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.     

Liver pathology in fatal drug addiction

Liver sections from 273 drug addicts submitted to medicolegal autopsy at the Institute of Forensic Medicine in Copenhagen in the period 1975 – 1979 were studied. In 65% of the cases non-specific portal inflammation only was found. Birefringent foreign material — identified as the mineral talc (magnesium silicate) was observed in 38% of the cases; in these cases non-specific portal inflammation was always present. Changes compatible with acute or chronic persistent hepatitis or hepatitis sequelae were observed in 8% of the cases; cirrhosis in 3%. HBs-antigen was detected in 4%. In 22% fatty infiltration was present; in 4% as the only abnormal finding. Finally no pathological changes were found in 6%. The results were related to anamnestic information of kind and duration of drug abuse and to the cause of death. Furthermore a comparison was performed between the groups with and without birefringent material. The data suggest that the birefringent material may be of importance to the pathogenesis of the non-specific portal inflammation.     

Lymph-node and thymus pathology in fatal drug addiction

Lymph-node sections from the porta hepatis, the lung hilus, the para-aortic and axillary regions and from the neck from totally 50 drug addicts submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen were studied together with tissue sections from 23 normal persons. In addition thymus sections from 30 drug addicts and 20 normal persons were investigated. Enlargement of lymph-nodes was found significantly more often in active drug addicts compared to normals except for the nodes on the neck. Birefringent material was seen in portal lymph-nodes in 42% of addicts, in para-aortic and lung hilus nodes in 18% each and in the axillary nodes in 12%. Signs of antigenstimulation evaluated by the number of germinal centre and plasma cells were found in about 60% or more in active drug addicts compared to about 30-40% in normals. There was not significant relation between the size of the lymph-nodes and the immunoactivity nor to the duration of the abuse. Examination of the thymus showed that the average weight in active drug addicts was 34 g, in normals 25 g. Histologically the tissue was in 48% of the active addicts composed of more than 80% lymphatic tissue compared to 15% of the normals. The results indicate that the enlargement and histological signs of activation in all the lymph-nodes investigated are caused by continuous antigenstimulation due to repeated injections of various antigens. The same may in part be applied to the thymus changes demonstrated.     

Toxicology and characteristics of fatal oxycodone toxicity cases in New South Wales, Australia 1999-2008

All cases of fatal oxycodone toxicity presenting to the New South Wales Department of Forensic Medicine over the period January 1, 1999, to December 31, 2008, were retrieved. A total of 70 cases were identified. The mean age was 48.9 years, 58.6% were men, 21.4% were suicides, and in 30% oxycodone had not been prescribed to the decedent. Injecting drug users constituted 27.1% of cases, and oxycodone tablets were injected immediately prior to death by 21.4%. The mean blood oxycodone concentration was 0.40 mg/L (range 0.06-53.00 mg/L). In all cases, psychoactive substances other than oxycodone were also detected, most frequently hypnosedatives (68.6%), other opioids (54.3%), antidepressants (41.4%), and alcohol (32.9%). Preexisting systemic disease was common: cardiovascular (64.2%), pulmonary (49.3%), hepatic (66.7%), and renal (43.9%).     

Spleen and portal lymphnode pathology in fatal drug addiction

Spleen and portal lymphnode sections from 86 drug addicts submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen in the year 1979 were studied together with tissue sections from 24 "normal" persons. In 70% of the drug addicts the spleen weight was more than 200 g, and in 71% portal lymphnode hyperplasia was found. Birefringent foreign material was found in spleen tissue of drug addicts in 72% and in portal lymphnode tissue in 44%. Signs of antigen stimulation in both spleen and portal lymphnode tissue evaluated by the number of germinal centre and plasma cells were found in more than 80% of the drug addicts compared with about 20% of the "normal" persons. The results were related to anamnestic information of duration of drug abuse, to the spleen weight, to the occurrence of birefringent material and to the liver changes. Examination of lysozyme and immunoglobulin containing cells using the indirect preoxidase technique was performed in a total of 72 cases of spleen tissue, 59 cases of portal lymphnode tissue from drug addicts, 24 cases of spleen tissue and 18 of portal lymphnode tissue from "normal" persons. Lysozyme, IgM and IgG containing cells were found significantly more often among drug addicts than "normal" persons. The results indicate that the splenomegalia and the portal lymphnode hyperplasia often found in drug addicts are caused by continuous antigen stimulation due to repeated injections of various antigens.     

