Michel Piette

Amphetamines as Potential Inducers of Fatalities: A review in the district of Ghent from 1976-2004

Abuse of amphetamine (AMP) and its derivatives, such as 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), 3,4-methylenedioxyethylamphetamine (MDEA, MDE), and 3,4-methylenedioxyamphetamine (MDA) is an important public issue. Fatalities following ingestion of these substances are not infrequent in current forensic practice. The aim of this study was twofold. Firstly, considering the wide range of blood levels reported in fatalities, to provide insight into the interpretation of a quantified blood level and, secondly, to examine and discuss possible causes, mechanisms and manners of death. All the medico-legal files between January 1976 and December 2004 were skimmed through to investigate whether amphetamine and/or derivatives were involved in the fatal outcome. Particularly, in addition to overdose cases due to or including amphetamines, all amphetamines-related fatalities were examined. In addition to AMP, MDMA, MDEA, and MDA, two other amphetamine derivatives, namely 4-methylthioamphetamine (4-MTA) and para-methoxyamphetamine (PMA) were considered. In 34 fatalities, amphetamines were involved and the majority were men, under the age of 25 years. A wide range of blood levels was found: e.g. MDMA blood concentrations in cases of ‘pure’ intoxication were found between 0.27 and 13.51 μg/ml. The age and sex distribution as well as the broad range of quantified amphetamines blood levels were in line with those reported in the literature. In our study group, ‘pure’ intoxications with amphetamines, polydrug overdoses, and the combination of amphetamines use and polytrauma were the most prominent causes of death. Considering the manner of death in these fatalities, unintentional overdoses were most frequent, though suicides, traffic accidents, and criminal offences associated with amphetamines use also accounted for significant percentages. Acute to subacute cardiopulmonary failure was the most frequent mechanism of death, followed by (poly)trauma, mechanical asphyxia, and hyperthermia, respectively. In conclusion, although amphetamines-related fatalities are only a fraction of the total number of fatalities studied at our Department, their contribution to current forensic practice has been increasing during the last few years. As there is still considerable debate as to what level of amphetamines can be toxic or even potentially lethal, it is strongly advisable to interpret the anatomo-pathological findings and the toxicological results together in arriving at a conclusion. This guideline is important in view of the different possible mechanisms of death which implicate quite different survival times following intake of amphetamine and/or its derivatives (e.g. cardiopulmonary complications, hyperthermia).

One fatal and seven non-fatal cases of 4-methylthioamphetamine (4-MTA) intoxication: clinico-pathological findings

Abstract We present a case history involving one fatal and seven survived cases of intoxication with 4-methylthioamphetamine (4-MTA), also called para-methylthioamphetamine (p-MTA) or methylthioamphetamine (MTA), a relatively new amphetamine analogue. Two of the seven survivors required a 24-h-period of observation in hospital. This report proves once again that the new amphetamine designer drugs are not without danger, as is thought by many young people. In addition, individually different subjective reactions are described. Finally, the medico-legal implications of new, as yet unregistered drugs are discussed.

Is vitreous humour useful for the interpretation of 3,4-methylenedioxymethamphetamine (MDMA) blood levels?

Abstract As drug instability and redistribution are factors known to affect the interpretation of post-mortem blood levels, we questioned whether post-mortem vitreous humour concentrations could be useful as predictors for the MDMA load at the time of death. In a first series of in vivo experiments using rabbits, 3,4-methylenedioxy-methamphetamine (MDMA) concentrations in plasma, blood and vitreous humour were studied as a function of time after intravenous (iv) administration of MDMA. Equilibration between the vascular compartment and vitreous humour was attained about 1 h after iv MDMA administration. In a second series of experiments, the post-mortem stability of MDMA in vitreous humour in relation to ambient temperature was investigated. Post-mortem MDMA concentrations in vitreous humour were closer to the ante-mortem blood levels when compared to cardiac blood samples. These preliminary investigations in the rabbit model indicate that measurements of vitreous humour concentrations could also be of interest for predicting the blood concentration at the time of death in humans.

Can routinely combined analysis of glucose and lactate in vitreous humour be useful in current forensic practice

To confirm and extend previous research concerning glucose and lactate in vitreous humour, we investigated a randomly selected study population of 271 forensic cases. On the whole, we find our results agree with those of previous studies, but we add certain observations. First, when we considered the sum value of glucose and lactate in the vitreous humour, we found that not only diabetes patients are included in the higher range group (values > or = 430 mg%): intensive reanimation or prolonged or intense agony should also be taken into account. Indeed, when we split our study group into acute agony and prolonged agony subgroups, we noticed a statistically significant difference; persons dying after protracted agony showed a higher sum value, which can be explained in terms of biophysical dynamics. Second, a positive correlation was found between the lactate and the sum values on one hand, and the postmortem interval on the other. However, the vitreous glucose, lactate, and sum values are so dispersed that a precise determination of the postmortem interval cannot be obtained on the basis of these parameters. Additionally, we compared several causes of death, but unfortunately, we did not manage to reveal that some causes of death were specifically limited to high or low concentrations. Indeed, the statistically significant differences in sum values could easily be explained by factors such as intensity of agony, reanimation attempts, or iatrogenic interventions (e.g., glucose infusions). Nonetheless, when the death scene as a whole is unclear or confusing, analysis of the vitreous humour can provide some insights, provided that the other autopsy findings are also taken into consideration.

