DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy.

Adriamycin (ADM, or doxorubicin hydrochloride) is an effective antineoplastic agent whose use is restricted by its well-described, dose-dependent cardiotoxicity. This study measures ADM DNA adduct formation by 32P-radiolabeling DNA, enzymatically digesting radiolabeled DNA, separating the formed adducts on two-dimensional thinlayer chromatography (2D-TLC), and quantitating the adducts with autoradiography and densitometry. Thirty-six male Sprague-Dawley rats are randomized to receive ADM at varying intraperitoneal (i.p.) injection concentrations: 0.9% saline i.p. controls, 4 mg/kg ADM i.p., and 6 mg/kg ADM i.p. Myocardial and pulmonary tissues are harvested 48 hours after i.p. injection for autoradiographic and histopathologic analyses. The results indicate differences in the amount and type of adduct formation as a function of ADM concentration. Increased partial depurination of dGMP and dAMP occurs with increasing ADM concentration at equal incubation times. This depurination correlates with the emergence of new adducts HM-dUMP, 8-OH-dGMP, HM-dCMP, and Me-dCMP. The quantification of these adducts can potentially represent an early marker of ADM cardiotoxicity and thereby optimize the efficacy of individual chemotherapy regimens while minimizing adverse effects.

Length-normalized pulse photoplethysmography: a noninvasive method to measure blood hemoglobin.

To determine whether blood hemoglobin concentration ([Hb]) could be measured noninvasively as the ratio of pulsatile changes in attenuation (absorbance plus scatter) of light (D) across a body part to changes in light path length (l), we measured transmission of near-infrared light (905 +/- 10 nm) through a finger, using a modified pulse oximeter, and simultaneously monitored fingertip diameter, using a sonomicrometer. In 25 subjects with [Hb] ranging from 3.1 to 18.2 gm/dl, and with normal oxygenation, average D/l ratio over 30-60 s correlated strongly with [Hb] measured by Coulter counter (r = 0.84, p << 0.001), though with considerable scatter, with absolute value of differences averaging 17% of the mean. Using 12 gm/dl and 0.75 mm(-1) as the lower limits of normal for [Hb] and D/l, respectively, two of nine normals had low (D/l) (78% specificity), and only one of 16 anemic subjects had borderline normal (D/l) (94%-100% sensitivity). The positive predictive value of a low (D/l) was 88% and the negative predictive value was 87.5%. With further development, this technique may reduce the need for phlebotomy, thereby reducing risks and costs and improving the experience of being a patient.