Post-mortem hypoxanthine levels in the vitreous humour an introductory report

Post-mortem hypoxanthine levels in vitreous humour were determined in 86 consecutive legal autopsy cases. In cases of sudden death caused by trauma or by myocardial infarction, levels ranging from 0 to 540 μmol/l were found. The mean value was about ten times higher than normal in vivo plasma levels. The hypoxanthine levels seem to be independent of time post-mortem, at least during the first 48 hours.It is known that augmentation of the hypoxanthine plasma, cerebrospinal fluid, and urine levels reflects tissue hypoxia. In the present material no elevation of hypoxanthine levels in the vitreous humour was found in cases of strangulation or suspension, while statistically significant elevation was found in cases of drug intoxication. It is concluded that this may reflect the effect of drug-induced prolonged tissue hypoxia caused by respiratory depression.     

Urinary excretion profiles of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol: a Delta9-THC-COOH to creatinine ratio study #2

Subjects with a history of chronic marijuana use were screened for cannabinoids in urine specimens with the EMIT((R)) II Plus cannabinoids assay with a cut-off value of 50 ng/ml. All presumptively positive specimens were submitted for confirmatory analysis for the major urinary cannabinoid metabolite (Delta(9)-THC-COOH) by GC-MS with a cut-off value of 15 ng/ml. Creatinine was analyzed in each specimen as an index of dilution. Huestis and Cone [J. Anal. Toxicol. 22 (1998) 445] reported that serial monitoring of Delta(9)-THC-COOH to creatinine ratios in paired urine specimens collected at least 24h apart could differentiate new drug use from residual Delta(9)-THC-COOH excretion. The best accuracy (85.4%) for predicting new marijuana use was a Delta(9)-THC-COOH/creatinine ratio > or =0.5 (dividing the Delta(9)-THC-COOH to creatinine ratio of specimen 2 by the specimen 1 ratio). In a previous study in this laboratory [J. Anal. Toxicol. 23 (1999) 531], urine specimens were collected from chronic marijuana users at least 24h apart and dilute urine specimens (creatinine values <2.2 micromol/l) were excluded from the data analysis. The objective of the present study was to determine whether creatinine corrected urine specimens positive for cannabinoids could differentiate new marijuana use from the excretion of residual Delta(9)-THC-COOH in chronic users of marijuana based on the Huestis 0.5 ratio. Urine specimens (N=946) were collected from 37 individuals with at least 48h between collections. All urine specimens were included in the data review irrespective of creatinine concentration. The mean urinary Delta(9)-THC-COOH concentration was 302.4 ng/ml, mean Delta(9)-THC-COOH/creatinine ratio (ng/ml Delta(9)-THC-COOH/(mmol/l) creatinine) was 29.3 and the Huestis ratio calculation indicated new drug use in 83% of all sequentially paired urine specimens. The data were sub-divided into three groups (A-C) based on the mean Delta(9)-THC-COOH/creatinine values. Interindividual Delta(9)-THC-COOH/creatinine mean values ranged from 2.2 to 13.8 in group A (264 specimens, N=15 subjects) where 80.7% of paired specimens indicated new drug use. In group B, mean Delta(9)-THC-COOH/creatinine values ranged from 15.3 to 37.8 in 444 specimens (N=14 subjects) and 83.3% of paired specimens indicated new drug use. In group C, individual mean Delta(9)-THC-COOH/creatinine values were >40.1 (41.3-132.5) in 238 urine specimens (N=8 subjects) and 85.3% of paired urine specimens indicated new marijuana use. Correcting Delta(9)-THC-COOH excretion for urinary dilution and comparing Delta(9)-THC-COOH/creatinine concentration ratios of sequentially paired specimens (collected at least 48h apart) provided an objective indicator of new marijuana use in this population.     

