Derrick J. Pounder

Four deaths related to the drug 4-methylmethcathinone (mephedrone) are reported. Qualitative and quantitative analysis of mephedrone was performed by high-performance liquid chromatography-diode-array detection. Of the four deaths, one was attributed to the adverse effects of mephedrone, with cardiac fibrosis and atherosclerotic coronary artery disease as a contributing factor. A 49-year-old female insufflated mephedrone; analysis disclosed mephedrone in femoral venous blood (0.98 mg/L). The second death was attributed solely to mephedrone. A 19-year-old male took mephedrone as well as alcohol and "ecstasy"; analysis disclosed mephedrone (2.24 mg/L femoral venous blood) and 3-trifluoromethylphenylpiperazine (3-TFMPP). In the third fatality, a 55-year-old female was found dead in bed; the death was attributed to the combined effects of mephedrone and methadone. Analysis of femoral venous blood revealed the prescribed drugs diazepam, nordiazepam, olazepine, and chlorpromazine metabolites together with methadone (0.3 mg/L) and mephedrone (0.13 mg/L). In the fourth case, a 17-year-old male car driver was involved in a vehicular collision and died of multiple blunt force injuries. Analysis revealed mephedrone in femoral venous blood (0.24 mg/L).

A 55-year-old bat conservationist was admitted to Ninewells Hospital, Dundee, Scotland, on November 11, 2002, with an acute haematemesis. He gave a 5-day history of pain and paraesthesia in the left arm, followed by increasing weakness of his limbs with evidence of an evolving encephalitis with cerebellar involvement. The patient had never been vaccinated against rabies and did not receive postexposure treatment. Using a hemi-nested reverse transcriptase-polymerase chain reaction (RT-PCR), saliva samples taken intravitam from different dates proved positive for rabies. A 400-bp region of the nucleoprotein gene was sequenced for confirmation and identified a strain of European bat lyssavirus (EBLV) type 2a. The diagnosis was confirmed using the fluorescent antibody test (FAT) and by RT-PCR on three brain samples (cerebellum, medulla, and hippocampus) taken at autopsy. In addition, a mouse inoculation test (MIT) was performed. Between 13 and 17 days postinfection, clinical signs of a rabies-like illness had developed in all five inoculated mice. Brain smears from each infected animal were positive by the FAT and viable virus was isolated. This fatal incident is only the second confirmed case of an EBLV type-2 infection in a human after exposure to bats.

A 25-year-old female died from a suicidal overdose of imipramine, acetaminophen, codeine, diphenhydramine, and ethanol. Blood samples from ten segregated arterial and venous sites, twenty-four tissue samples, cerebrospinal fluid, vitreous humor, and bile were analyzed. Imipramine and desipramine, which were highly concentrated in the liver and lungs, each showed marked site dependent differences in blood concentrations. The highest concentrations were in pulmonary venous blood and the lowest in peripheral venous blood. Imipramine concentrations in the ten blood samples differed by as much as 760% (range 2.1 to 16.0 mg/L). Blood desipramine concentrations ranged from 1.4 to 10.6 mg/L. In contrast, blood concentrations of acetaminophen differed by less than 20% (55 to 65 mg/L) and blood ethanol concentrations ranged from 151 to 175 mg/100 mL. Blood concentrations of diphenhydramine ranged from 0.34 to 2.07 mg/L and codeine from 0.33 to 0.89 mg/L. The data illustrates that a marked site dependent variability in postmortem blood concentrations exists for some drugs but not others.

We explored postmortem ethanol diffusion from the stomach using a human cadaver model with multiple blood site sampling. In all, 400 ml of alcohol solution (5%, 10%, 20%, or 40% methanol and ethanol weight/volume in water) was introduced into the stomach by oesophageal tube. Blood methanol concentrations correlated with ethanol concentrations (methanol range, 1–676 mg%; ethanol range, 1–531 mg%; r = 0.9973). The pattern of ethanol diffusion showed marked between-case variability. Typically, concentrations were highest in pericardial fluid and, in decreasing order, in left pulmonary vein, aorta, left heart, pulmonary artery, superior vena cava, inferior vena cava, right heart, right pulmonary vein, and femoral vein. Diffusional flux was broadly proportional to the concentration of ethanol used. It was time-dependent (as assessed by 24-h and 48-h sampling) and markedly inhibited by refrigeration at 4°C. After gastric instillation of 400 ml of 5% solution for 48 h at room temperature in paired cadavers, ethanol concentrations (mg%) were as follows: pericardial fluid 135, 222; aorta 50, 68; left heart 77, 26; right heart 41, 28; femoral vein 0. Using a 10% solution, ethanol concentrations (mg%) were as follows: pericardial fluid 401, 255; aorta 129, 134; left heart 61, 93; right heart 31, 41; femoral vein 5, 7. Introducing 50 ml of 10% alcohol solution into the oesophagus after oesophagogastric junction ligation produced similar aortic blood ethanol concentrations. This suggests that postmortem gastro-oesophageal reflux and diffusion from the oesophagus is the mechanism of artefactual elevation of aortic blood ethanol. Introducing 150 ml of 10% alcohol solution directly into the lesser sac resulted in marked reduction of diffusion into the pericardial sac. This finding suggests that close apposition of the gastric fundus against the diaphragm and a large gastric volume are significant factors that influence diffusional flux. Deflation and anchoring of the left lung at the apex had little effect, suggesting that diffusion into the left pulmonary vein is via the pericardial fluid rather than the lung substance. In nine fatalities with known alcohol consumption shortly before death, the highest observed stomach contents ethanol concentration was 8.7%. Two cases showed marked variations in blood ethanol concentrations in 10 samples with ranges (mg%) of 97–238 and 278–1395; pericardial fluid 1060 and 686; vitreous humour 34 and 225; and stomach contents 300 ml at 5.5% and 85 ml at 1.9%, respectively. We conclude that postmortem diffusion of ethanol from the stomach into the blood is a potentially significant artefact in a small minority of cases. Both aortic and cardiac chamber blood may be affected by this artefact. Between-case and within-case variability causes unpredictability. For postmortem ethanol analysis, the optimum sampling technique appears to be aspiration by needle puncture of the femoral vein (or external iliac vein) after cross-clamping proximal to the sampling site.