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Yoichi Ichikawa,
Terunobu Saito,
Hisasi Yamanaka,
Masashi Akizuki,
Hirobumi Kondo,
Shigeto Kobayashi,
Hisaji Oshima,
Shinichi Kawai,
Nobuaki Hama,
Hidehiro Yamada,
Tsuneyo Mimori,
Koichi Amano,
Yasushi Tanaka,
Yasuo Matsuoka,
Sumiki Yamamoto,
Tsukasa Matsubara,
Norikazu Murata,
Tomiaki Asai,
Yasuo Suzuki
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ABSTRACT: To investigate earlier prediction of future articular destruction in patients with early rheumatoid arthritis (RA).
We randomly allocated patients with RA with disease duration < 2 years to different nonbiologic disease modifying antirheumatic drug (DMARD) therapies in a double-blind trial. Progression of articular destruction over the 96-week treatment period was assessed using the modified Sharp method.
Progression of articular destruction correlated more strongly with the American College of Rheumatology (ACR) core set measures after 12 weeks of treatment than with pretreatment values. Multiple regression analysis of data after 12 weeks yielded a correlation coefficient of 0.711. The sensitivity and specificity to predict articular destruction over the 75th percentile of the cohort were 78.6% and 84.6%, respectively. Patients who showed articular destruction over the 75th percentile of the cohort had low response to treatment at 12 weeks, and continued to have high clinical disease activity thereafter. Contrasting data were found in patients with slow progression of articular destruction.
In patients with early RA, ACR core set measures after 12 weeks of nonbiologic DMARD treatment may predict articular destruction 2 years later. Low response to treatment at 12 weeks and continuing high disease activity thereafter were found in patients with rapid radiological progression. These data can be used to determine the appropriateness of treatment at 12 weeks and aid the decision to introduce biologic DMARD.
The Journal of Rheumatology 03/2010; 37(4):723-9. · 3.69 Impact Factor
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ABSTRACT: The patient was a 74-year-old female presenting with abrupt onset of fever and proximal muscle pains. She had been diagnosed with polymyalgia rheumatica (PMR). On physical examination, there was no tenderness or dilatation of the temporal artery and ocular fundi were normal. 18F-FDG-PET revealed accumulation of FDG in the aorta as well as in the bilateral subclavian arteries, which strongly suggested inflammation of the large blood vessels. Magnetic resonance angiography disclosed stenosis of the bilateral subclavian arteries, which was consistent with angitis. This case was considered to have developed PMR at an old age with positive HLA DR4, and to have a complication large-vessel giant cell arteritis (LV-GCA). Administration of prednisolone at a dose of 20 mg/day promptly relieved the fever and the myalgia as well. It is difficult to diagnose GCA in PMR if no tenderness or dilatation of the temporal artery is present. FDG-PET is considered useful, not only for exploration of tumors, but also for evaluation of inflammation of large vessels.
Japanese Journal of Clinical Immunology 05/2009; 32(2):129-34.
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ABSTRACT: Intravenous immunoglobulin (IVIG) therapy was administered to 15 patients who were refractory to traditional steroid therapy [eight with polymyosis (PM), seven with dermamyosis (DM)] to evaluate its efficacy. Serum creatine kinase (CK) significantly decreased from week 1, and manual muscle test scores (MMT) and activities of daily living (ADL) significantly increased from week 2. Efficacy rates were 93.3% (14/15 patients) as assessed using the MMT score, 80.0% (12/15 patients) using the ADL score, and 100% (15/15 patients) using the serum CK level. When changes in the serum CK level over two four-week periods, one before IVIG therapy (from week -4 to week 0) and one after IVIG therapy (from week 0 to week 4), were transformed to natural logarithms, the four-week change after IVIG therapy was significantly greater than that before IVIG therapy. The estimated duration of the serum CK level remaining normal in 50% of the patients after IVIG therapy was 334.5 days. Adverse reactions were observed in seven of 16 patients (43.8%) during the study period, but none of the adverse reactions were considered to be serious or required emergency treatment. In conclusion, the present study indicates that IVIG therapy is effective for steroid-resistant PM/DM.
Modern Rheumatology 02/2008; 18(1):34-44. · 1.58 Impact Factor
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ABSTRACT: A placebo controlled, double-blind trial (DBT) was conducted for Japanese patients with active rheumatoid arthritis (RA) despite treatment with low dose methotrexate (MTX) to evaluate the efficacy and safety of infliximab. Extended treatment with infliximab was conducted in an open-label trial (OLT).
In the DBT, 147 patients were randomly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0, 2 and 6, combined with MTX. In the OLT, 129 patients from the DBT received 3 mg/kg infliximab every 8 weeks.
The mean dose of MTX was 7.2 +/- 2.0 mg/week. Significantly more patients receiving 3 mg/kg (61.2%) and 10 mg/kg (52.9%)infliximab achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria at Week 14, compared to placebo (23.4%) (p < 0.001). There was no significant difference in incidence of adverse events among the treatment groups. In patients receiving infliximab in the DBT, 11.6% of patients with serum infliximab just before the OLT developed antibodies to infliximab (ATI) in the OLT, whereas 62.2% of patients without serum infliximab did. In patients receiving placebo in the DBT, 43.9% developed ATI.