Increased adrenaline to noradrenaline ratio is a superior indicator of antemortem hypothermia compared with separate catecholamine concentrations

The significance of urinary catecholamines and small gastric mucosal bleedings, Wischnewsky's spots, in postmortem diagnosis of hypothermia deaths was evaluated. Autopsy cases (n=358) were divided into hypothermia, suspected hypothermia, and control groups. The catecholamine levels did not correlate with the length of the postmortem period. The adrenaline to noradrenaline ratio was most effective in detecting hypothermia (68.9% sensitivity, 78.1% specificity). The median adrenaline concentrations were significantly higher in hypothermia than in control groups. The control group containing mostly sudden cardiac deaths with no cold exposure had a noradrenaline level comparable to the hypothermia groups. The sensitivity and specificity of determining Wischnewsky's spots in hypothermia deaths were 63.9% and 88.3%, respectively. The adrenaline to noradrenaline ratio is more suitable in proving antemortem cold stress than either of these independently, and its diagnostic value is comparable to that of Wischnewsky's spots.     

Anaphylactic death: the effect of aminoguanidine and heparin on histamine and stress hormones in guinea pigs

The modifying effect of aminoguanidine (a histaminase inhibitor) and heparin (a histaminase liberator) on anaphylactic shock in guinea pigs was studied using ovalbumin as an antigen and trigger. The animals died of the shock, the time to death remaining unaltered by the drugs. Serum histamine and cortisol values were high after shock, but were reduced by heparin. Both noradrenaline and adrenaline in plasma were also elevated after shock, the final concentration of the latter being lowered by heparin. The lungs were dilated, indicating bronchoconstriction. The results confirm the role of histamine in anaphylactic shock and its potential value for the diagnosis in this kind of rapid death, in which morphological signs are scarce or lacking. Its diagnostic value still requires confirmation, however, which only autopsy studies can supply. It also appears that pretreatment of the animals with heparin affected the blood cortisol and catecholamines, which are involved in the shock mechanism as countermeasures, although aminoguanidine did not have any effect.     

Can Birth Trauma Be Confused for Abuse?

Abstract: An unexpected infant death is usually investigated with a complete autopsy. If evidence of prior trauma is found at autopsy in these cases, suspicion is raised for nonaccidental trauma. In a young infant, the residua of trauma received during birth has the potential to be incorrectly interpreted as nonaccidental trauma. We report a the findings of a 4 1/2‐month‐old‐infant that died unexpectedly with a healing linear skull fracture and a circular lesion over the calvarium found at autopsy. Though this lesion was concerning, the remainder of the autopsy and the histological findings did not support a diagnosis of recent trauma. Review of the literature describing birth injuries made the diagnosis of healing, residual birth trauma more convincing in this case.     

The Role of Postmortem Cardiac Markers in the Diagnosis of Acute Myocardial Infarction*

Abstract: Sudden cardiac deaths because of acute myocardial infarction (MI) constitute a significant percentage of the caseload for death investigators, coroners, and forensic pathologists. Clinicians use cardiac markers, highly sensitive and specific for myocardial damage, to screen living patients for acute MI; however, to this point, the utility of these markers in the autopsy setting has not been fully established. The current study included 10 decedents, five who died of acute MI, and five subjects who died of noncardiac disease. Samples of pericardial fluid and blood from multiple sites were tested for creatine kinase, creatinine kinase MB, and troponin‐I. Three main conclusions were drawn: the levels of cardiac markers from all patients are significantly higher than the reference range for living patients, there are significant differences in cardiac marker levels between samples from different anatomic locations, and only three cardiac marker/anatomic site combinations were significantly different between the control and study groups.     

