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Understanding the actual conditions of methamphetamine (MA)-related death is important from the perspectives of criminal justice and public health. In this report, we review 104 cases of MA-related death handled by our departments between January 2014 and December 2020. Based on information from police and autopsy examinations, we classified the cases into the following categories: "accidental intoxication" ("MA only" and "multiple drugs or alcohol"), "fatal disease" ("definitively MA-related," "possibly MA-related," and "unlikely MA-related"), "accident," "suicide," "homicide," and "undetermined." The total number and annual trends for each category and their respective femoral blood concentrations were investigated. "Fatal disease" was the most common category (48 cases), followed by "suicide" (25 cases), "accidental intoxication" (14 cases), and "accident" (11 cases). "Definitively MA-related" in which MA may have played a role in their onset or exacerbation accounted for the majority of "fatal disease": 12 cases of heart disease, 4 cases of aortic dissection, 12 cases of cerebral hemorrhage, and 4 cases of subarachnoid hemorrhage. Cases classified as "definitively MA-related" died with lower femoral blood concentrations of MA compared with "MA only." Cases with "fatal disease" might have been misdiagnosed as "death by natural causes" if a proper autopsy and toxicology examinations were not performed. In death investigations, it is necessary to keep in mind that there are some MA-related deaths, and efforts should be made to increase awareness about the risk of death in using this drug., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The chemsex or slamsex phenomenon has attracted attention worldwide, with concerns also expressed by health professionals for the spread of sexually transmitted diseases. Mephedrone or 4-methylmethcathinone, a substituted cathinone homolog of ephedrine, is one of the most popular substances used as a cheaper alternative to other traditional drugs. Fatal cases of chemsex are still rare. We present here the first case-report to the best of our knowledge of a mephedrone-related acute toxicity case in Parma (Italy) detected and quantitated in biological specimens (2.0 mg/L in urine sample, 1.1 mg/L in bile and 1.0 mg/L in central blood while 0.8 mg/L in peripheral blood). None of the other most common drugs of abuse could be detected. Autopsy findings such as facies edematosa, oedema and polyvisceral congestion, interstitial petechiae are compatible elements with a death from acute cardio-respiratory failure, with peri-mortem agony of few minutes in which the cardiac hypertrophy, the moderate aortocoronary sclerosis and mephedrone injection have played a substantial role in the evaluation of the final cause due to an accidental acute intoxication with mephedrone., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The case described in this report is of a male infant who was found dead in a closet. His mother delivered the infant in the kitchen, left him wrapped in a towel, and called emergency medical services 4days after the delivery. At the autopsy, the growth suggests a full-term delivery, significant pathological findings were not observed, and the infant was estimated to be stillborn. After the autopsy, the police investigation discovered that the mother used a stimulant during the pregnancy and shortly before the rupture of the membrane. Toxicological analysis showed 1.60mg/L of methamphetamine in the blood, strongly suggesting that the fetal death was associated with this acute intoxication. Thus far, only a few cases of infant deaths have been reported in association with methamphetamine intoxication. The present case showed the highest blood concentration of methamphetamine compared to the past infant cases with this intoxication., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Methamphetamine (METH) neurotoxicity is involved in METH-related deaths. It has been suggested that the midbrain, together with the striatum, is affected by METH neurotoxicity and the endoplasmic reticulum (ER) stress is induced in the processes of METH neurotoxicity. In this study, we examined the effects of low-dose METH administration for 5d on GRP78 and C/EBP homologous protein (CHOP), both of which are induced under ER stress, and METH neurotoxicity in the rat midbrain. We showed that 1mg/kg of METH induced an increase in GRP78 protein and mRNA expression 1d after the last injection, but had no effect on the levels of CHOP, tyrosine hydroxylase (TH), or GFAP. Secondly, we evaluated the induction of ER stress and the extent of METH neurotoxicity in the midbrain of animals pretreated with METH. In animals pretreated with saline, we observed elevated CHOP levels, together with decreased TH levels and increased GFAP levels, indicative of METH neurotoxicity, after neurotoxic METH administration, while there was no significant change in GRP78 levels. In contrast, low-dose METH (1.0mg/kg) pretreatment increased GRP78 levels and inhibited the induction of CHOP in the midbrain without METH neurotoxicity. These findings of ER stress in animals pretreated with METH were associated with an early increase in SOD1 levels and upregulation of Bcl-2. Therefore, our study suggests that pretreatment with low-dose METH may be protective against METH neurotoxicity in the midbrain, leading to the suppression of oxidative stress and apoptotic mechanisms, in part via ER stress-related pathways. Because chronic human METH abusers administrate low-dose METH repeatedly over an extended period before lethal injection, investigation of the pathophysiology of METH neurotoxicity in animals pretreated with low-dose METH might provide useful information on the pathophysiology of chronic and/or lethal METH use in cases of METH-related deaths., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

