Multiexponential T2 analyses in a murine model of hepatic fibrosis at 11.7 T MRI

This study evaluated the effects of hepatic fibrosis on the multiexponential T₂ (MET₂) relaxation of ex vivo murine liver specimens using an 11.7 T MRI. This animal study was approved by the Institutional Animal Care and Use Committee. Eighteen male C57BL/6 mice were divided into control (n = 3) and experimental (n = 15) groups; the latter group was fed a 3,5‐dicarbethoxy‐1,4‐dihydrocollidine‐supplemented diet to induce hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7 T MRI scanner. A multi‐echo spin‐echo sequence was utilized for subsequent MET₂ analysis. Degrees of fibrosis were determined by a pathologist, as well as by digital image analysis. Scatterplot graphs comparing various features of the MET₂ signal decay with the degrees of fibrosis were generated, and correlation coefficients were calculated. Two distinct peaks of the MET₂ signal decay were identified in all liver specimens: a short T₂ component with a geometric mean T₂ (GMT₂) approximating 30 ms; and a long T₂ component with GMT₂ approximating 400 ms. Strong correlation was found between the degree of hepatic fibrosis and the amplitude of the short T₂ component, with a higher degrees of fibrosis associated with a lower amplitude. Moderate correlation was also found between hepatic fibrosis and the GMT₂ values of the long T₂ component, with higher degrees of fibrosis associated with lower GMT₂ values. The study of hepatic microenvironments using MET₂ analyses offers potential utility in the ongoing development of the noninvasive assessment of hepatic fibrosis using MRI. Copyright © 2012 John Wiley & Sons, Ltd.     

An inducible transgenic mouse breast cancer model for the analysis of tumor antigen specific CD8+ T-cell responses

In Simian virus 40 (SV40) transgenic BALB/c WAP-T mice tumor development and progression is driven by SV40 tumor antigens encoded by inducible transgenes. WAP-T mice constitute a well characterized mouse model for breast cancer with strong similarities to the corresponding human disease. BALB/c mice mount only a weak cellular immune response against SV40 T-antigen (T-Ag). For studying tumor antigen specific CD8⁺ T-cell responses against transgene expressing cells, we created WAP-T_NP mice, in which the transgene additionally codes for the NP_118–126-epitope contained within the nucleoprotein of lymphocytic choriomeningitis virus (LCMV), the immune-dominant T-cell epitope in BALB/c mice. We then investigated in WAP-T_NP mice the immune responses against SV40 tumor antigens and the NP-epitope within the chimeric T-Ag/NP protein (T-Ag_NP). Analysis of the immune-reactivity against T-Ag in WAP-T and of T-Ag_NP in WAP-T_NP mice revealed that, in contrast to wild type (wt) BALB/c mice, WAP-T and WAP-T_NP mice were non-reactive against T-Ag. However, like wtBALB/c mice, WAP-T as well as WAP-T_NP mice were highly reactive against the immune-dominant LCMV NP-epitope, thereby allowing the analysis of NP-epitope specific cellular immune responses in WAP-T_NP mice. LCMV infection of WAP-T_NP mice induced a strong, LCMV NP-epitope specific CD8⁺ T-cell response, which was able to specifically eliminate T-Ag_NP expressing mammary epithelial cells both prior to tumor formation (i.e. in cells of lactating mammary glands), as well as in invasive tumors. Elimination of tumor cells, however, was only transient, even after repeated LCMV infections. Further studies showed that already non-infected WAP-T_NP tumor mice contained LCMV NP-epitope specific CD8⁺ T-cells, albeit with strongly reduced, though measurable activity. Functional impairment of these ‘endogenous’ NP-epitope specific T-cells seems to be caused by expression of the programmed death-1 protein (PD1), as anti-PD1 treatment of splenocytes from WAP-T_NP tumor mice restored their activity. These characteristics are similar to those found in many tumor patients and render WAP-T_NP mice a suitable model for analyzing parameters to overcome the blockade of immune checkpoints in tumor patients.     

Impact of Type of Intervention on Youth Reoffending: Are Gender and Risk Level Involved?

