A case of fatal aconitine poisoning by Monkshood ingestion

Accidental aconitine poisoning is extremely rare in North America. This report describes the confirmation of a case of accidental aconitine poisoning using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The case involved a 25-year-old man who died suddenly following a recreational outing with friends where he consumed a number of wild berries and plants including one that was later identified as Monkshood (Aconitum napellus). Postmortem blood and urine samples were available for analysis. All routine urine and blood toxicology screens were negative. The LC-MS/MS method allowed sensitive quantification of aconitine, the main toxin in A. napellus, and showed 3.6 and 149 microg/L in blood and urine, respectively. These concentrations were similar to that reported in other aconitine-related deaths. This case illustrates the dangers of consuming unidentified plants, and documents concentrations of aconitine in blood and urine in a fatal case of A. napallus-related poisoning.     

Effects of long-term administrations of aconitine on electrocardiogram and tissue concentrations of aconitine and its metabolites in mice

Aconitum alkaloids are well known for their acute and high toxicity, for example, in the causation of severe arrhythmias leading to death. Aconitine, one of the major Aconitum alkaloids, is a highly toxic compound from the Aconitum species. However, there has been no studies reported on the influence of the chronic administration of aconitine. Thus, this study was conducted to investigate the influence of chronic administration of aconitine in experimental animal models. A dose of 1mg/kg per day was administered to the experimental animal models. We determined the concentration of aconitine and its metabolites (benzoylaconine and aconine) in organs and blood with gas chromatography/selected ion monitoring (GC/SIM). In addition, we concurrently recorded the electrocardiogram (ECG). Fifteen minutes after administration on day 0, the early aconitine administered group (acute group) revealed peak organ and blood concentration levels of aconitine with a gradual decrease, thereafter. The concentration of aconitine in organs and blood (from days 0 to 22; 90 min after the last administration of aconitine) gradually decreased according to repeated administration, whereas benzoylaconine and aconine increased. ECG revealed various types of arrhythmias. However, the frequency of arrhythmias remarkably decreased with time and repeated administration of aconitine. These results indicate two possibilities. First, the increase in the activity of aconitine metabolism. Secondly, the decrease of effectiveness to the heart due to long-term (chronic) administration of aconitine.     

Clozapine--a dangerous drug in a clozapine-naïve subject

Clozapine is a uniquely effective antipsychotic, but is very toxic in clozapine-na?ve subjects. A 34-year-old male patient in a mental health facility, who was not prescribed clozapine, took 350 mg clozapine obtained from another patient at night. He was found dead the next morning. The presence of cardiomegaly related to obesity may have increased the risk of suffering an acute cardiac event after ingestion of clozapine. The medication prescribed to the patient was not thought to have contributed to the fatal outcome. Post mortem femoral blood clozapine and norclozapine concentrations were 0.48 and 0.20mg/L, respectively. By way of comparison, audit of 104,127 plasma samples (26,796 patients) assayed for therapeutic drug monitoring purposes 1993-2007, showed plasma clozapine 0.35 mg/L or more in 57.5% samples (8.4% 1mg/L or more). Those involved in the investigation of clozapine-associated deaths need to be aware that that death in an adult may occur after a single 'therapeutic' dose. A diagnosis of fatal clozapine poisoning cannot be made solely on the basis of a post mortem blood clozapine measurement.     

Seven cases of fatal aconite poisoning: forensic experience in China

This paper presents seven fatal cases of aconite poisoning encountered in the Tongji Center for Medicolegal Expertise in Hubei (TCMEH), China, from 1999 to 2008 retrospectively. In six of the cases, deaths occurred after drinking homemade medicated liquor containing aconite, and in one case death was due to ingestion of traditional Chinese medication containing aconite. Forensic autopsy and pathological examinations ruled out the presence of physical trauma or life-threatening diseases. Diagnosis of aconite poisoning was made after postmortem toxicological analysis. Animal experiment was performed in one case demonstrating that the medicated liquor could cause death rapidly. We present the autopsy and histopathological findings, toxicological analysis, and results of animal experiment done on samples from those seven cases. As an important herbal Chinese medicine, Aconitum species deserve special attention, especially because it contains poisonous alkaloids.     

Determination of phenol and o-cresol by GC/MS in a fatal poisoning case

A fatality due to the ingestion of solution containing phenol and o-cresol is described. The pathological findings were typical of acute substantial poisoning. Blood, urine and stomach content were obtained during post mortem examinations. Phenol and o-cresol were identified using GC/MS. The extractions from autopsy materials were obtained as follows: by gel permeation with cyclohexane/dichloromethane from stomach content, by solid phase extraction (SPE) from urine and by deproteinization with acetonitrile from blood. The phenol and o-cresol concentrations in the samples were found, respectively, as follows: 115.0 and 5.0 microg/g in the stomach contents, 58.3 and 1.9 microg/ml in the blood, 3.3 and 20.5 microg/ml in the urine. Distributions of phenol in fatal poisonings have been reported, but, usually, colorimetry was used as the analytical method and it cannot exclude the interference of other phenolic compounds.     