A fatal interaction: The role of the victim and function of aggression in intrafamilial homicide

Abstract

This study examines the interaction between the victim and offender during intrafamilial homicide. It is hypothesised that in order to understand the fatal consequences of the interaction, a psychological model must take into account both the role of the victim, as either a significant person or non-significant object, and the function of the aggression, as either instrumental or expressive. The combination of these two proposed facets gives rise to four hypothesised styles of intrafamilial homicide. This hypothesis was tested by analysing 191 intrafamilial homicide cases from the Chicago HITS database. Fifty two crime-scene actions were analysed using Smallest Space Analysis which revealed four distinct thematic clusters of variables. These themes corresponded to the hypothesised facets of victim role and function of aggression. Two related to expressive acts, (a) those murders where the offender kills multiple members of his family and subsequently takes his own life, and (b) cases where the victim is not treated as a significant person in the interaction but is simply used as a target for the offender's rage. The other two relate to instrumental acts, (c) those murders that are a culmination of years of abuse in which the offender sees the killing as the only means of escape, and (d) homicides where the victim is seen as an obstacle to the offender achieving a goal and is removed.

A further test of the validity of these four themes in describing distinct forms of interaction within intrafamilial homicide was to examine the proportion of cases which could be classified according to the framework. The hypothesis that each relationship would map onto just one of the interactional styles was tested by χ² which confirmed that such exclusive relationships existed at the p < .001 level of significance. This has theoretical as well as practical implications in that in using this method of classification it may be possible to infer which family member is responsible for killing their relative.     

Etryptamine, a new designer drug with a fatal effect

Capsules with etryptamine have been commonly available on the market since the middle of 1985. Up to 1962 this CNS-stimulating, monoamine-oxidase-inhibiting drug was sold as an antidepressant (Monase). A case of fatal intoxication is reported. The exact amount of etryptamine taken several hours before death are not known, but it could have been in the range of 700 mg. This drug was detected in tissue by means of common analytical techniques (GLC, GC-MS, HPLC, TLC). Etryptamine cross-reacts with the Emit-st amphetamine assay and can also be detected in urine using these techniques. The level in postmortem blood was 1.1 mg/l. The effects the young man showed were like those known from intoxication with amphetamines, MAO inhibitors, and thymoleptics. Malignant hyperthermia is discussed as a possible cause of death. It is suggested that trade in etryptamine should be controlled.     

A fatal diazinon poisoning

A case of fatal suicidal ingestion of diazinon insecticide is presented. Diazinon concentrations in post-mortem body fluids and tissues were determined using electron capture and flame ionization gas-liquid chromatography. The highest concentrations of diazinon were found in blood, stomach contents, bile and adipose tissue.     

A fatal elephant attack

A rare case of an elephant attack is presented. A 44-year-old man working as an elephant keeper was attacked by a cow elephant when he tripped over a foot chain while the animal was being medically treated. The man fell down and was consequently repeatedly attacked with elephant tusks. The man sustained multiple stab injuries to both groin regions, a penetrating injury to the abdominal wall with traumatic prolapse of the loops of the small bowel, multiple defects of the mesentery, and incomplete laceration of the abdominal aorta with massive bleeding into the abdominal cavity. In addition to the penetrating injuries, the man sustained multiple rib fractures with contusion of both lungs and laceration of the right lobe of the liver, and comminuted fractures of the pelvic arch and left femoral body. The man died shortly after he had been received at the hospital. The cause of death was attributed to traumatic shock.     

