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Background: Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis., Aim: To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3mg) enema and foam versus mesalazine (2g) enema and foam in mild-moderate distal ulcerative colitis., Patients: In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate., Methods: Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline (T0), 4 (T4) and 8 weeks (T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student's t-test or the Wilcoxon-Mann-Whitney test., Results: Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6-0.8] versus mesalazine 79% [95% confidence interval 0.6-0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7-0.9] versus mesalazine 90% [95% confidence interval 0.7-1.0]; p=n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1-0.3] versus mesalazine 28% [95% confidence interval 0.1-0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2-0.5] versus mesalazine 52% [95% confidence interval 0.3-0.6]; p=n.s.). The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups (T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p<0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p<0.001 for all three groups; T8 versus T0: p<0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p<0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0-4 versus 3, range 0-12; p<0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0-9 versus 3.5, range 0-8; p=n.s.). The safety profile was favourable for all groups., Conclusions: Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis.

Introduction: Corticosteroids are the gold standard in the treatment of moderate to severe Crohn's disease but are often associated with severe and potentially dangerous side effects. Despite an initial clinical response many patients become steroid dependent or require further steroid courses in the long term. The aim of the present study was to assess the probability of the need for further steroid treatment in Crohn's disease patients following steroid-induced remission and to establish if clinical variables can predict further steroid needs. PATIENTS AND All, Methods: patients at their first steroid course and with corticosteroid-induced remission, defined as a Crohn's Disease Activity Index (CDAI) <150, 4 wk after steroid weaning, were studied and observed at follow-up for 12 months. The main outcome was clinical relapse requiring further steroid treatment. Statistical analysis was performed using the Kaplan-Meier method and multivariable Cox proportional hazard regression model taking into consideration gender, age at diagnosis, disease location and behavior, smoking habits, CDAI score before steroid treatment, and C reactive protein values at steroid weaning, as covariates., Results: A total of 77 patients with steroid-induced remission were included. One-year follow-up was available in 75 of the 77 patients (97.4%). During follow-up 49 of 75 patients (65.3%) maintained remission or presented mild relapse not requiring steroids while 26 of 75 patients (34.6%) had moderate to severe relapse requiring further steroid treatment. The cumulative probability of a course free from steroids was 93.3%, 82.6%, 78.6%, and 66.6% at 3, 6, 9, and 12 months, respectively. At multivariate analysis, increased C reactive protein at steroid weaning and penetrating complications were independent risk factors for further steroid requirement (OR 5.57, 95% CI 1.20-25.91, P= 0.001 and OR 4.20, 95% CI 1.76-10.04, P= 0.005, respectively)., Conclusion: Despite an initial clinical response and successful steroid tapering, 35% of patients required further steroid treatment within 1 yr. An increased C reactive protein value, at steroid weaning, despite clinical remission, and penetrating complications may predict further steroid requirement in already steroid responsive patients.

Background: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features., Aim: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids., Material and Methods: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology., Results: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients., Conclusions: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.

Background: Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn's disease. AIM.: To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms., Patients and Methods: Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets., Statistical Analysis: chi-square test, odds ratio (95% confidence interval)., Results: Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn's disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring-summer compared to autumn-winter (odds ratio 1.39; 95% confidence interval 1.03-1.87; p<0.03). This variation was observed in Crohn's disease (odds ratio 1.59; 95% confidence interval 1.00-2.51; p<0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86-1.88; p=0.27)., Conclusions: These data indicate that onset of Crohn's disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases.

