Nutmeg (myristicin) poisoning--report on a fatal case and a series of cases recorded by a poison information centre

In literature, cases of nutmeg abuse have been described repeatedly, but only one fatal case of poisoning was reported [1]. In the present case, myristicin (4 microg/ml) was detected for the first time in the postmortal serum of a 55-year-old woman. Identification was achieved with the aid of UV-VIS spectroscopy and TLC; for quantification, HPLC was used. Because also flunitrazepam (0.072 microg/ml) was found, death had probably been due to the combined toxic effect of both substances. From 1996 to 1998, in a series of cases, seven poisonings with nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed. In one of these cases, a myristicin blood level of 2 microg/ml was measured 8h after ingestion of two to three tablespoonful of nutmeg powder (approx. 14-21 g, or 280-420 mg/kg).     

Lethal mixed intoxication with propofol in a medical layman

The authors report on a drug fatality of a 21-year-old man with a propofol (2,6-di-isopropylphenol) dependency. Propofol was detected in tissues and body fluids using SPME-GC/MS methods. The postmortem concentrations of propofol were 364 ng/ml in urine, 71 ng/ml in heart blood and 79 ng/ml in femoral blood. The drug addict had only an autodidactic medical knowledge, but had inserted himself a permanent cannula for intravenous injection of propofol several times a day. The injection material was bought via online auctions from eBay. The case illustrates how job-related drug dependencies become indistinct due to the free access to information and goods via the Internet.     

Systemic Dissemination of Injected Foreign Material

A 32‐year‐old woman collapsed following an intravenous injection of material that included crushed pharmaceutical tablets. Resuscitation was attempted but was unsuccessful. She had an extensive past medical history of complications resulting from intravenous drug use. Death was due to mixed drug toxicity. The major findings at autopsy included a 10 mm deep skin sinus over the right femoral vein that was used as an injection site. Polarizable foreign material was present at the injection site and also within the lungs with a granulomatous reaction. Of note, a probe‐patent foramen ovale had permitted paradoxical embolization of this material into the systemic circulation with lodgement within the liver, portal lymph nodes, myocardium, spleen, kidneys, and pancreas. This case highlights the importance of checking for any intracardiac shunts, which may be quite small, and systemic dissemination of foreign material to multiple organs in intravenous drug users who present for medicolegal assessment.     

Methamphetamine in hair and interpretation of forensic findings in a fatal case

Hair analysis for drugs has been developing and is considered a significant tool for distinguishing between recent and long-term drug abuse in forensic and clinical toxicology. Chronic consumption of drugs can gradually induce certain harmful effects on the human organism and can exacerbate some pre-existing diseases. Analysis for drugs in blood or urine in isolation does not provide sufficient information about the history of drug-use by a person and their results cannot be correlated directly with the toxic effects displayed. The chronic abuse of methamphetamine is known to be associated with cardiovascular diseases. During or after autopsy certain types of morphologic alterations are found in the hearts of stimulant addicts. The rapid increase in blood pressure after an intravenous methamphetamine dose can be risky for addicts with arteriosclerosis. However, the anamnestic data about a deceased person may not always be available to explain the pathological findings and to classify the cause of death correctly. The aim of this study was to demonstrate the value of hair analysis for drugs in the context of explaining pathological cardiovascular alterations observed during the autopsy in a case where methamphetamine consumption was involved. In this case, only methamphetamine and metabolites were detected with traces of ephedrine. Ephedrine is the precursor chemical in the illicit synthesis of methamphetamine (known in the Czech Republic as "Pervitin"). The femoral blood level of methamphetamine was 1500 ng/ml. It was documented by a witness that the 31-year-old man died within 1h after an intravenous injection of the drug. The cause of death was established as cerebral edema due to cerebellar bleeding shortly after an intravenous dose of methamphetamine. Findings of methamphetamine in the first three 2-cm hair segments (numbered from the roots) were nearly equal (132+/-9 ng/mg). In the fourth 2-cm segment, it was approximately one-half of previous values. In the remaining, distal 7-cm hair segment sample, the value of methamphetamine was higher and comparable to the third segment. These results provide clear evidence that the man had been a chronic methamphetamine abuser for more than 8 months. This information can help to explain the pathology, the consequence of which could be the bleeding into the cerebellum after the last single methamphetamine dose.     

