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ABSTRACT: Objective. To evaluate the prevention of joint destruction and clinical efficacy of low-dose etanercept (ETN) (25 mg/week) compared with standard-dose ETN (50 mg/week) in RA.Methods. In this prospective, randomized, open-label study, 70 patients were assigned to receive ETN at either 50 or 25 mg/week for 52 weeks. The primary endpoint was the variation in modified total Sharp score (mTSS), and secondary endpoints were variations in disease activity score in 28 joints (DAS-28), modified HAQ and adverse event rate. Values of mTSS were calculated at baseline and after 52 weeks. Non-progression was estimated as ΔmTSS ≤0.5, and the non-progression rate was compared between groups.Results. Mean values at baseline were as follows: disease duration 9.2 years; DAS-28 5.45; and annual progression of mTSS 26.1. No significant differences in background were seen between groups. At 52 weeks, the non-progression rate was significantly less in the 25 mg/week group (36.7%) than in the 50 mg/week group (67.7%) (P = 0.041). Mean ΔmTSS was higher at 25 mg/week (1.03) than at 50 mg/week (-0.13). DAS-28 was significantly improved at 4 weeks, and the effect of treatment lasted for 52 weeks in both groups. No differences in adverse event rates were seen between groups.Conclusion. Low-dose ETN is not inferior to standard-dose ETN in terms of effects on clinical manifestations. However, in terms of the radiographic non-progression rate, the effects of low-dose ETN may be inferior to the effects of standard-dose ETN.Trial Registration: UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000001798.
Rheumatology (Oxford, England) 07/2012; · 4.24 Impact Factor
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ABSTRACT: Disease-modifying anti-rheumatic drugs (DMARDs) are typically used for the therapy of rheumatoid arthritis (RA), but most have some nephrotoxicity. In several clinical studies, etanercept had fewer adverse effects on renal function than other DMARDs. We report the case of a 64-year-old woman with RA and renal insufficiency on hemodialysis treated using etanercept therapy. This case suggests that etanercept therapy might be effective in the short term for such patients.
Modern Rheumatology 02/2008; 18(3):293-5. · 1.58 Impact Factor
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ABSTRACT: Extensor tendon rupture in rheumatoid wrists is a common problem and causes immediate dysfunction of the digits. The best treatment for tendon rupture may be prophylactic management, although the factors associated with tendon rupture must first be identified. The purpose of this study was to evaluate structures around rheumatoid wrists using magnetic resonance imaging with forearm rotation and to identify factors associated with extensor tendon rupture as indications for prophylactic surgery.
The subjects were 34 patients (40 wrists) with active rheumatoid arthritis. The extensor digitorum communis (EDC) tendons were ruptured in 15 wrists. Magnetic resonance imaging of the wrists was performed in maximally pronated and supinated positions of the forearm. Axial images of the distal radioulnar joints (DRUJs) were selected to evaluate DRUJ synovitis, dorsal tenosynovitis, volar dislocation of the extensor carpi ulnaris (ECU) tendon, sigmoid notch angle, and the radioulnar ratio (RUR) (ie, the degree of DRUJ subluxation).
No significant correlations were found between EDC tendon rupture and DRUJ synovitis, dorsal tenosynovitis, or RUR in pronation. Extensor digitorum communis tendon rupture correlated significantly with volar ECU tendon dislocation, sigmoid notch angle, and RUR in supination. Radioulnar ratio correlated significantly with volar ECU tendon dislocation only in supination and not in pronation. Thus, DRUJ subluxation was advanced even in the supinated wrist with volar ECU tendon dislocation. As a factor associated with EDC tendon rupture, volar ECU tendon dislocation had 87% sensitivity and 76% specificity.
Volar ECU tendon dislocation is associated with increased RUR in supination and EDC tendon rupture. Volar ECU tendon dislocation can thus be considered a factor associated with EDC tendon rupture, and its presence may indicate the need for prophylactic surgical intervention in a subset of rheumatoid arthritis patients.