Introduction: Despite the explosion of biological therapies, the old immunosuppressants continue to play a pivotal role in the management of inflammatory bowel diseases., Aim: To assess the appropriateness of immunosuppressants-azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and thalidomide-in the treatment of inflammatory bowel disease by using RAND/University of California Appropriateness Method., Methods: The RAND method consists of a combination of evidence from the literature and experts' opinions. Appropriateness has been defined to mean that the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin. A panel of 10 experts from the Italian Group for Inflammatory Bowel Disease has rated, in two rounds, on a scale from 1 to 9, the appropriateness of each indication selected by the Promoter Centre, on the basis of their own clinical experience. An indication was considered appropriate if the median of the panelists' ratings fell within the area 7-9, inappropriate in the area 1-3 and uncertain in the area 4-6. A total of 2781 indications were grouped into 13 categories (mild to moderate Crohn's disease; severe Crohn's disease; fistulizing Crohn's disease; steroid-dependant and -resistant Crohn's disease; maintenance of remission induced by medical treatment in Crohn's disease; maintenance of remission induced by surgery in Crohn's disease; mild to moderate ulcerative colitis; severe ulcerative colitis; steroid-dependant and -resistant ulcerative colitis; maintenance of remission induced by medical treatment in ulcerative colitis; extra-intestinal manifestations in inflammatory bowel disease; pregnancy and inflammatory bowel disease; azathioprine-resistant or -intolerant inflammatory bowel disease patients)., Results: Of the 2781 scenarios, 212 (7.6%) were rated appropriate, 645 (23.2%) uncertain and 1924 (69.2%) inappropriate. The most relevant results were: in steroid-dependant or -resistant Crohn's disease, azathioprine, 6-mercaptopurine and methotrexate were defined as appropriate in 25 (86.2%) and 14 (48.3%) of the 29 scenarios respectively; in Crohn's disease, azathioprine and 6-mercaptopurine were defined as appropriate combined with Infliximab (bridge therapy); in steroid-dependant or -resistant ulcerative colitis, azathioprine and 6-mercaptopurine were defined as appropriate in 45 (77.6%) out of 58 scenarios, while methotrexate was defined appropriate only after previous azathioprine failure; in severe ulcerative colitis, cyclosporine A was defined as appropriate only after previous failure with steroids; in azathioprine-intolerant or -resistant inflammatory bowel disease patients, methotrexate was appropriate in 20 (66.7%) out of 30 scenarios; it is inappropriate to stop azathioprine treatment before conception in the presence of active disease. The use of FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate or uncertain., Conclusions: Results of this study show that only azathioprine, 6-mercaptopurine and methotrexate are appropriate in the treatment of inflammatory bowel diseases. Cyclosporine A was found to be appropriate only in severe ulcerative colitis after the failure of steroids. FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate but experience with these agents is somewhat limited.

Background and Aims: Crohn's disease is a heterogeneous entity. The Vienna Classification defines three different clinical patterns: 'non-stricturing, non-penetrating', 'stricturing' and 'penetrating'. Aim of this study was to assess the change in clinical behaviour over time and to evaluate whether an evolution towards penetrating complications can be predicted., Methods: A total of 139 patients with non-penetrating behaviour at the time of diagnosis were included. The mean follow-up was 4.84 years (range 1-23.2 years). The clinical behaviour, according to the Vienna Criteria, was assessed at the diagnosis and at the end of follow up. Statistical analysis was performed by means of the Kaplan-Meier method and standard logistic regression analysis., Results: The cumulative probability of a change in clinical behaviour was 22, 38 and 63% at 3, 6 and 12 years, respectively, and the cumulative probability of developing penetrating complications was 22, 33 and 55% at 3, 6 and 12 years, respectively. Young age at diagnosis (<40 years) and a stricturing behaviour are independent risk factors of developing major penetrating complications (internal fistula, mass or abscess): OR=6.0, 95% CI 1.1-30.5; OR=4.0, 95% CI 1.5-10.9, respectively, but not perianal disease., Conclusions: The behavioural classification of Crohn's disease is a dynamic model in which each status should be considered as not fixed but evolutive. Perianal disease should be considered a distinct pattern of penetrating behaviour.

Treatment of symptomatic diverticular disease of the colon is aimed at the relief of symptoms and the prevention of major complications. The efficacy of fiber supplementation and of anticholinergic and spasmolytic agents remains controversial. Antibiotics are commonly used in the treatment of inflammatory complications of diverticular disease. Data from open labelled and randomized controlled trials do suggest the efficacy of rifaximin in obtaining symptomatic relief in patients with diverticular disease. Approximately 30% therapeutic gain compared to fiber supplementation only can be expected after one year of intermittent treatment with rifaximin. Considering the safety and tolerability of rifaximin, this drug can be recommended for patients with symptomatic uncomplicated diverticular disease., (Copyright (c) 2005 S. Karger AG, Basel.)

The diphosphate moiety of geranylgeranyldiphosphate (GGdP) was replaced with metabolically and hydrolytically stable analogous polar portions, in an attempt to obtain new geranylgeranyltransferase (GGTase) inhibitors, which could also be selective over congener enzyme farnesyltransferase (FTase). In particular, the phosphonomethylphosphorylmethoxy derivative showed the highest inhibition potency, accompanied by a satisfactory GGTase/FTase selectivity.

