• YAKHAK HOEJI
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• v.50 no.2
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• pp.70-77
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• 2006

A cost effective analysis was performed for comparing leflunomide+methotrexate, etanercept monotherapy and etanercept+methotrexate for 6 months. For the patients with methotrexate-resistant RA, ACR20 data were extracted from the published clinical trials searched from Pubmed. The direct medical cost was estimated based on ACR guideline and Korean National Health Insurance reimbursement. Combination therapy of etanercept+methotrexate was found to be more cost-effective than etanercept monotherapy, which meant it was a better therapeutic strategy for methotrexate- resistant RA.

• YAKHAK HOEJI
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• v.36 no.4
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• pp.345-349
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• 1992

Thymidylate synthase activity from extracts of various methotrexate-resistant strains was measured by spectrophotometric assay. Methotrexate-resistant strains of Lactobacillus, Pseudomonas sp., Micrococcus sp. HS-1, Klebsillela pneumonae, Cellulomonas fimi and Serratia marcescens elevated thymidylate synthase levels, especially, Pseudomonas sp. KL-9 resistant to $10^{-9}M$ methotrexate have a 156-fold increase in thymidylate synthase, which suggests that Pseudomonas sp. is a convenient source of thymidylate synthase. Several methotrexate strains of yeast were tested, however, their enzyme activity was generally lower than that of bacteria tested.

• Journal of Pharmaceutical Investigation
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• v.25 no.2
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• pp.101-108
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• 1995

The surface of albumin microspheres could be modified with methotrexate (MTX) by using 1,3-dicyclohexylcarbodiimide (DCC). Surface-modified albumin microspheres entrapping no MTX (SAMS), free MTX (SAMSF) and MTX-bovine serum albumin (BSA) conjugates (SAMSC) were prepared. respectively, and their release characteristics were investigated in the presence of trypsin using a dissolution tester. The mean diameters of all the microspheres were $5{\sim}8\;{\mu}m$, and their shapes was small and uniform. MTX bound tn their surfaces was released slower than the entrapped free MTX, and laster than the entrapped MTX-BSA conjugates. Also, surface-modified MTX was scarcely released in the absence of a proteolytic enzyme. Therefore, the surface-modified MTX may be released rapidly from SAMSC at the target site, and thereafter MTX may be released slowly from the encapsulated MTX-BSA conjugates in SAMSC for a long period.

• Journal of Dental Rehabilitation and Applied Science
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• v.29 no.2
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• pp.203-207
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• 2013

Psoriatic arthritis is a chronic inflammatory form of arthritis that is associated with psoriasis. A 54-yr-old male with chronic psoriatic temporomandibular joint arthritis and myofascial pain was treated using methotrexate and a myofascial pain protocol. Jaw pain improved after 3 weeks, however, tenderness to palpation of muscles remained. Comprehensive evaluation and multidisciplinary clinical treatment is required for the treatment of patients with psoriatic temporomandibular joint arthritis.

• YAKHAK HOEJI
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• v.36 no.6
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• pp.591-597
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• 1992

The organ distribution of $[^3H]$-methotrexate-lactosaminated bovine serum albumin conjugates ($[^3H]$-MTX-LBSA) was investigated to examine their role as a liver-specific anticancer drug. Synthesis of lactosaminated bovine serum albumin(LBSA) with BSA, lactose and sodium cyanoborohydride through reductive amination was followed by its conjugation with methotrexate (MTX) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), thereby synthesizing [$[^3H]$-MTX-LBSA conjugates. Organ distribution and plasma elimination profiles were studied in male Wistar rats after intravenous injection of [$[^3H]$-MTX-LBSA conjugates. The fates of $[^3H]$-MTX and the $[^3H]$-MTX-BSA conjugates´fates were also investigated for comparison. The results showed that the plasma level of $[^3H]$-MTX-LBSA conjugates declined more rapidly than those of $[^3H]$-MTX-BSA and their liver concentration was significantly higher than those of other treatment (p<0.01). In addition, their uptake compared to the amount taken up by the liver (1 : 33.1 at 10 min, 1 : 24.1 at 120 min). All these suggested that MTX-LBSA conjugate is one of the drug delivery system (DDS) that is advanced in concentrating MTX in the liver and minimizing the renal toxicity of MTX.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.105-112
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• 1996

