Osteoarthritis (OA) is a complex disease of the skeleton and is associated with aging. Both environmental and genetic factors contribute to its pathogenesis. We set out to identify novel genes associated with OA, concentrating on regulatory polymorphisms allowing for differential expression. Our strategy to identify differentially expressed genes included an initial transcriptome analysis of the peripheral blood mononuclear cells of six patients with OA and six age-matched healthy controls. These were screened for allelic expression imbalances and potentially regulatory single-nucleotide polymorphisms (SNPs) in the 5' regions of the genes. To establish disease association, disparate promoter SNP distributions correlating with the differential expression were tested on larger cohorts. Our approach yielded 26 candidate genes differentially expressed between patients and controls. Whereas BLP2 and CIAS1 seem to be trans-regulated, as the absence of allelic expression imbalances suggests, the presence of allelic imbalances confirms cis-regulatory mechanisms for RHOB and TXNDC3. Interestingly, on/off-switching suggests additional trans-regulation for TXNDC3. Moreover, we demonstrate for RHOB and TXNDC3 statistically significant associations between 5' SNPs and the disease that hint at regulatory functions. Investigating the respective genes functionally will not only shed light on the disease association but will also add to the understanding of the pathogenic processes involved in OA and may point out novel therapeutic approaches.
For a variety of medical applications, detailed knowledge on the statistical distribution of morphometric characteristics among specific patient groups is required. We present a novel approach for performing automated morphometric measurements on the surface of anatomical bone samples obtained from CT segmentation. The system developed supports various types of measurements (distances, angles, radii) on several kinds of features (points, lines, planes or circles), which are performed automatically for every bone sample in a given data set. The desired features can be specified by the user in two ways, either by marking them on a standardized template that is mapped to all samples via a correspondence mapping, or by hierarchically building new features from existing features. The system was implemented and tested on a database containing about 1200 segmented femur. The quality of the automated matching was assessed through a study comparing the performance of the system with results obtained from manual labeling by medical experts. It was found that the deviation between the two methods was generally less than 2mm.
Synovial fluid IL-6 levels may help to classify OA patients and may point to a subgroup with a particular impact from their immune system.
Background: Chronic radicular pain can occur after disc pathology and failed back surgery. An evidence-based effective therapeutic option is not available nor does a gold standard exist. Objectives: A randomized controlled trial to analyze the clinical efficacy of percutaneous epidural lysis of adhesions in chronic radicular pain. Study Design: Prospective randomized placebo controlled interventional trial. Power calculation based on a feasibility trial. Setting: Medical university centers. Methods: Within 4 years a total of 381 patients with chronic radicular pain lasting longer than 4 months which failed to respond to conservative treatments were screened and 90 patients were enrolled. They were randomly assigned to receive either percutaneous neurolysis or placebo with concealed allocation in permuted blocks of 4 to 8, stratified by treatment center. The primary outcome measure was the differences in percent change of Oswestry Disability Index (ODI) scores 3 months after intervention. Secondary outcome measures were difference in percent change of ODI scores and Visual Analog Scale (VAS) 6 and 12 months after intervention and success rates defined as at least 50% reduction in ODI scores and VAS scores (mean change from baseline) at 3, 6, and 12 months after treatment. Explorative, 2-sided group comparisons for baseline characteristics between active treatment and controls were done using the t-test for 2 independent samples for quantitative data and Fisher’s exact test for binary data. Results: The ODI and VAS scores as well as the success rates for ODI vs VAS were significantly better 3, 6, and 12 months in the lysis group vs the control group. The ODI in the lysis group improved from 55.3 ± 11.6 to 26.4 ± 10.8 after 3 months. The placebo group improved from 55.4 ± 11.5 to 41.8 ± 14.6 (P < 0.01). VAS improved from 6.7 ± 1.1 to 2.9 ± 1.9 in the active group and from 6.7 ± 1.1 to 4.8 ± 2.2 (P < 0.01) after placebo. Twelve month follow-up shows further improvement, the differences remain significant. In multiple linear regression, forward and backward variable selection methods resulted in the same covariate model confirming the univariate result for group comparison in the primary analysis. No severe side effects occurred but minor transient neurological effects such as partial sensomotoric deficits did. One dura puncture and one catheter displacement were found. Limitations: Specific effects of single treatment components cannot be specified because there was no imaging examination after treatment. Conclusion: Based on the findings of our study as well as other studies, we believe the minimally invasive percutaneous adhesiolysis procedure should be the first choice treatment option for patients with chronic lumbosacral radicular pain who present with clinical history and findings similar to those of the patients enrolled in our study. Key words: Lysis, low back pain, randomized controlled trial (RCT), placebo, epidural, radiculopathy, outcome, evidence-based medicine
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