Spontaneous intracerebral hemorrhage related to methamphetamine abuse: autopsy findings and clinical correlation

A healthy 31-year-old male abstinent from drug abuse during his recent incarceration developed slurred speech, a severe headache, and left-sided hemiparesis prior to his eventual death 9.5 hours after inhalation of methamphetamine. On postmortem examination, inspection of the brain revealed bilateral subarachnoid hemorrhage, with a prominent intralobar hemorrhage centered within the right frontal cerebral hemisphere. No evidence of vasculitis, infarction, intraventricular hemorrhage, or ruptured aneurysm could be observed. While this is not the first report of a methamphetamine-related stroke, this report describes the autopsy findings of an intracerebral hemorrhage secondary to methamphetamine abuse on autopsy and compares the findings and antemortem history to previously reported methamphetamine cerebral vascular deaths.     

A study of various morphologic variables and troponin I in pericardial fluid as possible discriminators of sudden cardiac death

Pathologists frequently examine victims of sudden cardiac death. In some cases, a firm diagnosis of cardiac-related death can be made based on conclusive gross and histologic findings. In many other cases, we find evidence supportive of, but not diagnostic of, cardiac death (e.g., atherosclerotic coronary artery disease, cardiomegaly, myocardial scarring). A final cohort consists of cases of sudden death with minimal to mild cardiac disease, no other significant pathology, and negative toxicologic studies. This prospective study compared 38 cardiac-related deaths with 52 control cases with respect to concentrations of pericardial cardiac troponin I (cTnI), heart weight, evidence of old and/or recent myocardial injury, and presence of significant coronary artery disease. The influence of documented chest trauma and/or perimortem cardiopulmonary resuscitation (CPR) on levels of cTnI was also analyzed. Even though median cTnI levels were significantly higher in cardiac deaths than in controls (p = .003), cTnI was not found to be a significant predictor of cardiac deaths, as determined by discriminant analysis (p = .52). Heart weight >500 g, evidence of old and recent myocardial injury, and significant coronary artery disease were seen statistically more often in cardiac deaths than in controls (p < or = .005 in each case), and median age was significantly higher in cardiac deaths than in controls (p = .001). Based on a stepwise logistic regression model, significant coronary artery disease, old and recent myocardial injury, and heart weight >500 g were found to contribute significantly to the prediction of cardiac death. Finally, neither chest injury nor CPR significantly affected concentrations of cTnI in pericardial fluid. These data confirm that the presence of acute and remote myocardial injury, significant coronary artery disease, and cardiomegaly (heart weight >500 g) strongly supports the diagnosis of a cardiac-related death. In contrast to a recently published report, we do not find that elevated concentrations of cTnI in pericardial fluid are strong indicators of cardiac-related deaths using our methodology.     

Microscopic lesions of the myocardium in acute coronary heart disease

A statisticomathematical analysis of microscopic changes in the myocardium has established pathognomonic and differential-diagnostic morphological signs for diagnosis of acute ischemic heart disease--acute coronary failure and acute myocardial infarction at the prenecrotic stage. The results of chromotrop 2B water blue staining of histological preparations and polarization microscopy were compared.     

Cardiac rupture in acute myocardial infarction: a reassessment

Cardiac rupture as a complication of acute myocardial infarction (AMI) has been described as occurring infrequently. Because of the recent dramatic decrease in autopsy rates, the authors believe that current studies do not accurately represent the frequency of this catastrophic complication. Autopsy protocols and archived histologic slides of patients with AMI were retrospectively reviewed to determine whether the frequency of cardiac rupture, as a complication of AMI, is altered when a non-hospital-based patient cohort after autopsy is evaluated. This review yielded 153 cases of 41 women and 112 men, whose postmortem examinations revealed gross and histologic evidence of AMI. Cardiac rupture was present in 30.7% of these cases. Of the 47 patients with rupture, 35 had no relevant medical history. The remaining 12 patients had various medical conditions. None of the patients in the rupture group had previously treated symptoms related to coronary artery conditions. Whereas women constituted 26.8% of the total AMI group, they had a cardiac rupture rate of 61%. By contrast, men with AMI had a cardiac rupture rate of 19.6%. All patients in the cardiac rupture group had heart weights over the predicted expected weight as a function of body weight. Age, gender, and heart weight were significant factors associated with cardiac rupture, whereas body mass index was not significantly related. When these factors were evaluated jointly, age was a significant explanatory factor for rupture among both men and women, whereas body mass index and heart weight were significant for men but not for women. When the rupture sites occurred on the left ventricular myocardium, the anterior wall was affected in 21 cases (45%), the posterior wall in 18 (38%), the lateral wall in 4 (9%), and the apex in 3 (6%). The right ventricular myocardium ruptured in 1 case (2%). Most of the patients had severe multivessel coronary artery disease. Histologic study of the specimens showed that the majority of ruptures occurred between 24 and 72 hours after myocardial infarction. This study showed a frequency of cardiac rupture of 30.7% in patients with AMI and sudden death according to medical examiner's records. These findings confirm and reinforce the importance of postmortem examination and autopsy as an adjunct to clinical medical practice.     

