Correlation of the incidence of cocaine and cocaethylene in hair and postmortem biologic samples

Hair samples are useful as a matrix for drug testing because drugs can be detected in hair for longer periods than in blood or urine. The authors report a prospective comparison of the detection of cocaine and cocaethylene in routine postmortem biologic specimens to the detection of cocaine and cocaethylene in hair. The authors collected hair samples from various areas of the head in 53 autopsy cases, prepared them, and analyzed them by gas chromatography/mass spectrometry (GC/MS) for cocaine and cocaethylene. The authors compared the results of hair analysis with the results of toxicologic analysis performed on routine postmortem samples by enzyme multiplied immunoassay technique and GC/MS. Cocaine was found in either biologic fluids or in hair in 16 of 53 samples tested. Nine samples were positive for cocaine in both biologic fluids and hair. Five samples contained cocaine only in biologic fluids, and two contained cocaine only in hair. Cocaethylene was present in two cases. Drug screening of hair provides additional information in some autopsy cases, but the authors have not made hair analysis a routine practice. It may prove useful to save hair samples in all cases for later analysis if warranted by additional history or autopsy findings.     

Restraint-related fatalities in mental health facilities: report of two cases

Mental health facilities are occasionally confronted with patients who display destructive or disruptive behaviors requiring physical restraint. Under these circumstances, restraint can be associated with death. This case report describes two fatalities associated with physical restraint applied by staff members at mental health facilities.     

A Classification Tree Approach to the Development of Actuarial Violence Risk Assessment Tools

Since the 1970s, a wide body of research has suggested that the accuracy of clinical risk assessments of violence might be increased if clinicians used actuarial tools. Despite considerable progress in recent years in the development of such tools for violence risk assessment, they remain primarily research instruments, largely ignored in daily clinical practice. We argue that because most existing actuarial tools are based on a main effects regression approach, they do not adequately reflect the contingent nature of the clinical assessment processes. To enhance the use of actuarial violence risk assessment tools, we propose a classification tree rather than a main effects regression approach. In addition, we suggest that by employing two decision thresholds for identifying high- and low-risk cases--instead of the standard single threshold--the use of actuarial tools to make dichotomous risk classification decisions may be further enhanced. These claims are supported with empirical data from the MacArthur Violence Risk Assessment Study.     

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.     

Segmental analysis for cocaine and metabolites by HPLC in hair of suspected drug overdose cases

Hair samples of eight postmortem cases were analyzed in segments of 1 to 3 cm for cocaine, benzoylecgonine and cocaethylene. Samples were prepared for analysis by digestion in 0.1 M HCl and subsequent extraction with mixed-mode solid-phase extraction columns. Measurement was made by reversed-phase, narrow-bore HPLC and fluorescence detection using two laboratory-made internal standards. The concentrations were in the region of 0.29-316 ng/mg of hair for cocaine, 0.43-141 ng/mg of hair for benzoylecgonine and 0.93-1.83 ng/mg of hair for cocaethylene. All eight investigated cases had cocaine-positive segments. In six of the cases, all segments were positive, suggesting regular cocaine use and two showed in-between negative segments indicating an interruption or a change of the abuse intensity. The results showed a second, remarkable observation, i.e. enormous concentration differences (factor >150) for both cocaine and benzoylecgonine between the different subjects. Furthermore, interindividual cocaine/benzoylecgonine ratios ranged from 0.02 to 8.43. We believe these observations could in part be attributed to both some of the still existing limitations in the analytical approach(es), especially the mandatory hair washing steps, and in our still too limited knowledge of the hair incorporation processes. Nevertheless, in some cases, segmental analysis proved to be an important tool to distinguish, together with postmortem examination, deadly chronic abuse from single acute drug overdosage.     

Alternative primers for DYS391 typing: advantages of their application to forensic genetics

The amplification of the STR DYS391, using the primers described in the Genome Data Base (GDB: G00-365-251), shows not only an additional band to the Y-specific one in males with a size range of 26 bp less than those of DYS391 locus alleles, but also a polymorphic pattern in females in the same size range as the additional band observed in males. The DYS391 pattern in families reflects a Y-specific linked locus and also a polymorphic X locus with an X-linked pattern of inheritance. A first screening in the X homologous locus allowed the identification of five different alleles. Allele frequencies were explored in different population groups for both the Y locus and the homologous locus in the X chromosome showing a similar allele distribution pattern in the X and Y homologous loci. An alternative reverse primer was designed to amplify the Y-chromosome specific STR in order to improve the specificity and applicability of this system to forensic genetics. Comparative results of the amplification with the new and the previously described primers proved that with this new primer there is a substantial increase in the specificity of the amplification. Moreover, a smaller fragment is amplified with a size out of the range of the alleles of the other Y-STRs usually used in forensic applications, therefore simplifying its inclusion in multiplex systems.     

An insurer's perspective on reform

Individual health insurance markets differ from state to state, and as a result approaches to individual market reforms need to be different. In evaluating approaches, policy makers need to remember that since the decision to purchase health insurance coverage is voluntary, the potential for adverse selection exists. In addition, rather than putting the focus of individual market reforms almost exclusively on access to health insurance for a small number of persons with high-cost health conditions, more attention needs to be put on how to decrease the number of uninsured persons. This includes making the premiums paid for individual health insurance 100 percent tax deductible, similar to those of employer-based health insurance. Finally, market reforms need to treat all types of coverage issued in the individual market the same, whether they are purchased direct for the insurer or through an out-of-state association.