A fatal maprotiline intoxication

A fatal maprotiline intoxication is presented. The postmortem anatomical and toxicologic findings are discussed, as is the mechanism of maprotiline toxicity. This report is, to the best of our knowledge, the sixth fatal maprotiline poisoning in the medical literature.     

A fatal dothiepin overdose

High pressure liquid chromatography coupled to photodiode array detector and capillary gas chromatography coupled to mass spectrometry were employed to quantify dothiepin in biological fluids, tissues and hair in a death attributed to oral dothiepin (Prothiaden^R) ingestion. The blood concentration of dothiepin was 5.75 mg/l. Hair analysis clearly indicated a chronic antidepressant exposure, with a dothiepin concentration of 1.89 ng/mg hair. Results are discussed in the light of the existing literature.     

A fatal chronic ketamine poisoning

A few papers in the literature reported incident deaths by acute ketamine poisoning. In this paper, we report an unusual homicide caused by chronic ketamine poisoning. The victim was a 34-year old married woman with no previous medical history (except as reported herein) who died in her own home. The court investigation revealed that she was chronically poisoned by her husband over a period of about one year in an act of homicide. Determination of ketamine concentrations in autopsy specimens was carried out with gas-chromatography/mass spectrometry (GC-MS). The results showed that ketamine concentration was 21 microg/mL in gastric contents, 3.8 microg/mL in blood and 1.2 microg/mL in urine. The most striking forensic findings were cardiac muscle fibrosis and hyaline degeneration of small arteries in victim's heart, the pathological features of ketamine poisoning previous reported only in animal studies.     

A fatal poisoning with LSD

Radioimmunoassay, high-performance liquid chromatography and capillary gas chromatography-mass spectrometry were used to detect and measure LSD in the first reported case of fatal poisoning by LSD. The levels found in ante-mortem serum and plasma and in post-mortem blood, liver blood and stomach contents are given.     

A fatal intoxication by chloroprene

Objective Chloroprene, 2-chloro-1,3 butadiene, is a volatile synthetic liquid. The chloroprene monomer is extremely reactive and is used for the production of latexes and synthetic rubber such as Neoprene. Up to now an acute lethal human exposure has been described only once in the literature [19]. The intoxication is associated with nervous system depression, pulmonary edema, narcosis, and respiratory arrest. Case report A 29-year-old chemistry company worker was found unconscious in an empty vessel (depth: 3m) used for chloroprene. The man was dressed in shoes, trousers, a helmet and a respiratory mask. The upper part of the body was unclothed. In spite of reanimation, the man died three hours later in a hospital. Material and methods: All analyses were performed by headspace gas chromatography (HS/GC/FID). In addition, brain, muscle and myocardial muscle were analysed by headspace GC-MS. Results and discussion Autopsy findings: The cause of death could not be determined as the macromorphological findings were unspecific. Toxicology findings The calibration curve of chloroprene in serum shows linearity from 1.0 to 200 μg/ml (r(2)=0.9999) using benzene as internal standard. The LOD is 0.28 μg/ml, the LLOQ is 0.99 μg/ml. Tissues and body fluids were stored at -20 °C till the analysis. Chloroprene was quantified after addition of benzene as the internal standard. It was found in nearly all tissues and body fluids except in the urine and lung. The highest concentrations were detected in the kidney, liver, myocardial muscle and especially in the brain. Furthermore, hexanal was found in all samples except in the urine. The amount of hexanal in some specimens is high, especially in the lung, bile, gastric content and myocardial muscle. Conclusion We assume that a significant amount of chloroprene was not only inhaled but also absorbed through the skin because the man wore a respiratory mask. Presumably the accident would not have happened if the works safety protocols had been followed. The reason why high concentrations of hexanal were found in the tissues could not be clarified.     

