Go Hirata

Possible Involvement of the Vascular Endothelial Growth Factor-Flt-1-Focal Adhesion Kinase Pathway in Chemotaxis and the Cell Proliferation of Osteoclast Precursor Cells in Arthritic Joints

Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction.

Tibial tubercle malposition in patellar joint instability: A computed tomography study in full extension and at 30° flexion

We evaluated the tibial tubercle position in knees with patellar instability. CT in full extension and at 30° flexion was used in 18 knees with instability and 18 control knees. Scans were taken at the level of the femoral epicondyles, tibial tubercle and distal tibia. We found that in full extension, the tibial tubercle was in a more lateral position in the unstable than in the control knees. At 30° flexion, the tibial tubercle in the unstable knees rotated internally, but it was never within the normal range. CT scans taken in full extension and at 30° flexion seem to be of value for ascertaining the degree of tibial tubercle malposition during knee flexion in patellar instability.

Comparative histopathological analysis between tenosynovitis and joint synovitis in rheumatoid arthritis.

Aims:  To clarify the histological and biological features of tenosynovitis accompanying rheumatoid arthritis (RA).

Quantification of bone volume on radiographs using NIH Image

Abstract We attempted to quantify periarticular bone atrophy from radiographs of the proximal phalanx in patients with rheumatoid arthritis (RA) by means of the National Institutes of Health (NIH) Image computer program. The degree of brightness or darkness in four squares, each 20 × 20 pixels, in the right third proximal phalanx was measured using NIH Image, and the mean value of the 400 pixels was defined as the brightness/darkness index (BDI). The BDI was used to express bone volume. The BDI value was set at zero for an area of complete darkness and at 255 for an area of maximum brightness. The mean coefficient of variation in our hospital was 2.28%. The BDI was measured in 54 RA patients and 146 normal volunteers. The mean BDI at the midpoint of the diaphysis was 100 in RA patients and 176 in normal volunteers, while at the medial side of the proximal end it was 75 and 145, respectively. The difference between normal volunteers and RA patients was greatest in younger people. In some young RA patients, the BDI was significantly low at the medial side of the proximal end, clearly demonstrating periarticular bone atrophy. Periarticular bone atrophy can be quantified using the NIH Image computer program.

Minimum 10-year results of cementless total hip arthroplasty in patients with rheumatoid arthritis.

Abstract Objectives: To retrospectively evaluate the long-term results of cementless total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) and postoperative patient mortality after THA. Methods: This study included 191 hips in 149 RA patients who underwent cementless THA between 1998 and 2005. Mean age at surgery was 54.2 years, and mean follow-up was 12.6 years. Implant and patient survivorships were determined using the Kaplan–Meier method, and the associated influencing factors were determined. Results: Implant survivals at 17 years were 99.5% for stems, 93.9% for cups, and 90.8% for liners. Among the liners used, THAs with highly cross-linked polyethylene showed better survivals compared with those with conventional polyethylene and alumina-bearing surface (93.4%, 90.9%, and 52.2%, respectively). A total of 64 deaths occurred; 45 patients died within 10 years and 19 patients died between 10 and 17 years. Malignancy (25.0%) was the leading cause of death, followed by pneumonia (20.8%) and sepsis (20.8%). The patient survival rate was 36.9% at 17 years after THA. Multivariate analysis exhibited that older age at operation and greater dose of concomitant corticosteroid resulted in shorter patient survivals. Conclusions: Cementless THA worked well in patients with RA. Mortality remained high among RA patients who needed THA.

Multicentric reticulohistiocytosis with hydrarthrosis in both knee joints: disease stabilization with synovectomy, and medication with a steroid and low-dose methotrexate.

Abstract  Multicentric reticulohistiocytosis is a rare systemic disease characterized by the infiltration of histiocytes and multinucleated giant cells with cutaneous nodules, and severe destructive arthritis. It is commonly the peripheral joints which are affected, and therefore symptoms in large joints have not been fully investigated. We describe the case of a 44-year-old woman with multicentric reticulohistiocytosis, who was suffering from swelling in both knee joints and cutaneous nodules, in addition to arthritis in the elbow, hip, and peripheral joints. Magnetic resonance imaging of both knee joints showed hydrarthrosis associated with a tumor-like overgrowth of synovial tissue. These symptoms were reduced following a resection of the synovial tissue and subsequent medication with prednisone and low-dose methotrexate. It should be noted that swelling in the knee joints can be one of the symptoms caused by multicentric reticulohistiocytosis, in addition to cutaneous nodules and arthritis in the peripheral joints. Resection of synovial tissue, and medication with prednisone and low-dose methotrexate were effective in the present case.

Menopausal syndrome in female patients with rheumatoid arthritis

Abstract This study was performed to assess the relationship between joint symptoms in rheumatoid arthritis (RA) and symptoms in menopausal syndrome. Detailed analyses of the clinical course, laboratory data, joint symptoms, and symptoms of menopausal syndrome were performed for five patients with stage I and monocyclic-type RA. The age when joint symptoms first appeared coincided with the age of menopause in all patients, and the mean age was 51.0 years. The mean period from menopause to this study was 5.4 years. All patients showed more than six menopausal syndrome symptoms. Two patients were confirmed gynecologically to have definite menopausal syndrome, and accordingly hormone replacement therapy (HRT) was given. In one patient, the polyarthralgia disappeared after she received HRT. All the American College of Rheumatology (ACR) criteria, with the exception of subcutaneous nodules, can be explained as symptoms related to estrogen deficiency in menopausal syndrome because estrogen regulates the production of inflammatory cytokines such as IL-1, IL-6, and TNFα, and these cytokines are produced in greater abundance in conditions of estrogen deficiency. Estrogen deficiency at the menopause influences joint symptoms and inflammatory parameters in rheumatoid arthritis. Estrogen deficiency in menopausal syndrome may induce joint symptoms resembling RA.