Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths

Compared to morphine and morphine-6-glucuronide (M6G), codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid μ-receptors. Analgesic effects of codeine are thus largely dependent on metabolic conversion to morphine by the polymorphic cytochrome P450 isoenzyme 2D6 (CYP2D6). How this relates to toxicity and post-mortem whole blood levels is not known. This paper presents a case series of codeine-related deaths where concentrations of morphine, M6G and morphine-3-glucuronide (M3G), as well as CYP2D6 genotype, are taken into account. Post-mortem toxicological specimens from a total of 1444 consecutive forensic autopsy cases in Central Norway were analyzed. Among these, 111 cases with detectable amounts of codeine in femoral blood were identified, of which 34 had femoral blood concentrations exceeding the TIAFT toxicity threshold of 0.3mg/L. Autopsy records of these 34 cases were retrieved and reviewed. In the 34 reviewed cases, there was a large variability in individual morphine to codeine concentration ratios (M/C ratios), and morphine levels could not be predicted from codeine concentrations, even when CYP2D6 genotype was known. 13 cases had codeine concentrations exceeding the TIAFT threshold for possibly lethal serum concentrations (1.6 mg/L). Among these, 8 individuals had morphine concentrations below the toxic threshold according to TIAFT (0.15 mg/L). In one case, morphine as well as M6G and M3G concentrations were below the limit of detection. A comprehensive investigation of codeine-related fatalities should, in addition to a detailed case history, include quantification of morphine and morphine metabolites. CYP2D6 genotyping may be of interest in cases with unexpectedly high or low M/C ratios.     

PryJector: a device for in situ visualization of chemical and physical property distributions on surfaces using projection and hyperspectral imaging

Traditional forensic methods that highlight the spatial distribution of properties such as blood and fingerprints have two main disadvantages: they often apply chemicals that may influence further analyses, and they cannot easily be modified to search for new compounds/properties. A new instrument (called PryJector) avoids these problems by dynamically projecting back onto the surface under study spatially distributed information of compounds/properties (chemical images) obtained from multivariate analysis of hyperspectral images. Selectivity to target compounds/properties is ensured by multivariate modeling which makes the instrument much more flexible compared to traditional methods. The functionality of the PryJector is demonstrated in an application related to the detection of counterfeit pharmaceuticals where compounds otherwise indistinguishable to the human eye are made clearly visible by projection of false-colored chemical images. The PryJector is shown to be a noninvasive and very flexible instrument for highlighting spatial distributions of various compounds/properties.     

Do Formalist Judges Abide By Their Abstract Principles? A Two-Country Study in Adjudication

International Journal for the Semiotics of Law - Revue internationale de Sémiotique juridique - Recent literature in experimental philosophy has postulated the existence of the...