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Biomedical subjects

M Vecchi

Publications and source records attributed to M Vecchi.

At least 19 recordsLinked to original sources
PubMed2006

Use of the Given Patency System for the screening of patients at high risk for capsule retention.

BACKGROUND: Capsule enteroscopy is a non-invasive diagnostic tool for the study of the small bowel. Due to the risk of capsule retention, capsule enteroscopy is contraindicated in patients with suspected small bowel strictures. The Given Patency Capsule is a disintegration time-controlled capsule developed to identify patients with strictures that may cause capsule enteroscopy retention. The presence of the patency capsule within the patient's body can be detected by a radio-frequency scanner. AIM OF THE STUDY: To evaluate safety and usefulness of the patency capsule in preventing capsule retention in patients at high risk. PATIENTS AND METHODS: Thirty-two patients were studied. Indications for patency capsule were: (A) Crohn's disease (18), (B) previous intestinal surgery (7), (C) previous obstruction (1), A+B (3), A+C (1), B+C (2). Patients were evaluated with the scanner at 72 h from ingestion. RESULTS: At 72 h, 24 patients had already excreted the intact capsule in the stool. Of these, two experienced abdominal pain during capsule passage. In the other eight patients, the scanner detected the presence of the patency capsule. Four of them excreted the capsule intact in the stool after 72-96 h, the remaining four never found the capsule in the stool. The 26 patients who excreted the patency capsule intact without experiencing abdominal pain were deemed eligible for the capsule enteroscopy procedure, which was performed uneventfully in the 25 who agreed to undergo the examination. CONCLUSIONS: The patency capsule is useful to identify, among patients at high risk, those who can be submitted to capsule enteroscopy without risks of capsule retention.

Adult↗
PubMed2006

Variants of OCTN1-2 cation transporter genes are associated with both Crohn's disease and ulcerative colitis.

BACKGROUND: Two variants in the organic cation transporter gene cluster have been recently reported to confer susceptibility to Crohn's disease (CD). AIM: To investigate these variants in CD and ulcerative colitis (UC), and their interaction with CARD15 gene and correlation to clinical subphenotypes. METHODS: Case-control association analysis was performed in 899 patients (444 CD and 455 UC) and 611 controls. The organic cation transporter gene cluster single nucleotide polymorphisms G207G-->C and 1672C-->T, the IGR2198a_1 single nucleotide polymorphism in the IBD5 locus, and the R702W, G908R and L1007finsC variants of CARD15 gene were genotyped by ABI-7700, restriction fragment length polymorphic analysis and multiplex pyrosequencing, respectively. RESULTS: The 1672TT and -207CC genotype frequencies were increased in both CD (OR = 1.5, P = 0.011; OR = 1.6, P = 0.002), and UC (OR = 1.5, P = 0.017; OR = 1.4, P = 0.033), respectively. Compared with controls, the TC haplotype frequency was increased in both CD (36% vs. 44%, P < or = 0.01) and UC (36% vs. 45%, P < or = 0.01). The frequency of the TC haplotype was 43% in CARD15-positive and 44% in CARD15-negative CD, respectively. Similar results were found in UC. In CD a significant association of the TC haplotype was found with presence of perianal fistulae (P = 0.007) and steno-fistulizing behaviour (P = 0.037). In UC, the TC haplotype was more frequent in patients with more extensive disease (P = 0.015), and those on immunosuppressives (P = 0.004). CONCLUSIONS: Organic cation transporter gene cluster variants may confer susceptibility to both CD and UC, and the TC haplotype may influence some clinical features of IBD, but does not interact with CARD15 variants.

