Impact of nervous system hyperalgesia on pain, disability, and quality of life in patients with knee osteoarthritis: a controlled analysis

OBJECTIVE: Refractory, disabling pain associated with knee osteoarthritis (OA) is usually treated with total knee replacement. However, pain in these patients might be associated with central nervous sensitization rather than peripheral inflammation and injury. We evaluated the presence of hyperalgesia in patients scheduled for a total knee replacement due to knee osteoarthritis with refractory pain, and we assessed the impact of pressure pain threshold measurements (PPT) on pain, disability, and quality of life of these patients. METHODS: Sixty-two female patients were compared with 22 age-matched healthy controls without reported pain for the last year. PPT was measured at the lower extremities subcutaneous dermatomes, over the vastus medialis, adductor longus, rectus femoris, vastus lateralis, tibialis anterior, peroneus longus, iliacus, quadratus lumborum and popliteus muscles and at the supraspinous ligaments from L1-L5, over the L5-S1 and S1-S2 sacral areas and at the pes anserinus bursae and patellar tendon. RESULTS: Patients with knee OA had significantly lower PPT over all evaluated structures versus healthy control subjects (P<0.001). Lower PPT values were correlated with higher pain intensity, higher disability scores, and with poorer quality of life, except for the role-emotional and general health status. Combined PPT values over the patellar tendon, at the S2 subcutaneous dermatome and at the adductor longus muscle were the best predictors for visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index pain scores. CONCLUSION: Patients with pain due to osteoarthritis who were scheduled for total knee replacement showed hyperalgesia of nervous system origin that negatively impacted pain, knee functional capacity, and most aspects of quality of life.     

Treatment with Steroids and Double Filtration Plasmapheresis for a Case of Anti-GQ1b Antibody-Positive Bickerstaff's Encephalitis

The treatment of Bickerstaff's brainstem encephalitis (BBE) is still controversial. We report a case of BBE with positive anti-GQ1b antibody. The patient was successfully treated with steroids and double filtration plasmapheresis.     

Cell-mediated graft rejection observed in two lines of human histocompatibility leukocyte antigen class I transgenic mice.

BACKGROUND: Human histocompatibility leukocyte antigen (HLA) class I molecules are essential for graft rejection. However, to determine the specific role of these molecules in clinical situations is difficult. We investigated the applicability of HLA class I transgenic mice (C3H.B35 and C3H.B51) for elucidation of the role of HLA class I molecules. METHODS: Skin or heart grafts were transplanted. Cytotoxic T cells (CTL) of C3H.B51 against C3H.B35 were generated and their cytotoxicity against various transfectant cell lines was determined. RESULTS: C3H.B35 skin and heart grafted to C3H.B51 were rejected within 17 and 28 days, respectively. Cytotoxic T cells generated from C3H.B51 showed cytotoxicity against a HLA-B*3501-transfectant cell line that did not express H-2 molecule, which indicates that these cytotoxic T cells recognize HLA-B35 molecules directly without H-2 restriction. CONCLUSION: Our results suggest that C3H.B51 recognize C3H.B35 grafts as allo-MHC class I-incompatible grafts, and these mice are valuable to elucidate the role of HLA class I molecules in transplantation.     

Differential expression of a stress‐regulated gene Nr4a2 characterizes early‐ and late‐born hippocampal granule cells

Neural progenitors acquire GFAP expression during the perinatal period and continue to generate granule cells (GCs) in the hippocampal dentate gyrus throughout adulthood. Cellular characteristics of GFAP+ progenitor‐derived late‐born GCs in comparison with early‐born GCs remain unknown. Using genetic fate mapping in mice, we show that early‐ and late‐born GCs are concentrated in the outer and inner side of the GC layer, respectively. We then identify that a nuclear orphan receptor Nr4A2 is preferentially expressed by early‐born GCs. Nr4a2 expression is dynamically regulated in response to restraint stress and glucocorticoid levels, indicating that Nr4a2 is a stress‐regulated gene in GCs. Acute stress suppresses but chronic stress conversely induces Nr4a2 expression in GCs. The survival of newly generated GCs is impaired by chronic restraint stress and long‐term stress after middle age decreases the proportion of late‐born GCs in aged mice. Thus, early‐ and late‐born GCs exhibit characteristic anatomical distribution, differential gene expression, and distinct response to environmental stress.     

Association between prehospital time interval and short-term outcome in acute heart failure patients

Background

Acute heart failure (AHF) is one of the most frequently encountered cardiovascular conditions that can seriously affect the patient’s prognosis. However, the importance of early triage and treatment initiation in the setting of AHF has not been recognized.

Methods and Results

The Tokyo Cardiac Care Unit Network Database prospectively collected information of emergency admissions to acute cardiac care facilities in 2005–2007 from 67 participating hospitals in the Tokyo metropolitan area. We analyzed records of 1,218 AHF patients transported to medical centers via emergency medical services (EMS). AHF was defined as rapid onset or change in the signs and symptoms of heart failure, resulting in the need for urgent therapy. Patients with acute coronary syndrome were excluded from this analysis. Logistic regression analysis was performed to calculate the risk-adjusted in-hospital mortality. A majority of the patients were elderly (76.1 ± 11.5 years old) and male (54.1%). The overall in-hospital mortality rate was 6.0%. The median time interval between symptom onset and EMS arrival (response time) was 64 minutes (interquartile range [IQR] 26–205 minutes), and that between EMS arrival and ER arrival (transportation time) was 27 minutes (IQR 9–78 minutes). The risk-adjusted mortality increased with transportation time, but did not correlate with the response time. Those who took >45 minutes to arrive at the medical centers were at a higher risk for in-hospital mortality (odds ratio 2.24, 95% confidence interval 1.17–4.31; P = .015).

Conclusions

Transportation time correlated with risk-adjusted mortality, and steps should be taken to reduce the EMS transfer time to improve the outcome in AHF patients.     

Ammocidin, a new apoptosis inducer in Ras-dependent cells from Saccharothrix sp. I. Production, isolation and biological activity.

A new apoptosis inducer, ammocidin, was isolated from the culture broth of Saccharothrix sp. AJ9571. Ammocidin induced apoptotic cell death in Ras-dependent Ba/F3-V12 cells with an IC50 of 66 ng/ml. No cell death was observed in IL-3-dependent Ba/F3-V12 cells at less than 100 microg/ml of ammocidin. Ammocidin significantly reduced the phosphorylation level of MAPK and S6K that mediate the anti-apoptotic function of Ras.