RESUMO
BACKGROUND: Autologous facial fat grafting has gained popularity in recent years and is considered to be safe. This paper presents the case of a patient who died due to massive cerebral microfat embolism after facial fat grafting. OBJECTIVES: The aim of this study was to raise awareness and provide more evidence on the prevention and treatment of this potentially lethal complication of facial fat grafting. METHODS: A detailed report was made of the case. Two online databases were searched for similar cases of facial fat embolism resulting in neurologic and/or visual symptoms. Thereafter a literature search was conducted to verify the etiology, current treatment options, and preventive measures. RESULTS: Forty-nine cases with similar events were found in the literature. The most common injected area was the glabella (36.1%), and an average of 16.7 mL fat was injected. The main complications were visual impairment, with 88.5% of cases resulting in permanent monocular blindness, and neurologic symptoms, some of which never fully recovered. Including the present patient, 7 cases were fatal. Fat embolism can occur in the veins and arteries of the face. Two possible pathways for fat embolism exist: the macroscopic, mechanical pathway with immediate signs, and the microscopic, biochemical pathway with delayed symptoms. Mechanical embolectomy and corticosteroids are suggested treatment options but evidence for their efficacy is lacking. Several different preventive measures are described. CONCLUSIONS: Although facial fat grafting is considered a safe procedure, one should be aware of the risk of fat embolism. Underreporting of this adverse event is likely. With no effective treatment and often detrimental outcomes, preventive measures are of utmost importance to improve patient safety.
Assuntos
Tecido Adiposo , Embolia Gordurosa , Tecido Adiposo/transplante , Embolia Gordurosa/etiologia , Embolia Gordurosa/terapia , Face/cirurgia , Testa , Humanos , Transplante Autólogo/efeitos adversosRESUMO
Murder followed by suicide (M-S) is a rare phenomenon that has been studied in several countries. Previous studies show that offenders of M-S are predominately men who live in an intimate relationship. Amorous jealousy is often the trigger to commit M-S. Shooting is the most common way to kill a partner and/or children. In general, women are likely to become victims. The aim of this study was to identify M-S and detect patterns of M-S in the district of Ghent and the surrounding areas, since no research on this event was conducted in Belgium. Over a period of 75 years, a total of 80 M-S incidents was recorded involving 176 individuals. Eighty-six percent of the offenders were males and 14% were females. Murder-suicides were mostly completed with firearms. The main motive for offenders to execute M-S is amorous jealousy (56%), followed by familial, financial, or social stressors (27%). In addition, three types of M-S were selected (e.g., spousal murder-suicides, filicide-suicides, and familicides-suicides). Our results suggest differences in these types of M-S in which younger couples' intentions were amorous jealousy; as for older couples the prominent motive was mercy killing; most likely women killed their children and only men committed familicides. Finally a study of the evolution during this period was carried out.
Assuntos
Homicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Adolescente , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Causas de Morte , Depressores do Sistema Nervoso Central/sangue , Etanol/sangue , Feminino , Patologia Legal , Homicídio/psicologia , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Suicídio/psicologia , Ferimentos e Lesões/mortalidade , Adulto JovemRESUMO
The smoking cessation agent varenicline acts as a partial agonist on α(4)ß(2) nicotinic acetylcholine receptors. Although debated, several reports have linked varenicline therapy to an increased risk of suicidal thoughts and/or suicide. In addition, several non-fatal overdose cases have been reported. In this report, we utilised a sample preparation procedure suitable for postmortem samples and gas chromatography coupled to mass spectrometry to analyse samples obtained from a suicidal case in which ingestion of an overdose of varenicline had occurred. Extremely high concentrations of varenicline (>250 ng/ml) were detected in the blood of the deceased, in addition to high concentrations in urine and vitreous humour. To the best of our knowledge, similar high concentrations have not been reported yet. Although, with respect to the mechanism of death in this case, confounding factors were concomitant ethanol consumption and, importantly, potentially fatal hypothermia, this is the first report of a fatality associated with the ingestion of an overdose of varenicline.