Adult↗
PubMed2006

Antibodies to tissue-type plasminogen activator (t-PA) in patients with inflammatory bowel disease: high prevalence, interactions with functional domains of t-PA and possible implications in thrombosis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased prevalence of thromboembolic events. The pathogenetic mechanisms of these events include reduced fibrinolysis, which may be caused by antibodies to tissue-type plasminogen activator (t-PA). OBJECTIVES: To evaluate anti-t-PA antibodies in patients with IBD, considering clinical, biochemical and functional characteristics. PATIENTS AND METHODS: We immunoenzymatically measured anti-t-PA antibodies in plasma from 97 consecutive IBD patients and 97 age- and sex-matched healthy controls. We also assessed the antibody interactions with different epitopes of t-PA, the antibody inhibition on t-PA activity and the correlations with clinical features and other serum antibodies. RESULTS: IBD patients had higher median anti-t-PA antibody levels (5.4 U mL(-1) vs. 4.0 U mL(-1); P < 0.0001): 18 patients were above the 95th percentile of the controls (OR 5.3; 95% CI 1.7-16.3; P < 0.003), and the six with a history of thrombosis tended to have high levels (6.9 U mL(-1)). Anti-t-PA antibody levels did not correlate with IBD type, activity, location or treatment, or with age, sex, acute-phase reactants or other antibodies. The anti-t-PA antibodies were frequently IgG1 and bound t-PA in fluid phase; they recognized the catalytic domain in 10 patients and the kringle-2 domain in six. The IgG fraction from the three patients with the highest anti-t-PA levels slightly reduced t-PA activity in vitro. CONCLUSIONS: The prevalence of anti-t-PA antibodies is high in IBD patients. By binding the catalytic or kringle-2 domains of t-PA, these antibodies could lead to hypofibrinolysis and contribute to the prothrombotic state of IBD.

Adult↗
PubMed2005

Carriage of CARD15 variants and smoking as risk factors for resective surgery in patients with Crohn's ileal disease.

BACKGROUND: It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated. AIM: To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor. METHODS: We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 +/- 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs). RESULTS: Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up (P < 0.05). Ileal resection was the only variable independently associated with CARD15 variants at multivariate analysis (OR 3.8; 95% CI 1.6-9.2; P = 0.003). Kaplan-Meier analysis showed that ileal resection was favoured both by CARD15 variant-carriage (P = 0.01) and by smoking (P = 0.05), but smoking did not affect progression to surgery in variant carriers (P = 0.31). Thirteen of 14 (93%) patients being resection-free at 15-year follow-up, had CARD15 wild-type genotype (P = 0.01), whereas only seven (50%) had never smoked (P = 1.0). CONCLUSIONS: In summary, CARD15 variant-associated Crohn's ileitis is virtually committed to stricturing and/or penetrating disease and, eventually, to resective surgery. Smoking accelerates progression to surgery in patients with wild-type CARD15 genotype, but it seems to exert no additional effect in CARD15-variant carriers.

Adult↗
PubMed2005

Appropriateness of immunosuppressive drugs in inflammatory bowel diseases assessed by RAND method: Italian Group for IBD (IG-IBD) position statement.

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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Kallikrein-kinin system in inflammatory bowel diseases: Intestinal involvement and correlation with the degree of tissue inflammation.

BACKGROUND: Tissue kallikrein and its natural inhibitor, kallistatin, play opposite roles in the generation of bradykinin, a potent mediator of inflammation. Observations on experimental models and humans with ulcerative colitis suggest a pathogenetic role of the kallikrein-kinin system in inflammatory bowel diseases. AIM: To evaluate tissue kallikrein and kallistatin in intestinal tissue samples from Crohn's disease and ulcerative colitis patients with different degrees of disease involvement. PATIENTS AND METHODS: Full-thickness surgical intestinal samples were obtained from 144 subjects (38 normal controls, 32 inflammatory controls, 38 Crohn's disease, 36 ulcerative colitis) and tested for kallikrein and kallistatin by immunoperoxidase techniques. RESULTS: Compared with controls, kallikrein immunoreactivity was significantly weaker in goblet cells (p=0.0001) and significantly stronger in interstitium (p=0.0001) of the Crohn's disease and ulcerative colitis samples. Kallistatin colocalised with kallikrein, with almost no reactivity in goblet cells but strong reactivity in interstitium of inflammatory bowel disease patients (p=0.0001 versus controls). The kallikrein and kallistatin depletion of goblet cells and the increased interstitial kallikrein and kallistatin reactivity correlated with the degree of tissue inflammation (p=0.0001). Disease-free samples had normal kallikrein and kallistatin patterns. CONCLUSIONS: Kallikrein-kinin system is actively involved in inflammatory bowel disease as a result of the release of kallikrein in the intestinal extracellular space; this involvement correlates with the degree of tissue inflammation. The normal pattern observed in the disease-free samples seems to rule out a genetic defect of kallikrein and kallistatin in inflammatory bowel diseases.

Adult↗
PubMed2005

Multidrug resistance 1 gene polymorphisms are not associated with inflammatory bowel disease and response to therapy in Italian patients.