A detailed mechanistic fragmentation analysis of methamphetamine and select regioisomers by GC/MS

A novel ring-substituted methamphetamine regioisomer, N,alpha,4-trimethyl phenmethylamine, was synthesized in order to study the validity of proposed structures for various mass spectrometry (MS)-derived peaks in a methamphetamine fragmentation pattern. While other research efforts have studied aspects of methamphetamine in detail, a full fragmentation study has not been reported previously. In addition to showing molecular structures represented by fragment peaks, mechanisms for selected processes are detailed. An empirically derived procedure to easily determine by simple spectral peak pattern recognition the geometry of dimethyl- or ethyl-substituted immonium ions (RRC = N+ RR) where m/z = 58 is outlined. These results are platform independent for electron ionization (EI) instruments, but have also proven to be helpful in explaining spectral peaks observed in spectra from ion trap systems. The spectrum for the synthesized methamphetamine regioisomer was accurately predicted using this methodology. While this approach is useful in some casework, the converse may be more useful: when an unexpected or unusual peak pattern arises in a spectrum, being able to analyze it to determine the structure of the molecule. This paper gives an analyst the means to begin such retro-synthetic analyses.     

Further evaluation of immunocytochemical staining in the diagnosis of early myocardial ischaemic/hypoxic damage

The pattern of immunocytochemical staining with antibodies to caeruloplasmin, myosin, myoglobin and C-reactive protein seen in myocardium taken from deaths with macroscopic evidence of myocardial infarction and/or significant coronary artery atherosclerosis and from deaths with neither of these lesions has been correlated with H&E, PTAH and HBFP staining of myocardium and circumstances of each death indicative of antemortem hypoxia and/or ischaemia. Loss of staining with these antibodies correlated well with fuchsinorrhagia and both techniques are more sensitive than H&E and PTAH staining in the detection of early ischaemic/hypoxic damage to myocardium. However, their sensitivity is such that they appear to detect agonal changes and, therefore, cannot be used for specific diagnosis of early myocardial infarction.     

Travel, time zones, and sudden cardiac death. Emporiatric pathology

In an 11-year retrospective study of coroner's autopsies on the Hawaiian island of Kauai, it was found that an unusual and apparently unique subset of travelers died suddenly. Death was caused by coronary arteriosclerosis, was characterized by acute coronary changes, and occurred in a group younger than the usual age for sudden cardiac death. Visitors with two-vessel disease had an incidence of sudden death nearly four times that of Kauaians (p less than 0.02), with a ninefold increase of coronary thrombosis (p less than 0.001), a sixfold prevalence of old myocardial infarcts (p less than 0.001), and three times the prevalence of cardiomegaly (p less than 0.001). The circadian pattern of these deaths was different from that previously described in acute myocardial infarction or sudden death, with the number of incidents rising steadily through the day in contrast to the morning peak described in previously published series. The syndrome was expressed in decedents with two-vessel coronary disease either with acute coronary artery lesions--thrombosis, hemorrhage in a plaque, or ruptured coronary artery--or no lesions, presumably spasm. Underlying chronic processes included enlarged heart or old myocardial infarct, which both occurred with a significantly greater incidence in travelers than in local residents, and in a totally different pattern from that occurring in subjects with three-vessel disease. It is postulated that the syndrome is caused by stress related to travel and time zone changes.     