Assuntos
Benzazepinas/intoxicação , Overdose de Drogas , Agonistas Nicotínicos/intoxicação , Quinoxalinas/intoxicação , Suicídio , Adulto , Benzazepinas/análise , Depressores do Sistema Nervoso Central/análise , Etanol/análise , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hipotermia/patologia , Masculino , Agonistas Nicotínicos/análise , Quinoxalinas/análise , Vareniclina , Corpo Vítreo/químicaRESUMO
The determination of the survival time after a crime as well as the concomitant physical and mental load of the victim is an important task for the forensic pathologist. The heat shock protein, ubiquitin, exerts an essential role in the cellular response to stress. We aimed to investigate the usefulness of the ubiquitin expression in the locus coeruleus as a marker for the evaluation of agonal stress. Is the amount of ubiquitin in this brain locus an indication of the length and/or intensity of the agonal period following various causes of death? The immunohistochemical (IHC) expression of ubiquitin is examined in formalin-fixed, paraffin-embedded slides of the human locus coeruleus (n = 48). The evaluation of the IHC staining is blindly performed, prior to the study of the medico-legal files. According to the length of agony, a division into subgroups is made. Three possible IHC staining patterns are observed: a staining of the neuronal nucleus or the cytoplasm or both. In addition, the number of neurons with ubiquitin expression per µm(2) is calculated in each locus coeruleus. Significant differences in the number of ubiquitin-immunoreactive neurons are noticed with respect to the length of the agony: A higher density of positive neurons is seen in case of a pronounced and extended death struggle.
Assuntos
Morte , Locus Cerúleo/metabolismo , Estresse Fisiológico , Ubiquitina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Medicina Legal , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/patologia , Ubiquitina/ultraestrutura , Adulto JovemRESUMO
In this paper, the distribution and redistribution of the amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is brought into focus. Animal experimental data were compared with internationally reported MDMA-related human fatalities: in general, these turned out to be parallel with each other. Due to its inherent properties (e.g. significant volume of distribution), MDMA is liable to postmortem redistribution. Indeed, very high concentrations have been found in cardiac blood and tissues located centrally in the body (blood-rich organs such as lungs and liver in particular). This confirms that post-mortem redistribution due to diffusion from higher to lower concentration can easily take place, mainly at longer post-mortem intervals and when putrefaction occurs. Therefore, we can conclude that for post-mortem quantitation of amphetamine and derivatives, and MDMA in particular, peripheral blood sampling (e.g. femoral vein) remains compulsory. However, if the latter is impossible, MDMA quantification in a few alternative matrices such as vitreous humour and iliopsoas muscle may provide additional information to come to a reliable conclusion. Furthermore, it should be stressed that--at present--it is impossible to estimate the individual susceptibility to the various possible adverse effects of MDMA, which implies that it is impossible to provide a "safe" or "therapeutic" blood MDMA level. Therefore, in current forensic practice, the post-mortem pathological and toxicological findings should form an entity in order to draw a well-grounded conclusion.
Assuntos
N-Metil-3,4-Metilenodioxianfetamina/sangue , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , Mudanças Depois da Morte , Animais , Humanos , Taxa de Depuração Metabólica , Especificidade de Órgãos , Especificidade da Espécie , Distribuição TecidualRESUMO
The party drug 3,4-methylenedioxymethamphetamine -better known as MDMA or ecstasy- has numerous effects on the human body, characterized by a rush of energy, euphoria and empathy. However, also a multitude of toxic/neurotoxic effects have been ascribed to MDMA, based upon case reports and studies in animals. Given the intrinsic difficulties associated with controlled studies in human beings, most of our insights into the biology of MDMA have been gained through animal studies. The vast majority of these studies utilizes a pharmacological approach to elucidate the mechanisms by which MDMA exerts its effects. Advances in genetics during the last decade have led to the development of several mouse models (transgenic or knockout) that have greatly contributed to our understanding of MDMA biology. This review provides an overview of these genetically modified animal models, in the light of some characteristic effects of MDMA, e.g. hyperlocomotion, neurotoxicity, hyperthermia, behaviour or rewarding. Without a shadow of a doubt, the next decade will bring many more advanced animal models, such as mice with site-specific deletion or rescue of genes and more genetically modified rat models. These models will further improve our knowledge on the pharmacology and toxicity of MDMA and, possibly, may assist in developing therapies coping with potential damage in abusers of MDMA and other drugs, as well as in patients suffering from specific neuronal pathologies.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Animais , Alucinógenos/toxicidade , Humanos , Camundongos , Camundongos Transgênicos , Ratos , Especificidade da EspécieRESUMO
