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.     

Whole body postmortem magnetic resonance angiography

Computed tomography (CT) and magnetic resonance (MR) imaging have become important elements of forensic radiology. Whereas the feasibility and potential of CT angiography have long been explored, postmortem MR angiography (PMMRA) has so far been neglected. We tested the feasibility of PMMRA on four adult human cadavers. Technical quality of PMMRA was assessed relative to postmortem CT angiography (PMCTA), separately for each body region. Intra-aortic contrast volumes were calculated on PMCTA and PMMRA with segmentation software. The results showed that technical quality of PMMRA images was equal to PMCTA in 4/4 cases for the head, the heart, and the chest, and in 3/4 cases for the abdomen, and the pelvis. There was a mean decrease in intra-aortic contrast volume from PMCTA to PMMRA of 46%. PMMRA is technically feasible and allows combining the soft tissue detail provided by MR and the information afforded by angiography.     

Diversifying Nature Protection: Evaluating the Changing Tools for Forest Protection in Canada and Norway

Governments increasingly struggle to protect representative nature types and ecological diversity within their territories only via the instrument of publicly designated protected areas. This article examines the rise of voluntary conservation and certification (i.e., private conservation) as tools for forest protection in Norway and Canada. We contrast the differing potential of these private conservation tools with protection through government legislation and regulation using four evaluative criteria: the representativeness of protected areas, the strength of protection, the longevity of protection, and the information generated through protection. We find that private conservation tools can match the strength of legal protection and help to dispel conflict, but that private tools create protection that is more likely to be reversed in the future. However, we also show that voluntary private conservation can become public protection, which highlights the importance of examining different paths toward secure and long‐lasting protection.     

SWEDISH DISARMAMENT POLICY AND WEAPONS EXPORTS,INVESTIGATED FROM A LARGE TECHNICAL SYSTEMS PERSPECTIVE

Disarmament policy is an established field in international relations. From the perspective of Swedish foreign policy, earlier an intense attention was given to this field, but it has now lost priority. This paper seeks to systematize some determinants in this development. One important factor is the increasing role of weapons exports--in terms of jobs, export income and technical development. The technical element is of decisive importance in combination with international law and international organizations. The analysis is based on concepts and theories from the research tradition Large Technical Systems.