The objective of this study was to analyse the impact of the type of intervention on youth reoffending. Moreover, the possible influence that the offender's gender and level of risk could have on this relationship was also explored. Juvenile offenders from four different types of educational interventions participated in the study (N = 210): victim–offender mediation (VOM) as a diversion procedure, and case closure, reprimand, and community service as dispositions. Aged between 14-18 years, they were assessed by means of the Youth Level of Service/Case Management Inventory (YLS/CMI). Recidivism rates were evaluated as the number of new records in a follow-up period of 24 months. Results of this study showed that type of intervention (diversion versus dispositions) had no apparent effect on youth recidivism. Furthermore, an important aspect to consider in youth assessment was the different impact that risk level had on boys’ and girls’ recidivism.     

pH,base deficit or lactate. Which is better for predicting neonatal morbidity?

Objective: To determine which parameter of the umbilical arterial cord gas analysis, pH, base deficit (BD) or lactate has a bigger predictive ability for neonatal morbidity at term.

Method: We conducted a four-year retrospective cohort study including all non-anomalous, singleton, vertex, term births with neonatal acidemia (umbilical arterial cord gas pH?≤?7.1). The primary outcomes were a composite neurological morbidity and a composite systemic morbidity. The predictive ability of lactate, BD and pH was compared using receiver operator characteristic (ROC) curves. Optimal cutoff values of lactate, BD and pH were estimated based on their maximal Youden Index.

Results: We identified 466 acidemic neonates who had paired and validated cord blood gas data. The ROC curve analysis revealed that pH, BD and lactate had a similar predictive ability for neurological (AUC: 0.81; 0.78; 0.83, respectively) and systemic neonatal morbidity (AUC: 0.77; 0.82; 0.82, respectively). The combination of pH?≤?7.0 and lactate?≥?7.0?mmol/L presented similar validity to that of pH?≤?7.0 and BD?≥?12?mmol/L, but both were comparable to pH alone.

Conclusions: pH, BD and lactate have similar predictive ability for adverse neonatal outcomes among acidemic neonates. Umbilical arterial lactate could replace BD as a measure of the metabolic component in acidemic neonates. However, neither BD nor lactate demonstrated in this study to improve the predictive ability of pH alone for short-term neonatal outcomes.     

Probability of liver cancer and survival in HCV-related or alcoholic-decompensated cirrhosis. A study of 377 patients.

BACKGROUND: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies. METHODS: This study identified factors related with probability of developing HCC and survival in a cohort of 377 consecutive patients with decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177 cases) without known HCC, hospitalized for their first hepatic decompensation, as well as to evaluate differences between both aetiologies. Patients were followed for a mean period of 39 +/- 2 months. RESULTS: During follow-up, 42 patients (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p = 0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol, respectively; p = 0.002). Age and HCV-cirrhosis were independently related to HCC development, while baseline age and Child-Turcotte-Pugh score were independently correlated with survival. CONCLUSION: Survival in decompensated HCV-related or alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score, without differences in cirrhosis aetiology. The risk of developing HCC is greater in HCV-related cirrhosis than in alcoholic cirrhosis.     

Serum bile acid levels in children with chronic persistent hepatitis and chronic aggressive hepatitis

A statistical study was carried out to determine if fasting serum bile acid levels are clinically useful in differentiating children with chronic persistent hepatitis from children with chronic aggressive hepatitis. Serum bile acid levels were determined in 27 patients with chronic aggressive hepatitis, 41 with chronic persistent hepatitis and 55 control children. Several other biochemical tests of liver function were also determined in these children. There were significant differences in the mean fasting serum bile acid levels between chronic hepatitis patients and control children (p less than 0.001). These levels were significantly higher for the chronic aggressive group than the chronic persistent hepatitis group (p less than 0.001). Other biochemical 'hepatic function' tests did not show statistically different values between these two groups. Using stepwise discriminant analysis for the biochemical 'liver function' tests studied, only serum bile acid levels are able to distinguish statistically between chronic aggressive hepatitis and chronic persistent hepatitis children. These data suggest that fasting serum bile acid levels may have clinical utility in identifying children with asymptomatic chronic hepatitis and differentiating between chronic aggressive hepatitis and chronic persistent hepatitis children.     

Impact of intestinal mannitol on hyperammonemia,oxidative stress and severity of hepatic encephalopathy in the ED

Hyperammonemia results from hepatic inability to remove nitrogenous products generated by protein metabolism of intestinal microbiota, which leads to hepatic encephalopathy (HE) in chronic liver disease (CLD). In ammonium neurotoxicity, oxidative stress (OxS) plays a pathogenic role. Our objective was to evaluate if intestinal mannitol is as effective and safe as conventional treatment for diminishing hyperammonemia, OxS, and HE in patients with CLD.