A gas chromatographic-mass spectrometric (GC-MS) method in positive ion chemical ionization mode in combination with a solid phase extraction was optimized for new-generation antidepressants and their metabolites in postmortem blood, brain tissue, and hair. Twelve antidepressants and their active metabolites (i.e., mirtazapine, viloxazine, venlafaxine, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine, desmethylfluoxetine, desmethylmianserin, desmethylmirtazapine, desmethylsertraline, desmethylmaprotiline, desmethylcitalopram, and didesmethylcitalopram) could be quantified. In this article, in addition to the validation of the GC-MS method, four postmortem cases are discussed to demonstrate the usefulness of the described method in forensic toxicology. In these cases, sertraline, fluoxetine, citalopram, and trazodone in combination with their active metabolites were quantified. Blood concentrations ranged from subtherapeutic to toxic concentrations, while brain to plasma ratios ranged from 0.8 to 17. Hair concentrations ranged from 0.4 to 2.5 ng/mg depending on the compound and hair segment.
Assuntos
Antidepressivos/análise , Química Encefálica , Cromatografia Gasosa-Espectrometria de Massas , Cabelo/química , Adulto , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Feminino , Toxicologia Forense , Humanos , MasculinoRESUMO
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.
Assuntos
Causas de Morte/tendências , Mortalidade Hospitalar/tendências , Acidentes por Quedas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica , Pré-Escolar , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Restrição Física/estatística & dados numéricosRESUMO
In this manuscript, a newly identified compound, 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDM or also called MDDA), was quantified. The substance was identified in the biological specimens of a 31-year-old man who died following a massive 3,4-methylenedioxymethamphetamine (MDMA) overdose. In addition, the postmortem distribution of the identified substance in various body fluids and tissues was evaluated. For MDDM quantitation, a formerly reported and validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method was adapted. The following quantitative results of the MDDM quantitation were obtained: Femoral blood, aorta ascendens, and right atrial blood contained 2.5, 21.7, and 11.6 ng MDDM/ml, respectively. In left and right pleural fluid and pericardial fluid, concentrations of 47.0, 21.7, and 31.9 ng/ml, respectively, were found. MDDM levels in urine, bile, and stomach contents were 42.4, 1,101, and 1,113 ng/ml, respectively. MDDM concentrations in lungs, liver, kidney, and left cardiac muscle ranged from 12.8 to 39.8 ng/g, whereas these levels were below the limit of quantitation (< LOQ) in right cardiac and iliopsoas muscle. In conclusion, for the first time, MDDM was unambiguously identified in a fatal MDMA overdose. MDDM was probably present as a synthesis by-product or impurity in the MDMA tablets, which were taken in a huge amount by the victim, or MDDM was ingested separately and prior to the MDMA overdose. A third option, i.e., the eventual formation of MDDM as a result of postmortem methylation of MDMA by formaldehyde, produced by putrefaction processes or during storage under frozen conditions, is also discussed. The MDDM levels, substantiated in various body fluids and tissues, are in line with the distribution established for other amphetamine derivatives and confirm that peripheral blood sampling, such as that of femoral blood, remains the "golden standard".
Assuntos
Alucinógenos/farmacocinética , Alucinógenos/intoxicação , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Adulto , Overdose de Drogas , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Alucinógenos/química , Humanos , Masculino , Estrutura Molecular , N-Metil-3,4-Metilenodioxianfetamina/química , Detecção do Abuso de Substâncias , Distribuição TecidualRESUMO
We describe a homicide complicated by an aconitine poisoning, which was initially thought to be a strangulation case. Routine toxicological analyses demonstrated only a small amount of alcohol in the blood and the urine. The case could not be clarified until 5 years after the event. A new element in the investigation made the wife the prime suspect, and finally, after thorough interrogation, she confessed her crime. She had mixed a decoction of three plants of Aconitum with red wine. Additional toxicological analyses, using the liquid chromatography-tandem mass spectrometry (LC-MS-MS) technique demonstrated 810 ng/ml of aconitine in urine, 6.5 ng/g in liver and 1.3 ng/g in the kidneys. Even though aconitine poisoning is still rare in Europe, it should be taken into account in suicides and homicides, particularly in unclarified cases.
