Forty-six patients with severe aplastic anemia (median age, 23 years) were treated with high-dose cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-v-host disease (GVHD), they were entered into a prospective randomized trial comparing the effect of a combination of methotrexate and cyclosporine (n = 22) to that of...

Previous investigations have suggested that high-dose methotrexate with leucovorin rescue is a potentially useful strategy for overcoming antifolate resistance. Interactions between methotrexate (MTX) and leucovorin and their respective metabolites appear to occur at multiple intracellular sites, including dihydrofolate reductase (MTX/MTX polyglutamates versus dihydrofolate) and other folate-de...

CONTEXT Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcut...

PURPOSE To test whether memantine can prevent methotrexate-induced cognitive deficits in a preclinical model. EXPERIMENTAL DESIGN After noting that methotrexate exposure induces prolonged elevations of the glutamate analog homocysteic acid (HCA) within cerebrospinal fluid, we tested whether intrathecal injection of HCA would produce memory deficits similar to those observed after intrathecal ...

Methotrexate has been used widely in dermatology, oncology and rheumatology fields. However, methotrexate-induced mucocutaneous lesions may occur in rare cases. In this case presentation, we report two cases of accidental poisoning with methotrexate. They had accidentally used methotrexate instead of digoxin. This case report emphasizes that early diagnosis and appropriate management is critica...

High-dose methotrexate is included in chemotherapy regimens used to treat a number of malignant neoplasms. Methotrexate plasma concentration is considered the best toxicity predictor. Monitoring methotrexate plasma concentrations is standard practice in the identification of at-risk patients, the titration of folinic acid doses, and the establishment of corrective measures. Methotrexate is a ki...

BACKGROUND Methotrexate is the most commonly used disease modifying antirheumatic drug in the treatment of juvenile idiopathic arthritis and can be effective in controlling disease in many patients. MAIN BODY A significant proportion of patients experience nausea and vomiting induced by methotrexate therapy, which can lead to decreased quality of life and discontinuation of treatment with met...

A pharmacokinetic study of methotrexate levels in blood and cerebrospinal fluid was performed in 42 patients who received one or more courses of high-dose methotrexate at 500 mg/sq m infused i.v. over a 24-hr period. Methotrexate level in the lumbar cerebrospinal fluid reached 1.2 x 10(-7) M at 0.5 hr and remained constant at that level for the 1st 24 hr. Similar methotrexate levels were noted ...

Methotrexate has been widely used for the treatment of rheumatoid arthritis (RA). The mechanisms of action of methotrexate are complex. Developed as a folic acid analogue, methotrexate inhibits purine and pyrimidine synthesis, which accounts for its efficacy in the therapy of cancer as well as for some of its toxicities. Recently, many studies have focused on the adenosine-mediated antiinflamma...

A total of 15 patients with advanced neoplastic disease, 13 with different solid tumors, one with lymphoma, and one with acute lymphocytic leukemia, underwent treatment consisting of continuous infusion of methotrexate (2 g/sq m/day) with concomitant thymidine (8 g/sq m/day) and leucovorin (1 mg/sq m/day). The dose of methotrexate was increased progressively by lengthening the methotrexate infu...