利多卡因在蛛网膜下腔和静脉注射致死犬体内的死后分布

目的比较利多卡因在蛛网膜下腔和静脉注射致死犬体内的死后分布特点。方法犬12只,其中6只经蛛网膜下腔,另6只经股静脉匀速注入利多卡因(5×15mg/kg)致死,迅速解剖动物,取大脑、侧脑室脑脊液、腰段脊髓腔脑脊液、不同脊髓节段(颈髓、胸髓、腰髓、骶髓),心、肺、肝、脾、肾、胆汁、尿、心血、周围血、注射部位肌肉和注射部位20 cm以外肌肉等脏器组织和体液,用气质联用法定性,气相色谱法定量检测其中利多卡因含量。结果蛛网膜下腔注射致死犬体内利多卡因的含量由高到低顺序依次为腰段脊髓腔脑脊液、骶段脊髓、胸段脊髓、侧脑室脑脊液、腰段脊髓、颈段脊髓、肺、肾、注射部位肌肉、心、大脑、脾、心血、肝、周围血、胆汁、注射部位20 cm以外的肌肉、尿;静脉注射致死犬体内利多卡因的含量由高到低顺序依次为肾、心、肺、脾、大脑、肝、周围血、胆汁、心血、颈段脊髓、胸段脑脊液、注射部位肌肉、腰段脊髓、注射部位20 cm以外的肌肉、侧脑室脑脊液、尿、腰段脊髓腔脑脊液、骶段脊髓。结论蛛网膜下腔注射致死犬背侧脊髓液中利多卡因含量最高,静脉注射致死犬肾脏利多卡因含量最高,此分布特征可为利多卡因麻醉意外法医学鉴定中入体途径的判定提供参考。     

Deaths after intravenous misuse of transdermal fentanyl

Fentanyl is a potent synthetic opioid used as a general anesthetic and analgetic. Fatal outcome from intravenous misuse of transdermal fentanyl is rare, and there are few such reports in literature. Here we report two cases of fatal intravenous injection of the content from fentanyl patches. Both were male drug addicts, found dead within a one week interval in the same apartment. Post-mortem femoral blood was screened for amphetamines, cannabinoids, cocaine, and opioids with immunological methods (EMIT II) and further with headspace gas chromatography for alcohol and with liquid chromatography mass spectrometry (LC-MS) for different drugs, including fentanyl. Confirmatory analysis of fentanyl and morphine was performed by gas chromatography-mass spectrometry (GC-MS). In the first case, the toxicological analysis revealed fentanyl (2.7 ng/mL), morphine (31.4 ng/mL), and ethanol (1.1 g/L) in postmortem blood and amphetamine, cannabinoids, morphine, and ethanol (1.4 g/L) in postmortem urine. In the second case, the analysis revealed fentanyl (13.8 ng/mL), 7-aminoclonazepam (57.1 ng/mL), and sertralin (91.9 ng/mL) in postmortem blood and a small amount of ethanol (0.1 g/L) in postmortem urine. Police investigation revealed that both the deceased had bought the patches from the same source. The present cases demonstrate the possibility of intravenous misuse of transdermal patches and the risk of fatal outcome.     

Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.     