Assuntos
Aconitina/intoxicação , Aconitum/intoxicação , Adjuvantes Imunológicos/intoxicação , Homicídio , Aconitina/análise , Adjuvantes Imunológicos/análise , Cromatografia Líquida , Medicina Legal , Humanos , Rim/química , Fígado/química , Masculino , Espectrometria de Massas , Pessoa de Meia-IdadeRESUMO
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 microg/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).
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/mortalidade , Anfetaminas/intoxicação , Estimulantes do Sistema Nervoso Central/intoxicação , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Autopsia , Bélgica/epidemiologia , Biometria , Causas de Morte , Overdose de Drogas/mortalidade , Medicina Legal , HumanosRESUMO
Investigation of bodies recovered out of water comprises an important proportion of the medico-legal requests. However, the key question whether the victim died due to "true" drowning can frequently not easily be solved. In addition, the diagnosis of hydrocution is even more difficult. In this manuscript, a review of reported diagnostic methods is discussed in order to provide guidelines, which can be used in current forensic practice. In particular, the (dis)advantages of various biological and thanato-chemical methods, described in literature during the last 20 years, will be confronted with the classical techniques such as the detection of diatoms and algae. Indeed, the diatom test is still considered as the "golden standard". In conclusion, the ideal diagnostic test as definite proof for drowning still needs to be established. At present, the combination of the autopsy findings and the diatom test is a good compromise in arriving at a conclusion. Additional biochemical and technical methods could be useful. Unfortunately, the cost-benefit analysis in current practice could be hard to defend. However, the importance of this subject asks for further scientific approaches and research.
Assuntos
Autopsia , Afogamento/diagnóstico , Autopsia/métodos , Causas de Morte , Afogamento/patologia , Medicina Legal , HumanosRESUMO
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy" is a currently used or abused designer drug and fatalities are frequently encountered in forensic practice. However, the question remains open whether an MDMA blood level can be toxic or even potentially lethal. In order to provide insight in the interpretation of a detected MDMA concentration, the distribution of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) in various body fluids and tissues was studied and discussed in two different fatalities. Apart from peripheral blood samples (such as femoral and subclavian blood), various blood samples obtained centrally in the human body and several body fluids (such as vitreous humour) were examined. In addition, various tissues such as cardiac muscle, lungs, liver, kidneys, and brain lobes were analysed. In contrast to the peripheral blood levels, high MDMA and MDA levels were found in cardiac blood and the majority of the organs, except for the abdominal adipose tissue. The high concentrations observed in all lung lobes, the liver and stomach contents indicate that post-mortem redistribution of MDMA and MDA into cardiac blood can occur and, as a result, blood sampled centrally in the body should be avoided. Therefore, our data confirm that peripheral blood sampling remains "the golden standard". In addition, a distinct difference in peripheral blood MDMA concentrations in our two overdose cases was established (namely 0.271 and 13.508 microg/ml, respectively). Furthermore, our results suggest that, if a peripheral blood sample is not available and when putrefaction is not too pronounced, vitreous humour and iliopsoas muscle can be valuable specimens for toxicological analysis. Finally, referring to the various mechanisms of death following amphetamine intake, which can result in different survival times (e.g. cardiopulmonary complications versus hyperthermia), the anatomo-pathological findings and the toxicological results should be considered as a whole in arriving at a conclusion.
Assuntos
3,4-Metilenodioxianfetamina/farmacocinética , Alucinógenos/farmacocinética , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , Mudanças Depois da Morte , 3,4-Metilenodioxianfetamina/análise , 3,4-Metilenodioxianfetamina/intoxicação , Adolescente , Adulto , Bile/química , Cromatografia Líquida de Alta Pressão , Overdose de Drogas , Medicina Legal/métodos , Alucinógenos/análise , Alucinógenos/intoxicação , Humanos , Rim/química , Fígado/química , Pulmão/química , Masculino , Miocárdio/química , N-Metil-3,4-Metilenodioxianfetamina/análise , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Hipófise/química , Músculos Psoas/química , Estômago/química , Distribuição Tecidual , Corpo Vítreo/químicaRESUMO
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.
