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Biomedical subjects

A Armuzzi

Publications and source records attributed to A Armuzzi.

At least 19 recordsLinked to original sources

Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis.

BACKGROUND: Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. AIM: To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. PATIENTS AND METHODS: 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 x 10(9) viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. RESULTS: Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05). CONCLUSIONS: Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.

Adult↗

Adhesion molecules in inflammatory bowel disease: therapeutic implications for gut inflammation.

Mucosal endothelium has become one of the major areas of investigation in gut inflammation. It is now well recognised that it plays an active role in the pathogenesis of both forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis, since endothelial cells regulate mucosal immune homeostasis, acting as "gatekeepers", controlling leukocyte accumulation in the interstitial compartment. This process is mediated by leukocyte-endothelial adhesion molecules. This paper reviews the major molecules that mediate leukocyte-endothelial interactions, and summarises the results of the most recent clinical trials targeting adhesion molecules in inflammatory bowel disease.

Animals↗

Sacroileitis and peripheral arthropathy associated with ulcerative colitis: effect of infliximab on both articular and intestinal symptoms.

Infliximab has been proven to be an effective therapy in a miscellany of rheumatic diseases and has been approved for the treatment of moderate-to-severe Crohn's disease with an inadequate response to conventional therapy and for the management of enterocutaneous fistulas. Data about the role of infliximab in ulcerative colitis are still controversial. Here, we report a case of a patient with sacroileitis and peripheral arthropathy associated with left-sided ulcerative colitis who achieved a sustained clinical remission after infliximab therapy.

Adult↗

Prevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease.

BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.

Adolescent↗

NOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population.

BACKGROUND: Crohn's disease affects people world-wide, but the incidence in Asia is lower than in Western countries. This difference may be due to genetic and/or environmental factors. Three single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene have been identified to be independently associated with the development of Crohn's disease in Caucasians. Whether these SNPs are involved in the pathogenesis of Crohn's disease in the Chinese population is unknown. AIM: To determine if NOD2/CARD15 gene polymorphisms are found in Chinese patients with Crohn's disease. METHODS: Sixty-five consecutive Chinese Crohn's disease patients had genotyping performed using sequence-specific PCR directed against the wild-type and the Arg702Trp, Gly908Arg and 3020insC variants of the NOD2/CARD15 gene. Controls consisted of 63 patients with ulcerative colitis and 70 patients with dyspepsia. RESULTS: None of the patients with Crohn's disease had heterozygous or homozygous SNP variants. Similarly none of the ulcerative colitis or dyspeptic controls had these SNPs. CONCLUSION: The three previously described SNPs associated with the development of Crohn's disease in Caucasians are not found in Chinese patients with Crohn's disease.

Adolescent↗

Study of liver function in healthy elderly subjects using the 13C-methacetin breath test.

BACKGROUND: The issue of whether or not liver function is compromised in the healthy elderly population remains unsolved. AIM: To investigate the putative age-related modifications of hepatic function using the 13C-methacetin breath test. Because endogenous CO2 production changes with age, motor activity and nutrition, a different form of processing the results was investigated. PATIENTS AND METHODS: Twenty-nine elderly subjects (mean age, 79.8 +/- 7.9 years; female/male ratio, 17/12) and 28 adult subjects (mean age, 40.6 +/- 12.3 years; female/male ratio, 13/15) underwent 13C-methacetin breath test and trans-abdominal echosonography with Doppler pulsed wave analysis of the coeliac axis and portal vein. RESULTS: Although the 13CO2 peak occurred within 15-30 min in both elderly and adult subjects, it was significantly decreased in the former (30.66% +/- 9.2% vs. 38.33% +/- 6.05%; P < 0.001), as was the cumulative excretion (33.07% +/- 7.06% vs. 39.81% +/- 5.68%; P < 0.001). When correcting for the effects of CO2 excretion by age, the age-related modification of the cumulative dose became more evident (elderly group 30.15% +/- 6.46% vs. adult group 37.97% +/- 5.92%; P < 0.0001). The elderly group also showed an increase in the intra-hepatic resistance index using Doppler pulsed wave analysis, which inversely correlated with the results of the breath test. CONCLUSIONS: Hepatic function is not well preserved in healthy humans throughout life and may be due to an increase in vascular resistance.

Acetamides↗

The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis.