甲基苯丙胺和氯胺酮在家兔体内毒代动力学及相互影响

目的比较家兔单独静脉注射甲基苯丙胺、氯胺酮及二种药物联合静注时的毒物代谢动力学过程,评价二种药物毒代动力学的相互作用。方法单用甲基苯丙胺组以3mg/kg剂量家兔静脉注射甲基苯丙胺,单用氯胺酮组以30mg/kg剂量家兔静脉注射氯胺酮,合用组以相同剂量同时注射两种药物。分别于给药后不同时间点收集血浆标本,测定各时间点药物浓度,WinNonLin软件拟合毒代动力学房室模型并计算参数。结果甲基苯丙胺在家兔体内的毒代动力学过程呈一级动力学特征,符合单室模型,合用氯胺酮后不改变其模型类型。氯胺酮在家兔体内的毒代动力学过程呈一级动力学特征,符合单室模型,合用甲基苯丙胺后符合二室模型。结论甲基苯丙胺和氯胺酮可以相互延缓其在体内的消除过程,增加彼此在体内的吸收,从而延长作用时间。     

The ratio of insulin to C-peptide can be used to make a forensic diagnosis of exogenous insulin overdosage

A 25-year-old man was killed by his lover by an intravenous injection of insulin and then air. We had difficulty in determining whether insulin had really been injected, so we have 18 control cases and proved that the ratio of insulin to C-peptide in a corpse can be used as positive evidence for the insulin overdosage.     

Disseminated granulomatosis through a patent foramen ovale in an intravenous drug user with pulmonary hypertension

Disseminated granulomatosis is a well-documented complication of intravenous narcotism. We present here an interesting case in which this complication was caused by a right-to-left shunt (following intravenous injection of medicinal tablets intended for oral use) through a patent foramen ovale resulting from pulmonary hypertension due to angiothrombosis.     

Morphine Concentrations in Stomach Contents of Intravenous Opioid Overdose Deaths

Abstract:  Death caused by heroin overdose is almost always the result of intravenous injection of the drug in Australia. We briefly describe a case where a heroin overdose was initially thought to be the result of oral ingestion of the drug, primarily as a result of higher concentrations of morphine in stomach contents than in blood. During the subsequent criminal trial and investigation, however, the issue of the entero-hepatic circulation of morphine was raised as a possible reason for the presence of morphine in the stomach contents. In this study, we report on the distribution of opioids in blood, stomach contents, urine, liver, and bile in 29 deaths caused by intravenous heroin overdose. The mean total and free blood morphine concentrations were 0.60 and 0.32 mg/L , respectively, and the mean stomach contents total morphine concentration was 1.16 mg/kg. All cases had detectable morphine in the stomach contents, and 24 of 29 cases (83%) had higher concentrations of total morphine in stomach contents than in blood. The mean total morphine concentration in bile was c. 100 times that in blood, and the liver total morphine concentration averaged twice that of blood levels. We conclude that the entero-hepatic circulation of morphine and subsequent reflux of duodenal contents back into the stomach can result in the deposition of morphine in gastric contents. Consequently, the relative levels of opioids in blood and stomach contents cannot be used to determine the site of administration of the drug.     

GHB. Club drug or confusing artifact?

GHB can be produced either as a pre- or postmortem artifact. The authors describe two cases in which GHB was detected and discuss the problem of determining the role of GHB in each case. In both cases, NaF-preserved blood and urine were analyzed using gas chromatography. The first decedent, a known methamphetamine abuser, had GHB concentrations similar to those observed with subanesthetic doses (femoral blood, 159 microg/ml; urine, 1100 microg/ml). Myocardial fibrosis, in the pattern associated with stimulant abuse, was also evident. The second decedent had a normal heart but higher concentrations of GHB (femoral blood, 1.4 mg/ml; right heart, 1.1 mg/ml; urine, 6.0 mg/ml). Blood cocaine and MDMA levels were 420 and 730 ng/ml, respectively. Both decedents had been drinking and were in a postabsorptive state, with blood to vitreous ratios of less than 0.90. If NaF is not used as a preservative, GHB is produced as an artifact. Therefore, the mere demonstration of GHB does not prove causality or even necessarily that GHB was ingested. Blood and urine GHB concentrations in case 1 can be produced by a therapeutic dose of 100 mg, and myocardial fibrosis may have had more to do with the cause of death than GHB. The history in case 2 is consistent with the substantial GHB ingestion, but other drugs, including ethanol, were also detected. Ethanol interferes with GHB metabolism, preventing GHB breakdown, raising blood concentrations, and making respiratory arrest more likely. Combined investigational, autopsy, and toxicology data suggest that GHB was the cause of death in case 2 but not case 1. Given the recent discovery that postmortem GHB production occurs even in stored antemortem blood samples (provided they were preserved with citrate) and the earlier observations that de novo GHB production in urine does not occur, it is unwise to draw any inferences about causality unless (1) blood and urine are both analyzed and found to be elevated; (2) blood is collected in NaF-containing tubes; and (3) a detailed case history is obtained.     