Unlabelled: This study provides the long-term follow-up data on the efficacy of infliximab in the treatment of chronic refractory pouchitis complicated by fistulae following ileo-pouch anal anastomosis (IPAA) for ulcerative colitis (UC)., Methods: Seven patients (4 F, 3 M) with chronic refractory pouchitis complicated by fistulae were included in an open study. Pouchitis was diagnosed by clinical plus endoscopical and histological criteria. Fistulae were: pouch-bladder in 1, vaginal in 3, perianal in 2, both vaginal and perianal in 1 patient. Extraintestinal manifestations were present in 4 patients. All the patients were refractory to antibiotics (3 patients also to steroids). Crohn's disease was carefully excluded in all patients after re-evaluation of the history, re-examination of the original proctocolectomy specimen, examination of the proximal small bowel. Patients received Infliximab 5 mg/kg at 0, 2 and 6 weeks. Azathioprine (2.5 mg/kg) was also started for all patients as bridge therapy. Clinical response was classified as complete, partial, and no response. Fistulae closure was classified as complete, partial, and no closure. The pouchitis disease activity index (PDAI) and quality of life (QoL) were also used as outcome measures., Results: Clinically, all patients improved. At 10-week follow-up, 6 out of 7 patients had a complete clinical response, and 5 out of 7 patients had complete fistulae closure. At 10- week follow-up, median PDAI dropped from 12 (baseline) (range, 10-15) to 5 (range, 3-8); median QoL decreased from 37 (range, 33-40) to 14 points (range, 9-18), respectively. Extraintestinal manifestations (erythema nodosum and arthralgiae) completely remitted soon after the first infusion of infliximab. Clinical response and fistulae closure were maintained in the long-term follow-up., Conclusions: These results seem indicate that infliximab plus azathioprine may be recommended for the treatment of refractory pouchitis complicated by fistulae following IPAA for UC.

In this paper, an HPLC method is proposed for a routine, rapid and simple analysis of heroin samples confiscated from the illicit market, based on a new type of packing for HPLC columns (monolithic silica). Acetonitrile and pH 3.5 phosphate buffer solution were used under both isocratic and gradient conditions. Under our analytical conditions, all the components of a typical mixture of an illicit heroin sample proved to be fully separated into well-resolved peaks in 7 min. Analytical linearity and accuracy of the method were also studied for all analytes using tetracaine hydrochloride as the internal standard.

Objective: To highlight the current available evidence in antireflux surgery through a systematic review of randomized controlled trials (RCTs)., Summary Background Data: Laparoscopic fundoplication is currently suggested as the gold standard for the surgical treatment of gastroesophageal reflux disease, but many controversies are still open concerning the influence of some technical details on its results., Methods: Papers related to RCTs identified via a systematic literature search were evaluated according to standard criteria. Data regarding the patient sample, study methods, and outcomes were abstracted and summarized across studies. Defined outcomes were examined for 41 papers published from 1974 to 2002 related to 25 RCTs. A meta-analysis was performed pooling the results as odds ratios (OR), rate differences (RD), and number needed to treat (NNT). Data given as mean and/or median values were pooled as a mean +/- SD (SD)., Results: No perioperative deaths were found in any of the RCTs. Immediate results showed a significantly lower operative morbidity rate (10.3% versus 26.7%, OR 0.33, RD -12%, NNT 8), shorter postoperative stay (3.1 versus 5.2 days, P = 0.03), and shorter sick leave (20.1 versus 35.8 days, P = 0.03) for laparoscopic versus open fundoplication. No significant differences were found regarding the incidence of recurrence, dysphagia, bloating, and reoperation for failure at midterm follow-up. No significant differences in operative morbidity (13.1% versus 9.4%) and in operative time (90.2 versus 84.2 minutes) were found in partial versus total fundoplication. A significantly lower incidence of reoperation for failure (1.6% versus 9.6%, OR 0.21, RD -7%, NNT 14) was found after partial fundoplication, with no significant differences regarding the incidence of recurrence and/or dysphagia. Routine division of short gastric vessels during total fundoplication showed no significant advantages regarding the incidence of postoperative dysphagia and recurrence when compared with no division. The use of ultrasonic scalpel compared with clips or bipolar cautery for the division of short gastric vessels showed no significant effect on operative time, postoperative complications, and costs., Conclusions: Laparoscopic antireflux surgery is at least as safe and as effective as its open counterpart, with reduced morbidity, shortened postoperative stay, and sick leave. Partial fundoplication significantly reduces the risk of reoperations for failure over total fundoplication. Routine versus no division of short gastric vessels showed no significant advantages. A word of caution is needed when implementing these results derived from RCTs performed in specialized centers into everyday clinical practice, where experience and skills may be suboptimal.

