Hiroki Tsuchiya

Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells.

We investigated chondrogenesis of cell-mediated sox9 gene therapy as a new treatment regimen for cartilage regeneration. pIRES2-EGFP vector containing a full-length mouse sox9 cDNA was transfected into bone marrow-derived mesenchymal stem cells (MSCs) by lipofection and chondrogenic differentiation of these cells was evaluated. In vitro high density micromass culture of these sox9 transfected MSCs demonstrated that a matrix-rich micromass aggregate with EGFP expressing MSCs was positively stained by Alcian blue and type II collagen. Next, sox9 transfected MSCs were loaded into the diffusion chamber and transplanted into athymic mice to analyze in vivo chondrogenesis. A massive tissue formation in about 2mm diameter was visible in the chamber after 4 weeks transplantation. Histological examinations demonstrated that both Alcian blue and type II collagen were positively stained in the extracellular matrix of the mass while type X collagen was not stained. These results indicated that cell-mediated sox9 gene therapy could be a novel strategy for hyaline cartilage damage.

Depression, inflammation, and pain in patients with rheumatoid arthritis

OBJECTIVE An association between depression and inflammation has been suggested. In patients with rheumatoid arthritis (RA), pain is a major symptom associated with depression and inflammation. We examined the independent associations between depression, the inflammation marker C-reactive protein (CRP) level, and pain in patients with RA. METHODS In total, 218 RA outpatients completed self-administered questionnaires, using the Beck Depression Inventory II to measure depressive symptoms and a visual analog scale to quantify their perceived pain. Functional disability and CRP level were also measured. RESULTS Depression scores were mildly and positively correlated with the CRP level (r = 0.46, P < 0.001). Both the depression score (standardized beta = 0.35, P < 0.001) and the CRP level (standardized beta = 0.35, P < 0.001) were significantly associated with pain, even after adjustment for clinical covariates in regression analysis. In logistic analysis, the combined effects on the risk of severe pain (pain score in the upper tertile) increased with depression scores and CRP levels linearly. CONCLUSION Depression severity and inflammation were associated with each other and appeared to have independent effects on perceived pain. Therefore, a clinical approach that takes into account both the body and the mind could have benefits and could enable optimal pain control.

Distraction Osteogenesis of the Lower Extremity in Patients With Achondroplasia/hypochondroplasia Treated With Transplantation of Culture-expanded Bone Marrow Cells and Platelet-rich Plasma

Background: Longer treatment period in distraction osteogenesis (DO) of the lower extremity leads to more frequent complications. We have developed a new technique of transplantation of culture-expanded bone marrow cells (BMCs) and platelet-rich plasma (PRP) during DO to accelerate new bone formation. To assess the efficacy of this cell therapy, retrospective comparative study was conducted between the bones treated with BMC and PRP and the bones treated without BMC and PRP during DO in patients with achondroplasia (ACH) and hypochondroplasia (HCH). Methods: Fifty-six bones in 20 patients (ACH, 16; HCH, 4) that were lengthened in our hospital were divided into 2 groups. Twenty-four bones (femora, 12; tibiae, 12) in 11 patients (boys, 7; girls, 4) were treated with BMC and PRP transplantation (BMC-PRP group), whereas 32 bones (femora, 14; tibiae, 18) in 9 patients (boys, 3; girls, 6) did not undergo additional cell therapy (control group). The parameters, including the age at operation, the increase in length, and the healing index, were compared between the 2 groups. The clinical outcome was also compared between the femoral and tibial lengthenings. Results: Bone marrow cells (average number, ± SD, 3.2 ± 1.37 × 107 cells) and PRP (average platelet concentration ± SD, 2.36 ± 0.57 × 106 cells/&mgr;L) were transplanted. Although there were no significant differences in the age at operation and the length gained between the 2 groups, the average healing index of the BMC-PRP group (27.1 ± 6.89 d/cm) was significantly lower than that of the control group (36.2 ± 10.4 d/cm) (P = 0.0005). The femoral lengthening showed significantly faster healing than did the tibial lengthening in the BMC-PRP group (P = 0.0092). Conclusions: Transplantation of BMC and PRP shortened the treatment period by accelerating new bone regeneration during DO of the lower extremity in patients with ACH and HCH, especially in the femoral lengthening. Level of Evidence: Therapeutic studies, level III (retrospective comparative study).

