Brain mapping analysis in patients with hepatic encephalopathy

Summary Topographical analysis of cerebral electrical activity was performed in 44 patients with hepatic encephalopathy. These patients were classified in 5 groups according to clinical criteria. Eight healthy subjects were used as a control group. All were studied in an awake, eyes closed, condition and some [Control Group (CG), Group 0 (G0), Group 1 (G1) and Group 2 (G2)] also in an awake, eyes open, condition. The awake, eyes closed, maps showed marked differences in the power spectral density (PSD) of the different bands, when comparing normal subjects with patients with several degrees of hepatic encephalopathy. These differences were related to the degree of clinical involvement, mainly in the alpha and delta PSD bands. The combination of a decreased alpha PSD, increased delta PSD, and decreased mean dominant frequency (MDF) allowed a clear discrimination between the different clinical groups. The differences observed between awake, eyes closed, and awake, eyes open, conditions were especially helpful to discriminate between CG subjects and G0, G1 and G2 patients.     

Orthotopic implantation of human hepatocellular carcinoma in mice: analysis of tumor progression and establishment of the BCLC-9 cell line.

PURPOSE: To allow the longitudinal investigation of molecular events associated with the progression of human hepatocellular carcinoma (HCC), we sought to develop a murine model by orthotopic implantation of tumor fragments obtained from patients diagnosed at early stage. EXPERIMENTAL DESIGN: Tumor pieces (2 x 2 mm) were implanted on the liver surface of nu/nu mice. After xenograft growing, subsequent passages were performed to achieve long-term implant viability. Isolation of tumoral hepatocytes was done to establish new cell lines. HCC characteristics, proliferation rate, apoptotic index (terminal deoxynucleotidyl transferase-mediated nick end labeling), and expression of cell-cycle regulators (cyclins E and A, p21(Cip1), p27(Kip1), p16(INK4a), pRb, and p53) were assessed by Western Blot and immunohistochemistry, to correlate them with tumor progression. RESULTS: Five (50%) of the 10 primary HCCs resulted in small slow-growing liver implants. Three of them are viable after 48 months, whereas the remaining two survived for 15 and 13 months. Xenografts throughout passages exhibited a more aggressive phenotype with a poorer degree of differentiation, intense proliferation, moderate apoptosis, cell-cycle deregulation, p53 alterations, microvascular invasion, and dissemination. In one single passage, we observed critical growth delay, which was associated with significant p27(kip1) overexpression. We established the anchor-free growing BCLC-9 cell line from one xenograft. This has gains of chromosomes 7, 5p, 6q, and 9q, is hepatitis B virus-DNA positive, does not secrete alpha-fetoprotein, and has TP53 missense mutations in codons 192 and 242. CONCLUSIONS: The orthotopic implantation of early HCC fragments in nude mice provides a useful model to investigate the mechanisms of human HCC evolution and to establish new cell lines.     

Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia.

PURPOSE: To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We analyzed the outcome of patients who underwent SCT according to their VH mutational status. RESULTS: Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01). CONCLUSION: These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL.     

Improvement to the Corrosion Resistance of Ti-Based Implants Using Hydrothermally Synthesized Nanostructured Anatase Coatings

The electrochemical behavior of polycrystalline TiO₂ anatase coatings prepared by a one-step hydrothermal synthesis on commercially pure (CP) Ti grade 2 and a Ti13Nb13Zr alloy for bone implants was investigated in Hank’s solution at 37.5 °C. The aim was to verify to what extent the in-situ-grown anatase improved the behavior of the substrate in comparison to the bare substrates. Tafel-plot extrapolations from the potentiodynamic curves revealed a substantial improvement in the corrosion potentials for the anatase coatings. Moreover, the coatings grown on titanium also exhibited lower corrosion-current densities, indicating a longer survival of the implant. The results were explained by considering the effects of crystal morphology, coating thickness and porosity. Evidence for the existing porosity was obtained from corrosion and nano-indentation tests. The overall results indicated that the hydrothermally prepared anatase coatings, with the appropriate morphology and surface properties, have attractive prospects for use in medical devices, since better corrosion protection of the implant can be expected.     

Effects of High-Fat Diet and Maternal Binge-Like Alcohol Consumption and Their Influence on Cocaine Response in Female Mice Offspring

BackgroundPrenatal alcohol exposure is a leading cause of neurobehavioral and neurocognitive deficits collectively known as fetal alcohol spectrum disorders, including eating disorders and increased risk for substance abuse as very common issues. In this context, the present study aimed to assess the interaction between prenatal and lactation alcohol exposure (PLAE) and a high-fat diet (HFD) during childhood and adolescence.MethodsPregnant C57BL/6 mice underwent a procedure for alcohol binge drinking during gestation and lactation periods. Subsequently, PLAE female offspring were fed with an HFD for 8 weeks, and thereafter, nutrition-related parameters as well as their response to cocaine were assessed.ResultsIn our model, feeding young females with an HFD increased their triglyceride blood levels but did not induce overweight compared with those fed with a standard diet. Moreover, PLAE affected how females responded to the fatty diet as they consumed less food than water-exposed offspring, consistent with a lower gain of body weight. HFD increased the psychostimulant effects of cocaine. Surprisingly, PLAE reduced the locomotor responses to cocaine without modifying cocaine-induced reward. Moreover, PLAE prevented the striatal overexpression of cannabinoid 1 receptors induced by an HFD and induced an alteration of myelin damage biomarker in the prefrontal cortex, an effect that was mitigated by an HFD-based feeding.ConclusionTherefore, in female offspring, some effects triggered by one of these factors, PLAE or an HFD, were blunted by the other, suggesting a close interaction between the involved mechanisms.     

Do patient-related blood donors represent a threat to the safety of the blood supply?

BACKGROUND AND OBJECTIVES: Patient-related blood donors contribute to a significant proportion of the blood units collected in hospital-based blood banks. However, there is some concern on the safety of this kind of donation because of the possible existence of incentives for the donor to conceal deferrable risk factors, thus increasing the risk of donation within the window-period of transfusion-transmitted infections. We tested the hypothesis that if patient-related blood donors are less safe than community ones, the former would display both a higher prevalence of viral markers and a predominance of undisclosed risk-factors with low social acceptability. DESIGN AND METHODS: Comparison of virus reactivity rates against hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV), and the associated risk-factors, between patient-related and community donors who donated whole blood in our center during a five-year period. RESULTS: During the period under study 72,226 donors gave 149,944 whole blood units, of which 22,888 (15.3%) were provided by patient-related donors. There were 273 confirmed virus-reactive donations (15 anti-HIV, 148 anti-HCV and 110 HBsAg). The adjusted prevalence of virus reactivity was 19 (95% CI: 11-35) times higher in first-time donors than in repeat donors, 3.5 (95% CI: 2.3-4.1) times higher in donors > or = 30 years old than in younger ones, and 2.5 (95% CI: 1.9-3.2) times higher in patient-related donors than in community donors. With regard to deferrable risk-factors not disclosed at the time of donation, there was no significant difference between patient-related and community donors in the frequency of people who denied any risk-factor or who admitted intravenous drug use or high-risk sex. Past household contact with individuals having liver disease was significantly more frequent in patient-related donors than in community ones. INTERPRETATION AND CONCLUSIONS: Our results do not support the hypothesis that patient-related donors represent an increased risk of window-period donation because they conceal deferrable risk factors more frequently than community donors.