1,720,960 research outputs found

    Colchicine in chronic hepatitis B: a pilot study

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    Abstract: Rationale: Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. Early in vitro studies have demonstrated that colchicine blocks mitosis in the metaphase and inhibits DNA synthesis. Aim: A pilot study of hepatitis B virus (HBV)-related/HBV-DNA+ve chronic liver disease. Patients: Nine biopsy-proven chronic hepatitis patients (three with cirrhosis) entered the study. Two of them were HBeAg+ve and seven were antiHBe(+). All patients were HBV-DNA+ve/antiHBc IgM+ve (index values of anti-HBc IgM ranged from 0.370 to 1.200). All of them had a major contraindication to interferon therapy or refused antiviral treatment. The known persistence of positive HBsAg ranged from 2 to 21 years. Methods: After informed consent, the patients received 1 mg colchicine a day orally for 5 days-a-week over 6 months. Testing for liver enzymes and viral markers was performed at the baseline and after 3 and 6 months. Results: None of the patients experienced side-effects during the treatment. The two HBeAg+ve patients seroconverted to anti-HBe with a normalization of AST/ALT during therapy. Among the seven antiHBe+ve patients, four had a complete normalization of transaminases (one patient cleared the HBsAg with seroconversion to anti-HBs). Six of the nine patients were HBV-DNA-ve at the end of therapy and were still negative after 12 months of follow-up. Conclusion: These preliminary results suggest that colchicine might have an antiviral activity in HBV-DNA+ve chronic liver disease, and it could be regarded as an alternative therapy to interferon

    Emerging role of monocytes and their intracellular calcium pattern in spondyloarthritis

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    Spondyloarthritis (SpA) comprises multifactorial diseases characterized by a complex interplay between an inherited background and environmental factors that lead to immune response dysregulation and inflammation. Unlike for other rheumatic diseases, no specific biomarkers are available in clinical practice for diagnosing SpA. The aim of the present study was to search new potential biomarkers for SpA diagnosis by focusing on the innate immune response. An evaluation was made of the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, TGF-β1, S100A8, S100A9) and matrix metalloproteinases (MMP3, MMP8, MMP9) in blood mononuclear cells of SpA patients (n = 64) with respect to controls (n = 100). In parallel, the pattern of intracellular calcium flows of blood monocytes was verified in order to ascertain whether any specific fingerprint characterizes innate immune cells in SpA patients. Inflammatory cytokines and MMPs expression levels were not correlated with SpA, while in this disease a reduced expression of the S100A8 and a decreased frequency of monocytes showing intracellular calcium flows were observed. In conclusion, no specific signs of systemic inflammation are detectable in SpA, but the disease affects the “on-off” mechanisms that regulate the concentration of intracellular calcium and calcium-related proteins. This potentially pave the way for the discovery of new biomarkers

    LEUKEMIA AND LIVER-DISEASE IN CHILDHOOD - CLINICAL AND HISTOLOGICAL-EVALUATION

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    Seventy-two consecutive patients with acute lymphocytic leukemia (ALL) who had undergone liver biopsy within 3 months of completing chemotherapy were studied to evaluate histological features after 2 to 3 years of chemotherapy and to correlate liver disease to the treatment schedule, the number of transfused blood units, and the identified etiology. Fibrosis due to antiblastic drugs was the most frequent histological finding. Histological liver disease was not related either to the chemotherapy schedule or the number of transfused blood units. HBV with or without delta virus and HCV infections were related to a more severe histological liver disease. In about 40% patients with chronic liver disease, no etiology was demonstrated. Immunohistochemistry revealed HBcAg in the liver of 3 HBsAg-negative patients. In conclusion, liver biopsy could be useful in patients with persistent abnormal liver function tests after the completion of chemotherapy and in patients with markers for hepatotropic virus infectio

    Anti-HCV positive hepatocellular carcinoma in cirrhosis. Prevalence, risk factors and clinical features.

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    Recent reports indicate that hepatitis C virus (HCV) may play a role in the pathogenesis of hepatocellular carcinoma in cirrhotics. Using an ELISA test, we evaluated the prevalence of anti-HCV antibodies in 97 patients with hepatocellular carcinoma (HCC) in cirrhosis and in a group of 223 patients, including: 49 patients with HBsAg-positive chronic liver disease (CLD), 42 with alcoholic CLD, 110 with cryptogenic CLD and 22 with post-transfusional HBsAg-negative CLD. All diagnoses were histologically confirmed. Overall, anti-HCV-positive HCC were 64% of the total, with no statistically significant difference with respect to CLD (60.9%). The prevalence of anti-HCV was higher in cryptogenic HCC (80%) than in HBsAg-positive (60%) or alcoholic HCC (42.8%) (p < 0.005). When HCC and cirrhosis of similar putative etiology were considered, anti-HCV prevalence was significantly higher in HCC than in cirrhosis only in the groups of patients with alcoholic liver damage (60% in HCC vs. 38% in cirrhosis, p < 0.005). In HBsAg-positive patients, anti-HCV prevalence was twice as high in HCC than in CLD, but the difference was not statistically significant. Overall, anti-HCV prevalence in HCC was significantly higher than in alcoholic or HBsAg-positive CLD (p < 0.001 and p < 0.01, respectively) but lower than in cryptogenic CLD (p < 0.001). Association between anti-HCV and anti-HBc was significantly more prevalent in patients with CLD than in those with HCC. From the clinical point of view, multifocal lesions and lack of a history of previous liver disease were more frequent in anti-HCV-positive HCC (p < 0.05) than in HBsAg-positive or alcoholic patients. Anti-HCV-positive HCC had a significantly worse prognosis (p < 0.005 with the Generalized Wilcoxon-Breslow test), when survival in the different subgroups was examined with life table analysis. No statistically significant differences were observed with respect to the remaining parameters considered. In conclusion, HCV infection appears to be a frequent event in HCC and CLD, particularly in patients with cryptogenic liver disease but, with the exception of patients with alcoholic liver damage, the prevalence of anti-HCV appears to be similar in HCC and cirrhosis. This could indicate that the infection plays an important role only in specific subgroups of HCC patients. Anti-HCV-positive HCC is frequently diagnosed in a more advanced stage and has a worse prognosis but, since the clinical history of this subgroup of patients frequently makes its debut with HCC, in our opinion the prognosis is worse due to late diagnosis

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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