Linkage and association studies implicate the human leucocyte antigen (HLA) region in genetic susceptibility to ulcerative colitis (UC). However, associations with specific variants have been inconsistent, even within defined ethnic groups. A genetic basis for the disease heterogeneity of UC may account for these discrepant findings from studies in unselected populations. Here, we examine the contribution of the HLA region to the clinical phenotype of UC. We studied 321 accurately phenotyped patients recruited from a single UK centre, with a median follow-up time of 15 years. Individuals were genotyped for 340 polymorphisms constructed into 25 gene-specific allelic haplotypes between HLA-A and Tapasin. Data were analysed with respect to age of onset, disease extent and severity. Strongest association with overall susceptibility was identified with HLA-DRB1 alleles replicating previous studies (DRB1*0103, DRB1*1502 and DRB1*0401). We report a novel association with homozygosity of a tumour necrosis factor (TNF) promoter haplotype (TNF-1031T, -863C, -857C, -380G, -308G and -238G) and distal disease extent that does not extend with time (distal vs total 40.9 vs 25.7%; RR = 2.0; 95% CI 1.23-3.24). We confirm the association of DRB1*0103 with total disease and/or disease requiring colectomy and further demonstrate that DRB1*0103 is associated with shorter time to surgery. Genes in the HLA play a role in modifying disease phenotype. Further studies are required to dissect how these genes functionally interact with each other and with environmental factors to determine clinical patterns of disease

Adolescent↗

Genotype-phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31.

BACKGROUND AND AIMS: Recent molecular data suggest that genetic factors may underlie the disease heterogeneity observed in both ulcerative colitis (UC) and Crohn's disease (CD). A locus on chromosome 5q has been implicated in susceptibility to CD, and recently refined by linkage disequilibrium mapping to a conserved 250 kb haplotype (5q31). No data regarding the contribution of this locus to clinical phenotype exist. In this case control study, we investigated the contribution of this haplotype to both susceptibility and phenotype of CD and UC. PATIENTS AND METHODS: We studied 330 Caucasian CD and 457 UC patients recruited from a single UK centre. Association with disease susceptibility and phenotype was analysed with haplotypes reconstructed from three single nucleotide polymorphisms chosen to span this susceptibility region. Evidence for possible genetic epistasis between IBD5 and NOD2/CARD15 was sought. RESULTS: Linkage disequilibrium across this region was confirmed, with two haplotypes comprising 88% of all chromosomes. Susceptibility to CD, but not to UC, was associated with homozygosity for a common haplotype, H2 (p(c)=0.002; relative risk (RR) 2.0). Genotype-phenotype analyses demonstrated that this association was particularly strong in patients with perianal disease (p(c)=0.0005; RR 1.7), especially in individuals homozygous for this haplotype (p(c)=0.0005; RR 3.0). Importantly, no association with H2 was found in 186 patients without perianal disease. No evidence of epistasis between IBD5 and NOD2/CARD15 was demonstrated. CONCLUSIONS: The IBD5 risk haplotype is associated with CD only. Genotype-phenotype analysis reveals that the strongest association is observed in patients with perianal CD. While the precise gene involved is unclear, these data provide further molecular evidence for a genetic basis of the clinical heterogeneity of CD.

Adolescent↗

Advances in extracorporeal detoxification by MARS dialysis in patients with liver failure.

Although liver transplantation has become standard procedure for patients with liver failure, a number of issues in the management of these patients remains to be addressed. Alternative approaches have been tested, such as hepatocytes containing liver-support systems and filtration devices. However, the replacement of detoxification has been difficult, as the majority of toxins accumulating in liver failure is albumin-bound. Albumin dialysis (MARS system) is characterized by the specific removal of albumin-bound toxins through an innovative membrane transport. In particular, the albumin acts as a specific molecular adsorbent that is regenerated on line in a recycling system. Nowadays MARS represents the most frequently used liver support system. This treatment has been shown to remove albumin-bound molecules, such as bilirubin, bile acids, aromatic amino acids and copper. The removal of these toxins is clinically accompanied with an improvement of liver, cardiovascular and renal functions and hepatic encephalopathy. In several trials MARS was found to improve the clinical situation in patients with acute exacerbation of chronic liver failure and acute hepatic failure, but also in hepatorenal syndrome and primary graft non function or chronic rejection after liver transplantation. In summary, a critical analysis of the literature confirms that MARS device can be a safe therapeutic choice to achieve a better clinical outcome, and, sometimes, a survival advantage in patients with liver failure, even if a multi-center randomized trial is the only reliable way to enforce today's results. Further advances in the MARS components will definitively state whether albumin dialysis may represent the future in the field of artificial liver devices.

Adsorption↗

Probiotics and Helicobacter pylori eradication.