急性心肌缺血猝死心肌中血红素加氧酶-1的表达

目的观察血红素加氧酶-1（HO-1）在急性心肌缺血猝死心肌细胞胞浆中的表达情况。方法应用免疫组织化学技术（SP法）,对27例可疑早期心肌缺血猝死（早期梗死组）、10例心肌梗死猝死（心肌梗死组）、11例冠心病非心性猝死（对照组1）以及10例正常心肌（对照组2）中HO-1的表达进行观察分析。结果早期梗死组与心肌梗死组在心肌细胞胞浆中HO-1均呈强阳性表达,对照组1和对照组2心肌细胞胞浆中HO-1弱阳性表达或无表达。早期梗死组和心肌梗死组与对照组1和对照组2之间心肌细胞内HO-1表达的差异有显著性意义（P（0.01）;镜下各组心肌细胞胞浆内HO-1表达的阳性面积率及平均光密度差别明显。结论 HO-1可以作为急性心肌缺血所致心性猝死的一个诊断指标。     

急性心肌梗死时人心脏房室结细胞糖蛋白表达

目的观察急性心肌梗死时心传导系统糖蛋白表达。方法运用花生凝集素(PNA),对8例急性心肌梗死亡者的心传导系统标本进行亲和组化染色。结果PNA有7例呈现强阳性,1例出现弱阳性。结论房室结传导细胞在缺血时细胞膜表达PNA受体,提示急性心肌梗死时房室结细胞和工作心肌都不同程度受累,并且细胞病理改变机制可能相关或类似。     

Impact of Myocardial Infarction and Abnormalities of Cardiac Conduction System on Sudden Cardiac DeathCSCD

Sudden cardiac death (SCD), most commonly seen in coronary heart disease, is a kind of sudden death caused by series of cardiac parameters, which usually combines with myocardial infarction. However, some SCDs (including early myocardial infarction) happen suddenly and cause death in a very short time. In these circumstances, typical morphological changes are lack in macroscopic or microscopic fields, which make such SCDs become the emphasis and difficulty in the present research. SCD caused by myocardial infarction and abnormalities of cardiac conduction system (CCS) is related to atherosclerosis of coronary artery closely. This paper reviews cardiac dysfunction caused by myocardial infarction and diseases of CCS from morphology and molecular biology, and explores potential relationship between them. This paper aims to provide clues to the mechanism of myocardial infarction related sudden death and possible assistance for forensic diagnosis of SCD. © 2017 by the Editorial Department of Journal of Forensic Medicine.     

Evaluation of postmortem serum calcium and magnesium levels in relation to the causes of death in forensic autopsy

There appears to be very poor investigation of postmortem serum calcium (Ca) and magnesium (Mg) for diagnostic evidence to determine the cause of death. The aim of the present study was a comprehensive analysis of the serum levels in relation to the causes of death in routine casework. Autopsy cases (total, n=360; 5-48 h postmortem), including blunt injury (n=76), sharp injury (n=29), asphyxiation (n=42), drownings (n=28: freshwater, n=11; saltwater, n=17), fire fatalities (n=79), methamphetamine (MA) poisoning (n=8), delayed death from traumas (n=37), and acute myocardial infarction/ischemia (AMI, n=61), were examined. In total cases, there was no significant postmortem time-dependent rise in serum Ca and Mg. Both Ca and Mg levels in the heart and peripheral blood were significantly higher in saltwater drowning compared with those of the other groups. In addition, a significant elevation in the Ca level was observed in freshwater drowning and fire fatalities, and in the Mg level in fatal MA intoxication and asphyxiation. Topographic analyses suggested a rise in serum Ca and Mg due to aspirated saltwater in drowning, that in serum Ca in freshwater drowning and fire fatalities of peripheral skeletal muscle origin and that in serum Mg in MA fatality and asphyxiation of myocardial and/or peripheral origin. These markers may be useful especially for diagnosis and differentiation of salt- and freshwater drownings and may be also helpful to determine the causes of death involving skeletal muscle damage, including burns and MA intoxication.     