A multiple drug fatality involving MK-801 (dizocilpine), a mimic of phencyclidine

MK-801 (dizocilpine) is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) family of glutamate receptors in the central nervous system. It is an anticonvulsant and also shares several pharmacological properties with phencyclidine and ketamine. It is not observed routinely as a substance of abuse. The deceased, a 45-year-old white male, obtained MK-801 surreptitiously in an attempt to treat a self-diagnosed depression. He was discovered the next morning, unresponsive on the bathroom floor. An empty bottle, labeled to contain 25mg of MK-801, was found near the body.The autopsy was performed at the Joseph A Jachimczyk Forensic Center, Houston, TX. Body weight at autopsy was 88kg. Lungs were edematous and congested (right: 775g; left 700g). The heart had proportionate chambers and was otherwise unremarkable. The kidneys (right: 220g; left 225g) were smooth surfaced. The brain (1550g) was congested and without trauma. Microscopic evaluation of the heart, kidneys and lungs showed normal histology and confirmed pulmonary congestion and edema. Samples of heart blood, liver, bile, vitreous humor, stomach contents and urine were collected at autopsy. There were 550ml of stomach contents.Drugs in blood were screened by EMIT II Plus immunoassay procedures and by gas chromatography/mass spectrometry (GC/MS) of an organic solvent extract of basified blood. Alcohol was determined by gas chromatography with headspace injection. MK-801, benzodiazepines and alcohol were detected in blood.Amounts of MK-801 present in blood, bile, liver, vitreous humor and urine were 0.15, 0.29, 0.92, less than 0.1 and 0.36 mg/l (kg), respectively.The cause of death was benzodiazepine, dizocilpine and ethanol toxicity and the manner accidental.     

Fatal intoxication involving 2-methyl AP-237

Novel synthetic opioids contribute considerably to the opioid epidemic, especially with the frequent emergence of structurally similar compounds. This case report describes a fatal intoxication involving 2-methyl AP-237. A 54-year-old Caucasian male was found deceased from an apparent drug overdose. A plastic container labeled “2MAP” and a cut straw were found in the decedent's backpack at the scene. A white substance found in the container tested positive for fentanyl by field testing. According to his medical history, the decedent was treated for a drug overdose 3 years prior to his death. With no diagnostic findings at autopsy, the case was submitted for toxicological analysis. An unknown substance was detected in peripheral blood and urine using gas chromatography with nitrogen phosphorous detection (GC-NPD). Further testing was conducted using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) which confirmed the presence of 2-methyl AP-237 and potential metabolites in blood and urine. Quantitation by GC-NPD revealed concentrations of 2-methyl AP-237 in blood and urine at 480 ng/mL and 4200 ng/mL, respectively. The toxicological analysis also identified and quantitated alprazolam in the blood at 55 ng/mL. Additionally, the metabolism of 2-methyl AP-237 was investigated and three hydroxylated metabolites were identified in peripheral blood and urine. Limited literature is available for the detection and quantitation of 2-methyl AP-237 in postmortem specimens. Given the toxicological findings with unremarkable autopsy findings, this case is an example of a fatal intoxication involving 2-methyl AP-237.     

Sudden cardiac death during exercise in a weight lifter using anabolic androgenic steroids: pathological and toxicological findings

A 21-year-old, previously healthy weight lifter collapsed during a bench press workout. He had taken anabolic androgenic steroids parenterally for the previous several months. Pertinent autopsy findings included marked cardiac and renal hypertrophy and hepatosplenomegaly, with regional myocardial fibrosis and focal myocardial necrosis. Nandrolone (19-nor-testosterone) metabolites were identified in postmortem urine. The possible etiologies of the cardiac findings are discussed.     

Creatinine analysis in single collection urine specimens.

Controlled and uncontrolled fluid intake studies were conducted on series of volunteers over the 6 or 12 h of the study periods. Urine specimens were obtained from each subject randomly or at specified times relative to fluid ingestion. Creatinine analysis performed by a modification of the Abbott TDx procedure demonstrates that the values obtained from single collection specimens fall almost in the same range as the values from 24 h pooled collection specimens. The creatinine concentration can be used to indicate possible adulteration of urine specimens by dilution as a means of avoiding detection of use of drugs of abuse. Between 4 and 7 h are required for a decrease in creatinine concentration to about 100 mg/dL from an initial mean of about 170 mg/dL. A minimum of 6 h is needed for any creatinine value to fall to 50 mg/dL or less. Thus, it appears that creatinine output is sensitive to the amount of fluid ingested, but the relationship is neither linear nor immediate. The absence of a significant creatinine concentration in a specimen can be used as an indication of direct or indirect adulteration of the urine specimen by dilution or replacement with water. At NDSL-Great Lakes, a decline of the creatinine concentration to 30 mg/dL is used as a cutoff for differentiating between urine specimens that might have been tampered with to avoid detection of drug use and those specimens that are dilute for other reasons. Values at 10 mg/dL or less are suggestive of replacement by water. The information is provided to local commands for investigation prior to initiation of punitive action by the command.     

