Tramadol (Ultram) concentrations in death investigation and impaired driving cases and their significance

We reviewed a series of 66 deaths in Washington State between 1995-2000 in which tramadol (Ultram and Ultracet, Ortho-McNeil) was detected in the decedent's blood, in order to assess the role tramadol was determined to have played. Additionally, we reviewed a series of 83 impaired driving cases in which tramadol was detected in order to establish a non-lethal blood tramadol concentration reference range. In both populations, tramadol was consistently found together with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely attributable to tramadol alone. However, tramadol may be a significant contributor to lethal intoxication when taken in excess with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased CNS depression. Although the incidence of tramadol detection has increased consistently over the last eight years, there is no evidence of a corresponding increase in the number of cases in which death was attributed solely to tramadol. Blood drug concentrations in many deaths exceeded the therapeutic serum range of 0.28-0.61 mg/L; however, the concentrations overlapped almost completely with the range identified in living subjects arrested for impaired driving. These findings suggest caution in the interpretation of blood tramadol concentrations outside of the recognized therapeutic range. It also suggests that the drug, even when used in moderate excess, is not a principle cause of death in suicidal or accidental deaths.     

Validation study of the TrueAllele automated data review system

The New York State Convicted Offender DNA Databank is the first U.S. lab to complete an internal validation of the TrueAllele expert data review system. TrueAllele is designed to assess short tandem repeat (STR) DNA data based on several key features such as peak height, shape, area, and position relative to a standard ladder and use this information to make accurate allele calls. The software then prioritizes the allele calls based on several user-defined rules. As a result, the user need only review low-quality data. The validation of this system consisted of an extensive optimization phase and a large concordance phase. During optimization, the rule settings were tailored to minimize the amount of high-quality data viewed by the user. In the concordance phase, a large dataset was typed in parallel with the ABI software Gene Scan and Genotyper (manual review) and TrueAllele (automated review) for comparison of allele calls and sample state assignment. Only one significant difference was discovered out of 2048 samples in the concordance study. In this case, TrueAllele revealed a spike in the profile that was interpreted as a DNA peak by the analyst in Genotyper. TrueAllele was designed to focus the review on poor data and to eliminate the need for complete reanalysis technical review. This validation project proved TrueAllele to be dependable for use at the NYS Convicted Offender DNA Databank.     

Oxycodone intoxication in an infant: accidental or intentional exposure?

A case is presented of a 10 month old male who went into cardiac arrest at a local store. The infant subsequently expired and was autopsied at the Office of the Chief Medical Examiner, State of Maryland. The only remarkable finding was the detection of oxycodone in the postmortem specimens; the blood and liver oxycodone concentrations were 0.6 mg/L and 1.6 mg/kg, respectively. Oxycodone was identified and quantitated by gas chromatography-nitrogen-phosphorus detection and confirmed by full scan electron ionization gas chromatography-mass spectrometry. The medical examiner ruled that the cause of death was oxycodone intoxication, and the manner of death was homicide. The key toxicologic question in this case was whether or not it was reasonable for the infant to be exposed to oxycodone exclusively through breast milk or through an alternate source. It was concluded that, at best, there were serious concerns about the likelihood of drug exposure through consumption of breast milk.     

Forensic analysis of hallucinogenic fungi: a DNA-based approach

Hallucinogenic fungi synthesize two controlled substances, psilocin and psilocybin. Possession of the fungal species that contain these compounds is a criminal offence in North America. Some related species that are morphologically similar, do not contain the controlled substances. Therefore, unambiguous identification of fungi to the species level is critical in determining if a mushroom is illegal. We investigate a phylogenetic approach for the identification of species that contain the psychoactive compounds. We analyzed 35 North American specimens representing seven different genera of hallucinogenic and non-hallucinogenic mushrooms. We amplified and sequenced the internal transcribed spacer region of the rDNA (ITS-1) and a 5' portion of the nuclear large ribosomal subunit of rRNA (nLSU rRNA or 28S). ITS-1 locus sequence data was highly variable and produced a phylogenetic resolution that was not consistent with morphological identifications. In contrast, the nLSU rRNA data clustered isolates from the same species and separated hallucinogen containing and non-hallucinogen containing isolates into distinct clades. With this information, we propose an approach that combines the specificity of PCR detection and the resolving power of phylogenetic analysis to efficiently and unambiguously identify hallucinogenic fungal specimens for legal purposes.     

Fatal diphenhydramine intoxication in infants

Diphenhydramine is an antihistamine available in numerous over-the-counter preparations. Often used for its sedative effects in adults, it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death. Reports of fatal intoxications in young children are rare. We present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child's father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities. We review the literature on diphenhydramine toxicity, particularly as it pertains to small children, and discuss the rationale for treating these cases as fatal intoxications.     

RECOMMENDATIONS OF THE COMMITTEE TO STUDY FAMILY ISSUES IN THE ARIZONA SUPERIOR COURT

Justice 2002, a strategic agenda for the Arizona court system over the next five years, has the goal to build public trust confidence in the Arizona courts. A focus of Justice 2002 is the protection of children, families, and communities. One of the number of projects that have been initiated is the establishment of The Committee to Study Family Issues in the Superior Court (Committee). On October 22, 1997, Chief Justice Thomas A. Zlaket established the Committee and charged the members to: "[E]xamine the manner in which cases involving family issues, including cases involving minor children, presently are processed and determined in the Superior Court,… leading to improvement in the manner in which these cases are resolved in the court system; and report to the Arizona Judicial Council its findings and recommendations…" This article is a summarization of the Final Report presented to the Arizona Judicial Council (AJC) in December, 1998. The reader will find that the report is rather general. The Committee has functioned under the assumption that an implementation committee would be formed to work out the details, should the AJC choose to adopt the recommendation to establish a Family Court in Arizona.