早期心肌梗死死后诊断的法医病理学研究进展

心源性猝死在成人猝死的死因中占首位,心肌梗死是冠心病猝死的主要机制之一,由于早期心肌梗死发生突然,且可在短时间内死亡,肉眼和镜下都缺乏典型的形态学改变,一直都是法医实践中研究的热点,本文回顾多年来心肌梗死的研究成果在法医学中的应用及局限,展望新的临床指标在法医工作中的可行性,期望提高死后心肌梗死诊断的准确率。     

Detection of apoptosis in ischemic heart. Usefulness in the diagnosis of early myocardial injury

Myocardial samples of hearts with histologic findings of acute myocardial infarction (group A), sudden coronary deaths without histologic changes (group B), and chronic ischemic heart disease (group C) were analyzed to investigate the appearance of apoptosis in acute and chronic ischemic cardiac disorders. This analysis involved the morphologic detection of DNA strand breaks in myocyte nuclei by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and the biochemical determination of DNA laddering in the myocardium using archival formalin-fixed, paraffin-embedded tissue sections of human myocardium. The authors demonstrated that apoptosis of myocardial cells could occur after ischemic myocardial cell injury. In all documented cases of acute myocardial infarction (group A), the infarcted area included extensive presence of both apoptosis and necrosis. In the tissue bordering on and away from the obviously infarcted areas, positive nuclei were intermingled with nonstained normal myocytes. The number of positive nuclei decreased with the distance from the infarction foci. In group B, myocardial samples showed focal or diffuse nuclear positivity of varying degrees for apoptosis, confirming the presence of myocardial ischemic cell death, whereas the histologic diagnosis remained inconclusive. This finding suggests that apoptosis could be used as a marker for acute ischemic injury. In group C, stained nuclei were dispersed with intermingled normal cardiomyocytes.     

A case of fatal hemorrhage in the cerebral ventricles following intravenous use of methamphetamine

We describe a case of massive hemorrhage in the cerebral ventricles, probably caused by methamphetamine abuse. A 44-year-old male was found dead in a prone position in a hotel room. Old and new injection marks were observed in his right cubital fossa. Petechiae were observed on the conjunctiva of his right eye, laryngeal mucosa, epicardium and under the capsule of the liver (to a slight or moderate degree). The brain, weighing 1.67 kg, was heavily edematous; the lateral and fourth ventricles were filled with hematomas. Subarachnoid, intracerebral hemorrhages were not observed. Cerebral vascular abnormalities were not evident. There were no remarkable changes in other organs, other than congestion. Gas chromatographic-mass spectrometric analysis of the urine disclosed the presence of methamphetamine and amphetamine. The concentration of methamphetamine within the femoral venous blood and intraventricular hematoma was 0.347 microg/ml and 0.189 microg/g, respectively. Amphetamine was not detected in either sample. Urine contained 3.15 microg/ml methamphetamine and 0.063 microg/ml amphetamine. These results indicate that intraventricular hemorrhage might have occurred shortly after intravenous self-administration of methamphetamine. Cerebral arterial spasm and hypertension resulting from the administration of methamphetamine might have resulted in intraventricular hemorrhage.     

Stereoselective analyses of selegiline metabolites: possible urinary markers for selegiline therapy

The stereoselective analysis of selegiline metabolites in human urine and plasma by gas chromatography using the chiral column with the non-chiral reagent was investigated for the differentiation of selegiline therapy from the methamphetamine (MA) abuse. This method gave clear separations of MA and amphetamine (AM) isomers without any artifactual optical-opposite peaks due to the reagent. After the administration of selegiline tablets, desmethylselegiline (DMS), MA and AM were observed as (−)-isomers in the urine and plasma. Within the first 48 h after dosing, approximately 40% of selegiline administered was excreted in urine as these three metabolites. The parent drug, selegiline, was not detected in any urine or plasma samples. On the other hand, MA and AM were observed only as (+)-isomers in the urine of MA abusers. For the distinction of selegiline users from street MA abusers in urinalysis, (−)-DMS, a specific metabolite of selegiline, was not a suitable marker. (−)-DMS rapidly disappeared from urine and was excreted only 1% of the given dose. By the moment analysis with the trapezoidal integration, the mean residence times of (−)-DMS in plasma and urine were 2.7 and 3.8 h, respectively, which were 5–20 times shorter than those of (−)-MA or (−)-AM. The values of AM/MA in the urine increased from 0.24 to 0.67 (r=0.857) along with time after the selegiline administration. This ratio was not a sufficient marker to differentiate selegiline users from MA abusers, although the values of AM/MA in 74% of MA abusers were less than 0.24. The present GC technique improved the chiral analyses of MA and AM. This chiral analysis is the most useful technique to avoid the misinterpretation in the discrimination between clinical selegiline therapy and illicit MA use.     

