Plasma phenylalanine: tyrosine ratios during high-dose methotrexate-citrovorum "rescue".

  title={Plasma phenylalanine: tyrosine ratios during high-dose methotrexate-citrovorum "rescue".},
  author={M. Hilton and C. C. Patel and S. Bertolone and D. Kmetz and L. Clark},
  journal={Medical and pediatric oncology},
  volume={10 4},
We have measured phenylalanine and tyrosine in the plasma of patients with osteogenic sarcoma undergoing chemotherapy with high-dose methotrexate (HDMTX) citrovorum factor rescue (CFR). During 14 treatments in six different patients, the phenylalanine to tyrosine ratio (PHE/TYR) at 21 to 38 hours was elevated over pretreatment levels. The observed increase in plasma phenylalanine is attributed to inhibition by MTX of the phenylalanine hydroxylase system of the liver, which is not folate… Expand
Daily profiles of plasma phenylalanine and tyrosine in patients with osteogenic sarcoma during treatment with high-dose methotrexate-citrovorum rescue.
In the adolescent patients, although MTX levels in plasma declined steadily, Phe concentrations, which fell between 24 and 48 hours, rose to a new peak at 4-7 days, suggesting damage to liver parenchymal cells not indicated by standard tests of liver function. Expand
Use of the phenylalanine:tyrosine ratio to test newborns for phenylketonuria in a large public health screening programme
Having applied the methods to the routine clinical screening of a large population, it was confirmed that the clinical sensitivity and specificity of the PKU screening test are higher when the phenylalanine:tyrosine ratio is incorporated into the cut off than when the cutoff is based on the phenolalanine concentration alone. Expand
Acute high‐dose methotrexate neurotoxicity in the rat
A model of acute high‐dose methotrexate neurotoxicity in the rat characterized by a profound dose‐dependent depression of cerebral glucose metabolism in association with behavioral and electroencephalographc abnormalities is described. Expand
Liquid-chromatographic direct determination of phenylalanine and tyrosine in serum or plasma, with application to patients with phenylketonuria.
  • M. Hilton
  • Chemistry, Medicine
  • Clinical chemistry
  • 1982
With this method, picomole amounts of phenylalanine and tyrosine can be rapidly separated and directly measured by absorbance at 206 nm and used to measure phenylAlanine in plasma from six children with phenylketonuria. Expand
Reduced cerebral glucose metabolism and increased brain capillary permeability following high‐dose methotrexate chemotherapy: A positron emission tomographic study
Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug‐induced alteration in blood–brain barrier function. Expand
Methotrexate Induced Seizures Associated with Acute Reversible Magnetic Resonance Imaging (MRI) Changes in a Patient with Acute Lymphoblastic Leukemia
A 27-year-old woman with acute lymphoblastic leukemia (ALL) had an episode of generalized tonic-clonic seizure after therapy with intrathecal and intravenous methotrexate (MTX). Magnetic resonanceExpand


Plasma amino acids during high-dose methotrexate-citrovorum "rescue".
Data indicate the inhibition by high dose methotrexate of liver phenylalanine hydroxylase, an enzyme system which is apparently not rescued by citrovorum factor, in a patient with osteogenic sarcoma. Expand
The biochemistry of the citrovorum factor rescue effect in normal bone marrow cells after high-dose methotrexate.
It could be shown that the usually administered citrovorum factor doses are not sufficient for an effective rescue for the bone marrow cells as long as serum methotrexate concentrations are equal or higher than 10 −6 M. Expand
The reversal of methotrexate toxicity by thymidine with maintenance of antitumour effects
The effects of thymidine (TdR) on the toxicity and therapeutic effect of MTX in mice bearing leukaemia L1210 and allopurinol because this drug has been reported to impair the antitumour effects ofMTX are studied. Expand
Evaluation of overall toxicity of high-dosage methotrexate regimens.
Overall toxicity was assessed for 43 patients with osteosarcoma who received 349 high-dosage courses of methotrexate (HD-MTX) with citrovorum factor (Leukovorin) "rescue" (CF) and three patients died from causes related to MTX toxicity. Expand
A rapid and specific radioimmunoassay for methotrexate.
A sensitive and precise radioimmunoassay for methotrexate has been developed using antibody induced in rabbits, tritium-labeled methotrexate, and a nitrocellulose membrane separation technique.Expand
Daily rhythms in the concentrations of various amino acids in human plasma.
Tyrosine, tryptophan, phenylalanine, methionine, cysteine and isoleucine underwent the greatest per cent changes; the amino acids whose plasma concentrations were highest (that is, alanine, glycine and glutamic acid) showed the least tendency to vary. Expand
Inhibition of Dihydrofolic Reductase by Aminopterin and Amethopterin.∗ †
The enzyme, dihydrofolic reductase, is inhibited non-competitively by the folic acid antagonists, Aminopterin and Amethopterin, respectively. Expand
The isolation and characterization of dihydropteridine reductase from sheep liver.
Evidence indicates that the activity of this enzyme is far greater than that of the known pterindependent hydroxylases in all tissues examined. Expand