BACKGROUND: Host genetic factors may be important in determining not only disease susceptibility, but also disease behaviour and response to therapy in inflammatory bowel disease. Two polymorphisms (C3435T and G2677T/A) of the multidrug resistance 1 gene have been correlated with the altered P-glycoprotein expression and function in humans, and associated with predisposition to ulcerative colitis and Crohn's disease. AIM: To investigate the contribution of these polymorphisms to disease susceptibility and response to medical therapy. METHODS: A total of 946 inflammatory bowel disease patients (478 Crohn's disease, 272 males, mean age 43 +/- 14 years and 468 ulcerative colitis, 290 males, mean age 48 +/- 15 years) and 450 healthy controls were genotyped for the single nucleotide polymorphisms C3435T and G2677T/A. Patients were also classified on the basis of response to medical therapy (mesalazine, steroids, immunosuppressives and infliximab). RESULTS: Both single nucleotide polymorphisms were in Hardy-Weinberg equilibrium and significant linkage disequilibrium. No significant difference in the allele, genotype, and haplotype frequencies was found in both Crohn's disease and ulcerative colitis patients compared with the controls. No correlation with clinical features was found, except for a reduced frequency of extra-intestinal manifestations in Crohn's disease patients with the G2677T genotype (40%) compared with GG2677 and 2677TT genotypes (54% and 58%, respectively) (P = <0.02). No significant difference was also found after stratifying the patients on the basis of their response to medical therapy. CONCLUSION: The investigated polymorphisms of the multidrug resistance 1 gene have no significant role in disease susceptibility and response to medical therapy in our Italian population of inflammatory bowel disease patients.

Case-Control Studies↗
PubMed2005

Heartburn and multiple-site foregut perforations as primary manifestation of Crohn's disease.

SUMMARY: Crohn's disease may affect any segment of the digestive tract, more commonly the distal ileum, colon and/or perianal region. There is an increasing number of reports dealing with foregut Crohn's disease. We present the case of a patient with a history of heartburn and multiple spontaneous perforations of the esophagus, duodenum and jejunum as a primary manifestation of Crohn's disease who required emergency surgical and endoscopic procedures. Early detection of Crohn's disease may decrease the incidence of acute life-threatening complications provided that appropriate medical treatment is administered and a multidisciplinary approach is offered to these patients.

Aminosalicylic Acids↗
PubMed2004

Frequency of NOD2/CARD15 variants in both sporadic and familial cases of Crohn's disease across Italy. An Italian Group for Inflammatory Bowel Disease Study.

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.

Adult↗
PubMed2004

Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels in inflammatory bowel diseases.

OBJECTIVES: Hypofibrinolysis has been proposed as a possible mechanism underlying the known risk of thrombosis observed in patients with inflammatory bowel diseases (IBD). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis. Increased TAFI plasma levels are associated with a risk for venous thrombosis. The objective was to evaluate TAFI plasma levels and their possible correlations with clinical features and acute-phase reactants in IBD patients. METHODS: Eighty-one IBD patients (47 Crohn's disease and 34 ulcerative colitis) and 81 sex- and age-matched healthy controls were enrolled in the study; moreover, we studied 30 inflammatory controls (13 Reiter's syndrome, 4 Behçet's syndrome, and 13 patients with newly diagnosed celiac disease). TAFI plasma levels were assessed by means of a commercially available ELISA kit. Erythrocytes sedimentation rate, C-reactive protein, and alpha1-acid glycoprotein were measured as acute-phase reactants. Statistical analysis was performed by means of nonparametric tests and Fisher's exact test and chi(2) test for independence. RESULTS: Median TAFI plasma levels were significantly higher in IBD patients (116.0%, range: 39.0-232.0%) and in inflammatory controls (176.0%, 50.0-435.0%) than in healthy controls (99.0%, 40.0-170.0%) (p< or = 0.05 and p< or = 0.001, respectively). TAFI plasma levels higher than the 95th percentile of control values were significantly more frequent in IBD patients (19.7%) and in inflammatory controls (53.3%) than in healthy controls (4.9%) (p< or = 0.008 and p< or = 0.0001, respectively) and more frequent in clinically active IBD than in clinically quiescent IBD (31.4%vs 10.9%, p< or = 0.03). Finally, in IBD, significant correlations were observed between TAFI plasma levels and erythrocytes sedimentation rate (p< or = 0.02), C-reactive protein (p< or = 0.001), and alpha1-acid glycoprotein (p< or = 0.05). CONCLUSIONS: TAFI plasma levels are increased in IBD patients and correlate with acute-phase reactants. Increased TAFI plasma levels might contribute to the prothrombotic state observed in IBD through the induction of hypofibrinolysis.