The surface of albumin microspheres was modified with methotrexate(MTX) by using 1,3-dicyclohexylcarbodiimide (DCC). Surface-modified albumin microspheres entrapping no MTX (SAMS), free MTX (SAMSF) and MTX-bovine serum albumin(BSA) conjugates(SAMSC) were prepared. The organ-targeting ability of free $[^3H]MTX,\;[^3H]MTX-BSA$ conjugate and the above microspheres was evaluated after i.v. administration of the preparations, equivalent to 150 nCi via the tail vein of mice. The total radioactivity in the lung increased immediately in a few minutes after i.v. injection of the microspheres, and then declined for the period of 3-4 weeks. However, the radioactivity in the liver, spleen and kidney increased slowly during the rapid decrease in radioactivity in the lung. This suggested that the microspheres could be entrapped rapidly in the lung through mechanical filtration because of their large size and slowly redistributed to the liver, spleen and kidney due to either the microspheres being degraded enough for the size to allow passage through the capillary beds of the lung and/or the release of $[^3H]MTX\;or\;[^3H]MTX-BSA$ conjugates from the microspheres. The amount of $60{sim}70%$ of the dose was targeted to the liver after the i.v. injection of SAMS, SAMSF and SAMSC, and the values of $(R_e\;^*\;_{e)liver}$ from the microspheres were $5{\sim}7$ compared to free MTX. This suggested that the liver-targeting ability from surface-modified albumin microspheres could be $5{\sim}7$ times as that of free MTX. The liver-targeted drug was accumulated in the Kupffer cells at the initial stage, thereafter the drug in the Kupffer cell was slowly transferred into the hepatocytes. The value of AUQ for liver from SAMS was higher than that from SAMSF, but much lower than that from SAMSC. This suggest that MTX bound to their surface could be eliminated slower than the entrapped free MTX, and faster than the entrapped MTX-BSA conjugates. This is consistent with the in vitro release rates order in the presence of a proteolytic enzyme. Also, surface-modified MTX was scarcely released in the absence of a proteolytic enzyme. Therefore, the surface-modified MTX nay be released (or eliminated) rapidly from SAMSC at the target site, and thereafter MTX may be released (or eliminated) slowly from the entrapped MTX-BSA conjugates in SAMSC for a long period.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.424-430
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• 2006

Purpose : Juvenile rheumatoid arthritis(JRA) is one of the most common rheumatic diseases of childhood and is an important cause of short- and long-term disability. The purpose of this study was to determine the disease course and outcome in childhood patients with JRA. Methods : Fifty nine patients with JRA who were diagnosed and treated in the Department of Pediatrics, Asan Medical Center from August 1990 to November 2004 were enrolled in this study. Sex, age, type, affected joints, extra-articular manifestations, laboratory and radiologic findings, treatments, and outcomes of JRA patients were reviewed retrospectively. Results : Among JRA patients, 32.2 percent had pauciarticular type, 30.5 percent had polyarticular type and 37.3 percent had systemic type. The ratio of boys to girls was 1.7 : 1 and the mean age at onset was $9.3{\pm}3.7$(1.3-15.9) years. The most commonly affected joints were knee, ankle and wrist. The extra-articular manifestations observed were fever, rash, myalgia and lymph node enlargement, etc. The main laboratory findings observed were leukocytosis, anemia, thrombocytosis, elevated ESR, and elevated CRP. Rheumatoid factor and antinuclear antibody(ANA) were positive in 5.3 percent and 18.0 percent. Nonsteroid anti-inflammatory drugs(NSAID) were used most frequently and methotrexate with or without steroids was added in 27.1 percent of patients unresponsive to NSAID. 88.1 percent of patients were cured without functional disability and only one patient was in functional status IV. One patient, who had pulmonary involvement, died. Conclusion : Our results showed an even distribution in type of onset, male predominance, older age of onset, low incidence of iridocyclitis, and low positivity of ANA in JRA patients; this differs from occidental data. This study may suggest regional differences and variability in disease groups of JRA among different racies, but further multi-center trials and large scale epidemiological studies are needed to confirm our conclusion.

• The Korean Journal of Medicine
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• v.99 no.1
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• pp.37-49
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• 2024

Background/Aims: In Korea, the incidence of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is increasing and autologous stem cell transplantation (ASCT) has improved the survival of younger patients. We explored our real-world experience with PCNSL at Asan Medical Center (AMC). Methods: We used the AMC lymphoma registry to collect patient data prospectively. We analyzed 279 patients diagnosed from 2002 until August 2019. Results: The PCNSL incidence at AMC increased progressively and comprised 7.4-8.9% of new non-Hodgkin lymphoma patients annually during the most recent 4 years. The median age was 60 years (range, 17-85) and males comprised 55%. Patients under 65 years of age (n = 183) had no significant differences in characteristics compared to those aged 65 years or over, with the exception of less occipital lobe involvement and lower beta-2 microglobulin levels. Rituximab, methotrexate, procarbazine, and vincristine (R-MPV) combination induction had the best overall response, of 95%. The median overall survival was 3.8 years with 5- and 10-year survival rates of 41.5% and 30.2%, respectively. Survival was better in younger patients and those treated with ASCT. Thiotepa, busulfan, and cytoxan (TBC) conditioning chemotherapy had better survival than other combinations. The International Extranodal Lymphoma Study Group and Memorial Sloan Kettering Cancer Center prognostic score systems were valid in this cohort. Age and performance status were independent prognostic factors. Exclusive extra-central nervous system failure occurred in six patients (5.6%) among 107 failures. Conclusions: The incidence of PCNSL is rising. R-MPV induction therapy followed by ASCT with TBC has improved the survival of young, fit PCNSL patients.