Assuntos
Solventes/farmacocinética , Solventes/intoxicação , Tricloroetileno/farmacocinética , Tricloroetileno/intoxicação , Acidentes , Administração por Inalação , Adulto , Bile/química , Cáusticos , Cromatografia Gasosa/métodos , Espaços Confinados , Humanos , Rim/química , Fígado/química , Pulmão/química , Masculino , Espectrometria de Massas , Estômago/química , Distribuição Tecidual , Ácido Tricloroacético/urina , Tricloroetileno/sangueRESUMO
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.
Assuntos
3,4-Metilenodioxianfetamina/metabolismo , Encéfalo/metabolismo , Alucinógenos/metabolismo , N-Metil-3,4-Metilenodioxianfetamina/metabolismo , Hipófise/metabolismo , Detecção do Abuso de Substâncias/métodos , 3,4-Metilenodioxianfetamina/sangue , 3,4-Metilenodioxianfetamina/intoxicação , Adulto , Cromatografia Líquida de Alta Pressão , Evolução Fatal , Cromatografia Gasosa-Espectrometria de Massas , Alucinógenos/sangue , Alucinógenos/química , Alucinógenos/intoxicação , Humanos , Imuno-Histoquímica , Masculino , N-Metil-3,4-Metilenodioxianfetamina/sangue , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Distribuição TecidualRESUMO
Post-mortem redistribution is known to influence blood and tissue levels of various drugs. An animal model was used in an attempt to elucidate this problem for the amphetamine analogue, 3,4-methylenedioxymethamphetamine (MDMA). Rabbits received 1 mg/kg MDMA intravenously (iv) and were killed 2 h later in order to simulate the state of complete distribution in the body. MDMA and 3,4-methylenedioxyamphetamine (MDA) concentrations were determined in blood, urine, bile, vitreous humour, and various tissues (eye globe walls, brain, cardiac muscle, lungs, liver, kidneys, iliopsoas muscle and adipose tissue) using a high pressure liquid chromatographic (HPLC) procedure with fluorescence detection. In the first group (control group, sampling immediately post mortem) considerable MDMA concentrations were found in the brain and both lungs. In addition, our data indicate the elimination of MDMA by hepatic biotransformation and excretion via the bile. When the animals were preserved either 24 or 72 h post mortem (second group), an increase of MDMA and MDA levels in the liver and the eye globe walls was noticed. In the lungs, on the other hand, they tended to decline as a function of increasing post-mortem interval. MDMA levels in cardiac and iliopsoas muscle were fairly comparable and remained stable up to 72 h after death. In the third group, ligation of the large vessels around the heart took place immediately post mortem, but significant differences in blood and tissue MDMA concentrations between rabbits of group 2 and 3 could not be demonstrated. We therefore conclude that post-mortem redistribution of MDMA at the cellular level (viz. by pure diffusion gradient from higher to lower concentrations) is more important than its redistribution via the vascular pathway. Finally, MDA levels were relatively low in all samples, thus indicating that this is not a major metabolite in the rabbit, at least within the first 2 h after administration.