Homicide by intravenous injection of naphtha

A case of homicide by the intravenous injection of Energine, a petroleum distillate spot remover, is presented. This case is the only known homicide committed with naphtha. This elderly man had severe natural disease in addition to chest trauma sustained in the assault leading to death; however, the rapid injection of approximately 25 mL of Energine was the overwhelming cause of death.     

An oxcarbazepine-related fatality with an overview of 26 oxcarbazepine postmortem cases

We present an oxcarbazepine-related fatality together with an overview of 26 postmortem cases involving oxcarbazepine observed during the period 2001-2006. The fatality case concerned a 27-year-old woman with epilepsy, who was found dead in her bed. Oxcarbazepine and its active metabolite, 10-hydroxycarbazepine, were the only compounds detected. The concentrations of oxcarbazepine were as follows: femoral blood, 2.9mg/kg; muscle, 1.8mg/kg; liver, 0.9mg/kg; gastric content (300ml), 860mg/kg; and vitreous humour, not detected. The concentrations of 10-hydroxycarbazepine were as follows: femoral blood, 66mg/kg; muscle, 40mg/kg; liver, 62mg/kg; gastric content, 27mg/kg; and vitreous humour, 25mg/kg. The analyses were performed by HPLC-DAD after liquid-liquid extraction. Oxcarbazepine intoxication was regarded as a possible cause of death. For the other 26 cases, the 10-hydroxycarbazepine concentrations ranged from 2.2 to 48mg/kg with a median of 25mg/kg.     

Amphetamine derivative related deaths in northern Greece

Until 1997, only one amphetamine related derivatives (AMPs) fatality had been reported in Greece. Since then, amphetamine (AMP) or AMPs have been found in seven out of 1,500 post-mortem toxicological cases. The cause and manner of death of these seven cases were: 3,4-methylenedioxy-N-methamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) poisoning (n = 1), drowning in water (n = 4), cranial injuries caused by a traffic accident (n = 1) and heart failure (n = 1). In the case where the use of AMP or AMPs was considered, the immediate cause of death post-mortem toxicological analysis revealed 2 microg/ml MDMA and 0.7 microg/ml MDEA in blood. MDMA was identified in two cases of drowning (2 microg/ml in blood in the first case and 1.7 microg/g in liver in the second case) and in the traffic accident case (0.4 microg/g in liver). Methamphetamine was detected in two cases of drowning (2.5 microg/ml in blood in the first case and 6 microg/g in liver in the second case). AMP was found in the heart failure case (0.2 microg/g in liver). Alcohol was present, together with AMP or AMPs, in four cases. These findings indicate an increase in the illegal abuse of AMPs in Greece. Because of this, we now routinely screen for AMPs.     

Lipomatosis cordis as a cause of ventricular perforation in implantation of a pacemaker probe

A case report is given on lethal perforation of the right ventricle during emergency implantation of a pacemaker probe. The forensic autopsy revealed extensive lipomatous infiltration of the right ventricle in the rupture area. Lethal complications occur occasionally in spite of the standardization of implantation techniques, especially as a result of reanimation attempts. Such cases are discussed with regard to the forensic aspects with reference to the literature. Lipomatosis cordis as "locus minoris resistentiae" has special significance for ventricular perforation.     

