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Fentanyl deaths have increased with availability of transdermal patches. Interpretation of postmortem fentanyl levels may be complicated by postmortem redistribution and absorption of fentanyl from a patch. We applied an unused 100-μg/h fentanyl patch onto the lower abdomen of a decedent with no premortem fentanyl exposure. Ocular fluid, blood, and urine were collected prior to placement, and the decedent was refrigerated for 23 h. Prior to the autopsy, urine, subcutaneous tissue under the patch, and samples from the same anatomic sites were obtained. We observed no fentanyl in any postpatch placement samples (LOD: 0.1 ng/mL for blood and vitreous fluid, 1.0 ng/mL urine, 2.0 ng/g for tissues). Although we observed no postmortem absorption of fentanyl, this was only a single case; therefore, we recommend that patches be removed after receipt of a cadaver before initiation of an autopsy, with the location of removed patch documented.

Background: Pre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy., Materials and Methods: Data were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry., Results: Median values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001)., Conclusion: Consistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposure to hydrogen sulfide (H2S) has been associated with death as well as survival following coma with or without hypoxic brain damage. The release of H2S at a beachfront construction site led to the emergency evaluation and treatment of 37 people, with six admissions and one death. At least one victim, who underwent extensive therapy with hyperbaric oxygen, developed persistent neurological sequelae. Despite increased awareness of the potentially life-threatening consequences of exposure to H2S, significant poisoning continues to occur, even in workplaces where the hazards are well-known and can be avoided. Recommended therapy includes nitrites, hyperbaric oxygen, and supportive care, but documentation of efficacy is lacking. Because patients with chronic neurological sequelae after acute H2S exposure continue to be reported, we suggest that any survivor of H2S poisoning who presents in coma or who manifests objectively verifiable evidence of neurotoxicity on physical examination or lab testing should undergo baseline and annual neurological and neuropsychological testing for at least five years. This approach could standardize and enhance our knowledge of, and ability to detect, the subtle but permanent alterations of central nervous system function that follow H2S exposure.

In decomposed, formalin-fixed, embalmed, exhumed, and some fire-dried cases in which normal blood is unavailable, the usual methods for determination of carboxyhemoglobin saturation frequently fail. To address these specimens, a method utilizing both gas chromatography/mass spectrometric (GC/MS) determination of carbon monoxide (CO) and flame atomic absorption spectrophotometry (FAAS) determination of iron (Fe), in the same specimen, was developed. The method is reported here, along with its application to seven pertinent forsensic death investigations. The CO analytical methodology involves acid liberation of the gas from the specimen aliquot in a headspace vial. After heating and equilibrating, a sample of the headspace vapor is injected into the GC/MS system with a gastight syringe. Quantitation is achieved by standard addition comparison utilizing the ideal gas law equation. Iron is quantified by FAAS analysis of the same aliquot used for the CO determination, following nitric acid digestion. The concentration is determined by comparison to a standard curve. A formula for determining the minimum percent carboxy-heme saturation was derived by using the ratio of the amount of CO to the amount of Fe in the aliquot analyzed. Tissue types analyzed include spleen, liver, muscle, dried blood, and unspecified decomposed tissue.

1. N-Acetylamoxapine is formed nonenzymically in vitro, and in mice, from amoxapine, a tricyclic antidepressant, and aspirin. 2. Formation of acetylamoxapine from amoxapine and aspirin in vitro was maximal at pH 5.0 since this pH optimized reactant solubilities as well as decreasing aspirin hydrolysis. 3. Formation of aceylamoxapine from amoxapine and aspirin in mouse stomachs was rapid, and the pH study indicates that the intestinal pH would favour formation even more. 4. Acetylamoxapine administered to mice produced the same CNS-related signs, leading to death, as with amoxapine, but much larger doses and longer time periods were required to elicit these effects. As brain and liver levels of amoxapine in animals dying from acetylamoxapine administration were less than half those found in animals given lethal doses of amoxapine, the toxicity in mice of acetylamoxapine may not be due solely to deacetylation of acetylamoxapine to the parent compound.

The identification of a novel by-product in the tissue and fluid extracts of a victim of fatal overdoses of the tricyclic antidepressant amoxapine and aspirin is presented. Gas chromatography/mass spectrometry suggested that amoxapine was transacetylated by aspirin to form N-acetylated amoxapine. When standard N-acetylated amoxapine was prepared and subjected to the same analytical testing as extracted tissues and fluids, the metabolite was identified as N-acetylamoxapine. Quantitation of N-acetylamoxapine was obtained by gas chromatography. Concentrations of N-acetylamoxapine compared to those of amoxapine and salicylates in blood, liver, stomach, and small bowel are given.