The need for new strategies for Helicobacter pylori eradication, alternative or complementary to antibiotic therapy, has recently claimed the attention of many investigators. Pre-clinical studies have shown the inhibition of Helicobacter pylori growth by Lactobacilli and the anti-Helicobacter pylori action of Lactobacillus salivarius, Lactobacillus acidophilus and Lactobacillus casei subspecies rhamnosus strains, possibly due to the production of lactic acid or to the secretion of an autolysin. Clinical studies have demonstrated a persistent reduction in delta over baseline values at the 13C urea breath test independently of omeprazole administration with Lactobacillus acidophilus La1, the eradication in 6 out of 14 patients with Lactobacillus acidophilus alone, positive results in patients in which a standard Helicobacter pylori triple therapy was randomly supplemented with Lactobacillus acidophilus.

Helicobacter Infections↗

High resolution MIC genotyping: design and application to the investigation of inflammatory bowel disease susceptibility.

The highly polymorphic nonclassical MHC class I chain-related (MIC) genes MICA and MICB encode stress inducible glycoproteins expressed on a variety of epithelial cells including intestinal cells. Interaction with the receptor NKG2D is likely to provide an important costimulatory signal for activation and proliferation of NK cells, activated macrophages and CD8 alphabeta and gammadelta T cells. Fifty-four MICA and 17 MICB alleles have been described to date. Although the functional significance of this polymorphism is not known, the high degree of nonconservative substitution, concentration to the putative ligand-binding site and recent observation that different MICA alleles bind to NKG2D with varying affinity has generated much interest. The MIC genes are attractive functional and positional candidate genes for inflammatory bowel disease susceptibility as a consequence of their position in the HLA region and expression on the gastrointestinal epithelium. We developed a robust, high-resolution PCR-SSP genotyping method that can be incorporated into the standard 'Phototyping' system and which effectively identifies 46 of 54 MICA alleles, and all 17 MICB alleles. We applied this system in combination with microsatellite genotyping of the exon 5 variable number of tandem repeats (VNTR) to the investigation of genetic susceptibility to the inflammatory bowel diseases, ulcerative colitis and Crohn's disease. We studied 248 patients with Crohn's disease, 329 with ulcerative colitis and 354 ethnically matched controls. Linkage disequilibrium patterns between HLA-B, MICA and MICB are presented. Analysis by individual allele or by multilocus haplotype failed to identify any significant disease associations.

Alleles↗

Review article: breath testing for human liver function assessment.

Carbon-labelled breath tests were proposed as tools for the evaluation of human liver function 30 years ago, but have never become part of clinical routine. One reason for this is the complex role of the liver in metabolic regulation, making it difficult to provide essential information for the management of patients with liver disease with a single test and to satisfy the hepatology community. As a result, a battery of breath tests have been developed. Depending on the test compound administered, different metabolic pathways (microsomal, cytosolic, mitochondrial) can be examined. Most available data come from microsomal function tests, whilst information about cytosolic and mitochondrial liver function is more limited. However, breath tests have shown promise in some studies, in particular to predict the outcome of patients with chronic liver disease or to monitor hepatic function after treatment. Whilst we await new substrates that can be used to measure liver function in a more valid manner, and large prospective studies to assess the usefulness of available test compounds, the aim of this review is to describe how far we have come in this controversial and unresolved issue.

Breath Tests↗

The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy.

BACKGROUND: One-week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side-effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug-related manifestations. AIM: To determine whether adding the probiotic Lactobacillus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden. METHODS: Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side-effects and an overall judgement of tolerability. RESULTS: Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1-0.9; relative risk=0.3, 95% CI: 0.1-0.9; relative risk=0.5, 95% CI: 0.2-0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04). CONCLUSIONS: Lactobacillus GG supplementation showed a positive impact on H. pylori therapy-related side-effects and on overall treatment tolerability.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Helicobacter pylori CagA-positive strains affect oxygen free radicals generation by gastric mucosa.

BACKGROUND: Helicobacter pylori plays a key role in production of reactive oxygen metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori strains remains to be determined. The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori. Results were correlated to CagA status and acute inflammatory infiltration. METHODS: Patients undergoing gastroscopy were enrolled. H. pylori infection was assessed by histology and 13C urea breath test. CagA status was assessed through serology. ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence (CLS). Gastric mucosal inflammation was histologically graded and neutrophils were individually counted. Macroscopical damage was scored according to a modified Lanza score. RESULTS: 40 out of 60 patients evaluated were H. pylori (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected. ROMs production showed a significant correlation to neutrophil infiltrate in all groups. CONCLUSIONS: Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects. Since ROMs production is associated with DNA oxidative damage, a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies. Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable.

Antigens, Bacterial↗