Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis

Background

Factors responsible for the progression of primary biliary cirrhosis (PBC) are still poorly understood. In the present study, we investigated the associations between the stage of PBC and the immune reaction triggered by oxidative stress; the presence of obesity, steatosis, steatohepatitis; and other toxic, metabolic, or steatogenic factors.

Methods

We studied clinical, laboratory, and histological data for 274 untreated patients with serum antimitochondrial antibody (AMA)-positive PBC. Circulating IgG against human serum albumin adducted with malondialdeyde, the major product of lipid peroxidation, was measured in these patients and in a group of 98 sex-, age- and body mass index (BMI)-matched controls.

Results

Steatosis was present in 40.5% of all patients. Steatohepatitis was present in 14.9% of all patients. There was a significant association between the frequencies of steatosis and steatohepatitis and the worsening of PBC. Circulating IgG against lipid peroxidation products was significantly higher in the PBC patients than in the controls. Titers of lipid peroxidation-related antibodies were significantly increased in patients with steatosis and in patients at more advanced stages. Bivariate analysis revealed a significant association between indirect evidence of oxidative stress, steatosis, steatohepatitis, age, BMI, frequency of diabetes, alcohol intake, iron grade after Perl’s stain, and PBC stage. Logistic regression analysis confirmed that the titers of antibodies against lipid peroxidation products (odds ratio 4.5, p < .001, 95% confidence interval 3.9–14.4), the presence of steatosis (odds ratio 4.1, 95% confidence interval 2.5–15.4, p < .001), higher BMI (odds ratio 3.9, p < .021, 95% confidence interval 1.4–9.5), and alcohol intake (males ≥ 30 g/day, females ≥ 20 g/day, odds ratio 4.5, 95% confidence interval 1.3–19.8, p < .029) were independently associated with more advanced stages of the disease.

Conclusions

The immune reactions triggered by oxidative stress, steatosis, obesity, and alcohol intake are independent predictors of PBC stage progression.     

A systematic review of psychosocial interventions for men with prostate cancer and their partners

Objective

To systematically review interventions aiming to improve adjustment in men with prostate cancer and their partners.

Methods

Medline, EMBASE, CINAHL and PsycINFO databases were searched. Inclusion criteria were: randomized controlled trials; relevant to specified clinical questions; included men who had prostate cancer (at least 80% prostate cancer patients or prostate cancer sub-group analysis); published in English between December 1999 and December 2009. Trial quality was assessed.

Results

21 studies met inclusion criteria. Trial quality was low; had not improved over the study timeframe; men with advanced disease were not targeted; minority groups were seldom included. Group cognitive-behavioral and psycho-education interventions appear helpful in promoting better psychological adjustment and QOL for men with prostate cancer; coping skills training for patient–spouse dyads improved QOL for partners.

Conclusion

There are limitations in the research on effective ways to improve adjustment for men with prostate cancer of any stage and their partners; and scant research targeting minority groups and the concerns of men with advanced disease.

Practice implications

Interventions for men with advanced prostate cancer could usefully target the implications of advancing disease and caregiver burden. There is an urgent need for researchers to focus efforts specifically on such men and their families.     

High-frequency and adaptive-like dynamics of human CD1 self-reactive T cells

CD1 molecules present lipid antigens to T cells. An intriguing subset of human T cells recognize CD1‐expressing cells without deliberately added lipids. Frequency, subset distribution, clonal composition, naïve‐to‐memory dynamic transition of these CD1 self‐reactive T cells remain largely unknown. By screening libraries of T‐cell clones, generated from CD4⁺ or CD4^?CD8^? double negative (DN) T cells sorted from the same donors, and by limiting dilution analysis, we find that the frequency of CD1 self‐reactive T cells is unexpectedly high in both T‐cell subsets, in the range of 1/10–1/300 circulating T cells. These T cells predominantly recognize CD1a and CD1c and express diverse TCRs. Frequency comparisons of T‐cell clones from sorted naïve and memory compartments of umbilical cord and adult blood show that CD1 self‐reactive T cells are naïve at birth and undergo an age‐dependent increase in the memory compartment, suggesting a naïve/memory adaptive‐like population dynamics. CD1 self‐reactive clones exhibit mostly Th1 and Th0 functional activities, depending on the subset and on the CD1 isotype restriction. These findings unveil the unanticipated relevance of self‐lipid T‐cell response in humans and clarify the basic parameters of the lipid‐specific T‐cell physiology.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

用于鼻腔测量的声反射技术——应用与进展

本文综述了声反射鼻腔测量（acoustic rhinometry,AR）近年来在临床中的应用和研究。主要阐述了声反射测量的工作原理,在鼻周期以及正常人鼻腔测量相关参数建立等基础研究,在耳鼻喉科疾病诊断和药物作用等临床研究中的进展。     

Auditory processing in a patient with a unilateral lesion of the inferior colliculus

The role of the inferior colliculus (IC) in human auditory processing is still poorly understood. We report here the results obtained with a 12-year-old boy (FX) who suffered a very circumscribed lesion of the right IC without additional neurological damage. The child underwent an extensive battery of psychophysical hearing tests. Results revealed normal peripheral auditory functioning, bilaterally. Furthermore, masking-level differences and frequency-pattern recognition were normal for each ear. When the right ear was stimulated, behavioural tests assessing central auditory processing yielded normal results. However, when the left ear was stimulated, speech recognition in the presence of a competing ipsilateral signal and duration-pattern recognition were impaired. Similarly, performance on two dichotic speech recognition tests was poor when the target stimulus was presented in the left and the competing signal in the right ear. Finally, sound-source localization in space was deficient for speakers located on the side contralateral to the lesion. The pattern of results suggests that auditory functions such as recognition of low-redundancy speech presented monaurally, recognition of tone duration patterns, binaural separation and integration, as well as sound-source localization in space, depend on the integrity of the bilateral auditory pathways at the IC level.     

Enhancement of sound motion detection in acallosal individuals

It has been proposed that the corpus callosum may play an important role in spectral cue processing that allows vertical auditory movement perception. The purpose of the present study was to assess the contribution of the corpus callosum to this type of auditory processing. Noise bursts were presented to 10 control and two callosal agenesis individuals from different positions located within midsagittal and coronal planes. Although acallosal participants were comparable with controls in their ability to correctly identify the trajectory direction or its length, they showed greater capability in detecting motion per se when the task was difficult. These results suggest that in the absence of the corpus callosum, compensatory reorganization of the brain allowed for superior auditory spectral cue processing.