阿维菌素在急性中毒死家兔体内的再分布研究

目的考察阿维菌素在急性中毒死家兔体内的再分布。方法按最小致死量一次性灌胃250mg/kg阿维菌素,HPLC法检测家兔死后0h、24h、48h和72h中阿维菌素的含量。结果给家兔一次性灌胃250mg/kg阿维菌素的临床死亡时间为120.6±9.2min(±s,n=10);测定了阿维菌素的致死血浓度和致死组织浓度;家兔死后0h~72h心血和各主要脏器组织中阿维菌素含量存在体内再分布现象;确定肝、肾、肺为最佳组织检材。结论阿维菌素在急性中毒死家兔体内的再分布数据,对法医办理此类案件具有重要参考价值。     

Relation of Kinetic Energy to Contact Wounds of the Head by Centerfire Rifles and Shotgun Slugs

Wounds of high‐energy centerfire rifles and shotguns represent distinctive injuries of forensic importance. Previous studies of contact wounds have shown variability in the potential of these weapons to produce bursting wounds of the head. The present study analyzed contact head wounds owing to 26 centerfire rifles and nine shotgun slugs and compared them with respect to weapon, ammunition, entry wound site, and projectile kinetic energy. The bursting effect, defined for this study as disruption of at least 50% of the head, occurred in 25/35 of cases and was related to kinetic energy. Bursting was associated with energies <2700 ft‐lbs in 12/22 cases and energies >2700 ft‐lbs in 13/13 cases. The volume of gunpowder gas injected into the wound was considered as contributing to the bursting phenomenon. There was no relation of bursting to the specific entrance wound site, type of ammunition, or projectile fragmentation.     

Cocaine poisoning

Lethal cocaine intoxications in the Federal republic of Germany are still rather unusual. The present article describes chemical findings in a suicide case after oral/nasal intake. Our experience as well as the results of literature leads to the conclusion that if a cocaine intoxication is suspected, examinations are required which should include parts of the brain, the kidneys and the spleen. The application of RIA or rather the EMIT-Procedure only are not sufficient to clear up an intoxication.     

Validation of Large White Pig as an animal model for the study of cannabinoids metabolism: application to the study of THC distribution in tissues

This study presents a new animal model, the Large White Pig, which was tested for studying cannabinoids metabolism. The first step has focused on determination of plasma kinetics after injection of Delta(9)-tetrahydrocannabinol (THC) at different dosages. Seven pigs received THC by intravenous injections (50, 100 or 200 microg/kg). Plasma samples were collected during 48 h. Determination of cannabinoids concentrations were performed by gas chromatography/mass spectrometry. Results showed that plasma kinetics were comparable to those reported in humans. Terminal half-life of elimination was 10.6 h and a volume of distribution of 32 l/kg was calculated. In a second step, this model was used to determine the kinetic profile of cannabinoids distribution in tissues. Eight Large White male pigs received an injection of THC (200 microg/kg). Two pigs were sacrificed 30 min after injection, two others after 2, 6 and 24 h. Different tissues were sampled: liver, kidney, heart, lung, spleen, muscle, fat, bile, blood, vitreous humor and several brain areas. The fastest THC elimination was noted in liver tissue, where it was completely eliminated in 6 h. THC concentrations decreased in brain tissue slower than in blood. The slowest THC elimination was observed for fat tissue, where the molecule was still present at significant concentrations 24 h later. After 30 min, THC concentration in different brain areas was highest in the cerebellum and lowest in the medulla oblongata. THC elimination kinetics noted in kidney, heart, spleen, muscle and lung were comparable with those observed in blood. 11-Hydroxy-THC was only found at high levels in liver. THC-COOH was less than 5 ng/g in most tissues, except in bile, where it increased for 24 h following THC injection. This study confirms, even after a unique administration, the prolonged retention of THC in brain and particularly in fat, which could be at the origin of different phenomena observed for heavy users such as prolonged detection of THC-COOH in urine or cannabis-related flashbacks. Moreover, these results support the interest for this animal model, which could be used in further studies of distribution of cannabinoids in tissues.