Background: Three variants of the NOD2/CARD15 gene are strongly associated with susceptibility to Crohn's disease; however, striking racial and geographic differences of their frequency have been described., Aims: We have compared the allele frequencies of familial cases of Crohn's disease recruited in a multicentre study across Italy, in order to disclose possible geographic heterogeneity. Moreover, we also compared the allele frequencies in sporadic cases of Crohn's disease and healthy controls from Southern Italy with those reported in other two populations from Central and Northern Italy., Subjects and Methods: A total of 731 subjects were genotyped for the polymorphism of three main variants (R702W, G908R and 1007 fs): 152 patients were familial cases of Crohn's disease, 183 were healthy first-degree relatives, 180 were sporadic cases of Crohn's disease, and 216 were unrelated healthy subjects., Results: The frequency of the frameshift mutation (1007 fs) was significantly higher in both familial and sporadic cases of Crohn's disease (P = 0.000001), and healthy first-degree relatives (P = 0.0001) compared to controls. At least one risk allele was found in 44% of familial Crohn's disease patients, compared to 7% of healthy controls (OR = 4; CI = 2-6.5). Two risk alleles were found in 14% of familial Crohn's disease, compared to less than 1% of controls (OR = 26: CI = 4-129)., Conclusions: Our data confirm the strong correlation between the 1007 fs variant and Crohn's disease, in both familial and sporadic cases. Moreover, no significant difference of allele frequencies was detected in familial cases, sporadic cases and healthy controls among different geographic areas of Italy.

Objectives: To compare early with delayed cholecystectomy for the treatment of acute lithiasic cholecystitis: a meta-analysis of prospective randomized trials., Methods: Pertinent studies were selected from the Medline, Embase, Cancerlit, HealthSTAR and Cochrane Library Databases, references from published articles, and reviews. Twelve prospective randomized trials (9 addressing open cholecystectomy and 3 laparoscopic cholecystectomy) were selected. Conventional meta-analysis according to the DerSimonian and Laird method was used for the pooling of the results. The rate difference (RD) (95% CI) and the number needed to treat (NNT) were used as a measure of the therapeutic effect., Results: Cumulative operative and perioperative mortality and morbidity were 0.9% and 17.8%, respectively, for open cholecystectomy and 0% and 13.1%, respectively, for laparoscopic cholecystectomy. The pooled RD for operative complications in early surgery was 1.37% (95% CI =-3.78% to 6.53%; p= 0.2) for open cholecystectomy and 3.11% (95% CI =-15.10% to 8.87%; p= 0.6) for laparoscopic cholecystectomy. In laparoscopic cholecystectomy the cumulative conversion rate to open cholecystectomy was 21.5%. The pooled RD for conversion rate in early laparoscopic cholecystectomy was -7.99% (95% CI =-18.46% to 2.47%; p= 0.1; NNT = 13). Total hospital stay (mean +/- SD) was significantly shorter in the early surgery group (9.6 +/- 2.5 days vs 17.8 +/- 5.8 days; p < 0.0001). More than 20% of patients referred to delayed surgery fail to respond to conservative management or suffer recurrent cholecystitis in the interval period., Conclusions: Early operation (open or laparoscopic) does not carry a higher risk of mortality and morbidity compared to delayed operation and should be the preferred surgical approach for patients with acute lithiasic cholecystitis.

Phosphonoacetamido(oxy) groups have proven to be good mimics of the diphosphate portion in geranylgeranyl protein transferase I (GGTase I) inhibitors. The introduction of small alkyl groups (Me, Et) into the diphosphate mimic moiety caused a further decrease in collateral farnesyl protein transferase (FTase) inhibitory activity, thereby improving GGTase I over FTase selectivity.

