24 research outputs found

    Cirrhotic thrombocytopenia is a multifactorial condition: evidence of reduced platelet production and incresed platelet destruction

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    Background: Thrombocytopenia is a common manifestation of liver cirrhosis (LC), but the underlying mechanism is not fully understood. The purpose of our work was to evaluate the platelet kinetics in LC of different etiology by examining platelet production and destruction. Patients: 91 consecutive LC patients (36 HCV, 49 alcoholics, 15 HBV) were enrolled in the study. As controls, 25 cases with idiopathic thrombocytopenic purpura (ITP), 10 with aplastic anemia (AA), and 40 healthy blood donors were studied. Methods: Plasma thrombopoietin (TPO) was measured by ELISA. Absolute reticulated platelet (RP) count was determined by Thiazole Orange method. Plasma glycocalicin (GC) was measured by monoclonal antibodies. Platelet associated and serum circulating antiplatelet antibodies were detected by flow cytometry. The B-cell monoclonality in the PBMC were performed by isotype-specific immunoglobulin fingerprinting. Results: The serum TPO was significantly (p<0.0005) lower in the patients with LC (29.9 \ub1 18.1 pg/ml) than in normals (82.3 \ub1 47.6 pg/ml). The GC index was 1.96 \ub1 1.40 in HCV+ LC (p<0.0005 vs. normals 0.9 \ub1 0.2), 1.79 \ub1 1.51 in alcoholic LC (p<0.006) and 1.71 \ub1 1.69 in HBV + LC (p<0.006). In the patients affected by ITP, the GC index was 12.9 \ub1 4.4 (p<0.000002). The absolute levels of RP were 4.233 \ub1 2.367 109/L in alcoholic LC (p<0.0000000012 vs normals) 4.996 \ub1 3.143 x 109/L in HBV+ LC (p<0.006) and 6.629 \ub1 7.409 x 109/L in HCV+LC (p<0.005). The prevalence of platelet-associated and circulating anti-platelet antibodies was higher in HCV+ LC than in healthy subjects (p<0.0064), than in alcoholic LC (p<0.018) and than in HBV+ LC (p<0.0001). The B-cell monoclonality was found in 8 (27%) of the HCV-positive patients, whereas no monoclonality was found in HBV (p<0.004) or alcoholic patients (p<0.003). Conclusions: Patients with LC present a decreased plasma TPO, an accelerated platelet turnover and a low platelet production. These findings indicate that cirrhotic thrombocytopenia is a multifactorial condition, involving both increased platelet clearance and impaired thrombopoiesis. The HCV-LC is characterized by an increased prevalence of autoimmune phenomena, including anti-platelet antibodies and, as consequence, a platelet turnover more accelerated than in HBV or alcoholic LC

    Giant omphaloceles with a small abdominal defect: Prenatal diagnosis and neonatal management

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    A giant omphalocele is a liver-containing protrusion through an abdominal defect wider than 5 cm in diameter. The giant form with a small abdominal wall defect is a rare condition which, to our knowledge, has not been described previously. We describe three cases with the typical features of elongated vascular liver pedicle and angiomatosis of the hepatic portal system. The abnormal liver organogenesis, due to extra-abdominal development, represented a significant risk factor for hepatic thrombosis after visceral reduction and liver rotation. All the neonates underwent surgery on the first day of postnatal life. One died because of a postoperative liver infarction, and the survivors needed prolonged respiratory support. Prenatal sonographic features, timing, delivery, type of surgical repair, and postnatal outcome are reviewed. A prenatal sonographic diagnosis could be useful to evaluate the abdominal ring and serial ultrasound examinations are recommended to detect promptly ominous signs of hepatic and bowel damage. Color Doppler may be useful to assess the anatomy of the abdominal vessels and their relationships with the herniated organs, although it was not used in any of the cases reported here. This congenital malformation might be considered as a pathological entity separate from giant omphalocele with large abdominal defect, with a severe prognosis due possibly to its different embryological development