Evaluation and applicability of Alere iCup DX 14 for rapid postmortem urine drug screening at autopsy

Performing point‐of‐care urine drug screen testing at autopsy by a forensic pathologist may provide an early indication of the presence of analytes of interest during autopsy. An evaluation for the screening of 14 classes of common drugs of abuse in postmortem urine by the point‐of‐care screening device, Alere iCup DX 14, is presented. One hundred ninety postmortem urine samples were screened with the iCup occurring at autopsy by the forensic pathologist. Positive and negative results obtained from the screening kit were evaluated against confirmatory test results obtained using routine forensic toxicology analyses that employed LC‐MS/MS and GC‐MS to detect a combination of over 85 common drugs of abuse and medications. Sensitivity for each respective iCup drug class ranged from 66% (buprenorphine) to 100% (methadone, tricyclic antidepressants). Specificity for each respective iCup drug class ranged from 89% (benzodiazepines) to 100% (amphetamines, barbiturates, buprenorphine, 3,4‐methylenedioxymethamphetamine, methadone). Positive predictive values ranged from 44% (benzodiazepines) to 100% (amphetamines, barbiturates, buprenorphine, methylenedioxymethamphetamine, methadone), while negative predictive values ranged from 96% (methamphetamine) to 100% (barbiturates, methadone, tricyclic antidepressants). A high false‐positive rate was yielded by the benzodiazepine class. The lack of fentanyl screening in the point‐of‐care device is a significant limitation considering its prolific prevalence in forensic casework. The results obtained in the study should be acknowledged when considering the use of the Alere iCup DX 14 in the context of postmortem casework to help indicate potential drug use contemporaneously with autopsy and when requiring such preliminary results prior to the release of a final forensic toxicology report.     

Urinary excretion profiles of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol. Study III. A Delta9-THC-COOH to creatinine ratio study

Huestis and Cone reported in [J. Anal. Toxicol. 22 (1998) 445] that serial monitoring of Delta9-THC-COOH/creatinine ratios in paired urine specimens collected at least 24h apart could differentiate new drug use from residual Delta(9)-THC-COOH excretion following acute marijuana use in a controlled setting. The best accuracy (85.4%) for predicting new marijuana use was for a Delta(9)-THC-COOH/creatinine ratio > or = 0.5 (dividing the Delta9-THC-COOH/creatinine ratio of specimen no. 2 by the specimen no. 1 ratio). In previous studies in this laboratory [J. Anal. Toxicol. 23 (1999) 531 and Forensic Sci. Int. 133 (2003) 26], urine specimens were collected from chronic marijuana users > or = 24 h or > = 48 h apart in an uncontrolled setting. Subjects with a history of chronic marijuana use were screened for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/ml) followed by confirmation for Delta9-THC-COOH by GC-MS (cut-off 15 ng/ml). Creatinine was analyzed as an index of dilution. The objective of the present study was to evaluate whether creatinine corrected specimens could differentiate new marijuana or hashish use from the excretion of residual Delta(9)-THC-COOH in chronic marijuana users based on the Huestis 0.5 ratio. Urine specimens (N=376) were collected from 29 individuals > or = 96 h between urine collections. The mean urinary Delta9-THC-COOH concentration was 464.4 ng/ml, mean Delta9-THC-COOH/creatinine ratio (ng/(ml Delta9-THC-COOH mmoll creatinine)) was 36.8 and the overall mean Delta9-THC-COOH/creatinine ratio of specimen 2/mean Delta9-THC-COOH/creatinine ratio of specimen 1 was 1.37. The Huestis ratio calculation indicated new drug use in 83% of all sequentially paired urine specimens. The data were sub-divided into three groups (Groups A-C) based on mean Delta9-THC-COOH/creatinine values. Interindividual mean Delta9-THC-COOH/creatinine values ranged from 4.7 to 13.4 in Group A where 80% of paired specimens indicated new drug use (N=10) and 20.4-39.6 in Group B where 83.6% of paired specimens indicated new drug use (N=7). Individual mean Delta9-THC-COOH/creatinine values ranged from 44.2 to 120.2 in Group C where 84.5% of paired urine specimens indicated new marijuana use (N=12). Correcting Delta9-THC-COOH excretion for urinary dilution and comparing Delta9-THC-COOH/creatinine concentration ratios of sequentially paired specimens (collected > or = 96 h apart) may provide an objective indicator of ongoing marijuana or hashish use in this population.     