A fatal poisoning involving Bromo-Dragonfly

This paper reports a fatal overdose case involving the potent hallucinogenic drug Bromo-Dragonfly (1-(8-bromobenzo[1,2-b; 4,5-b′]difuran-4-yl)-2-aminopropane). In the present case, an 18-year-old woman was found dead after ingestion of a hallucinogenic liquid. A medico-legal autopsy was performed on the deceased, during which liver, blood, urine and vitreous humour were submitted for toxicological examination. Bromo-Dragonfly was identified in the liver blood using UPLC–TOFMS, and was subsequently quantified in femoral blood (0.0047 mg/kg), urine (0.033 mg/kg) and vitreous humour (0.0005 mg/kg) using LC–MS/MS. Calibration standards were prepared from Bromo-Dragonfly isolated from a bottle found next to the deceased. The structure and purity of the isolated compound were unambiguously determined from analysis of UPLC–TOFMS, GC–MS, HPLC–DAD, ¹H and ¹³C NMR data and by comparison to literature data.The autopsy findings were non-specific for acute poisoning. However, based on the toxicological findings, the cause of death was determined to be a fatal overdose of Bromo-Dragonfly, as no ethanol and no therapeutics or other drugs of abuse besides Bromo-Dragonfly were detected in the liver, blood or urine samples from the deceased. To our knowledge, this is the first report of quantification of Bromo-Dragonfly in a biological specimen from a deceased person. This case caused the drug to be classified as an illegal drug in Denmark on 5th December 2007.     

Postmortem oxycodone and hydrocodone blood concentrations

There is limited data on postmortem oxycodone concentrations, consisting of three published reports with a total of 11 cases, many of which were polypharmacy cases. This report presents the results of a review of autopsy and coroner's reports from 10 counties for the years 2000 and 2001 to locate cases with oxycodone or hydrocodone exposure as a leading cause of death. Eighty-eight cases were located. Twenty-four deaths were attributed to oxycodone alone. Mean and median postmortem oxycodone blood concentrations were 1.23 mg/L and 0.43 mg/L, respectively. The range was 0.12 to 8.0 mg/L, with 13 cases (54%) < or = 0.5 mg/L. Seventeen deaths were attributed to hydrocodone alone. Mean and median postmortem hydrocodone blood concentrations were 0.53 mg/L and 0.40 mg/L, respectively. The range was 0.12 to 1.6 mg/L, with 11 cases (65%) < or = 0.5 mg/L. There were seven cases where the cause of death was attributed to the effects of a combination of hydrocodone and oxycodone. Mean oxycodone and hydrocodone blood concentrations were 0.34 mg/L and 0.14 mg/L, respectively. Forty cases involved polysubstance overdoses with significant involvement of other drugs and ethanol. Mean oxycodone and hydrocodone blood concentrations were 0.18 mg/L and 0.29 mg/L, respectively. The list of other substances involved was extensive but included ethanol, amitriptyline, methadone, codeine, propoxyphene, and acetaminophen. The findings of this study report oxycodone values associated with a fatality at blood concentrations lower than previously reported. This may represent enhanced information because of the larger sample group. Hydrocodone values associated with a fatality were similar to previously published values.     

A fatal poisoning caused by methomyl and nicotine

A 35-year-old male was found lying in a prone position in his room. He was in cardiopulmonary arrest on arrival to hospital and was pronounced dead. There was no attempt at resuscitation. No miosis was observed on admission. At post-mortem his stomach contained 170 g greenish liquid with a small amount of shredded tobacco leaves. The serum cholinesterase activities were 47-90 IU (normal range for male: 200-440 IU). GC and GC-MS analyses showed nicotine (21.8 mg), methomyl (304 mg), and triazolam (1.69 mg) in his stomach. He had consumed tobacco leaves, Lannate containing water soluble methomyl (45%), and Halcion tablets containing 0.25 mg triazolam. Methomyl concentrations in blood were 3-8 ng/ml. Substantial amounts of methomyl (2260-2680 ng/ml) were detected in cerebrospinal fluid and vitreous humor. Nicotine concentrations in blood ranged from 222 to 733 ng/ml. A small amount of triazolam was detected only in bile (176 ng/ml) and liver (23 ng/g). The cause of death was respiratory paralysis produced by the additive effects of methomyl and nicotine shortly after consumption.