A case of acute mathamphetamine (MA) poisoning death was occasionally found in autopsy by leaking into alimentary tract from package in drug traffic. A Korean man (39-year-old) was found dead in his apartment in Shenyang and 158 columned-shaped packages (390 g) of MA were found in his alimentary tract by autopsy, in which four packages were found in the esophagus, 118 in the stomach and 36 in the lower part of small intestine. The packages were wrapped with tinfoil and plastic film, from which one package in the stomach was empty and ruptured. Extreme pulmonary edema, congestion and hemorrhage as well as moderate edema, congestion and petechial hemorrhage in the other viscera were observed at autopsy and microscopically. Simultaneously AMP (amphatamine) in urine was tested positive by Trige DOA kit. Quantitative analysis was performed by gas chromatography/mass spectrometry. Extremely high concentrations of MA were found in the cardiac blood (24.8 microg/mL), the urine (191 microg/mL), the liver (116 microg/mL) and the gastric contents (1045 microg/mL), and no alcohol and other conventional drugs or poisons were detected in the same samples. The poisoning dosage is 5 microg/mL in the plasma and lethal dosage is 10-40 microg/mL in the plasma according the report. This high concentrations of MA in blood indicated that the cause of death was result from acute MA poisoning due to MA leaking into stomach. Much attention must be paid in the body packer of drugs in illegal drug traffic.

A female in her late thirties, who was hospitalized for 13 days with rib fractures suffered in a traffic accident, was found in supine position on the patient's bed in a state of cardiopulmonary arrest. The resuscitation failed to recover consciousness and her death was confirmed 1.75 h later. The autopsy revealed neither severe injuries nor lesion as a cause of death. Histological examinations revealed contraction band necrosis (CBN) in the cardiac muscle of the left and right ventricles, as well as congestion and edema in both lungs. Toxicological screening of urine using Triage revealed the presence of methamphetamine (MA). By gas chromatography-mass spectrometry (GC/MS), the concentrations of MA and its metabolite amphetamine (AP) in the heart blood were shown to be 0.178 and 0.051 microg/ml, respectively. From these findings, we conclude that the cause of her death was circulatory failure due to MA poisoning. Further, the stored scalp hair analysis demonstrated both MA and AP in 0-3 cm segments from the scalp. The results suggested that she was a MA abuser at least about 3 months before her death. In this case, preservation of hair samples collected during an autopsy was useful for providing evidence of MA abuse.

A man in his late twenties collapsed shortly after intravenously injecting himself with methamphetamine (MA). He slipped into a deep coma and remained in this condition for 9 days, until his death. Autopsy revealed severe brain edema and localized subarachnoid hemorrhages in the cerebrum and cerebellum. Histopathological examination revealed myocardial necrosis in the left ventricle, rhabdomyolysis and bronchopneumonia. Blood derived from the cadaver was found to have high levels of blood urea nitrogen and creatinine, suggesting he experienced acute renal failure probably due to rhabdomyolysis. Most of the postmortem findings were consistent with MA poisoning. The patient's bronchopneumonia may have represented a hypostatic pneumonia that developed as a result of his deep coma. While the patient's brain edema, myocardial necrosis and rhabdomyolysis were diagnosed soon after admission, his bronchopneumonia and acute renal failure only occurred 6 and 8 days later, respectively. Although MA was not detected in the cadaver's blood, urine or liver, analysis of the decedent's hair using gas chromatography-mass spectrometry confirmed its presence at a concentration of 1.1 ng/mg. Based on these findings, we concluded that the patient's cause of death was multiorganopathy resulting from MA poisoning. This case suggests that the postmortem diagnosis of MA poisoning in patients who survive for relatively longer periods after drug injection should include toxicological hair analysis in combination with histopathological and postmortem physiochemical examination.