乌头类生物碱对心肌的毒性作用及分子毒理学研究进展

乌头属植物是被子植物亚门毛茛科中一类重要的有毒植物,也是我国最早有记载的药用有毒植物之一;其块根中多含有剧毒的二萜类双酯型生物碱?乌头碱,因个体差异、用法不当以及误服或投毒等原因而发生乌头中毒、甚至死亡的报道屡见不鲜。目前,对乌头碱的研究多局限在临床救治方面,缺乏对乌头碱毒性作用机制研究。本文参考国内外相关文献资料,对乌头碱的心肌细胞毒性作用机制进行了综述。     

Implications of Genital Mutilation at Autopsy

Given the potential significance of mutilation of the external genitalia in medicolegal fatalities, a review of the literature was undertaken to identify subcategories. Such mutilations may have been sustained sometime before death, around the time of death, or after death. The most common type of ante mortem genital mutilations involves cultural practices such as male circumcision. Less common male mutilations such as subincisions are tribally based. Female genital mutilation is found particularly in African, Middle Eastern, or Asian populations. Self‐inflicted genital injuries are most common in males and may be related to attempts at suicide, or to self‐harming practices. The latter have a strong association with psychiatric illnesses. Postmortem injuries may arise from animal predation or deliberate mutilation of a corpse. The latter may be associated with ante mortem genital injuries in sadistic homicides. The range of possible causes of genital mutilations in forensic cases necessitates extremely careful evaluation.     

乌头中剧毒生物碱的提取分离

目的从乌头属植物中提取分离剧毒生物碱乌头碱、中乌头碱、次乌头碱;方法酸性水溶液提取,碱化后中性氧化铝柱层析,IR、EI-MS确认结构;结果利用该方法提取以上3种生物碱得到的回收率与碱性苯溶液法相似。结论该方法所用试剂成本低、毒性小,适用于制备乌头碱、中乌头碱、次乌头碱对照品。     

Identification of unknown human remains by comparison of antemortem and postmortem radiographs

The identification of unknown human remains by comparison of ante mortem and post mortem radiographs has found wide acceptance in recent years. This report documents two recent cases in Hong Kong in which unequivocal positive identifications were achieved by comparison of radiographs. In both cases, comparison of radiographs was the only available means of establishment of personal identity. The first case involved the identification of a very badly burned body of a 22-year-old male by the matching of the ante mortem and post mortem radiographic images of the cranial base (in particular the sella turcica), hard palate, paranasal air sinuses, mastoid air cells, the lambdoid suture, and the upper molar teeth as revealed on comparable lateral skull films. The second was the identification of a deliberately mutilated torso of a 28-year-old female by comparison of the radiographic images of the lumbar spine, pelvis, and head of the femur as revealed on plain abdominal films taken before and after death. While evidence of injury or surgery did not figure in either of the identifications, the presence of a mild scoliosis and the absence of the twelfth ribs aided identification in the latter case. Emphasis is placed in this account on the value of radiographic comparison as a means of identification because it draws upon the matching of intricate and highly individual patterns of external and internal bony anatomy that are stable over long periods of time. In cases where ante mortem radiographs and photographs are available, establishment of personal identity by comparison of radiographs is deemed preferable to identification by photographic superimposition because radiographic comparison permits the matching of a potentially larger number of unique anatomical features and is less time consuming and technically exacting.     

A fatal interaction of methocarbamol and ethanol in an accidental poisoning

A case is presented of a fatal drug interaction caused by ingestion of methocarbamol (Robaxin) and ethanol. Methocarbamol is a carbamate derivative used as a muscle relaxant with sedative effects. Therapeutic concentrations of methocarbamol are reported to be 24 to 41 micrograms/mL. Biological fluids were screened for ethanol using the Abbott TDx system and quantitated by gas-liquid chromatography (GLC). Determination of methocarbamol concentrations in biological tissue homogenates and fluids were obtained by colorimetric analysis of diazotized methocarbamol. Blood ethanol concentration was 135 mg/dL (0.135% w/v) and urine ethanol was 249 mg/dL (0.249% w/v). Methocarbamol concentrations were: blood, 257 micrograms/mL; bile, 927 micrograms/L; urine, 255 micrograms/L; gastric, 3.7 g; liver, 459 micrograms/g; and kidney, 83 micrograms/g. The combination of ethanol and carbamates is contraindicated since acute alcohol intoxication combined with carbamate usage can lead to combined central nervous system depression as a result of the interactive sedative-hypnotic properties of the compounds.     