Purpose: To assess the role of magnetic resonance enteroclysis (MRE) in patients with Crohn's disease, in order to identify involved segments, define the extension and evaluate transmural alterations., Materials and Methods: Eighteen patients with known Crohn's disease were studied with MR (1.5 T), with breath-hold T2-weighted TSE, T2-weighted TSE SPIR and 3D T1-weighted sequences before and after gadolinium injection (0.2 mmol/kg) in the coronal and axial planes. The small bowel was distended by the administration of 2 l of methylcellulose through a nasojejunal tube and drug induced hypotony. Typical patterns of Crohn's disease, such as mucosal abnormalities, parietal thickening and narrowing of the bowel, prestenotic dilation, fibrofatty proliferation and enlarged lymph nodes were analysed on radiological and MRE images. MRE was performed within 30 days from conventional radiological studies (conventional enteroclysis and small bowel follow-through)., Results: Good distension of the bowel wall was obtained in all cases. MRE assessed the presence of parietal thickening and narrowing of the bowel wall (14/18 cases) and the presence of prestenotic dilatation (12/18 cases). Vascular enhancement (14/18 cases), transmural abnormalities (8/18 cases), fibrofatty proliferation (3/18 cases), abscess formation (2/18 cases) and enlarged mesenteric lymph nodes (6/18 cases) were also observed. MRE missed small fistulas which were visible in radiological studies in two patients., Conclusions: MRE appears to be a promising technique in patients with Crohn's disease. Due to limited spatial resolution MRE could be a useful adjunct to radiological studies and in following up selected groups of patients with prior known disease.

Severe gastrointestinal hemorrhage is an uncommon complication of Crohn's disease. Most bleeding episodes originate from colonic ulcers or ulcerated areas. The management of severe gastrointestinal bleeding in Crohn's disease is a therapeutic challenge. Several approaches including surgical resection, specific medical therapy of Crohn's disease, endoscopic treatment, or angiographic intervention have been attempted, but recurrence of bleeding is high. Monoclonal anti TNFalpha antibodies (infliximab) can induce relatively rapid mucosal healing. We report two cases of severe recurrent Crohn's disease presenting with massive lower gastrointestinal bleeding in which infliximab induced rapid mucosal healing and prevented recurrent bleeding.

New fluorescent ligands for adenosine receptors (ARs), obtained by the insertion, in the N(6) position of NECA, of NBD-moieties with linear alkyl spacers of increasing length, proved to possess a high affinity and selectivity for the A(3) subtype expressed in CHO cells. In fluorescence microscopy assays, compound 2d, the most active and selective for human A(3)-AR, permitted visualization and localization of this human receptor subtype, showing its potential suitability for internalization and trafficking studies in living cells.

The phenolic "A-ring" of natural and synthetic estrogen receptor (ER) ligands was effectively replaced by a planar six-member ring formed through an intramolecular hydrogen bond within a salicylaldoxime. Thus, oxime 1, a structural analogue of a triarylethylene estrogen, showed a significant binding affinity for the ER. The OH of the oxime function appears to mimic the phenolic OH present in more "classical" ER ligands because the binding reduced when the oxime OH is methylated (2) or absent (3).

Background: Death rate for patients with ulcerative colitis has changed over last few decades. Recent studies indicate that cumulative long-term mortality is comparable to that in general population, and that deaths may depend on causes not strictly related to colonic disease., Aim: To evaluate overall and cause-specific mortality rate in a large group of Italian patients with ulcerative colitis., Methods: A total of 2,066 ulcerative colitis patients aged >18 years consecutively diagnosed in twenty Italian Gastroenterology Units between 1964 and 1995 were followed-up from diagnosis until 1997. Standardised Mortality Ratios and Relative Survival Ratios were calculated., Results: Overall mortality of patients with ulcerative colitis was comparable to that in general population with 93 deaths observed versus 92.1 expected (standardises mortality ratio, 1.0; 95% confidence interval, 0.8-1.2). Significantly higher mortality was observed in patients under 30 years of age at diagnosis (standardised mortality ratio, 2.7; 95% confidence interval, 1.3-4.9), and in those diagnosed before 1974 (standardised mortality ratio, 2.7; 95% confidence interval, 1.1-5.7). Proctocolitis and complications from surgery were mentioned in 11 and 5 certificates, respectively. A significant excess of deaths was observed for colorectal cancer (colon: standardised mortality ratio, 3.0; 95% confidence interval, 1.0-6.9; rectum: standardised mortality ratio, 4.4; 95% confidence interval, 1.2-11.3), and haemolymphopoietic neoplasms (standardised mortality ratio, 2.8; 95% confidence interval, 1.0-6.1), in particular multiple myeloma and non-Hodgkin lymphoma. A significant deficit of deaths was observed for cancer of the respiratory system (standardised mortality ratio, 0.3; 95% confidence interval, 0.1-1.0)., Conclusions: This study confirms that, also in Italy, mortality of patients with ulcerative colitis is comparable to that in general population. Only 12% of deaths were due to ulcerative colitis itself, whereas 10% of deaths were attributed to colorectal cancer. Deaths from colorectal cancer occurred, on average, 9 years after diagnosis of ulcerative colitis, suggesting that the risk of cancer is not limited to patients with long-standing colitis. As to mortality for causes unrelated to colitis, there was an excess of deaths due to malignancies of the haemolymphopoietic system.

