Natsuko Nakagawa

Giant geode at the olecranon in the rheumatoid elbow – two case reports

Abstract A single giant geode at the olecranon in a patient with rheumatoid arthritis (RA) is relatively rare, and may cause diagnostic difficulties or cause a spontaneous pathological fracture owing to weakness of the cortical bone associated with osteoporosis. We report two cases of patients presenting with single giant geodes at the olecranon. In one case we performed an open reduction and internal fixation with bone grafting for a pathological fracture due to the geode. In the other case we performed curettage of the geode with bone grafting to prevent a pathological fracture, and a synovectomy of the elbow. We suggest that the presence of a giant geode at the olecranon may necessitate surgical intervention to prevent the occurrence of a spontaneous pathological fracture.

Comparison of the Sauvé–Kapandji procedure and the Darrach procedure for the treatment of rheumatoid wrists

Abstract In surgical treatment of the rheumatoid wrist, the Darrach procedure combined with synovectomy has been the treatment of choice in the past. However, owing to the significant ulnar carpal shift observed after the Darrach procedure, the Sauvé–Kapandji (S–K) procedure has become increasingly popular. The purpose of this study was to compare the clinical results of the S–K and Darrach procedures. Thirty-two wrists in the S–K-procedure group and 31 wrists in Darrach-procedure group were examined. Before and after surgery, clinical evaluations of pain, swelling, range of motion, grip strength, and radiological findings were performed and the results were compared. Both procedures resulted in decreased pain and swelling, as well as improved rotatory motion of the forearm. The S–K procedure was shown to be superior to the Darrach procedure in reducing ulnar carpal migration and improving grip strength. On the other hand, the prevention of carpal bone destruction could not be completely achieved in either procedure.

Total knee arthroplasty for rheumatoid knee with bilateral, severe flexion contracture: report of three cases

The treatment of patients with severe flexion contracture of the rheumatoid knee, deprived of ambulation for long periods of time, is challenging. Based on three cases, we indicate the potential risks of posterior dislocation of the knee after total knee arthroplasty. In this pathological condition, surgeons must carefully select the type of implant in order to avoid this serious complication. We also emphasize the importance of working on disuse muscle atrophy of trunk (back, abdominal) and lower limbs, both of which play an integral role in ambulation. The personality of each rheumatoid patient should be carefully considered when considering surgical and rehabilitation options.

THE EFFECTIVENESS OF RA WRIST FUSION USING BETA-TCP WITHOUT AUTOGENOUS ILIAC BONE GRAFTING: A REPORT OF FOUR CASES

Wrist arthrodesis is indicated for the rheumatoid hand especially in cases with severe destruction of the carpal bones. In the arthrodesis procedure for the rheumatoid wrist, autogenous iliac bone grafting is required in most cases. However, autogenous iliac bone graft necessitates the additional surgical intervention, and can be associated with the problem of inadequate bony quality or quantity. It is thought that use of the artificial bone substitute in the procedure can lessen the surgical morbidity while supplying the consistent material without shortage of graft quantity. We have performed arthrodesis of the rheumatoid wrist using beta-TCP for four patients. Clinical results of these patients were satisfactory both in pain relief and functional improvement with complete bony healing. Therefore, this procedure seems to be an effective option for the rheumatoid wrist with severe destructive changes.

TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells

Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca2+ chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α. Oscillation phase and amplitude of Bmal1, transcriptional activator Rorα, transcriptional repressor Rev-erbα, and histone acetyltransferases (p300 and Cbp) were evaluated by quantitative real-time PCR. As results, TNF-α did not influence the oscillation phase of Rev-erbα, while enhanced those of Rorα, resulting in over-expression of Bmal1. When Ca2+ influx was inhibited by BAPTA-AM, TNF-α-mediated up-regulation of Rorα was cancelled, however, that of Bmal1 was still apparent. When we further explored another pathway between TNF-α and Bmal1, TNF-α suppressed the expression of Rev-erbα in the absence of Ca2+ influx, as well as those of p300 and Cbp genes. Finally, actions of TNF-α, in increasing Bmal1/Rorα and decreasing Rev-erbα, were cancelled by C646 treatment or silencing of both p300 and Cbp. In conclusion, we determined a novel role of TNF-α in inducing Bmal1 via dual calcium dependent pathways; Rorα was up-regulated in the presence of Ca2+ influx and Rev-erbα was down-regulated in the absence of that. Results proposed that inhibition of p300/CBP could be new therapeutic targets for RA.

Methotrexate upregulates circadian transcriptional factors PAR bZIP to induce apoptosis on rheumatoid arthritis synovial fibroblasts

BackgroundEffects of methotrexate (MTX) on the proliferation of rheumatoid arthritis (RA) synovial fibroblasts are incompletely understood. We explored actions of MTX in view of circadian transcriptions of synovial fibroblasts.MethodsUnder treatment with MTX, expression of core circadian clock genes, circadian transcriptional factor proline and acidic amino acid-rich basic leucine zipper (PAR bZIP), and proapoptotic molecule Bcl-2 interacting killer (Bik) was examined by real-time polymerase chain reaction. Protein expression of circadian clock gene PERIOD2 (PER2) and CYTOCHROME C was also examined by western blotting and ELISA. Promoter activities of Per2 and Bik were measured by Luciferase assay. Expression of PER2, BIK, and CYTOCHROME C and morphological changes of the nucleus were observed by fluorescent immunostaining. Synovial fibroblasts were transfected with Per2/Bik small interfering RNA, and successively treated with MTX to determine cell viabilities. Finally, synovial fibroblasts were treated with MTX according to the oscillation of Per2/Bik expression.ResultsMTX (10 nM) significantly decreased cell viabilities, but increased messenger RNA expression of Per2, Bik, and PAR ZIP including D site of the albumin promoter binding protein (Dbp), hepatic leukemia factor (Hlf), and thyrotroph embryonic factor (Tef). MTX also increased protein expression of PER2 and CYTOCHROME C, and promoter activities of Per2 and Bik via D-box. Under fluorescent observations, expression of PER2, BIK, and CYTOCHROME C was increased in apoptotic cells. Cytotoxicity of MTX was attenuated by silencing of Per2 and/or Bik, and revealed that MTX was significantly effective in situations where Per2/Bik expression was high.ConclusionsWe present here novel unique action of MTX on synovial fibroblasts that upregulates PAR bZIP to transcribe Per2 and Bik, resulting in apoptosis induction. MTX is important in modulating circadian environments to understand a new aspect of pathogenesis of RA.