Homicide by methane gas

Two cases of sudden death due to myocardial infarction which were associated external injuries on the chest are discussed here. Injuries were in the form of abraded contusions on the anterior part of chest. Both the cases were declared dead on arrival to the casualty section (Accident and Emergencies Department). In these cases, mention of injuries was not made in the inquest report. In both the cases, suspicion of foul play or the trauma induced myocardial infarction were ruled out by inquiring into the incidents by the autopsy surgeon. The cases highlight the importance of detailed history by the autopsy surgeon in cases of sudden death with associated injuries on the front of the chest.     

实验性心脏震荡的法医病理学研究

本研究应用可产生稳定打击速度并可同时测定瞬间冲击速度及冲击力大小的机械式弹性拉力打击器，分别以６．７ｍ／ｓ及８．０ｍ／ｓ速度冲击大胸骨部心前区建立了心脏震荡动物模型，在左右心室压力及心电图监测下冲击后６０分钟进行尸体剖验检查，并应用多种组织化学染色、透射电镜技术、免疫组织化学染色以及硝酸镧示踪电镜技术对心肌组织学行系统性研究。结果表明：１．心前区受冲击瞬间左右心室内压力急骤升高，随即可恢复至正常水平。心电图在冲击后即刻表现为持续短暂的异常心律，逐渐恢复至正常心律。２．心脏血管麻痹性扩张，但宏观及微观均无损伤性所见。３．心肌超微结构有一定程度损害，心肝细胞膜破裂或通透性增高。本研究提示：心脏震荡者心脏宏观、微观无特殊改变，但超结构及心肌细胞膜轻度损害。     

Aminopeptidase and cathepsin A activity in vitreous humor in relation to causes of death

Brain autolysis happens rapidly, especially when environmental temperatures are high, and poses serious limitations for evaluating damage using morphologic methods. In the present study we have measured total proteins, cathepsin A and aminopeptidase activity in the vitreous humor in relation to cause of death and survival time. We have studied vitreous humor samples from 106 cadavers autopsied in the I.A.F. of Granada. The samples were classified according to causes of death as follows: myocardial infarction; hanging; other mechanical asphyxias; multiple trauma; craniocerebral trauma; other violent death; pulmonary functions; and other natural deaths. Total protein was measured by Lowry's method, and cathepsin A and aminopeptidase activity by the Bowen and Davison (1973) and Greenberg (1962) methods, respectively. Results are expressed in IU/l and in mIU/mg of protein. We found higher values of aminopeptidase and cathepsin A activity in groups with severe brain damage (craniocerebral trauma, multiple trauma, etc.) and lower values in groups of natural deaths. We believe, therefore, that aminopeptidase activity in vitreous humor may be a useful parameter for evaluating brain damage.     