We have recently shown that open reading frame Rv1086 of the Mycobacterium tuberculosis H37Rv genome sequence encodes a unique isoprenyl diphosphate synthase. The product of this enzyme, omega,E,Z-farnesyl diphosphate, is an intermediate for the synthesis of decaprenyl phosphate, which has a central role in the biosynthesis of most features of the mycobacterial cell wall, including peptidoglycan, arabinan, linker unit galactan, and lipoarabinomannan. We have now purified Z-farnesyl diphosphate synthase to near homogeneity using a novel mycobacterial expression system. Z-Farnesyl diphosphate synthase catalyzed the addition of isopentenyl diphosphate to omega,E-geranyl diphosphate or omega,Z-neryl diphosphate yielding omega,E,Z-farnesyl diphosphate and omega,Z,Z-farnesyl diphosphate, respectively. The enzyme has an absolute requirement for a divalent cation, an optimal pH range of 7-8, and K(m) values of 124 micrometer for isopentenyl diphosphate, 38 micrometer for geranyl diphosphate, and 16 micrometer for neryl diphosphate. Inhibitors of the Z-farnesyl diphosphate synthase were designed and chemically synthesized as stable analogs of omega,E-geranyl diphosphate in which the labile diphosphate moiety was replaced with stable moieties. Studies with these compounds revealed that the active site of Z-farnesyl diphosphate synthase differs substantially from E-farnesyl diphosphate synthase from pig brain (Sus scrofa).

The synthesis of the two enantiomers of 3-(3,4-dimethylphenyl)-1-propylpiperidine 1, a potent and selective D4 dopaminergic ligand, was performed. The 3-(3,4-dimethylphenyl)- 1-propylpiperidine with the R configuration showed an affinity for the D4 receptors 6-fold higher than the corresponding enantiomer with the S configuration. Furthermore, the (R)-1 enantiomer proved to be highly selective for D4 receptors with respect to D2-D3 receptors, with a Ki ratio higher than 25,000, while the (S)-1 enantiomer was about 100-fold less selective than the (R)-1 one.

Aim: To perform a meta-analysis to assess the effectiveness and safety of oral budesonide for inducing remission in active Crohn's disease and for preventing relapse in Crohn's disease with medically- or surgically-induced remission., Methods: All randomized, double-blind controlled trials involving oral budesonide therapy in Crohn's disease were retrieved from a Medline search, reviews articles or their bibliographies. Of 83 articles retrieved, 12 met the inclusion criteria. Data extraction was performed by three independent observers and scoring disagreements were resolved by consensus., Results: Six trials tested budesonide in active disease and six in quiescent disease. Budesonide was less effective than conventional corticosteroids for inducing remission of active Crohn's disease (pooled rate difference, RD -8.5%; 95% CI: -16.4 to -0.7%; P=0.02), but corticosteroid-related adverse events were reduced (RD -22.4%; 95% CI: -32 to -12.8%; P < 0.001). In quiescent Crohn's disease, budesonide was as effective as placebo for preventing relapse in medically induced remission (RD -0.8%; 95% CI: -9.9 to 8.3%; P=0.42) and endoscopic recurrence in surgically induced remission (RD -3.5%; 95% CI: -16.9 to 9.8%; P=0.30). In the long term treatment, budesonide had an occurrence rate of corticosteroid-related adverse effects similar to placebo (RD 5.3%; 95% CI: -3.9 to 14.5%; P=0.30)., Conclusions: Budesonide is significantly less effective than conventional corticosteroids for inducing remission in active Crohn's disease, but the risk of corticosteroid-related adverse effects is significantly reduced. Budesonide is not effective in preventing relapse of Crohn's disease after medically- or surgically-induced remission.