Adult↗
PubMed2004

Immune reconstitution in HIV-1 infected children with discordant response to antiretroviral therapies: patterns of HIV-1 env gene evolution driven by restoration of thymic function.

The evolution of human immunodeficiency virus type 1 (HIV-1) env gp120 region was addressed in HIV-1 infected children showing virological failure to antiretroviral therapy (ART). Sequence analysis of the replicating plasma virus at baseline and after one year of therapy documented evolution of gp120 in all subjects but one. Analysis of the host's selective pressure showed that the values of Ka/Ks ratios were higher in the V3 sequence than in the whole C2-V5 region in 4 of 5 children with improvement of thymic output. Moreover, in 2 of the 4 chidren, the V3 evolution paralleled with a reverse shift of the viral phenotype (from CXCR4-tropic to CCR5-tropic). These results suggest that, under ART, the V3 evolution towards less pathogenic viral variants may be driven by the host's increased selective pressure following restoration of thymic function and immune reconstitution.

Amino Acid Sequence↗
PubMed2003

Diagnostic role and clinical correlates of anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (p-ANCA) in Italian patients with inflammatory bowel diseases.

BACKGROUND: Anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) are serological markers associated, respectively, with Crohn's disease and ulcerative colitis, whose clinical significance and possible diagnostic role are still poorly defined. AIMS: (a) To evaluate the sensitivity, specificity and predictive values of isolated and combined ASCA and p-ANCA assays in a large cohort of Italian patients with inflammatory bowel disease (IBD) and (b) to assess whether their presence is associated with particular clinical features of the disease. PATIENTS AND METHODS: Hundred and forty-six IBD patients (93 with Crohn's disease and 53 with ulcerative colitis) and 54 control patients were enrolled in the study. ASCA (IgA and IgG) and p-ANCA were determined by means of enzyme-linked immunosorbent assay and indirect immunofluorescence, respectively. RESULTS: The specificities were excellent for both tests (ASCA in Crohn's disease, 98.1% both for IgA and IgG, and p-ANCA in ulcerative colitis, 92.5%); however, the sensitivities of both tests were low (59.1% for ASCA IgA, 44.1% for ASCA IgG, 39.6% for p-ANCA). ASCA specificity and positive predictive value reached 100% when positivity for both IgA and IgG was present. No significant association was found between the presence of a specific serological marker and patients' clinical features. CONCLUSIONS: This study confirms the low prevalence of p-ANCA observed in ulcerative colitis patients from the Mediterranean area. The low sensitivity of ASCA and p-ANCA, despite their rather high specificity, renders them of little value in the screening of the general population, where the prevalence of IBD is low. However, in our series, a double positivity for ASCA IgA and IgG identifies with certainty the presence of Crohn's disease.

Adult↗
PubMed2003

Val34Leu factor XIII polymorphism in Italian patients with inflammatory bowel disease.

BACKGROUND: Coagulation Factor XIII is implicated in fibrin stabilization and wound healing. Plasma levels of Factor XIII are reduced in inflammatory bowel disease patients; recently, a valine 34 to leucine polymorphism of the Factor XIII-A subunit gene with a defined protective effect against thrombosis and as yet undetermined effect on wound healing has been described. AIM: To evaluate Val34Leu Factor XIII polymorphism distribution and to find possible correlations with clinical features in Italian inflammatory bowel disease patients. STUDY POPULATION: A total of 152 inflammatory bowel disease patients, 90 with ulcerative colitis and 62 with Crohn's disease and 130 healthy volunteers were studied. METHODS: Val34Leu polymorphism was detected by RFLP with BsaH I. Statistical analysis was performed by means of Fisher exact test. RESULTS: In inflammatory bowel disease, 57.2% of patients showed the wild type status, 37.5% were heterozygous and 5.3% were homozygous for the 34Leu allele; the frequency of the mutated allele was 24.0%. In controls, 66.1% of subjects showed the wild type status, 28.5% were heterozygous and 5.4% were homozygous for the 34Leu allele; the frequency of the mutated allele was 19.7%. There was no difference in genotype distribution and prevalence of the mutated allele between inflammatory bowel disease patients and controls. CONCLUSIONS: The present data do not show any differences in Val34Leu Factor XIII polymorphism distribution between inflammatory bowel disease patients and controls. The prothrombotic state described in inflammatory bowel disease patients does not depend on an altered distribution of Val34Leu Factor XIII polymorphism.