The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study. The data from the DBT and OLT also supported the importance of an induction treatment of infliximab, followed by a maintenance treatment without a long interval, giving stable serum concentrations in order to prevent formation of ATI.
The Journal of Rheumatology 01/2006; 33(1):37-44. · 3.69 Impact Factor
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Yoichi Ichikawa,
Terunobu Saito,
Hisashi Yamanaka,
Masashi Akizuki,
Hirobumi Kondo,
Shigeto Kobayashi,
Hisaji Oshima,
Shinichi Kawai,
Nobuaki Hama,
Hidehiro Yamada,
Tsuneyo Mimori,
Koichi Amano,
Yasushi Tanaka,
Yasuo Matsuoka,
Sumiki Yamamoto,
Tsukasa Matsubara,
Norikazu Murata,
Tomiaki Asai,
Yasuo Suzuki
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ABSTRACT: Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group), 200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 +/- 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 +/- 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.
Modern Rheumatology 02/2005; 15(5):323-8. · 1.58 Impact Factor
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Masako Hara,
Masao Kinoshita,
Eizo Saito,
Hiroshi Hashimoto,
Nobuyuki Miyasaka,
Tadashi Yoshida, Yoichi Ichikawa,
Takao Koike,
Yukinobu Ichikawa,
Jun Okada,
Sadao Kashiwazaki
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ABSTRACT: High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating many autoimmune and systemic inflammatory diseases. In the present prospective study, we evaluated the efficacy of IVIG for patients with polymyositis (PM) and dermatomyositis (DM) refractory to treatment with high-dose corticosteroids. PM/DM was defined as steroid-resistant when the muscle strength of a patient did not improve despite the administration of more than 50mg prednisolone per day for more than 4 weeks. A total of 12 patients with biopsy-proven, steroid-resistant PM/DM received one infusion of polyethylene glycol-treated human IgG at a dose of 0.4g per kg per day for five successive days. Three of the patients received a second infusion. All patients were followed for up to 3 months after the infusion. Finally, 8 patients (6 PM and 2 DM; 5 men and 3 women) aged 29–67 years (mean 48 years) were analyzed. Their clinical response was assessed by changes in (a) subjective signs, i.e., fatigue (visual analog scale, VAS), muscle pain (VAS), activities of daily living (ADL), (b) objective signs, i.e., manual muscle strength (MMT) and serum level of creatine kinase (CK). At 12 weeks after the infusion, the patients showed significant improvement in their scores of muscle strength (from a mean of 67.0 to 81.0) and their ADL scores (from a mean of 27.1 to 39.1). The mean serum CK level decreased significantly from 1287.4 to 612.6IU/l. In addition, the mean VAS of fatigue decreased significantly from 5.5 to 1.3cm. The physicians assessment showed that 87.5% of patients had improved. The average reduced dose of prednisolone was 47.1mg/day at 12 weeks after infusion in 7 patients who exhibited improvement. Adverse effects, i.e., asymptomatic myocardial infarction and increased blood urea nitrogen (BUN), were noted with two of the 15 infusion (13%). Overall, IVIG was found to be safe and effective for refractory PM and DM.
Modern Rheumatology 11/2003; 13(4):319-325. · 1.58 Impact Factor
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Yoichi Ichikawa
Ryūmachi. [Rheumatism] 01/2003; 42(6):859-62.
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ABSTRACT: An atmospheric dispersion model was developed for the environmental impact assessment of thermal power plants in Japan, and a method for evaluating topographical effects using this model was proposed. The atmospheric dispersion model consists of an airflow model with a turbulence closure model based on the algebraic Reynolds stress model and a Lagrangian particle dispersion model (LPDM). The evaluation of the maximum concentration of air pollutants such as SO2, NOx, and suspended particulate matter is usually considered of primary importance for environmental impact assessment. Three indices were therefore estimated by the atmospheric dispersion model: the ratios (alpha and beta, respectively) of the maximum concentration and the distance of the point of the maximum concentration from the source over topography to the respective values over a flat plane, and the relative concentration distribution [gamma(x)] along the ground surface projection of the plume axis normalized by the maximum concentration over a flat plane. The atmospheric dispersion model was applied to the topography around a power plant with a maximum elevation of more than 1,000 m. The values of alpha and beta evaluated by the atmospheric dispersion model varied between 1 and 3 and between 1 and 0.4, respectively, depending on the topographical features. These results and the calculated distributions of y(x) were highly similar to the results of the wind tunnel experiment. Therefore, when the slope of a hill or mountain is similar to the topography considered in this study, it is possible to evaluate topographical effects on exhaust gas dispersion with reasonable accuracy using the atmospheric dispersion model as well as wind tunnel experiments.