    Platelet production and destruction in liver cirrhosis

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    BACKGROUND &#38; AIMS: Thrombocytopenia is common in liver cirrhosis (LC) but the mechanisms are not fully understood. The purpose of our work was to evaluate platelet kinetics in LC with different etiologies by examining platelet production and destruction. METHODS: Ninety-one consecutive LC patients (36 HCV, 49 alcoholics, 15 HBV) were enrolled. As controls, 25 subjects with idiopathic thrombocytopenic purpura, 10 subjects with aplastic anemia, and 40 healthy blood donors were studied. Plasma thrombopoietin (TPO) was measured by ELISA. Reticulated platelets (RP) were determined using the Thiazole Orange method. Plasma glycocalicin (GC) was measured using monoclonal antibodies. Platelet associated and serum antiplatelet antibodies were detected by flow cytometry. B-cell monoclonality in PBMC was assessed by immunoglobulin fingerprinting. RESULTS: Serum TPO was significantly lower in LC (29.9\ub118.1 pg/ml) compared to controls (82.3\ub147.6 pg/ml). The GC levels were higher in LC (any etiology) than in healthy cases. Conversely, the absolute levels of RP were lower in LC (any etiology) than in healthy controls. The platelet-associated and serum anti-platelet antibodies were higher in HCV+ LC compared to healthy subjects (p<0.0064), alcoholic LC (p<0.018), and HBV+ LC (p<0.0001). B-cell monoclonality was found in 27% of the HCV+LC, while it was not found in HBV+ or alcoholic LC. CONCLUSIONS: Patients with LC present decreased plasma TPO, accelerated platelet turnover, and reduced platelet production. This indicates that LC thrombocytopenia is a multifactorial condition involving both increased platelet clearance and impaired thrombopoiesis

    GIANT OMPHALOCELES WITH A SMALL ABDOMINAL DEFECT: PRENATAL DIAGNOSIS AND NEONATAL MENAGEMENT.

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    8nonenonePELIZZO G; MASO G; DELL'OSTE C; D'OTTAVIO G; BUSSANI R.; UXA F; CONOSCENTI G; SCHLEEF J.GIANTPelizzo, G; Maso, G; Dell'Oste, C; D'Ottavio, G; Bussani, Rossana; Uxa, F; Conoscenti, G; SCHLEEF J., Gian

    Inhibitory effects of fenofibrate on apoptosis and cell proliferation in human endothelial cells in high glucose

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    Fenofibrate has beneficial effects on the progression and clinical emergence of atherosclerosis in normoglycemic and in diabetic patients. Given the involvement of endothelium in these processes, we speculated that fenofibrate may influence endothelial cell apoptosis and proliferation, regulators of endothelium integrity. Fenofibrate effects on apoptosis and proliferation were studied in human umbilical vein endothelial cells under normal (5.5 mmol/l, NG) and high (22 mmol/l, HG) glucose with or without fenofibrate (50 micromol/l). Apoptosis was evaluated by annexin V, by poly(ADP-ribose) polymerase protein cleavage, and cyclooxygenase-2 (COX-2), Bax/Bcl-2, and p53 protein levels; proliferation was assessed by determining cell cycle phase distribution and the amounts of the cell cycle regulators E2F1, cyclin D1, E1, and A and the levels of the hyper-phosphorylated form of the retinoblastoma protein (ppRb). HG resulted in increased (p<0.05) apoptosis rate associated with COX-2 protein overexpression, without modification of Bax/Bcl2 ratio and p53 levels. Fenofibrate decreased apoptosis and normalized increased COX-2 expression in HG (p<0.05). Both in HG and NG, fenofibrate dramatically reduced cell proliferation (p<0.05) through a G1/G0 block mediated by the reduction in ppRb and the decrease in E2F1, cyclin E1, A, and D1 protein expression, with a mechanism that, for cyclin E1, occurred at the posttranscriptional level. In conclusion, our data show that fenofibrate reduces apoptosis caused by HG but severely interferes with endothelial cell proliferation both in NG and HG. The resulting effect may influence endothelium integrity in vivo and may impact the outcome of acute complications of atherosclerosis in diabete

    Comparative study of a whole-cell pertussis vaccine and a recombinant acellular pertussis vaccine.

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    The safety and immunogenicity of an acellular pertussis vaccine containing the genetically detoxified pertussis toxin PT-9K/129G, filamentous hemagglutinin, and pertactin, together with diphtheria and tetanus toxoids, were compared with those of a whole-cell pertussis component-diphtheria-tetanus vaccine. Four hundred eighty infants were enrolled into this prospective, multicenter, double-blind study. Each infant was randomly given three doses of one of the two vaccines at 2, 4, and 6 months of age. Both local and systemic adverse reactions, reported within 48 hours and 7 days of each injection, were less frequent after the acellular vaccine than after the whole-cell vaccine. The enzyme-linked immunosorbent assay titers to pertussis toxin, filamentous hemagglutinin, and pertactin, as well as the pertussis toxin-neutralizing titer measured by the Chinese hamster ovary cell assay, were significantly higher after the acellular vaccine was given. Both vaccines induced adequate levels of anti-diphtheria and anti-tetanus antibodies. We conclude that the recombinant acellular pertussis vaccine produces fewer reactions than the whole-cell vaccine and provides a high antibody response against the antigens of Bordetella pertussis involved in bacterial adhesion and systemic toxic effects
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