Frome Edward L, Newman Lee S, Cragle Donna L, Colyer Shirley P, Wambach Paul F
Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37830, USA.
Toxicology. 2003 Feb 1;183(1-3):39-56. doi: 10.1016/s0300-483x(02)00439-0.
The potential hazards from exposure to beryllium or beryllium compounds in the workplace were first reported in the 1930s. The tritiated thymidine beryllium lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely used to screen beryllium exposed workers in the nuclear industry for sensitivity to beryllium. The clinical significance of the BeLPT was described and a standard protocol was developed in the late 1980s. Cell proliferation is measured by the incorporation of tritiated thymidine into dividing cells on two culture dates and using three concentrations of beryllium sulfate. Results are expressed as a 'stimulation index' (SI) which is the ratio of the amount of tritiated thymidine (measured by beta counts) in the simulated cells divided by the counts for the unstimulated cells on the same culture day. Several statistical methods for use in the routine analysis of the BeLPT were proposed in the early 1990s. The least absolute values (LAV) method was recommended for routine analysis of the BeLPT. This report further evaluates the LAV method using new data, and proposes a new method for identification of an abnormal or borderline test. This new statistical-biological positive (SBP) method reflects the clinical judgment that: (i) at least two SIs show a 'positive' response to beryllium; and (ii) that the maximum of the six SIs must exceed a cut-point that is determined from a reference data set of normal individuals whose blood has been tested by the same method in the same serum. The new data is from the Y-12 National Security Complex in Oak Ridge (Y-12) and consists of 1080 workers and 33 non-exposed control BeLPTs (all tested in the same serum). Graphical results are presented to explain the statistical method, and the new SBP method is applied to the Y-12 group. The true positive rate and specificity of the new method were estimated to be 86% and 97%, respectively. An electronic notebook that is accessible via the Internet was used in this work and contains background information and details not included in the paper.
workplace were first reported in the 1930s. The tritiated thymidine beryllium lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely used to screen beryllium exposed workers in the nuclear industry for sensitivity to beryllium. The clinical significance of the BeLPT was described and a standard protocol was developed in the late 1980s. Cell proliferation is measured by the incorporation of tritiated thymidine into dividing cells on two culture dates and using three concentrations of beryllium sulfate. Results are expressed as a 'stimulation index' (SI) which is the ratio of the amount of tritiated thymidine (measured by beta counts) in the simulated cells divided by the counts for the unstimulated cells on the same culture day. Several statistical methods for use in the routine analysis of the BeLPT were proposed in the early 1990s. The least absolute values (LAV) method was recommended for routine analysis of the BeLPT. This report further evaluates the LAV method using new data, and proposes a new method for identification of an abnormal or borderline test. This new statistical-biological positive (SBP) method reflects the clinical judgment that: (i) at least two SIs show a 'positive' response to beryllium; and (ii) that the maximum of the six SIs must exceed a cut-point that is determined from a reference data set of normal individuals whose blood has been tested by the same method in the same serum. The new data is from the Y-12 National Security Complex in Oak Ridge (Y-12) and consists of 1080 workers and 33 non-exposed control BeLPTs (all tested in the same serum). Graphical results are presented to explain the statistical method, and the new SBP method is applied to the Y-12 group. The true positive rate and specificity of the new method were estimated to be 86% and 97%, respectively. An electronic notebook that is accessible via the Internet was used in this work and contains background information and details not included in the paper.
20世纪30年代首次报道了工作场所接触铍或铍化合物的潜在危害。氚化胸腺嘧啶铍淋巴细胞增殖试验（BeLPT）是一种体外血液检测方法，广泛用于筛查核工业中接触铍的工人对铍的敏感性。20世纪80年代后期描述了BeLPT的临床意义并制定了标准方案。通过在两个培养日期将氚化胸腺嘧啶掺入分裂细胞中并使用三种浓度的硫酸铍来测量细胞增殖。结果表示为“刺激指数”（SI），即模拟细胞中氚化胸腺嘧啶的量（通过β计数测量）与同一培养日未刺激细胞的计数之比。20世纪90年代初提出了几种用于BeLPT常规分析的统计方法。推荐使用最小绝对值（LAV）方法进行BeLPT的常规分析。本报告使用新数据进一步评估了LAV方法，并提出了一种识别异常或临界检测的新方法。这种新的统计生物学阳性（SBP）方法反映了临床判断：（i）至少两个SI对铍显示“阳性”反应；（ii）六个SI中的最大值必须超过一个切点，该切点由同一血清中使用相同方法检测血液的正常个体参考数据集确定。新数据来自橡树岭的Y-12国家安全综合体（Y-12），包括1080名工人和33个未接触对照的BeLPT（均在同一血清中检测）。给出了图形结果以解释统计方法，并将新的SBP方法应用于Y-12组。新方法的真阳性率和特异性估计分别为86%和97%。本研究使用了一个可通过互联网访问的电子笔记本，其中包含本文未包含的背景信息和详细信息。
