Parisotto R, Gore C J, Hahn A G, Ashenden M J, Olds T S, Martin D T, Pyne D B, Gawthorn K, Brugnara C
Department of Physiology and Applied Nutrition, Australian Institute of Sport, Canberra.
Int J Sports Med. 2000 Oct;21(7):471-9. doi: 10.1055/s-2000-7421.
This study investigated using reticulocyte (retic) parameters as indirect markers of human recombinant erythropoietin (r-HuEPO) abuse in elite athletes. Absolute reticulocyte count (# retic), the per cell haemoglobin content of reticulocytes (CHr), reticulocyte haemoglobin mass per litre of blood (RetHb) and red blood cell:reticulocyte haemoglobin (RBCHb:RetHb) ratio were assessed using flow cytometry. Venous blood was drawn from 155 elite athletes from six sports during regular training to establish reference ranges (95% confidence interval) for these parameters. The reference ranges were compared with those of a non-athletic population (n = 23), four groups of athletes (n = 24) before and after exposure to simulated altitudes (2,500-3,000 m for 11-23 nights), two groups of elite cyclists (n = 13) before and after four weeks of training at natural altitude (1,780 and 2,690 m), and with those of non-athletic subjects from a separate study (n =24) before and 1-2 days after they were injected with 1,200 U x kg(-1) r-HuEPO over a 9-10 day period. Generally the changes induced by r-HuEPO injection exceeded by approximately 100% the magnitude of the changes associated with natural altitude exposure. Simulated altitude exposure did not significantly alter the reticulocyte parameters. From the sample of 155 non-users and 24 r-HuEPO users, the population mean and variance, as well as the 95% confidence limits for the population mean and population variance, were estimated. Relative to arbitrarily chosen cut-off levels, the confidence limits for the rate of true positives and rate of true negatives were also calculated. Based on the lowest rate of false positives and highest rate of true positives, the best discriminator between r-HuEPO users and non-users was # retic, marginally superior to RBCHb: RetHb ratio and RetHb. At a cut-off for # retic of 221 x 10(9)x L(-1) we could be 95% sure that we would find no more than 7 false positives in every 100,000 tests. We would expect to pick up 51.8% of users, and could be 95% sure of picking up at least 38% of current or recent users. This result highlights the potential power of retic parameters for detecting r-HuEPO abuse among athletes. However, the efficacy of these cut-offs for detecting r-HuEPO abuse is unknown if an athlete is a chronic user or stops using r-HuEPO several weeks before being tested.
本研究调查了使用网织红细胞（retic）参数作为精英运动员中人类重组促红细胞生成素（r-HuEPO）滥用的间接标志物。使用流式细胞术评估绝对网织红细胞计数（#retic）、网织红细胞的每细胞血红蛋白含量（CHr）、每升血液中网织红细胞血红蛋白质量（RetHb）以及红细胞：网织红细胞血红蛋白（RBCHb:RetHb）比值。在常规训练期间，从六个运动项目的155名精英运动员中采集静脉血，以建立这些参数的参考范围（95%置信区间）。将这些参考范围与非运动员人群（n = 23）、四组运动员（n = 24）在暴露于模拟海拔（2500 - 3000米，持续11 - 23晚）前后、两组精英自行车运动员（n = 13）在自然海拔（1780米和2690米）进行四周训练前后的参考范围进行比较，并与另一项单独研究中未注射药物的非运动员受试者（n = 24）以及在9 - 10天内注射1200 U x kg(-1) r-HuEPO后1 - 2天的非运动员受试者（n = 24）的参考范围进行比较。一般来说，r-HuEPO注射引起的变化比与自然海拔暴露相关的变化幅度大约高出100%。模拟海拔暴露并未显著改变网织红细胞参数。从155名未使用者和24名r-HuEPO使用者的样本中，估计了总体均值和方差，以及总体均值和总体方差的95%置信限。相对于任意选择的临界值，还计算了真阳性率和真阴性率的置信限。基于最低的假阳性率和最高的真阳性率，r-HuEPO使用者和非使用者之间的最佳判别指标是#retic，略优于RBCHb:RetHb比值和RetHb。当#retic的临界值为221 x 10(9)x L(-1)时，我们可以95%确定在每100,000次检测中发现的假阳性不超过7例。我们预计能检测出51.8%的使用者，并且可以95%确定至少能检测出38%的当前或近期使用者。这一结果凸显了网织红细胞参数在检测运动员中r-HuEPO滥用方面的潜在作用。然而，如果运动员是长期使用者或在检测前几周停止使用r-HuEPO，这些临界值检测r-HuEPO滥用的有效性尚不清楚。