Psychosocial factors, disease status, and quality of life in patients with rheumatoid arthritis ☆

OBJECTIVE To explore the interrelationships between the psychosocial and illness factors that determine the disease status of patients with rheumatoid arthritis (RA) and to identify how each factor is associated with quality of life (QOL). METHODS The study group comprised 120 RA outpatients who completed a series of health examinations and questionnaires. Disease severity, functional disability, counts of swollen and/or tender joints, duration of RA, frequency of arthritis surgery, and C-reactive protein level were assessed by rheumatologists. Self-report inventories completed by the patients were used to assess perceived degree of pain, fatigue (visual analogue scales), depression (Beck Depression Inventory-II), anxiety (Hospital Anxiety and Depression Scale), and social support (Social Support Questionnaire). Mental and physical components of health-related QOL were evaluated using the Short-Form 36 Health Survey. RESULTS After z-transformation of the data, a principal axis factor analysis was conducted. A four-factor structure was identified in which the components reflected psychosocial factors, disease activity, current symptoms, and physical functional status, respectively. There was no significant association between psychosocial factors and disease activity, while the other components were moderately correlated with each other. Multiple regression analysis revealed that physical QOL was determined by current symptoms and physical functions. Mental QOL was determined by psychosocial factors, current symptoms, and physical functions. CONCLUSION Disease activity was independent from psychosocial factors and failed to reflect the perceived physical and mental QOL of RA patients. Clinicians should therefore evaluate psychosocial factors, as well as subjective disease status, to improve the QOL of patients with RA.

Distraction osteogenesis enhanced by osteoblastlike cells and collagen gel

Femoral distraction was done in rats to determine whether the injection of osteoblastlike cells with collagen gel into the distracted callus was useful for new bone formation. The cells were obtained from the femoral marrow of Sprague-Dawley rats and cultured for approximately 3 weeks. These rats were divided into four groups. The rats in Group A received injections of physiologic saline, those in Group B received injections of collagen gel, those in Group C received injections of cells, and those in Group D received injections containing a mixture of cells and collagen gel. The distracted areas were harvested and evaluated by histologic analysis, radiography, three-point bending testing, and the weight of femoral ash. Histologic evaluation did not show an immunoreaction between the donor and recipient. Radiographs showed that Group D had the most callus, and the fracture strength in this group as determined by the three-point bending test was higher than in Group A at 2, 4, and 6 weeks after elongation was completed. Group D showed a significant difference in the ash weight of the distracted femurs at 2 weeks. The current study showed that osteoblastlike cells with collagen gel promoted new bone formation in the distracted gap, and shortened the consolidation period.

Reduction of the incidence of development of venous thromboembolism by ultrasound-guided femoral nerve block in total knee arthroplasty

Background Venous thromboembolism (VTE) and the subsequent development of pulmonary embolism (PE) is a major cause of post-operative mortality in total knee arthroplasty (TKA). We evaluated whether the addition of an ultrasound-guided femoral nerve block with general anesthesia affected the incidence in the development of VTE following TKA. Methods This was a retrospective non-randomized comparative study with patients assigned to groups based on the surgery date (pre-femoral nerve block versus post-femoral nerve block periods). All anesthesia and medical records of the patients who had undergone computer-navigated TKA in our facility between January 2009 and March 2010 were retrospectively reviewed. Results Forty patients were identified; 15 patients underwent computer-navigated TKA under general anesthesia alone (Group G) and 25 patients underwent surgery under general anesthesia combined with ultrasound-guided femoral nerve block (Group F). The incidence of development of VTE post-operatively was significantly lower in Group F (P = 0.037). Logistic regression analysis identified the use of a femoral nerve block as the most significant variable correlating with the incidence of post-operative development of VTE, and the odds ratio for VTE development in Group G was 3.12 (95% CI, 0.57-20.56). Conclusions We suggest the possibility that the addition of a femoral nerve block on general anesthesia may reduce the incidence of the development of VTE following TKA.

Deep vein thrombosis: how long will it remain?

To the Editor: A 75-year-old woman underwent computer-navigated left total knee arthroplasty (TKA) under general anesthesia with sevoflurane, fentanyl, and remifentanyl combined with ultrasound-guided femoral nerve block with a total amount of 25 mL of 0.3% ropivacaine, followed by intravenous fentanyl PCA postoperatively. She had undergone right total knee arthroplasty 3 years prior to the present surgery, and her past history was otherwise unremarkable. All the surgical and anesthesiological procedures were uneventful, and the intermittent pneumatic compression (IPC) system was immediately started after the surgery. The initial dose of once-daily subcutaneous injection of 1.5 mg of fondaparinux was started