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Objective. Methotrexate (MTX) is used as an anchor drug for rheumatoid arthritis (RA). Lymphoproliferative disease (LPD) occasionally develops in patients treated with MTX, and is known as MTX-associated LPD (MTX-LPD).Although MTX-LPD occurs mainly in RA patients, it has not been established if MTX administration is an independent risk factor for LPD in RA patients. We examined the clinical characteristics of MTX-LPD in Japanese RA patients and attempted to determine the risk factors for MTX-LPD development. Methods. We performed a nested case-control study on RA patients. We enrolled 5,753 RA patients from Kagawa, Japan. In age-and sex-matched patients, we separated patients who did not develop LPD under MTX treatment (MTX non-LPD group) from those that did (MTX-LPD group) and conducted a comparative examination. We used multivariate analysis to determine the independent risk factors for MTX-LPD onset. Results. There were 28 patients in the MTX-LPD group and 125 patients in the MTX non-LPD group. Multivariate analysis of the parameters extracted by univariate analysis revealed that the mean MTX dose was a risk factor for MTX-LPD after adjusting for age; therefore, higher MTX dose is associated with LPD onset in RA patients. Conclusion. MTX is an independent risk factor for LPD onset in Japanese RA patients.

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Addresses

Gamma knife radiosurgery (GKRS) for mesial temporal lobe epilepsy (MTLE) has been proposed as an alternative to surgical resection. We report serious adverse effects of the treatment after follow-up periods over 9 years in 11 patients treated with GKRS between 1997 and 2000. The target volume of the entorhinoamygdalohippocampectomy area was 4.8-17.1 ml. Marginal dose of 20-25 Gy to the 50% isodose was delivered. One patient was drowned after suffering seizure 7 months after GKRS. Two patients did not show any reduction in seizure frequency over 9 and 18 months. Both patients requested open surgery and became seizure-free postoperatively. Four of the other eight patients were classified as Engel's class I within 4 years after GKRS. One of the four patients experienced symptomatic radiation-induced cerebral edema transiently, one developed radiation necrosis and required surgery 5 years after GKRS, and one developed cognitive impairment with hemiparesis 10 years after GKRS. Magnetic resonance (MR) imaging showed a large cyst in the irradiated temporal lobe. This patient recovered fully after the cyst excision. Only one patient became seizure-free and antiepileptic drug-free without symptomatic radiation-induced complications. However, MR imaging revealed abnormal enhancement, cyst formation, and diffuse white matter change in the irradiated temporal lobe 9 years after GKRS. GKRS for MTLE causes adverse effects of delayed seizure remission and symptomatic radiationinduced complications. Therefore, GKRS cannot be considered as an ideal alternative to surgery for MTLE. Long-term follow-up studies including MR imaging with contrast medium are required for the patients even after successful control of seizures.