Fibrate for treatment of primary biliary cirrhosis

Recent studies of the effectiveness of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC) reported that UDCA therapy did not necessarily stop the progression of liver fibrosis in all patients, even those with early stage PBC. Thus, there is a need for more effective treatments that could prevent asymptomatic PBC from progressing to the icteric stage. Bezafibrate is effective in approximately two-thirds of non-icteric patients who have not shown a complete response to UDCA. Serum bilirubin, aspartate aminotransferase and γ-guanosine 5'-triphosphate levelswere significantly lower in patients who responded to additional bezafibrate on univariate analysis. The putative mechanism by which bezafibrate acts in cholestasis is by increasing phospholipid output into bile, which forms micelles with the hydrophobic bile acid that reduces its toxicity.     

Pegylated interferon ��-2b plus ribavirin for older patients with chronic hepatitis C

AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk.RESULTS:At 24 wk after the end of combination therapy,the overall sustained virologica...     

Significance of immature platelet fraction and CD41-positive cells at birth in early onset neonatal thrombocytopenia

Early thrombocytopenia is a common hematological abnormality in sick neonates. Here, we examined the relationship between early thrombocytopenia in neonates and parameters associated with thrombopoiesis to identify predictive factors at birth. Two hundred and forty-four neonates admitted to the neonatal intensive care unit were divided into thrombocytopenic (n = 55, 23%) and non-thrombocytopenic (n = 189, 77%) groups based on platelet counts, which were monitored within 72 h of birth. Immature platelet fraction (IPF) and platelet count at birth were determined simultaneously soon after phlebotomy with an automated hematology analyzer. Megakaryocytes and their precursors positive for CD41 in peripheral blood were examined at birth by flow cytometry. The thrombocytopenic group showed significantly higher IPF percentage and lower percentage of CD41⁺ mononuclear cells (MNCs) than did the non-thrombocytopenic group (P < 0.01). Moreover, the percentage of CD41⁺ MNCs significantly differentiated neonates with platelet counts >150 × 10³/μL at birth and nadir platelet count <150 × 10³/μL over the clinical course from neonates without thrombocytopenia. These observations suggest that the percentage of CD41⁺ MNCs at birth and IPF percentage are useful predictors of early thrombocytopenia in the majority of sick neonates.     

HLA-DRB1*1602 allele is positively associated with HPV cervical infection in Bolivian Andean women

Incidence of cervical cancer is high among Bolivian Andean women. Human papillomavirus (HPV) infection is known as the major risk factor of cervical cancer. The host immune system plays an important role in the outcome of HPV infection and associated malignancies. In order to study the immunogenetic background of Bolivian Andean women with regard to HPV infection status, we compared HLA class I and class II allele frequencies between 37 HPV positive and 68 HPV negative Bolivian women. Demographic variables, including distribution of Andean ethnicities, were similar in both groups. Comparison of HLA class I allele frequencies between both groups indicated no significant difference. In contrast, HLA class II DRB1*1602 allele, an Amerindian allele, was significantly higher in the HPV positive women compared with HPV negative controls (chi(2) = 5.2, p < 0.05, odds ratio = 3.17; 95% confidence interval = 1.4-8.8). HPV types present in the HPV positive group were HPV-18, -16, -31, -33, and -58. These results suggest that HLA class II DRB1*1602 may confer susceptibility to infection with genetically related HPV types. This is the first report of an HLA class II association with HPV infection in an Andean population.     

Radiation-induced reactive oxygen species formation prior to oxidative DNA damage in human peripheral T cells

Previously, we demonstrated that human peripheral T lymphocytes revealed early apoptotic changes (annexin V-positive) and late apoptotic changes (propidium iodide-positive), at 13 and 24 h, respectively, after irradiation of 5 Gy. Changes in mitochondrial membrane potential were observed at 10 h after irradiation of 5 Gy. Subsequently, mitochondrial cytochrome c-release was confirmed. In order to elucidate the mechanism which acts prior to the mitochondrial membrane potential changes, we examined in the previous study the radiation dose and the timing of oxidative DNA damage induced in human peripheral T lymphocytes following 10 MV X-ray irradiation. As a result, the production of 8-oxoguanine, i.e., the product of oxidative DNA damage, was clearly identified starting at 10, 6, and 3 h, after 2, 5, and 20 Gy of irradiation, respectively. Therefore, we examined in the present study reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy of irradiation. Using a CCD camera system, we monitored fluorescence in T lymphocytes loaded with the succinimidyl ester of dichlorodihydrofluorescein diacetate (H2DCFDA), which is non-fluorescent until oxidized by ROS. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation.     

Role of macrophage migration inhibitory factor in otitis media with effusion in adults

Otitis media with effusion (OME) is one of the most common ear diseases. Bacterial endotoxins and several inflammatory cytokines appear to be involved in the pathogenesis of OME in children; however, little is known of the immunological aspects of the onset of OME in adults. We sought to determine the presence of macrophage migration inhibitory factor (MIF) as well as interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), and endotoxin in middle ear effusions (MEEs) from adult patients with OME. In addition, the levels of MIF in MEEs from adults and children were compared. MEE was obtained from 95 adults and 11 children. The levels of MIF, IL-1beta, TNF-alpha, and RANTES were determined by enzyme-linked immunosorbent assay, and the concentrations of endotoxin and total protein were determined by the Endospec assay and bicinchoninic acid assay, respectively. MIF was detected in 97.9% of the MEEs from adults, while endotoxin, IL-1beta, TNF-alpha, and RANTES were detected in 96.8, 12.6, 5.3, and 43.9%, respectively. In addition, the level of MIF was significantly higher than those of endotoxin, IL-1beta, and TNF-alpha. A positive correlation between the levels of MIF and endotoxin was observed. MIF and endotoxin were detected in 81.8 and 72.7%, respectively, of the MEEs from the children. The level of MIF was significantly higher in the children, and conversely that of endotoxin was significantly higher in the adults. These results suggest that the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults.     

Periventricular leukomalacia with late-onset circulatory dysfunction of premature infants: correlation with severity of magnetic resonance imaging findings and neurological outcomes

The incidence of late-onset circulatory dysfunction (LCD) of premature infants, which is characterized by sudden hypotension and oliguria, has recently increased in Japan. This condition suddenly occurs after several days of age without obvious causes in preterm infants with stable respiration and circulation. Intravenous steroids frequently improve the hypotension. The main problem with LCD is the subsequent and frequent onset of periventricular leukomalacia (PVL), and neurological development appears to be worse in PVL patients with LCD than those without LCD. The aim of this study was to determine whether the severity of magnetic resonance imaging (MRI) findings and neurological outcomes differ between infants who developed PVL after LCD and those who developed PVL without LCD. We retrospectively studied preterm infants who were delivered at less than 33 weeks of gestation between the years 2000 and 2003. During the study period, 10 and 26 infants developed PVL with and without LCD, respectively. The incidence of severe or moderate MRI findings was significantly higher in PVL patients with LCD (100%) than those without LCD (50%; p < 0.05). The incidence of severe cerebral palsy was 88% in PVL infants with LCD and 43% in PVL infants without LCD (p < 0.05). Moreover, the incidence of visual disorders was significantly higher in PVL infants with LCD (63%) than those without LCD (9%; p < 0.01). In conclusion, neurological outcomes are worse in preterm infants who develop PVL with LCD than those without LCD, which is well correlated to the severity judged by MRI findings.