Alcohol addiction of methamphetamine abusers in Japan.

Fifty-eight methamphetamine (MAMP) abusers were surveyed to demonstrate the types of nature of MAMP abuse. In-depth interviews using psychophysiological techniques assessed the subjects to be truthful or deceptive about their abuse histories. Research diagnostic criteria determined the subjects clinical symptoms. The results show that three factors characterize MAMP abuse: significant correlation was found between the years of abuse; the manifestation of somatic or mental disorders or both, and alcohol (Alc) addiction. MAMP abusers who were nondrinkers or light drinkers developed a tendency to dislike Alc after MAMP abuse, while there was no change in Alc consumption in heavy drinkers. The findings suggest that the combined abuse of MAMP and Alc aggravates somatic and mental disorders and that Alc plays an important role in the fatal effect of MAMP, especially from small doses. This provides support for the synergistic effects between MAMP and Alc. Coadministration of MAMP and Alc appears to produce long-acting and more complicated changes in the brain's neurotransmitter function.     

大鼠早期心肌缺血CX43免疫组化研究

目的探讨早期心肌缺血的法医病理学诊断依据。方法通过建立大鼠心肌缺血模型,用免疫组化染色方法检测大鼠心肌缺血15、30、60、120、180min以及正常对照组心肌CX43的表达情况。结果在各组早期心肌缺血区内,见CX43阳性着色的分布与正常组相比,表现为部位的不同及数量上的差异。结论CX43的免疫组化染色对诊断早期心肌缺血有一定的价值,但尚需进一步研究证实。     

Pulmonary thromboembolism after air travel: Two case reports, the review of literature and forensic implications

Anabolic androgenic steroids (AAS) are the main class of doping agents and their consumption produces adverse effects involving several organs and systems. Three cases of sudden cardiac death (SCD) and one of death due to congestive heart failure of previously healthy athletes who were AAS users are herein reported. Concentric cardiac hypertrophy with focal fibrosis (one case), dilated cardiomyopathy with patchy myocyte death (two cases) and eosinophilic myocarditis (one case) were observed and most probably relate to the final event. Molecular investigation for viral genomes was positive in one case (Ebstein virus). Our data confirm previous findings, showing that the most typical cardiac abnormality in AAS abusers is left ventricular hypertrophy, associated with fibrosis and myocytolysis. An exceptional cardiovascular substrate was represented by the case with drug induced eosinophilic myocarditis. These features are at risk of ventricular arrhythmias as well as congestive heart failure. The cause-effect relationship between AAS abuse and cardiac death can be established only by a rigorous methodology with the use of standardized protocols, including precise morphological studies of all target organs to search for chronic toxic effects. Laboratory investigations should focus on AAS searching on a wide range of biological matrices to demonstrate type, magnitude and time of exposure.     

Quantification of Methamphetamine in Mouse Thighbones Buried in Soil

Bone samples are used for analysis of drugs in decomposed or skeletonized bodies. Toxicological analyses of buried bones are important for determining the causes and circumstances of death. In this study, methamphetamine and amphetamine concentrations in heart blood, thigh muscles, and thighbones were analyzed using solid‐phase extraction with liquid chromatography–tandem mass spectrometry. Methamphetamine concentrations in heart blood, thigh muscle, and thighbone ranged from 0.041 to 0.873 μg/mL, 0.649 to 2.623 μg/g, and 56.543 to 643.371 μg/g, respectively. Thighbone concentrations were significantly higher than those in heart blood or thigh muscles were. Methamphetamine concentrations in buried thighbone (4.010–45.785 μg/g) were significantly lower than those of unburied thighbones were (56.543–643.371 μg/g). Methamphetamine and amphetamine were detected in thighbones buried for 7–180 days. These findings indicate that the methamphetamine concentrations in bone are higher and decrease after burial in soil.