The Journal Of Hand Surgery 12/2006; 31(9):1454-60. · 1.35 Impact Factor
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ABSTRACT: To investigate the effects of electrical pulses on the ability of methotrexate (MTX) to attenuate inflammation and subsequent joint destruction in rats with adjuvant-induced arthritis (AIA).
Rats in the experimental group received an intraperitoneal injection of MTX (0.125 mg/kg body weight), followed 30 minutes later by application of direct electrical pulses (50V, 8 Hz) to their left hind paws with an electroporation apparatus (M+/E+ group; n = 8). The procedure was repeated twice weekly for 3 weeks. Three control groups received the following treatments, respectively: MTX without electrical treatment (M+/E- group; n = 9), electrical treatment but no MTX (M-/E+ group; n = 10), or no electrical treatment and no MTX (M-/E- group; n = 9). Progression of AIA was monitored by joint swelling and radiologic and histologic changes in the ankle joint.
Three weeks after injection of the adjuvant, and at the height of the arthritic reaction, the swelling and radiologic and histologic changes in the left hind paws in the M+/E+ rats were significantly reduced, as compared with changes observed in the control groups.
These results demonstrate that application of electrical pulses in combination with use of systemic low-dose MTX can ameliorate local arthritic reactions. This response probably occurs because electrical stimulation promotes transient passage of MTX through pores in the cell membranes, with a resultant local increase in the concentration of the drug within the cells. These results point to a potential use of electrochemotherapy to increase the efficacy of MTX or other drugs in an arthritic joint that is refractory to treatment, without increasing the dose of the drug.
Arthritis & Rheumatism 03/2005; 52(2):637-41. · 7.87 Impact Factor
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ABSTRACT: An 8-year-old girl with systemic-onset juvenile idiopathic arthritis (JIA) required surgical reduction for a dislocated left hip joint following failure of skin traction for 1 week. Unaided walking was achieved by 3 months postoperatively. Incongruence and irregularity of the hip joint remained but may resolve with maturation. Joint laxity caused by synovitis, flexion/adduction contracture with pain, and acetabular dysplasia by growth disturbance apparently caused hip dislocation.
Modern Rheumatology 02/2004; 14(5):399-401. · 1.58 Impact Factor
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ABSTRACT: We describe the case of a 44-year-old Japanese woman with severe nodular erythematous skin lesions and arthritis mutilans who was admitted for further treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies showed heavy infiltration with tartrate-resistant acid phosphatase-positive histiocytes and multinucleated giant cells. Immunohistochemical analysis showed that some of the mononuclear cells in the skin were positive for RANKL. After 1 month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a week intravenously for the first 6 weeks and then once a month thereafter, the arthritis and skin nodules improved, and the remission has continued for more than 2 years. The findings in this patient suggest that osteoclast-like multinucleated giant cells differentiate locally in the skin from infiltrating histiocytes with the help of RANKL-positive stromal cells and that alendronate acts directly on cells of monocyte/macrophage lineage in humans. Thus, alendronate should be added to the list of drugs for the treatment of multicentric reticulohistiocytosis.
Arthritis & Rheumatism 01/2004; 48(12):3538-41. · 7.87 Impact Factor
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Mayumi Nagata-Sakurai,
Masaaki Inaba,
Hitoshi Goto,
Yasuro Kumeda,
Yutaka Furumitsu, Kentaro Inui,
Hidenori Koyama,
Masanori Emoto,
Eiji Ishimura,
Tetsuo Shoji,
Yoshiki Nishizawa
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ABSTRACT: We recently reported that rheumatoid arthritis (RA) patients had increased intima-media thickness (IMT) of the common carotid artery (CCA). The present longitudinal study was performed to determine whether the change in arterial thickness was accelerated in RA patients and to determine which factor was important in the progression of arterial wall changes.