We reviewed 32 cases where a forensic autopsy detected methamphetamine in the blood, and all of these autopsies were performed at two institutes between 1991 and 2003. In accordance with several criteria, the blood concentration in 11 cases was classified as above the toxic level, and 10 of these cases were diagnosed as methamphetamine poisoning. In 20 cases (62.5% of total cases), the blood concentration was of a 'toxic level', and 10, 2 and 1 of these cases were diagnosed as methamphetamine poisoning, cardiomyopathy and intracerebral hemorrhage, respectively. Since it is unclear how the effects of methamphetamine may contribute to the death of an individual, a diagnosis of the exact cause of death is often difficult to make in cases where the blood concentration of methamphetamine was of a 'toxic level'. Therefore, a diagnosis has to be carefully made in consideration of the pathological findings, the pharmacological effects of methamphetamine and the process until death in such cases. Additionally, the mechanism of methamphetamine-related death needs to be more fully studied to enable an appropriate diagnosis to be made easily.

In forensic pathology, previous studies have suggested the possible application of cardiac troponins in the diagnosis of myocardial infarction. However, there appears to be insufficient practical data on other causes of death. The present study was a comprehensive analysis of the cardiac, peripheral blood and pericardial levels of cardiac troponin T (cTnT) in serial medicolegal autopsy cases (n = 405) with a survival time <24 h and within 48 h postmortem to assess the validity of investigating myocardial damage with special regard to traumatic causes of death. These included blunt and sharp instrument injury (n = 122 and 21, respectively), asphyxiation (n = 35), drowning (n = 27), fire fatalities (n = 94), hyperthermia (n = 13), hypothermia (n = 6), fatal methamphetamine (MA) abuse (n = 12) and carbon monoxide (CO) poisoning (n = 5) in comparison with myocardial infarction (MI, n = 57) and cerebrovascular diseases (n = 13). Cases within 12h postmortem usually showed lower cardiac and pericardial cTnT levels than did those of longer postmortem time of 12-48 h. In the early postmortem period of <12 h, significantly elevated serum cTnT levels were observed for hyperthermia. Thereafter, fatal MA abuse, CO poisoning and MI cases also showed higher levels. However, cTnT remained at lower levels for hypothermia and drowning. The elevation of cTnT was associated with the pathology of advanced myocardial damage involving swelling and liquefactive necrosis. The above-mentioned differences were the smallest for peripheral blood. These findings suggest that elevations in postmortem serum and pericardial cTnT levels depend on the severity of myocardial damage at the time of death and are related to the pathological findings, although postmortem interference should be taken into consideration.

Serum endotoxin is a clinical marker of sepsis. However, it is vulnerable to bacterial contamination, and the postmortem stability has not been established. In the present study, to evaluate the forensic pathological significance of postmortem endotoxemia in relation to the causes of death, we investigated a series of 111 autopsy cases (postmortem interval<48 h), in part, using bacteriological investigations. Systemic endotoxemia involving both the cardiac and peripheral blood was observed in some specific causes of death, including pneumonia (n=1/3), peritonitis (n=2/5), delayed traumatic death with severe secondary infection (n=7/33), drownings (freshwater, n=3/9; saltwater, n=3/16), fire deaths (n=3/16), and also in protracted deaths under critical medical care (n=2). Most cases of fatal blunt injury (n=4/5) showed sporadic endotoxemia in cardiac or peripheral blood, whereas there was no elevation of serum endotoxin in acute hemorrhagic death from sharp instrument injury (n=6). The bacteriological investigation showed some characteristic profiles in infections and drownings. These observations suggested that, although endotoxin is a vulnerable serum marker to ante and postmortem interference, systemic postmortem endotoxemia involving peripheral blood may be a possible indicator of antemortem bacteremia related to some specific causes of death accompanied by advanced infection or pulmonary alveolar damage in the dying process especially due to drownings and fires.