Adult↗
PubMed2003

Unsuspected ileal stenosis causing obscure GI bleeding in patients with previous abdominal surgery--diagnosis by capsule endoscopy: a report of two cases.

Peri-anastomotic ulcerations may occur in patients with previous abdominal surgery. They may present only with obscure GI bleeding. We report two cases in whom capsule endoscopy identified postsurgical stenoses with ulcers as the cause of obscure GI bleeding. Case 1. A 57-year-old male operated on in 1970 for a post-traumatic diaphragm hernia followed by displacement of the caecum in the upper left abdominal quadrant. Case 2. A 32-year-old female with a salpingectomy for tuberculosis (1978) followed by segmental ileal resection for intestinal obstruction. Both patients had undergone extensive work-up including bidirectional endoscopies and enteroclysis with negative results. Capsule endoscopy with the GIVEN diagnostic system was done. Ileal stenoses with mucosal ulcers in dilated prestenotic loops were observed in both cases. The capsule was retained at the stenosis site, requiring ileal resection and anastomosis. Pathology reports showed mucosal ulcers. In case 2, tuberculosis was ruled out by tissue and faecal polymerase chain reaction and culture. Ileal stenoses with prestenotic ulcerations causing GI bleeding may occur in patients with previous abdominal surgery. Capsule endoscopy may clarify the diagnosis and shorten the diagnostic work-up. However, these patients should be warned that capsule retention requiring surgery might occur.

Adult↗
PubMed2003

Review article: diagnosis, monitoring and treatment of distal colitis.

The diagnostic work-up of ulcerative colitis at presentation is based on the collection of clinical, microbiological, radiological, endoscopic and histologic data. Serological markers are characterized by too low a sensitivity to be commonly utilized in clinical practice. Although endoscopic and histologic features are characterized by very high sensitivity and specificity for the diagnosis of ulcerative colitis, negative stool cultures and parasites are mandatory to exclude an infectious aetiology at presentation. The treatment of choice of an acute flare-up of distal ulcerative colitis is represented by oral or topical mesalazine, or a combination of both, whereas the use of topical or systemic steroids should be restricted to patients who prove to be refractory to first-line treatments. Preliminary data suggest that the achievement of endoscopic and histologic remission after an acute flare of the disease might be associated with a prolonged remission.

Acute Disease↗
PubMed2003

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

BACKGROUND: The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. AIMS: To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. PATIENTS: CD, UC, and normal control subjects were studied. METHODS: The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). RESULTS: Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. CONCLUSIONS: Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Adult↗
PubMed2003

High rate of positive anti-tissue transglutaminase antibodies in chronic liver disease. Role of liver decompensation and of the antigen source.

BACKGROUND: Since the recognition of tissue transglutaminase (tTG) as the target antigen of anti-endomysium antibodies, several ELISA assays using either guinea pig or human recombinant tTG have been developed. The aim of the study was to compare the behaviour of anti-tTG and anti-endomysium antibodies assays in coeliacs and in patients with chronic liver disease. METHODS: 34 patients (24 women, 34.9 +/- 12.5 years) with coeliac disease and 41 with chronic liver disease (14 women, 57 +/- 11.2 years), including 19 cirrhotics, were evaluated for anti-endomysium antibodies by indirect immunofluorescence and for anti-tTG IgA antibodies by ELISA, using guinea pig liver or human recombinant transglutaminase. RESULTS: The prevalences of anti-tTG and anti-endomysium antibodies were 100% in patients with coeliac disease at diagnosis, 75% and 64.3% in patients on a gluten-free diet. All liver disease patients were negative for anti-endomysium antibodies, while 11 (26.8%) were positive for anti-tTG. All these patients had liver cirrhosis and represented 57.9% of all cirrhotics. The presence of anti-tTG was associated with higher Child-Pugh scores. The use of human transglutaminase determined a reduction in the rate of positive results; however, the rate of positive anti-tTG was still 17.1% in all liver disease patients and 31.6% in cirrhotics. CONCLUSIONS: Our data confirm that anti-tTG have a similar sensitivity compared with anti-endomysium antibodies assay in coeliacs. However, a high prevalence of positive anti-tTG results is observed in cirrhotic patients, even when human recombinant tTG is used. The high prevalence of positive results among cirrhotic patients is associated with more advanced liver disease.

Adult↗