ABSTRACT
BACKGROUND: Laboratory tests are standard part of a routine check-up of current medical status and an important tool in diagnostic workup, in planning or evaluation of treatment, and disease monitoring. To reduce misdiagnosis, accurate reference intervals reflecting age, sex, ethnicity and other relevant clinical parameters must be established. We aimed to explore ethnic difference in basic blood parameters relevant for the Czech Republic. PATIENTS AND METHODS: The study was performed analyzing blood tests from 13,126 individuals in cancer prevention program. Individuals were divided into two subgroups - 1. Czech, 2. Vietnamese, and laboratory parameters were compared. RESULTS: Statistically significant differences were observed in majority of basic blood tests. These could be explained either by ethnical differences in basic biological parameters (weight, body mass) or dietary habits, such as in case of lower blood cholesterol levels and lower creatinine levels respectively in individuals of Vietnamese origin. Observed differences in erythrocyte-related parameters likely reflect higher incidence of haematogical disorders such as hemoglobinopathies. CONCLUSION: We observed statistically significant difference in basic blood tests between individuals of Czech and Vietnamese origin. Taking into consideration routinely used creatinine-based estimation of glomerular function, the most clinically relevant ethnic-based difference is substantially lower creatinine plasma level in individuals of Vietnamese origin.Key words: lab tests - reference range - ethnic specificity The work was supported by Czech Ministry of Health via DRO 00209805 and by MEYS via NPS I (LO1413). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 3. 2017Accepted: 26. 3. 2017.
Subject(s)
Neoplasms/prevention & control , Creatinine/blood , Czech Republic , Ethnicity , Hematologic Tests , Humans , Reference Values , VietnamABSTRACT
Methotrexate is an anti-cancer drug used to treat several malignancies including pediatric acute lymphoblastic leukemia and choriocarcinoma. Despite recent advances in cancer chemotherapy, it remains a mainstay of therapy since its discovery in the early second half of the previous century. Moreover, low-dose methotrexate is a gold standard antirheumatic drug in the treatment of rheumatoid arthritis, psoriasis, systemic scleroderma and other autoimmune disorders. Side effects of methotrexate treatment are well known and described; however, their occurrence may often be unpredictable due to lack of specific biomarkers of toxicity. Methotrexate plasma levels are routinely monitored by therapeutic drug monitoring, nevertheless, occurrence and concentrations of its metabolites are not measured. During methotrexate treatment 7-âhydroxymethotrexate and 2,4-âdiamino-âN10-âmehylpteroic acid appear in plasma. The latter can further be hydroxylated and glucuronidated resulting in five possible extracellular methotrexate metabolites. In addition, methotrexate is intracellularly converted to its active polyglutamylated forms. Therapeutic efficacy is dependent on formation of methotrexate polyglutamates as it keeps intracellular pool of the drug and enhances its affinity towards various target enzymes. In this study, we describe pharmacokinetic and pharmacodynamic characteristics of methotrexate metabolites. We also review methotrexate blood brain barrier transport to cerebrospinal fluid regarding its use in the prevention of leukemic central nervous system involvement and management of methotrexate toxicity with the use of carboxypeptidase-âG2. Finally, we discuss laboratory methods for monitoring methotrexate metabolites and benefits of simultaneous determination of methotrexate and metabolites as possible biomarkers of therapeutic efficacy and clinical toxicity.