Occlusion of left and right coronary arteries and coronary sinus following blunt chest trauma

Blunt chest trauma from rapid automobile airbag deployment causing coronary artery occlusion and myocardial infarction is a rare but potentially fatal condition. We present the case of a 37-year-old man who developed extensive anterior and inferior myocardial infarction because of occlusion of both left anterior and right coronary arteries following blunt injury to the chest in a car accident. The patient was scheduled for emergency coronary angiography but left and right coronary ostia were not cannulated because of thrombus formation probably. The patient died, and the autopsy revealed external compression by epicardial hematomas involving separately left and right coronary arteries and the coronary sinus without signs of coronary and/or aortic dissection. To our knowledge, this is the first case presenting occlusion of both coronary arteries secondary to blunt chest trauma causing acute myocardial infarction in a young man without signs of prior coronary artery disease.     

Urinary catecholamines in hyperthermia-related deaths

A group of five hyperthermia-related deaths is presented in which urinary noradrenaline (NA) concentrations were elevated (172.1 +/- 119.4 ng/ml) compared with a control group of rapid violent deaths (43.7 +/- 26.1 ng/ml). Urinary adrenaline (A) concentrations were not elevated in the hyperthermia cases, nor were there any significant differences in urinary dopamine (DA) concentrations between the two groups. All except one of the hyperthermia victims were under the influence of ethanol. It is suggested that a combination of heat stress and ethanol consumption was responsible for the elevated urinary NA in the hyperthermia cases, reflecting increased sympathetic nervous system activity. A combination of high urinary NA with low A seems to be characteristic of hyperthermia fatalities, in contrast to hypothermia deaths, where both NA and A are usually elevated.     

钝力性心脏外伤38例尸检病理学研究

本文研究表明钝力作为原始致伤因素作用于胸部通过压、拉、剪切、旋转等可引起钝力性心脏外伤包括心脏震荡、心脏挫裂伤、心脏玻裂、心脏断离等原发性心脏外伤和继发性乃至迟发性心脏外伤，诸如外伤性心脏炎、冠脉血管炎、血栓形成、外伤性心肌梗塞、外伤性冠状动脉瘤、外伤性室壁瘤、迟发性外伤性心脏破裂等。致命性的心脏震荡，除急性冠循环障碍和心失常外，还可有心脏传导系统和神经组织损伤，尤其心肌肌膜爆裂（ｓａｒｃｏｌｅｍｍａｂｕｒｓｔ）及相应的原纤维膨出畸形变可以作为心脏震荡性外伤的形态学指证。外伤性心肌梗塞和迟发性外伤性心脏破裂以突然发生在外伤后的一定间隔期为特征，应予特殊注意．     

Postmortem serum catecholamine levels in relation to the cause of death

Catecholamines are major humoral factors and neurotransmitters that contribute to various stress responses. However, they have been considered unstable due to agony, terminal medical care and postmortem interference. The present study was a comprehensive investigation of postmortem serum levels of adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) with regard to the cause of death in serial medicolegal autopsy cases (n=542) including fatalities from various traumas and diseases. There was a slight tendency toward postmortem increases of Nad and DA in cardiac blood as well as Adr and Nad in peripheral blood, a slight age-dependent decrease in Adr and DA in right heart blood, and a marked increase in serum DA due to administration during critical medical care. When these factors were taken into consideration, significantly higher cardiac blood levels were observed for Adr and Nad in injury and asphyxiation cases and for Adr in fatal methamphetamine (MA) abuse and other poisoning cases, whereas those levels were lower in fatal hypothermia. Drowning, fire fatality, acute cardiac death and cerebrovascular disease showed intermediate Adr and Nad levels. The DA level was elevated in cases of injury, hyperthermia, MA fatality and other poisoning. Topographical analyses suggested that the major sources of increased serum catecholamines in cases of injury was abdominal viscera including adrenal glands, and that in cases of asphyxiation, drowning, fire fatality, hyperthermia, MA fatality, other poisoning, acute cardiac death and cerebrovascular disease was the extremities in addition to abdominal viscera. However, there was in part a large case-to-case difference in each marker related to individual causes of death. These findings differed markedly from clinical observations and suggest that the postmortem serum catecholamine levels may reflect the magnitude of physical stress responses during the process of death in individual cases.