During the last years in Germany a marked increase in the use of amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been observed. The use of these recreational drugs is especially common among young people participating in rave parties. Occasionally ring-methoxylated phenethylamine derivatives like paramethoxymethamphetamine (PMMA) or paramethoxyamphetamine (PMA) are found in street drugs offered as ecstasy. These compounds exhibit a higher toxicity than the methylenedioxyamphetamine derivatives. We report on the death of a 22-year-old man after the ingestion of ecstasy pills containing PMMA and PMA. The PMMA concentration in femoral blood was 0.85 mg/l. Besides PMA (0.61 mg/l), amphetamine (0.21 mg/l), benzoylecgonine (<0.01 mg/l) and ethanol (0.46 per thousand ) were found in the blood. The case reflects the well-known fact that street drugs offered as ecstasy pills contain not necessarily MDMA but frequently differ in composition even if they have the same logo. Users of these pills therefore always take the risk of consuming pills with dangerous life-threatening ingredients. In many laboratories paramethoxyamphetamines are not detectable in routine analytical procedures. If the cause of an intoxication cannot be discovered by analytical routine methods, rarely occurring designer drugs such as PMA or PMMA should also be kept in mind.

It is known that methamphetamine (MA) causes rhabdomyolysis, myoglobinuria, and acute renal failure. We conducted an immunohistochemical study on the kidney of 22 forensic autopsy cases in which MA had been detected. Myoglobin was positive in 17 cases. The concentration of the blood MA in the myoglobin-positive cases (8.39+/-3.43 micromol/dl) was higher than -negative cases (0.198+/-0.076 micromol/dl). And, the 70 kDa heat shock protein (HSP70), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), 4-hydroxy-2-nonenal (4-HNE), and Cu/Zn superoxide dismutase (SOD) were also stained positively in five, ten, 11, nine cases of examined, respectively. In addition, 80% of HSP70-positive cases were myoglobin-positive. Myoglobin was also observed in 60% of 8-OH-dG-positive, in 82% of 4-HNE-positive, and in 78% of SOD-positive cases, respectively. Therefore, myoglobin rather than MA itself might induce oxidative damage. From these results, it was considered that MA abuse had caused the skeletal muscle damage before death. In forensic autopsy cases of drug abusers, the antemortem situation is not often known. The present research suggested that in addition to the measurement of the concentration of MA, immunohistochemical staining of myoglobin, HSP70, 8-OH-dG, 4-HNE, and SOD offers important information for the diagnosis of MA poisoning.

The aim of the present study was to review the immunohistochemical and biochemical findings with reference to the causes of death in routine casework (total, n=492). In the immunohistochemistry (n=283), an increase in intra-alveolar granular SP-A (SP-A score) was often observed in asphyxiation (n=21/34, 61.8%) and freshwater drowning (n=15/24, 62.5%), and also in fire and methamphetamine (MA) fatalities (n=22/76, 28.9% and n=5/16, 31.3%). Serum SP-A level (n=134) was elevated in acute respiratory distress syndrome and in some cases of drowning, fire and MA fatalities, hyperthermia and chest traumas. A quantitative analysis of SP-A subclass-gene expression (SP-A1/A2 mRNA) in the lung tissue specimens (n=126) revealed an increase in the SP-A1/A2 mRNA ratio in asphyxiation (n=17/21, 80.9%), freshwater drowning (n=7/9, 77.7%), fire and MA fatalities (n=20/35, 57.1% and n=8/10, 80.0%). These findings suggested the usefulness of SP-A as a marker of asphyxiation, respiratory distress and alveolar injury.