Exhumation for suspected poisoning--reticulum cell sarcoma (author's transl)]

A 57-year-old woman showed somnolence, extreme stiffness of the neck and atypical CSF findings which led to her death within a few days. During legacy controversy the possibility of poisoning was considered. The post mortem, pathological and toxological examinations of the exhumed corpse permitted the diagnosis of reticulum cell sarcoma 16 months after death. Such a diagnosis 16 months after death has, to our knowledge, not previously been reported.     

Unexpected double lethal oleander poisoning

Nerium oleander is a very popular urban ornamental plant in Europe, but it is also extremely dangerous because it contains several types of glycosides, accidental ingestion of which can cause cardiac arrhythmias and even deaths. The rarity of such cases makes it difficult to think of oleander poisoning without evidences that suggest this possibility as the cause of the unexpected death. This report concerns the discovery of the bodies of 2 young people, a man and a woman, in a forest in conditions of extreme malnutrition. Medicolegal investigations showed neither pathologic nor traumatic causes of death, but the presence of vegetal remains in the stomach was noticed. A common toxicological analysis resulted negative, but the implementation of more detailed investigations showed the presence of digoxin in the blood of both cadavers, excluding the possibility of a pharmaceutical provenience of digoxin, this laboratory result was interpreted as evidence of ingestion of oleander, which contains oleandrine, the cross reaction of which with digoxin is widely described in the literature. Identification of the 2 subjects, which occurred after 4 years, strengthened the hypothesis of accidental poisoning by oleander because it was ascertained that the 2 young people were vegans--extreme vegetarians who reject the ingestion of foods of animal origin and live by eating only what they find in nature.     

Another death due to ingestion of Nicotiana glauca

Deaths attributed to ingestion of Nicotiana glauca are extremely rare. We report here a case where a 43-year-old man was found dead after apparently drinking a water extract of Nicotiana glauca. The primary alkaloid in the plant is anabasine. Toxicological analysis by capillary gas chromatography showed the deceased had a blood anabasine concentration of 2.2 mg/L. Clinically, the features of poisoning are nicotine-like and if death occurs it results from respiratory paralysis. The case further supports the view that, in the human, anabasine is considerably more toxic than nicotine.     

Using DNA-barcoding to make the necrobiont beetle family Cholevidae accessible for forensic entomology

Although many cases of fatal hydrogen sulfide poisoning have been reported, in most of these cases, it resulted from the accidental inhalation of hydrogen sulfide gas. In recent years, we experienced 17 autopsy cases of fatal hydrogen sulfide poisoning due to the inhalation of intentionally generated hydrogen sulfide gas. In this study, the concentrations of sulfide and thiosulfate in blood, urine, cerebrospinal fluid and pleural effusion were examined using GC/MS. The sulfide concentrations were blood: 0.11-31.84, urine: 0.01-1.28, cerebrospinal fluid: 0.02-1.59 and pleural effusion: 2.00-8.59 (μg/ml), while the thiosulfate concentrations were blood: 0-0.648, urine: 0-2.669, cerebrospinal fluid: 0.004-0.314 and pleural effusion: 0.019-0.140 (μmol/ml). In previous reports, the blood concentration of thiosulfate was said to be higher than that of sulfide in hydrogen sulfide poisoning cases, although the latter was higher than the former in 8 of the 14 cases examined in this study. These results are believed to be strongly influenced by the atmospheric concentration of hydrogen sulfide the victims were exposed to and the time interval between exposure and death.     

Accidental potassium dichromate poisoning. Toxicokinetics of chromium by ICP-MS-CRC in biological fluids and in hair

Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (Cr(VI)), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically Cr(VI) reactive intermediates and reactive oxygen species. After Cr(VI) has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of Cr(VI) to Cr(III) reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of Cr(VI) is cleared in urine as Cr(III). We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30 g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7 days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49 days. During this period Cr decreased respectively from 2088 μg/L to 5 μg/L, 631 μg/L to 129 μg/L and 3512 μg/g to 10 μg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2 months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells.     