Journal of the Air & Waste Management Association (1995) 04/2002; 52(3):313-23. · 1.52 Impact Factor
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ABSTRACT: Our objective was to evaluate the effect of low-dose methotrexate therapy on periarticular and generalized osteopenia in patients
of rheumatoid arthritis (RA). Fifty-five women received one of four therapeutic regimens. The periarticular radial bone mineral
density (BMD) was analyzed by dual energy X-ray absorptiometry. Generalized osteopenia was assessed by measuring the BMD and
height of the lumbar spine (L2-L4). Vertebral deformity was also assessed on plain Xray film. Physical activity, age and menopausal status were similar among
the four treatment groups. The decrease of lumbar BMD was greatest in the group given steroids plus another disease modifying
antirheumatic drug (DMARD), followed by the steroid/methotrexate group, methotrexate group and the other DMARD group. The
decreases of lumbar vertebral height was greatest in the steroid/methotrexate group, followed by the steroid/DMARD group,
methotrexate group and the other DMARD group. Vertebral compression was found in 22% of the steroid/methotrexate group and
14% of the steroid/DMARD group. Radial periarticular BMD was significantly lower in patients with active wrist joint synovitis
than in patients without synovitis, but was increased by methotrexate therapy. We conclude that low-dose methotrexate did
not increase lumbar osteopenia or vertebral compression in RA patients and might preven periarticular osteopenia by suppressing
synovitis
Modern Rheumatology 04/1999; 9(1):75-85. · 1.58 Impact Factor
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ABSTRACT: Parathyroid function and calcium metabolism were studied in 44 patients under glucocorticoid therapy (steroid group) and in 25 control subjects. Nephrogenous cAMP and serum immunoreactive parathyroid hormone levels in the steroid group were significantly higher than those in control subjects (p < 0.001). Nephrogenous cAMP in the steroid group correlated positively with prednisolone dosage (r = 0.424, p < 0.01), and most patients who showed obvious elevations of nephrogenous cAMP had received over 10 mg/day of prednisolone for at least 2 mo. Fasting urinary calcium in the steroid group [166.1 ± 78.5 (±SD) mg/g creatinine] was about 2 times greater than that in control subjects (74.1 ± 35.6) (p < 0.001). Fasting urinary calcium in control subjects correlated negatively with nephrogenous cAMP (r = −0.486, p < 0.02). In contrast, these values in steroid group showed significant positive correlation (r = 0.631, p < 0.001), suggesting that increased urinary calcium excretion is an important factor in the development of secondary hyperparathyroidism. Elevated nephrogenous cAMP and serum immunoreactive parathyroid hormone levels decreased after the administration of trichlormethiazide and/or 1 alpha hydroxy-vitamin D3.We conclude that increased urinary calcium excretion plays an important role in the development of secondary hyperparathyroidism in patients under glucocorticoid therapy and that the administration of thiazide and/or vitamin D could improve the secondary hyperparathyroidism caused by glucocorticoid therapy.
Metabolism.
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ABSTRACT: The radioactivities of cortisol and cortisone in plasma were determined following simultaneous injection of 14C-cortisol and 3H-cortisone. The plasma concentrations of 14C-cortisol and 3H-cortisone decreased as a first-order function of time after an initial rapid drop, while there was a prompt appearance of 14C-cortisone and 3H-cortisol in plasma, which also decreased as a first-order function. The biologic half-lives of these four isotopic steroids were essentially identical. The ratio of 14C-cortisone to 14C-cortisol and that of 3H-cortisone to 3H-cortisol in plasma were constant after 60 min following injection and were identical, which suggested that cortisol and cortisone in plasma were at dynamic equilibrium. This ratio was 0.36 ± 0.01 (SE) in normals; it was decreased in patients with hypothyroidism (0.21 ± 0.03) and inflammatory diseases (0.18 ± 0.01) and was variable in hyperthyroid patients (0.42 ± 0.11). The ratio of the metabolic clearance rate of cortisone to that of cortisol was significantly increased in hypothyroid patients and in patients with inflammatory diseases, while urinary 11-ketonic metabolites of cortisol are known to decrease relative to its 11-hydroxy metabolites in these patients. These data and the decreased cortisone-to-cortisol ratio at equilibrium were consistent with the altered equilibrium between cortisol and cortisone, favoring cortisol, in these patients. It was suggested that the altered equilibrium between these steroids may be an important factor in determining the effectiveness of secreted or exogenously administered cortisol and the plasma concentration of cortisone in several disorders.
Metabolism.
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ABSTRACT: To clarify the interactions between mononuclear cells and polymorphonuclear leukocytes, and to identify the cytokine(s) that mediate the interaction, the effects of a culture supernatant of LPS-stimulated mononuclear cells on production of arachidonic acid metabolites of polymorphonuclear cells were studied. The culture supernatant of LPS-stimulated mononuclear cells increased production of prostaglandin E2 of polymorphonuclear cells. TNFα, but not IL-1, IL-2, IL-6, or IFNγ, enhanced the prostaglandin E2 production when added in vitro. Additionally, an anti-rTNFα monoclonal antibody inhibited the stimulating activity of the culture supernatants. TNFα, produced by mononuclear cells, appears to play an important role in the development of inflammation, such as rheumatoid arthritis, by enhancing the arachidonic acid metabolism of the polymorphonuclear cells.
Biochemical and Biophysical Research Communications.