Clinical-endoscopic parameters of UC presentation were studied in 1705 out-patients, observed consecutively in 17 Italian gastroenterology centers (males 60.2%; average age at diagnosis 38.5 +/- 16.4 years), and were subdivided arbitrarily into quartile age groups at diagnosis (0-25, 26-35, 36-50, >50). A significantly greater prevalence in males, increasing with age, was shown at diagnosis (P = 0.0002), which seems to correlate with the condition of being an ex-smoker, most frequently found in males. The greater frequency of exsmokers could also, in part, justify the second peak of incidence in old age. Greater colitis extent, greater clinical activity, and greater use of steroids as the first therapeutic step are shown to prevail among younger patients and among women (P = 0.02 and P = 0.019, respectively). The same is observed for symptoms mainly representing clinical severity such as diarrhea, fever, and weight loss (P = 0.004; P = 0.006; P = 0.009, respectively). This study confirms the UC risk factor represented by the condition of being an ex-smoker and shows a greater severity of illness on diagnosis in younger patients.

Intestinal ischaemia is an uncommon complication of recreational cocaine abuse. We report the case of a 36-year-old male who underwent emergency surgery for acute abdomen. At laparotomy, the transverse colon appeared markedly oedematous, dilated and with subserosal haemorrhage. Segmental resection was performed and microscopic examination of the resected specimen showed focal necrosis of the mucosa with a patchy polymorphonuclear and mononuclear infiltrate. The submucosa was markedly thickened due to oedema; focal haemorrhage was observed and blood vessels were dilated but showed no structural abnormalities or thrombosis. These findings were consistent with ischaemic colitis. No risk factors for intestinal ischaemia were present but the patient stated that he had injected cocaine i.v. the day before the onset of symptoms. He was not a cocaine abuser but occasionally sniffed, smoked or injected cocaine. Cocaine use should be considered in the aetiological diagnosis of intestinal ischaemia in young patients.

Carcinoid tumours are rare neoplasms and their behaviour seems to change with the localization; in fact, appendiceal and rectal carcinoids show a better long-term survival than the more aggressive ileal and colonic analogues. The Authors report their experience in the surgical treatment of 13 G.I. carcinoid neoplasms, in which the clinical course was sometimes unpredictable suggesting there is much to discover about the behaviour of these particular tumours.

Thromboembolic disease is a well-recognized but very uncommon complication of inflammatory bowel disease. The mechanisms of the increased risk of thrombosis are not well understood: although several coagulation abnormalities have been described in inflammatory bowel disease patients, it is not clear whether they actually contribute to hypercoagulation or whether they are nonspecific markers of inflammation. Antiphospholipid antibodies (anticardiolipin antibodies and/or lupus anticoagulant) have recently been associated with an increased risk of thrombosis, particularly cerebrovascular disease in young patients. We report the case of a 33-yr-old female with severe ulcerative colitis at first attack who developed thrombosis of the superior and inferior longitudinal dural sinuses. No risk factors for thrombosis or coagulation abnormalities were observed; however, lupus anticoagulant was detected in the serum. The patient was successfully treated with osmotic agents, prophylactic anticonvulsant, and antiplatelet therapy, combined with i.v. steroids. After 6 months, the colitis is in remission, and the neurological recovery is good even if not yet complete.

Background: Adhesion molecules play a major role in the pathogenesis of inflammatory skin diseases by regulating lymphocyte trafficking and homing in an inflamed area., Methods: The expression of the lymphocyte function-associated antigen-1 (LFA-1) and of its ligand, the intercellular adhesion molecule-1 (ICAM-1) has been studied in psoriatic skin lesions of 10 patients with guttate, nummular, and palmoplantar psoriasis. In addition, the peculiar immunophenotype of infiltrating cells (CD3, CD4, CD8, CD25) and their correlation with HLA-DR expression before and after treatment with oral cetirizine, a highly selective, third generation H1-receptor antagonist has been examined using the labeled avidin biotin (LAB) system., Results: Cetirizine treatment modulated in vivo the expression of adhesion molecules LFA-1/CAM-1 as shown in all cases by decreased levels of their expression on keratinocytes and on dermal endothelial cells (P < 0.001). The expression of HLA-DR on keratinocytes and endothelial cells was also inhibited after treatment. The numbers of infiltrating CD3-, CD4-, CD8-positive cells were reduced, whereas there was no significant modification of CD25-positive cells within the epidermis and the dermis., Conclusion: This open clinical trial suggests that cetirizine could be effective in treating psoriasis: (1) for its symptomatic control on itching; (2) for its immunopharmacologic modulation of leukocyte integrins and on the immunophenotype pattern of infiltrating and resident cells, and (3) for contributing to the clearing of the lesions clinically.