Determination of strontium in human whole blood by ICP-AES

The determination of strontium in human blood samples by ICP-AES is described. For the analysis no chemical separations were required after microwave destruction. A mean value of 11.4 +/- 0.83 micrograms/l is found for normal whole blood. The limit of detection of the method is 0.3 microgram/l. As a possible application the enhancement of the strontium level in blood of human beings who died from drowning is examined.

Deaths in the Bath

A retrospective survey of fatalities in the bath during the period 1934–83 is presented. The deaths were investigated in the Department of Legal Medicine at the University of Ghent. More than half of the deaths were caused by carbon monoxide intoxication (52 per cent). The remaining deaths were due to suicide (20 per cent), natural causes, e.g. epilepsy or cardiac arrest (8.5 per cent) or to accidental drowning, e.g. unattended infants (8.5 per cent). We found two cases of homicide; one being the murder of a child, the other a case of manual strangulation, the body having subsequently been placed in the bath. In one unusual case the autopsy was not performed until after the body had been buried for eight months. Although murder was suspected, neither the autopsy nor toxicological findings revealed the exact cause of death.

Immunohistochemical demonstration of the amphetamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) in human post-mortem brain tissues and the pituitary gland

Abuse of amphetamine derivatives such as 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) is an important issue in current forensic practice and fatalities are not infrequent. Therefore, we investigated an immunohistochemical method to detect the amphetamine analogues MDMA and MDA in human tissues. For the staining procedure, the Catalysed Signal Amplification (CSA) method using peroxidase (HRP) provided by Dako® and specific monoclonal antibodies were used. Appropriate controls for validation of the technique were included. The distribution of these designer drugs was studied in various brain regions including the four lobes, the basal ganglia, hypothalamus, hippocampus, corpus callosum, medulla oblongata, pons, cerebellar vermis and, additionally, in the pituitary gland. A distinct positive reaction was observed in all cortical brain regions and the neurons of the basal ganglia, the hypothalamus, the hippocampus and the cerebellar vermis but in the brainstem, relatively weak staining of neurons was seen. The reaction presented as a mainly diffuse cytoplasmic staining of the perikaryon of the neurons, and often axons and dendrites were also visualised. In addition, the immunoreactivity was present in the white matter. In the pituitary gland, however, distinct immunopositive cells were observed, with a prominent heterogeneity. The immunohistochemical findings were supported by the toxicological data. This immunostaining technique can be used as evidence of intake or even poisoning with MDMA and/or MDA and can be an interesting tool in forensic practice when the usual samples for toxicological analysis are not available. Furthermore, this method can be used to investigate the distribution of these substances in the human body.

Tissue distribution of trichloroethylene in a case of accidental acute intoxication by inhalation.

This article describes the toxicological findings in a fatality due to an accidental inhalation of trichloroethylene which took place during wall coating of a poorly ventilated well using trichloroethylene. The man was wearing protective clothing and a mouthmask with adsorbent. He was found dead on the floor of the well 5h after descending. Trichloroethylene was added to the mortar to enhance drying. Identification and quantitation of trichloroethylene in the postmortem samples (blood, lung, liver, kidney, stomach content and bile) and identification of its metabolite trichloroacetic acid in urine was performed using static headspace gas chromatography with mass spectrometric detector. The compounds were separated on a CP-SIL 5CB Low Bleed/MS column using n-butanol as internal standard. The method was linear over the specific range investigated, and showed an accuracy of 104% and an intra-day precision of 11%. Trichloroethylene concentrations of 84mg/l in subclavian blood, 40mg/l in femoral blood, 72mg/kg in liver, 12mg/kg in kidney, 78mg/kg in stomach content, 104mg/l in bile and 21mg/kg in lung were found. Trichloroacetic acid was identified in the urine.

Endocardial fibroelastosis as a cause of sudden unexpected death.

We present a case of primary endocardial fibroelastosis (EFE) which had been diagnosed in a 16-year-old girl who died suddenly and unexpectedly. This exceptional cause of death in adolescence led to a short literature review comparing our findings with previous medicolegal reports.

Hospital bed related fatalities: a review.

All medico-legal cases of unexpected death during hospitalisation or accommodation in rest or nursing homes, which were investigated at the Department of Forensic Medicine during a 30-year-period, have been reviewed. In the majority of cases, the fatal outcome was bedrail or restraint related, but falls out of bed or from a patient hoist lift can also trigger a death. As expected, the manner of death was mainly accidental. In about 70% of cases, mechanical asphyxia (such as smothering and thoraco-abdominal compression) was substantiated as the mechanism of death. A substantial number of the patients had important medical antecedents, such as cognitive impairment due to cerebro-vascular accidents. In about half of the cases, human negligence was clearly related to the event whereas in only 15% of cases was there a technical mistake. We believe that some sudden and unexpected fatalities, due to physical restraint or other devices (such as a patient hoist lift), are under-reported because of the medico-legal implications. However, reporting such events could induce better precautions and prevent recurrences. Therefore, this study may be important not only for forensic pathologists, but also for a larger group of social workers.