"Decrease in childhood neuroblastoma death in Japan," Hanawa et al. (1990)
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Biomedical subjects
Publications and source records attributed to A Craft.
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Using molecular cloning, we earlier isolated the "retinoblastoma gene"; mutations or deletions at this locus are associated with the hereditary predisposition to some human cancers, especially retinoblastoma and osteosarcoma. To develop diagnostic tests for such a predisposition, we identified restriction-fragment-length polymorphisms (RFLPs) within the retinoblastoma gene and tested their usefulness in predicting the risk of cancer in 20 families with members who had hereditary retinoblastoma. We were able to make predictions in 19 of the 20 kindreds. In 18 kindreds, we demonstrated a consistent association of marker RFLPs with the mutation predisposing to retinoblastoma. In the 19th kindred, there may be a lack of cosegregation of the DNA polymorphisms within the gene and the site of the mutation predisposing to retinoblastoma. However, there is uncertainty about the clinical diagnosis of the retinal lesion in a key member of this kindred; if the lesion is not a retinoblastoma, there is no discrepancy between the DNA polymorphisms and the retinoblastoma trait. We conclude that it is feasible and clinically useful to use these DNA polymorphisms to determine the risk of cancer.
Twelve children with severe systemic juvenile chronic arthritis, all requiring high dose corticosteroids, have been admitted to a pilot study to evaluate the effect of low-dose methotrexate (mean dose: 8.5 mg/M2) on disease activity over a 6 month period. Definite improvement occurred in 4 children, allowing reduction of the steroid dose in 2 cases. Two children showed an acute flare of disease activity during the treatment period and in three, steroids had to be increased. Overall, side effects were rare with a rise in transaminases only occurring once. MTX blood levels taken on 14 occasions in 8 children documented absorption in all cases with a mean level of 3.45 x 10(-7) mol/l on a mean dose of 9 mg/M2. Low-dose MTX appears to be a safe drug in the short term treatment of severe systemic JCA with beneficial effect in about a third of patients. Long-term controlled trials will be needed to evaluate its role in the treatment of systemic disease as well as side effects.