Study on imatinib trough concentration, efficacy and their relation in chronic myelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To determine plasma imatinib concentration, intracellular imatinib concentration, and hOCT1 and ABCB1 mRNA expression in bone marrow cells of CML patients to further evaluate the potential usefulness of these measures as markers of imatinib efficacy and their clinical relationships.</p><p><b>METHODS</b>Eighty CML patients in chronic phase receiving imatinib were enrolled in this study, including 56 males and 24 females with a median age of 39.5 (6 - 76) years. Imatinib was administered at a median dose of 400 (200 - 800) mg/d orally per day with a median course of 24 (3 - 90) months. The intracellular imatinib concentrations in bone marrow cells of 28 patients were simultaneously determined. Real-time quantitative PCR with a taqman probe was used to assess hOCT1 and ABCB1 mRNA expression on bone marrow cells of 36 patients. Imatinib trough concentration was determined by high-performance liquid chromatography-tandem mass spectrometry with a detectability of 2 - 10 000 µg/L. Serum α1-acid glycoprotein (AGP) was measured by immune turbidimetry on a BNProspec protein analyzer (Dade Behring, USA). All patients were divided into MMR, CCyR, PCyR or drug-resistant groups according to response.</p><p><b>RESULTS</b>Plasma imatinib trough concentration of 80 patients was (1274.1 ± 559.1) (109.0 - 3400.0) µg/L. The plasma imatinib trough concentration of 59 (73.8%) patients with a dose of 400 mg/d was (1252.0 ± 569.5) (109 - 3400) µg/L, including 37 (62.7%) patients with concentrations of more than 1000 µg/L and 9 (15.2%) patients more than 800 µg/L. Plasma imatinib trough concentration in the MMR group \[(1531.9 ± 634.1) µg/L\] was significant higher than in the PCyR \[(812.8 ± 480.3) µg/L\] or drug-resistant group \[(875.2 ± 243.1) µg/L\] (P < 0.05). Plasma imatinib trough concentration in the CCyR group \[(1288.4 ± 498.2) µg/L\] was significant higher than in the PCyR group (P = 0.027). There was no significant difference between CCyR and MMR groups with regard to plasma imatinib trough concentration (P = 0.136). The intracellular imatinib concentration in bone marrow cells in the CCyR group \[12.6 (2.4 - 90.4) µg/L\] was significantly higher than drug-resistant \[6.6 (2.6 - 111.0) µg/L\] or PCyR \[2.7 (2.4 - 4.7) µg/L\] groups (P = 0.013). The hOCT1 mRNA expression on bone marrow cells in the CCyR group \[25.9(0.7 - 123.9) × 10(-5)\] was significantly higher than in drug-resistant \[7.8 (2.5 - 33.5) × 10(-5)\] or PCyR \[4.2 (1.4 - 11.9) × 10(-5)\] groups (P = 0.036). The ABCB1 mRNA expression on bone marrow cells in drug-resistant group \[136.7 (15.0 - 1604.9) × 10(-5)\] was significantly higher than in CCyR \[129.1 (12.9 - 783.3) × 10(-5)\] or PCyR \[34.4 (2.2 -108.2) × 10(-5)\] groups (P = 0.013). Plasma imatinib trough concentration was positively correlated with AGP (r = 0.446, P = 0.000) or dose (r = 0.346, P = 0.002). There were no significant correlations between plasma imatinib trough concentration and height, weight or body surface area (P > 0.05). There were no significant differences among different courses with regard to plasma imatinib trough concentration (P > 0.05).</p><p><b>CONCLUSION</b>Clinical responses in CML patients were correlated with plasma and intracellular imatinib trough concentrations. Imatinib concentration was regulated by AGP and the activities of hOCT1 and ABCB1.</p>

A forensic pathological study of eighty-two cases of adrenal hemorrhage / 法医学杂志

OBJECTIVE@#To analyze the relationship between adrenal hemorrhage and the cause of death, age and gender.@*METHODS@#Eighty-two cases of adrenal hemorrhage were statistically analyzed.@*RESULTS@#Adrenal hemorrhage occurred mostly in cases of sudden death, infection, trauma and asphyxia. Male had more chance than female to have adrenal hemorrhage. Adrenal hemorrhage caused by sudden death, trauma and poisoning was more frequently seen in young adults, whereas adrenal hemorrhage in children as well as in fetus and newborns was often caused by infection as well as sudden death and asphyxia respectively. Adrenal hemorrhage caused by sudden death and asphyxia was mainly located in medulla, while the infection usually induced hemorrhage in cortex. Adrenal hemorrhage caused by trauma showed an equal opportunity in either the cortex or medulla.@*CONCLUSION@#Our data indicate that adrenal hemorrhage might provide some clues in searching for the cause of death.