Cerebrospinal fluid analysis in fatal thallium poisoning: evidence for delayed distribution into the central nervous system

The neurologic manifestations of thallium poisoning include a severely painful ascending peripheral neuropathy, autonomic dysfunction, cranial nerve abnormalities, and a toxic encephalopathy. Although thallium has a short half-life, these neurologic manifestations commonly progress, even as the blood concentration of thallium decreases. This suggests either that thallium persists in neuronal tissues or that it initiates an injury cascade that takes time to fully manifest. As the latter mechanism is consistent with many toxin exposures, the concept of a central nervous system reservoir for thallium is often discounted. A recent case provided a unique opportunity to evaluate this possibility. A 48-year-old man was acutely and chronically thallium poisoned by his common-law wife. During his initial exposures, only gastrointestinal symptoms manifested. Following an acute ingestion, hospitalization was required. Over 3 days, his symptoms rapidly progressed from a severely painful neuropathy to slurred speech, ptosis, confusion, coma, respiratory insufficiency, and death. Because of considerations of alternative diagnoses, 2 lumbar punctures were performed, one on admission and another on the day of his death. Serum thallium concentrations obtained from stored blood samples were paired with spinal fluid concentrations from the same days. On day 1, serum and spinal fluid concentrations were 8700 mu/L and 1200 mu/L, respectively. On day 3, although the serum concentration had fallen to 7200 mu/L, the spinal fluid concentration had increased to 2100 mu/L. This case provides evidence to support the hypothesis that thallium distributes into the central nervous system more slowly than the blood compartment, and this may in part account for the progression of neurologic findings in the setting of decreasing serum concentrations.     

Fatal intoxication with 1,4-butanediol: Case report and comprehensive review of the literature

A fatal case of 1,4-butanediol (1,4-BD) oral ingestion is reported here, in which a 51-year-old man was found dead in his bed. According to the police report, the deceased was a known drug user. A glass bottle labeled (and later confirmed to be) “Butandiol 1,4” (1,4-BD) was found in the kitchen. Furthermore, the deceased's friend stated that he consumed 1,4-BD on a regular basis. The autopsy and histological examination of postmortem parenchymatous organ specimens did not revealed a clear cause of death. Chemical-toxicological investigations revealed gammahydroxybutyrat (GHB) in body fluids and tissues in the following quantities: femoral blood 390 mg/L, heart blood 420 mg/L, cerebrospinal fluid 420 mg/L, vitreous humor 640 mg/L, urine 1600 mg/L, and head hair 26.7 ng/mg. In addition, 1,4-BD was qualitatively detected in the head hair, urine, stomach contents, and the bottle. No other substances, including alcohol, were detected at pharmacologically relevant concentrations. 1,4-BD is known as precursor substance that is converted in vivo into GHB. In the synoptic assessment of toxicological findings, the police investigations and having excluded other causes of death, a lethal GHB-intoxication following ingestion of 1,4-BD, can be assumed in this case. Fatal intoxications with 1,4-BD have seldom been reported due to a very rapid conversion to GHB and, among other things, non-specific symptoms after ingestion. This case report aims to give an overview to the published of fatal 1,4-BD-intoxications and to discuss the problems associated with detection of 1,4-BD in (postmortem) specimens.     

Diagnostic implication of blood and urine morphine content in alcohol intoxication

A total of 198 cases of acute parenteral poisoning with opiates are characterized. The range of concentrations of opiates metabolites in the blood and urine, main causes of death due to opiate poisoning in alcohol intoxication are analysed. Opiates toxicity was assessed with the logit-regression method and dose-effect curves valid for analysis of relationships between probability of death and opiate metabolites concentration in blood and urine. Correlation between probability of death and detection of morphine and ethanol in biological media of the victims is considered. Concentrations of morphine in blood and urine definitely indicating opiates poisoning in alcohol intoxication as a cause of death are determined.     

Forensic-medical diagnostic implication of morphine levels in the blood and urine

Toxicological characteristics are presented for 198 cases of acute parenteral poisoning with morphine and heroin. The range of their metabolites concentration in the blood and urine encountered in practice are analysed. Principal causes of death due to opiate poisoning in inpatients are shown. Opiates toxicity was assessed by the method of logit-regression and dose-effect curves for analysis of probability of death depending on opiate metabolite concentration in blood and urine. Relations between probability of death and detection of morphine in biological media of the victims are considered. Morphine concentrations in the blood and urine undoubtedly indicating morphine poisoning are determined.     

大鼠乌头碱中毒心肌酶的研究(Ⅳ)——乳酸脱氢酶的组织化学和细胞化学定位

本文用组织化学和细胞化学相结合的方法,对乌头碱染毒后不同时间的大鼠心肌乳酸脱氢酶(LDH)进行了显微和超微结构定位。染毒后30min、2h 和4h,大鼠心肌 LDH 酶反应增强,至染毒后12h,24h 活性仍高于对照组。表明在有氧氧化障碍的同时,中毒鼠的心肌糖酵解增强,为乌头碱造成心肌能量代谢障碍的中毒机理进一步提供了证据。