Internal dose markers

Bonithon-Kopp et al. (1986b) investigated another potential marker for lead exposure. Maternal and infant hair lead levels, determined from hair samples taken at birth, were found to be correlated inversely with results on neurobehavioral tests (McCarthy Scales of Children s Abilities) when the children were tested at 6 years of age. Other studies have also reported associations between hair lead levels and behavioral or cognitive test scores, but measures of lead in hair may not accurately reflect internal body burden of lead, and such data should not be used to evaluate internal dose-response relationships (EPA 1986a). 

Gatsonis and Needleman (1992) identified a different set of statistical and methodological issues that have contributed to the inconsistencies (1) selection of adequate markers of exposure or internal dose,... 

Blood lead Weeks to months Biological Markers of Internal Dose... 

PAHs are known to be absorbed through the skin after topical application as demonstrated by elevated levels of several PAHs in blood (22). Urinary excretion of 1-hydroxypyrene, a fluorescent metabolite of pyrene, has also been used as a marker of internal dose of coal tar (23—24). Elevated levels of sister chrcmiatid exchange (SCE) and chromosomal aberrations in peripheral blood lynphocytes and of urinary mutagens, measured by the Salmonella mutagenesis assay, have also been found (24-26). 

Warfarin efficacy is currently monitored with functional assays [12,13]. Patients on warfarin have a prothrombin time (PT) measured frequently, usually at least every 2 weeks. The corrected PT, or international normalized ratio (INR), is used to determine if the patient is taking a sub- or suprather-apeutic dose of warfarin. INR testing is often performed more frequently in patients being initiated on warfarin or those with very labile INRs. The INR has been used for many years and is a good marker of anticoagulation status. However, high INRs do not directly indicate that patients will have a bleeding event and low INRs do not necessarily predict thrombosis [14,15]. 

A variant of this method was described by Malvano et al. (1982) standard unit response curves are constructed with aliquots of a highly positive serum diluted with a negative sample. This approach is based on the assumption that dose-response curve parallellism eliminates the necessity to employ many different sera for the calibration curve. This positive serum is then calibrated against a WHO standard serum and the antibody content of the positive serum is expressed in international units (lU). Calibration samples of the positive serum diluted with a negative serum are included as internal markers for between-run, between-laboratory and between-method normalizations to provide analytical consistency to the measurements. 

Calculations of the absorbed dose resulting from the oral application of Tc-(Re)-sulfide colloid are based on ICRP Publication 53 (International Commission on Radiological Protection 1987 b) for nonabsorbable markers. The effective dose in adults (70 kg) resulting from 37 MBq (1 mCi) of orally administered Tc-(Re)-sulfide colloid is approximately 1 mSv. 

International Commission on Radiological Protection (1987 a) Technetium-labelled colloids (1987) In Annals of the ICRP, radiation dose to patients from radiopharmaceuticals, biokinetic models and data. ICRP publication 53, vol 18, no 1-4. Pergamon, Oxford, pp 179-183 International Commission on Radiological Protection (1987b) Technetium-labelled non-absorbable markers (1987) In Annals of the ICRP, radiation dose to patients from radiopharmaceuticals, biokinetic models and data. ICRP publication 53, vol. 18, no. 1-4. Pergamon, Oxford, pp 225-226... 

Two types of experiments were simulated (i) Bolus Injection. A 02-mL bolus of [ N]ammonia was injected rapidly (02 s) into the right common carotid artery. Based on previously determined recoveries of a diffusible marker, only 85% of the dose was assumed to have reached the brain 22). (ii) Continuous Infusion. [ N]-Ammonia dissolved in physiological saline was infused at a rate of 02 mL/min via the common carotid artery. The external carotid ai ry was ligated so at 80% of the dose was assumed to have reached the brain via the internal carotid artery it was assumed that the remainder was lost via the pterygopalatine artery. 

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