Assuntos
N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , Mudanças Depois da Morte , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Modelos Animais , N-Metil-3,4-Metilenodioxianfetamina/sangue , Coelhos , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Distribuição TecidualRESUMO
Drug concentrations in autopsy samples can also be influenced by post-mortem gastric diffusion when the stomach contains a substantial amount of the drug or by diffusion from the trachea when agonal aspiration or post-mortem regurgitation of vomit occurs. This was studied in a rabbit animal model in which MDMA solutions were infused post mortem either in the trachea or in the stomach. At 24, 48 or 72 h post mortem, samples including cardiac blood, vitreous humour, urine, bile, gastric content and several tissues were taken for toxicological analysis. After post-mortem tracheal infusion, MDMA can easily diffuse not only into the lungs but also in great quantities into the cardiac blood and, to a lesser extent, into the cardiac muscle. MDMA was also found in the closely adjacent diaphragm and in the upper abdominal organs, including the liver and the stomach. Following post-mortem infusion into the stomach, considerable MDMA levels were found in cardiac blood and muscle, both lungs, diaphragm and liver tissue when the solution was concentrated nearby the lower oesophageal sphincter. However, when the MDMA solution was present deeper in the stomach, MDMA levels were high in the spleen and the liver and relatively low in cardiac blood and muscle. In both experiments, MDA levels in most tissues were low or below the limit of quantitation, but were substantial in cardiac blood and muscle, lungs and diaphragm, indicating that MDMA can be metabolised to MDA after death. These results in the rabbit model indicate that the diffusion of MDMA out of the stomach content, or due to aspirated vomit and gastro-oesophageal reflux can lead to considerable post-mortem redistribution and thus should be taken into account in current forensic practice in order to draw the right conclusions when a peripheral blood sample is not available.
Assuntos
N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , Mudanças Depois da Morte , Estômago/fisiologia , Traqueia/fisiologia , Animais , Modelos Animais , N-Metil-3,4-Metilenodioxianfetamina/sangue , Coelhos , Sensibilidade e Especificidade , Distribuição TecidualRESUMO
In this study, regional tissue distributions of the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and its metabolite 3,4-methylenedioxyamphetamine (MDA) in a fatal overdose are presented. Quantitation of MDMA and MDA levels occurred in blood samples taken centrally (right and left heart and main adjacent great vessels) and peripherally (subclavian and femoral blood). In addition, MDMA and MDA concentrations were determined in cardiac and iliopsoas muscle, both lungs, liver, both kidneys, spleen, the four brain lobes, cerebellum and brainstem, and adipose tissue. Finally, MDMA and MDA levels were determined in serum, vitreous humor, urine, and bile. For all samples, a fully validated high-pressure liquid chromatography procedure with fluorescence detection was used. The found substances were also identified with liquid chromatography-tandem mass spectrometry. Our data confirm that blood sampling from an isolated peripheral vein is recommended for MDMA and MDA. In addition, the vitreous humor MDMA level indicates that this fluid can be an interesting alternative when a suitable blood sample is missing. Considering the substantial differences in concentrations in blood samples taken from various sites in the body and the high levels in some tissues (e.g., in liver), we concluded that the influence of postmortem redistribution should be taken into account in the interpretation of toxicological data when an appropriate peripheral sample cannot be obtained or when blood samples are not available because of putrefaction.
Assuntos
3,4-Metilenodioxianfetamina/farmacocinética , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , 3,4-Metilenodioxianfetamina/intoxicação , Adulto , Cromatografia Líquida de Alta Pressão , Evolução Fatal , Humanos , Masculino , N-Metil-3,4-Metilenodioxianfetamina/intoxicação , Espectrometria de Massas por Ionização por Electrospray , Corpo Vítreo/químicaRESUMO
This report describes a fully elaborated and validated method for quantitation of the hydrocarbons n-propane, iso-butane, and n-butane in blood samples. The newly developed analytical procedure is suitable for both emergency cases and forensic medicine investigations. Its practical applicability is illustrated with a forensic blood sample after acute inhalative intoxication with lighter fluid; case history and toxicological findings are included. Identification and quantitation of the analytes were performed using static headspace extraction combined with gas chromatography-mass spectrometry. In order to reconcile the large gas volumes injected (0.5 mL) with the narrowbore capillary column and thus achieve preconcentration, cold trapping on a Tenax sorbent followed by flash desorption was applied. Adequate retention and separation were achieved isothermally at 35 degrees C on a thick-film capillary column. Sample preparation was kept to a strict minimum and involved simply adding 2.5 microL of a liquid solution of 1,1,2-trichlorotrifluoroethane in t-butyl-methylether as an internal standard to aliquots of blood in a capped vial. Standards were created by volumetric dilution departing from a gravimetrically prepared calibration gas mixture composed of 0.3% of n-propane, 0.7% of iso-butane, and 0.8% of n-butane in nitrogen. In the forensic blood sample, the following concentrations were measured: 90.0 microg/L for n-propane, 246 microg/L for iso-butane, and 846 microg/L for n-butane.