Cerebrospinal fluid of chronic osteoarthritic patients induced interleukin-6 release in human glial cell-line T98G.

BACKGROUND: Chronic osteoarthritic pain is not well understood in terms of its pathophysiological mechanism. Activated glial cells are thought to play a role in the maintenance of chronic pain. T98G glioblastoma cell line was previously observed to release higher amounts of interleukin-6 (IL-6) when treated with cerebrospinal fluid (CSF) from patients with another chronic pain condition, post-herpetic neuralgia. In this study, we investigated the ability of CSF from patients diagnosed with knee osteoarthritis suffering from chronic pain, to trigger the release of pro-inflammatory cytokines, IL-6, IL-1beta and tumour necrosis factor alpha (TNF-α) from T98G. Characterization of upstream signalling was also explored. METHODS: Fifteen osteoarthritis patients undergoing total knee replacement due to chronic knee pain and 15 patients without pain undergoing other surgeries with spinal anaesthesia were prospectively recruited. CSF was collected during anaesthesia. CSF were added to cultured T98G cells in the presence of lipopolysaccharide. IL-6, IL-1ß and TNF-α release from T98G cells were measured using enzyme immunoassay. Antibody array and western blotting were performed using CSF-triggered T98G cell lysates to identify possible signalling targets. Age, gender and pain scores were recorded. Mann-Whitney U test was used to compare IL-6 release and protein expression between groups. Association between IL-6 and pain score was analysed using linear regression. RESULTS: Significant higher levels of IL-6 were released by T98G cells when induced by osteoarthritis patients' CSF in the presence of LPS. The IL-6 levels showed positive association with pain score (adjusted B estimate = 10.1 (95% Confidence Interval 4.3-15.9); p = 0.001). Antibody array conducted with 6 pooled T98G cell lysate induced with osteoarthritis pain patient CSF identified greater than 2-fold proteins including STE20-related kinase adaptor protein and spleen tyrosine kinase. Further validation done using western blotting of individual CSF-triggered T98G cell lysate showed non-significant increase. CONCLUSION: Higher IL-6 release from T98G when triggered by OA-CSF, in the presence of LPS, suggest the presence of "unknown molecule" in CSF that may be crucial in the maintenance phase of chronic pain in our osteoarthritis population. Further studies on the signalling pathways involved in pain and relevance of IL-6 release from T98G cells in other pain models are needed.

Evaluation of the Efficiency and Safety of a Safe Label System: A Prospective Simulation Study.

OBJECTIVES: Our study aims to investigate the safety and efficiency of the Codonics Safe Label System (SLS) in a prospective simulation study. METHODS: Three sets of simulated experiments involving 82 anesthetists were carried out on patient simulator mannequins. The primary outcome assessed through the simulated experiments was the effectiveness of the SLS in avoiding vial swap errors. Secondary outcomes analyzed included the efficacy of the SLS in preventing syringe swap and the difference in time taken to prepare standardized drugs as compared with conventional methods. RESULTS: The SLS was associated with a significant reduction in all 4 stages of vial swap error. The incidence of wrong ampoule breakage was significantly lower in the SLS group compared with the conventional group (12.1% versus 38.5%, P = 0.007). The number of staff who drew the wrong ampoule was similarly lower in the SLS group compared with the conventional group (4.9% versus 33.3%, P = 0.001). The proportions of staff who eventually wrongly labeled the loaded syringe were 0% in the SLS group and 17.9% in the conventional group (P = 0.005).Drug preparation time was longer for the SLS group than for the conventional group (239.6 ± 45.9 versus 160.3 ± 46.5 seconds, P < 0.001).There was no significant difference in the incidence of syringe swap with the use of the SLS. CONCLUSIONS: The use of the SLS is effective in reducing vial swap error, but not syringe swap errors, and is associated with increased time taken for anesthetic drug preparation.

Patient safety culture among medical students in Singapore and Hong Kong.

INTRODUCTION: Undergraduate education in medical schools plays an important role in promoting patient safety. Medical students from different backgrounds may have different perceptions and attitudes toward issues concerning safety. This study aimed to investigate whether patient safety cultures differed between students from two Asian countries, and if they did, to find out how they differed. This study also aimed to identify the educational needs of these students. METHODS: A voluntary, cross-sectional and self-administered questionnaire survey was conducted on 259 students from two medical schools - one in Hong Kong and the other in Singapore. None of the students had received any formal teaching on patient safety. We used a validated survey instrument, the Attitudes to Patient Safety Questionnaire III (APSQ-III), which was designed specifically for students and covered nine key factors of patient safety culture. RESULTS: Of the 259 students, 81 (31.3%) were from Hong Kong and 178 (68.7%) were from Singapore. The overall response rate was 66.4%. Significant differences between the two groups of students were found for two key factors - 'patient safety training', with Hong Kong students being more likely to report having received more of such training (p = 0.007); and 'error reporting confidence', which Singapore students reported having less of (p < 0.001). Both groups considered medical errors as inevitable, and that long working hours and professional incompetence were important causes of medical errors. The importance of patient involvement and team functioning were ranked relatively lower by the students. CONCLUSION: Students from different countries with no prior teaching on patient safety may differ in their baseline patient safety cultures and educational needs. Our findings serve as a reference for future longitudinal studies on the effects of different teaching and healthcare development programmes.

Elevated prepronociceptin, nociceptin/orphanin FQ and nocistatin concentrations in rat chronic constriction nerve injury and diabetic neuropathic pain models.

Nociceptin/orphanin FQ (N/OFQ) and nocistatin are derived from the same precursor peptide, prepronociceptin. N/OFQ and nocistatin have been postulated to participate in pain modulation. In this study, we investigated whether the prepronociceptin, N/OFQ and nocistatin concentrations in the brain and spinal cord would be altered in chronic constriction injury and diabetic rat neuropathic pain models. Total brain and spinal cord lysates as well as serum from rats that had undergone chronic constriction injury and streptozocin-induced diabetic neuropathy were used to determine the concentrations of three peptides using competitive radioimmunoassay. We found that N/OFQ and prepronociceptin concentrations were significantly raised in both rat neuropathic pain models. Nocistatin was raised in the brains of post traumatic neuropathy pain rats. Overall, our data have demonstrated for the first time that prepronociceptin, N/OFQ and nocistatin concentrations are significantly altered at different tissues of two rat neuropathy pain models.