Diverticular disease of the colon is a common health problem in western societies. Most patients with colonic diverticula are asymptomatic; it has been estimated that only 20% of individuals harboring diverticula will develop symptoms and signs of illness and a minority will develop major complications. Medical treatment of diverticular disease is aimed to the relief of symptoms and to prevent inflammatory complications. High fiber diets and antispasmodics are widely used in the treatment of uncomplicated diverticular disease although their real efficacy has not been fully elucidated. Antibiotics are used to treat major inflammatory complications of diverticular disease but apparently there is no rationale for their use in uncomplicated disease where an inflammatory component is, by definition, excluded. However two recent papers suggest a possible role of rifaximin, a broad-spectrum poorly absorbable antibiotic, in the management of mild acute diverticulitis and in obtaining symptomatic relief in patients with uncomplicated disease. Prospective studies with an adequate sample size per group of treatment are needed to assess the efficacy of cyclic long term administration of poorly absorbable antibiotics in preventing major complications of diverticular disease.

Diverticular disease of the colon is a common health problem in western societies. Most patients with colonic diverticula are asymptomatic; it has been estimated that only 20% of individuals harboring diverticula will develop symptoms and signs of illness and a minority will develop major complications. Although the efficacy of a high fiber diet in the management of symptomatic uncomplicated diverticular disease is still controversial, bran and bulking agents are commonly used. Antibiotics are used to treat major inflammatory complications of diverticular disease but apparently there is no rationale for the use of antibiotics in uncomplicated disease where an inflammatory component is by definition excluded. In a multicenter open trial, 217 patients with symptomatic uncomplicated diverticular disease were treated with glucomannan (110 pts) or with glucomannan plus a poorly absorbable antibiotic (rifaximin 400 mg bid for 7 days each month) (107 pts). Clinical evaluation was performed bimonthly for 12 months using a global score system for 8 clinical variables. After 12 months, patients treated with glucomannan plus rifaximin showed a 63.9% reduction of the score as compared to 47.6% in patients treated with glucomannan only (p < 0.001). Cyclic administration of rifaximin appears to be of some advantage in obtaining symptomatic relief in uncomplicated diverticular disease.

The aim of the present study was to evaluate the role of sulglycotide, a molecule with gastroprotective properties, in monotherapy and in association with H2-antagonists in the maintenance treatment of duodenal ulcer. The study was performed using a fully randomized experimental design. Following endoscopic confirmation, 626 patients with healed duodenal ulcer were treated for 6 months with sulglycotide 200 mg tid (293 patients) or sulglycotide + H2-antagonists (333 patients). After 2, 4 and 6 months patients underwent a clinical control whereas an endoscopic control was performed after 6 months. The cumulative percentage of recidivation was 3.6% in the sulglycotide + H2-antagonist treated group, whereas the group treated with sulglycotide alone showed a recidivation rate of 15.4% (p < 0.001). These findings suggest the utility of combined sulglycotide and H2-antagonist treatment in the maintenance therapy for duodenal ulcer.

Endoscopic morphology of duodenal ulcer (DU) have been studied in 188 patients repeatedly observed in the course of medical therapy (120 with conventional therapy and 68 with Cimetidine alone). The evolutive behaviour under treatment reveals a clear speeding up effect of Cimetidine on the healing time with a smaller number of failed and delayed recoveries and a lower frequency of relapses than after conventional therapy. Endoscopic morphology allows a limited but significant forecast of therapeutic outcome of DU. The shape, the number and partly the location of ulcer in the bulb appear to be the most significant parameters with prognostic influence both on the healing time and on the frequency and early development of relapses.

Segregation analysis of 996 families in which the gene for beta-thalassemia was segregating showed no distortion of expected Mendelian ratios. No appreciable frequency of sporadic cases was detected. It was suggested that segregation distortion is not a mechanism which contributes to the maintenance of polymorphism in the beta-thalassemia system in the population of the Ferrara area.