Rheumatoid Factor and Its Interference with Cytokine Measurements: Problems and Solutions

Use of cytokines as biomarkers for disease is getting more widespread. Cytokines are conveniently determined by immunoassay, but interference from present antibodies is known to cause problems. In rheumatoid arthritis (RA), interference of rheumatoid factor (RF) may be problematic. RF covers a group of autoantibodies from immunoglobulin subclasses and is present in 65–80% of RA patients. Partly removal of RF is possible by precipitation. This study aims at determining the effects of presence of RF in blood and synovial fluid on cytokine measurements in samples from RA patients and finding possible solutions for recognized problems. IL-1β, IL-4, IL-6, and IL-8 were determined with multiplex immunoassays (MIA) in samples from RA patients prior to and after polyethylene glycol (PEG 6000) precipitation. Presence of RF does interfere with MIA. PEG 6000 precipitation abolishes this RF interference. We recommend PEG precipitation for all immunoassay measurements of plasma samples from RA patients

Test-retest of computerized health status questionnaires frequently used in the monitoring of knee osteoarthritis: a randomized crossover trial

<p>Abstract</p> <p>Background</p> <p>To compare data based on touch screen to data based on traditional paper versions of questionnaires frequently used to examine patient reported outcomes in knee osteoarthritis patients and to examine the impact of patient characteristics on this comparison</p> <p>Methods</p> <p>Participants were recruited from an ongoing trial (<url>http://ClinicalTrials.Gov</url> Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00655941">NCT00655941</a>). 20 female participants, mean age 67 (SD 7), completed KOOS, VAS pain, function and patient global, SF-36, Physical Activity Scale, painDETECT, and the ADL Taxonomy. Patients were randomly assigned to one of two subgroups, completing either the paper or touch screen version first. Mean, mean differences (95% CI), median, median differences and Intraclass Correlation Coefficients (ICCs) were calculated for all questionnaires.</p> <p>Results</p> <p>ICCs between data based on computerized and paper versions ranged from 0.86 to 0.99. Analysis revealed a statistically significant difference between versions of the ADL Taxonomy, but not for the remaining questionnaires. Age, computer experience or education-level had no significant impact on the results. The computerized questionnaires were reported to be easier to use.</p> <p>Conclusion</p> <p>The computerized questionnaires gave comparable results to answers given on paper. Patient characteristics did not influence results and implementation was feasible.</p

The Relationship between Mechanical Hyperalgesia Assessed by Manual Tender Point Examination and Disease Severity in Patients with Chronic Widespread Pain: A Cross-Sectional Study

The clinical utility of tender point (TP) examination in patients reporting chronic widespread pain (CWP) is the subject of contemporary debate. The objective of this study was to assess the relationship between mechanical hyperalgesia assessed by manual TP examination and clinical disease severity. 271 women with CWP were recruited from a clinical setting. Data collection included patient-reported symptoms, health-related quality of life variables, and observation-based measures of functional ability, muscle strength, 6-minute walk, and pressure pain thresholds measured by cuff algometry. TP examination was conducted according to ACR-guidelines. Relationships between disease variables and TP count (TPC) were analyzed with logistic regression in a continuum model, allowing the TPC to depend on the included disease variables and two regression models carried out for a TPC threshold level, varying between 1 and 17. The threshold analyses indicated a TPC threshold at 8, above which a large number of disease variables became consistently significant explanatory factors, whereas none of the disease variables reached a significance level in the continuum model. These results support the premise that the presence of mechanical hyperalgesia influences symptomatology in CWP and that the severity of clinical expression is related to a threshold of TPs, rather than being part of a continuum

Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans

<p>Abstract</p> <p>Background</p> <p>There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders.</p> <p>Results</p> <p>At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (S_A/S_Aand S_A/L_G) as compared to those with high expression(L_A/L_A), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression.</p> <p>Conclusion</p> <p>This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.</p

Tumor volume and cancer stem cell expression as prognostic markers for high-dose loco-regional failure in head and neck squamous cell carcinoma - A DAHANCA 19 study

BACKGROUND AND PURPOSE: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint.MATERIALS AND METHODS: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n = 340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16 + OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx).RESULTS: Higher risk of HDF was seen for patients with larger primary and nodal volume (&gt;25 cm3, Hazard Ratio (HR): 3.00 [95 % CI: 1.73-5.18]), high SLC3A2 (HR: 2.99 [1.28-6.99]), CD44 (&gt;30 % positive, HR: 2.29 [1.05-5.00]), and p16- tumors (HR: 2.53 [1.05-6.11]). p16- tumors had a higher CSC marker expression than p16 + OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 [1.79-6.04]) for p16- tumors (n = 178) and high SLC3A2 (HR: 6.19 [1.58-24.23]) for p16 + OPSCC (n = 162).CONCLUSION: Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16 + OPSCC may contribute to better tumor control.</p