We studied 62 female RA patients with stable disease activity and 63 healthy female controls. IMT of the CCA was measured twice by high-resolution B-mode ultrasonography. The second examination was performed 18-36 months after the first, and changes were expressed as millimeters of increase per year. Baseline examinations included blood markers of inflammation and urinary calcium excretion (expressed as the calcium-to-creatinine ratio).
RA patients showed a significantly greater increase in IMT of the CCA compared with controls. In univariate analyses of the RA patient data, the C-reactive protein (CRP) level correlated with the increase in CCA IMT. Other markers of inflammation (the erythrocyte sedimentation rate and white blood cell and platelet counts) also showed significant positive associations with the annual increase in CCA IMT in multiple regression models when adjusted for age, smoking status, blood pressure, and serum cholesterol level. The urinary calcium-to-creatinine ratio was also significantly associated with an increase in CCA IMT. Moreover, both the CRP level and the urinary calcium-to-creatinine ratio were significantly and independently associated with the increase in IMT of the CCA.
Patients with RA have a higher rate of increase in thickening of the arterial wall. Inflammation and calcium mobilization are factors closely associated with the accelerated arterial wall changes.
Arthritis & Rheumatism 12/2003; 48(11):3061-7. · 7.87 Impact Factor
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ABSTRACT: This work was performed to investigate the role of vitamin K (VK) in the pathogenesis of ossification of posterior longitudinal ligament (OPLL), by analyzing the biochemical markers of the blood samples of OPLL patients and responses of ligament cells derived from OPLL lesion to VK2.
The pathogenesis of OPLL, classified as a form of diffuse idiopathic skeletal hyperostosis, is still unclear. In this study, we investigated the role of menaquinone (VK2) in patients with OPLL (OPLL patients) and the effects of VK2 on ligament cells isolated from OPLL lesion.
Serum levels of intact osteocalcin, glu-osteocalcin, MK-4, -7 (VK2 variants) and other minerals in spot blood samples were measured in 24 OPLL patients and in 24 age-matched control patients (non-OPLL patients). The cultured cells isolated from an OPLL patient were treated with MK-4. Alkaline phosphatase (Al-p) activity and osteocalcin release were measured after 2 weeks of culture.
In the clinical study, the serum MK-4 in male OPLL patients was significantly higher than that in male non-OPLL patients. However, among female patients, the difference was not significant. Although the serum osteocalcin in females was significantly higher than that in males, there was no significant difference between the OPLL and non-OPLL groups. In in vitro study, MK-4 did not increase Al-p activity in the ligament cells isolated from nonossified region of OPLL patient. Osteoblastic activity of the cultured cells was not stimulated by MK-4.
From these results and previous reports, we propose the possibility of the impediment in VK2 metabolism in OPLL patients. The results also implicate the gender tendency in OPLL, because the difference of serum level of MK-4 in OPLL patients was significant only in male.
Spine 09/2003; 28(16):1789-93. · 2.08 Impact Factor
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ABSTRACT: Intermittent cyclical therapy with etidronate increases bone mineral density in spine and hip, and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis, as well as steroid-induced osteoporosis. Seven years treatment with etidronate was reported to be safe, effective and well-tolerated. And additive effects of etidronate were documented in bone mineral density when hormone replacement therapy was combined. Recently many bisphosphonates have been commercially available in clinics. Although the potency of etidronate to inhibit bone resorption is relatively weak among those bisphosphonates, equal effects for others in osteoporosis can be obtained with the intermittent therapy, which is easy to be complied for the patients with less adverse events. In conclusion cyclical etidronate therapy is still important for osteoporosis therapy.
Nippon rinsho. Japanese journal of clinical medicine 03/2003; 61(2):226-30.
