Discrepancy between CYP2D6 phenotype and genotype derived from post-mortem dextromethorphan blood level

OBJECTIVE: To describe the death of a toddler after a therapeutic dose of dextromethorphan and its investigation. STUDY DESIGN: Case report, cytochrome P450 phenotype and genotype determination in the victim and post-mortem drug redistribution study performed in rats. RESULTS: A 20-month Asian male who received 3 mg of dextromethorphan once at 09:00 h and again at 22:00 h was found dead at 04:35 h. Post-mortem examination showed signs of early bronchopneumonia (bacterial cultures were negative); dextromethorphan and dextrorphan blood concentrations taken from the heart cavity were 500 ng/ml (1. 84 micromol/l) and 200 ng/ml (0.78 micromol/l), respectively. Despite the dextromethorphan level being almost 100-fold higher than expected after therapeutic doses, intentional or unintentional overdose was extremely unlikely; other potential causes were investigated. Post-mortem drug redistribution study performed in rats showed that dextromethorphan does not undergo extensive redistribution after death (6+/-5-fold increase) and could not explain the observed dextromethorphan level. The dextromethorphan/dextrorphan concentration ratio of 2.5 found in this toddler was compatible with a slow CYP2D6 metabolizer phenotype. However, the toddler exhibited a fast metabolizer genotype. Potential reasons for this discrepancy are discussed. CONCLUSION: CYP450 phenotypes derived from post-mortem blood levels should be interpreted with caution and preferably confirmed by a genotype analysis.     

Insights on Technology Transfer from the Bureau of Mines

The U.S. Bureau of Mines was established in 1910 to reduce the high accident rate in the nation's coal mines. For 85 years, it conducted a wide variety of tasks related to mining before it was abolished in 1995. The BOM had many technology transfer successes in its lifetime, including more than a dozen R&D100 awards. This essay identifies and discusses five transfer factors that can explain the success (or failure) of many Bureau of Mines projects. These five factors are termed pressure, pitfalls, path, price, and profit.     

大鼠肝细胞DNA含量与早期死亡时间关系的图像分析研究

实验选择 15只大鼠 ,处死后 ,在 2 4h内 ,每隔 1h取肝组织块进行细胞学涂片、福尔马林液固定、Feul gen染色、自动图像分析仪测量、统计学处理数据。结果表明 ,肝细胞DNA含量在死后 2 4h内 ,随死亡时间的延长而较有规律的下降。其中积分光密度、平均光密度、异形指数是用来研究死亡 2 4h内肝细胞DNA降解规律 ,并准确推断死亡时间的较好指标。     

The Process of Globalisation and Class Transformation in the West

In this article the contemporary international capitalist system is examined and a rising New International Division of Labour is defined. It is argued that while in previous epochs an international market of commodities existed, during the post-war period a global network of closely interconnected production units and financial institutions has been created as well. But while production, finance and commerce are decentralised worldwide, their management and control is centralised in a few headquarters in the advanced capitalist countries. A colossal concentration of economic power and control over the world means of production, resources and labour force, unprecedented in the history of capitalism, is taking place. Information Technology is shown to be the current day means of centralisation of organisation and control of both material and service production by capital. It, at the same time, allocates work and degrades its knowledge content. Coupled with the prevalence of services in western society, it changes the features of its class structure.