91% at 6 months, 84% at 12 months, and 72% at 24 months; the corresponding rates in the control group were 77%, 60%, and 52%. A second meta-analysis, conducted using the additional information deriving from four randomized trials published as abstracts, gave essentially the same results. CONCLUSIONS: Whereas our meta-analysis shows that the effectiveness of 5-ASA is statistically significant, a simple pharmacoeconomic assessment indicates that the cost for preventing each relapse can lie between $4,000 and $10,000. This cost compares favorably with the average cost for treating a relapse.

5-Aminosalicylic acid in pregnancy: clinical report.

Ulcerative colitis (UC) is a disease condition which typically affects young people; pregnancy is therefore frequent in women with this disease. 5-aminosalicylic acid (5-ASA) is known to be efficacious in maintaining remission of UC, but its safety in pregnancy has not yet been established. In the present study, the safety of 5-ASA was assessed in 16 women with UC (mean age: 31 years, range 25-35) who had a total of 19 pregnancies over the period from 1988 to 1992. All the patients were in clinical remission of UC at the beginning of pregnancy and were receiving a regular maintenance therapy with 5-ASA (ASACOL tablets, 1.2 g/day). During pregnancy, 4 women had a clinical relapse requiring treatment with higher doses of 5-ASA and, in some cases, with steroids. Our observations confirm that the treatment with 5-ASA does not affect the course of pregnancy nor does it damage the fetus, but it can protect from recurrences of UC.

Epidemiology of inflammatory bowel disease over a 10-year period in Florence (1978-1987).

The epidemiology of inflammatory bowel disease (IBD) in southern Europe is still not well-known. Sporadic reports have suggested a lower incidence and a milder course of the disease in Italy, but conclusive data are still lacking. To shed light on this issue, we conducted a retrospective study of IBD incidence (from January 1978 to December 1987) in the metropolitan area of Florence (650,000 inhabitants). We also estimated IBD prevalence at December 31, 1987. Our study included both in-patients and out-patients referred to the Gastroenterological and Surgical Departments of the area. The diagnosis was based on well-established clinical, endoscopical, radiological, histological and surgical criteria. Overall, nine-hundred IBD patients were identified, but only 359 (195 males, 164 females) met the eligibility criteria for inclusion in the incidence study (area of residence and period of diagnosis); of these, 263 had ulcerative colitis (UC), 96 had Crohn's disease (CD), and 6 had IBD. The average incidence rate of CD was 1.5/100,000 per year while its prevalence was 17.3/100,000. The average incidence rate of UC was 4.0/100,000 per year and the prevalence was 49.6/100,000. Both the incidence and the prevalence rates for UC and CD were higher in males than in females. This retrospective, hospital-based study shows that, in this area, the incidence rate of IBD has steadily increased over the period considered. Further studies specifically focused on risk factors are needed.

Combined therapy with 5-aminosalicylic tablets and enemas for maintaining remission in ulcerative colitis.

A combined therapy with 5-aminosalicylic (5-ASA) tablets (1.6gr/day) and 5-ASA enemas (4gr/twice weekly) was evaluated for maintaining remission of ulcerative colitis in 40 patients. All patients were in complete remission which had been maintained for at least 1 month. The remission was assessed by clinical, endoscopic and histological criteria. Clinical and endoscopical evaluations were performed at intervals of 2 and 6 months, respectively. The relapse-rate associated with this combined therapy was 7.5% at 6 months and 16% at 12 months. In comparison with previous investigations using continuous sulphasalazine, our study showed that the combination of 5-aminosalicylic tablets and enemas provided low relapse rates both at 6 and 12 months, suggesting a potential effectiveness in this form of treatment. Further studies are needed to confirm this result with controlled clinical trials.