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ABSTRACT: Enormous effort has been devoted to the generation of a synthetic guidance conduit for nerve repair instead of utilizing autograft. Several studies show neural guidance conduit is more effective when coated with Schwann cells. In this study, we synthesized bioabsorbable conduit consist of L-lactide and epsilon-caprolactone which was useful clinically and examined adhesion of Schwann cells to bioabsorbable conduits. In vivo studies were done in which these polymer conduits coated with Schwann cells were implanted across a 12 mm gap in the rat sciatic nerve. Silicone conduits were implanted across the same gap as control. At 12 weeks, axonal regeneration was observed in the midconduit region of these polymer conduits and was not in control. This study assesses the feasibility of a tissue engineering approach to constructing bioabsorbable conduits coated with Schwann cells.
Bio-medical materials and engineering 02/2003; 13(3):223-9. · 1.23 Impact Factor
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Yasuro Kumeda,
Masaaki Inaba,
Hitoshi Goto,
Mayumi Nagata,
Yasuko Henmi,
Yutaka Furumitsu,
Eiji Ishimura, Kentaro Inui,
Yasutaka Yutani,
Takami Miki,
Tetsuo Shoji,
Yoshiki Nishizawa
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ABSTRACT: To determine whether arterial wall thickening is advanced in rheumatoid arthritis (RA) patients compared with healthy controls by measuring the intima-media thickness (IMT) of the common carotid and femoral arteries, and to evaluate the factors associated with arterial IMT in patients with RA.
We studied 138 RA patients and 94 healthy controls (matched for age, sex, and other major risk factors for atherosclerosis). IMT was measured on digitized still images of the common carotid and femoral arteries obtained by high-resolution ultrasonography (10-MHz in-line Sectascanner). Laboratory variables relevant to RA activity were measured by routine methods. The degree of RA progression was assessed by scoring (Larsen method) metacarpophalangeal (MCP) joints on hand radiographs. Activities of daily living were determined by a modified Health Assessment Questionnaire (M-HAQ) score, and physical activity levels were assessed by ultrasound measurement of the calcaneus (expressed as the osteo-sono assessment index [OSI] Z score).
Common carotid and femoral artery IMTs were significantly higher (P < 0.05) in RA patients (mean +/- SD 0.641 +/- 0.127 and 0.632 +/- 0.125 mm, respectively) compared with controls (0.576 +/- 0.115 and 0.593 +/- 0.141 mm, respectively). Multiple regression analysis revealed a significant association between RA and the common carotid artery IMT. Moreover, the common carotid artery IMT in RA patients was positively associated with disease duration, the MCP joint Larsen score, and the M-HAQ score, and was negatively associated with the calcaneus OSI Z score. No significant association was found between corticosteroid treatment and common carotid artery IMT.
RA patients exhibited greater thickness of the common carotid and femoral arteries than healthy controls. The duration and severity of RA and decreased activities of daily living, but not corticosteroid treatment, were independently associated with the increased arterial wall thickness.
Arthritis & Rheumatism 06/2002; 46(6):1489-97. · 7.87 Impact Factor
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ABSTRACT: An immortal human chondrocytic cell line (HCS-2/8) derived from a chondrosarcoma was used as a source of human antigens to find humoral antibodies to cell surface proteins of human chondrocytes in sera from patients with rheumatoid arthritis (RA). Membrane fractions prepared from the cell line were subjected to Western blot analysis using RA and normal sera as probes. RA sera recognized about a dozen bands, but three of these bands, with molecular weights of 105 kDa, 65 kDa, and 47 kDa, were found to be specific for the RA sera (P<0.05). These bands disappeared following V8 protease digestion, indicating that they were proteins. Among patients with 4 years or more of RA disease activity, reactivity against 105-kDa and 68-kDa proteins was relatively high in those whose joints showed a high degree of erosion. We suspect that levels of these two antibodies are suggestive of changes associated with the natural course of RA.
Journal of Bone and Mineral Metabolism 08/1996; 14(3):146-152. · 2.27 Impact Factor
