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We reported the first comprehensive autopsy case of death due to intravenous injection of nicotine. We examined the distribution of nicotine in the body tissues and fluid and exposed the pathophysiology of nicotine poisoning. A 19-year-old woman was rushed to the hospital in cardiorespiratory arrest and was confirmed dead upon arrival. Liquid nicotine, hydrogen peroxide water, and a syringe were found in the hotel room where she stayed. On autopsy, nicotine concentration was the highest (15,023 μg/mg) in the tissue around the injection mark on the right upper arm. Among the body fluids, the intraperitoneal fluid had the highest, whereas the pericardial fluid had the lowest (0.736 μg/mL) nicotine concentration. Among the organs, the brain had the highest (11.637 μg/mg), whereas the fat tissue had the lowest (1.307 μg/mg) nicotine concentration. The concentration of cotinine, which is the metabolite of nicotine, was the highest in the tissue around the injection mark on the right arm (5.495 μg/mg) and was almost the same among the other body fluids and organs. The respective concentrations of nicotine and cotinine were 1.529 μg/mL and 0.019 μg/mL in the left heart blood and 3.157 μg/mL and 0.002 μg/mL in right heart blood. In this case, the nicotine concentrations in blood reached the lethal level. The distributions of nicotine and cotinine, as indicated by the intravenous injection, were related to the distribution of organs that metabolize nicotine and the distribution of nicotinic acetylcholine receptors.

This study aimed to characterize the pathophysiology, including possible correlations, of clock gene expression and erythropoietin (EPO) production in the acute stage of blood hemorrhage. Specimens of human cortical tissues (right and left kidneys) and cardiac blood were collected at autopsy from 52 cases following mortality due to acute-stage blood hemorrhage following sharp instrument injury. BMAL1 and PER2 mRNA levels were determined by reverse transcription-polymerase chain reaction; BMAL1 and PER2 protein levels were assessed using immunohistochemistry; BMAL1 protein levels were quantitatively measured by western blotting; and serum EPO levels were measured by chemiluminescent enzyme immunoassay. Separately, a rat model of hemorrhagic conditions was generated and used to confirm the results obtained with autopsy-derived specimens. A positive correlation was observed between BMAL1 protein and serum EPO levels, but not between BMAL1 mRNA levels and serum EPO levels. We also noted that Per2 mRNA expression became elevated in humans who survived for > 3 h after acute hemorrhagic events, with subsequent decreases in serum EPO levels. The rat model showed that even short (30-min) intervals of blood loss yielded increases in both Bmal1 mRNA and serum EPO levels; longer (60-min) intervals resulted in increases in Per2 mRNA expression along with decreases in serum EPO. Thus, the acute-stage human hemorrhage cases and the rat hemorrhage model yielded similar tendencies for clock gene expression and EPO secretion. In conclusion, our results indicated that clock genes are involved in the regulation of EPO production during the early stages of hypoxia/ischemia resulting from the acute hemorrhagic events.

Oral antidiabetics can cause fatal hypoglycemia; although they can be chemically identified and quantified, biochemical investigations are important for assessing the biological consequences of an overdose. Such cases of overdose involving oral antidiabetics may involve other drugs for treating lifestyle-related diseases, particularly antihypertensives. Here, we report a toxicological and biochemical investigation of drugs and biochemical profiles in a fatal overdose involving multiple oral antidiabetics and antihypertensives. A 55-year-old woman died about 2 days after the ingestion of around 110 tablets of antidiabetics and antihypertensives that had been prescribed for her husband. A forensic autopsy and histological analysis demonstrated no evident pathology as the cause of death. A toxicological analysis suggested hypoglycemia and an overdose of antihypertensives as well as the retention of antidiabetics and diuretics in the pericardial fluid. A relatively low pericardial amlodipine concentration was observed, which may have been the result of its long half-life (slower distribution and reduction rate) and/or possible affinity with the myocardium. In addition, a biochemical analysis indicated hypoglycemia, without increased serum insulin and C-peptide, but with increased glucagon levels, as the possible influence of glibenclamide overdose. These observations suggest the usefulness of a combination of toxicological and biochemical analyses in postmortem investigations involving a fatal overdose of such drugs.

A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings.

Naoto Tani,1,2 Tomoya Ikeda,1,2 Tomomi Michiue,1,2 Shigeki Oritani,1 Fumiya Morioka,1 Takaki Ishikawa1,2 1Department of Legal Medicine, Osaka City University Medical School, Abeno, Osaka, Japan; 2Forensic Autopsy Section, Medico-legal Consultation and Postmortem Investigation Support Center, c/o Department of Legal Medicine, Osaka City University Medical School, Abeno, Osaka, Japan Objective: The aim of this study was to investigate the occurrence of deaths due to psychotropic drugs in south Osaka during a 10-year period and discuss societal factors from a medical viewpoint.Methods: Psychotropic drug-related deaths were retrospectively investigated based on the forensic postmortem data of 1,746 decedents in 2005–2014, and we excluded cases in which stimulant drugs were detected. Of these, 133 cases (7.6%) were found to be psychotropic drug-related deaths and were analyzed.Results: Psychotropic drug-related deaths occurred in 78 males (59%; age range, 14–95 years) and 55 females (41%; 20–84 years). The direct cause of death was acute drug intoxication in many cases, and of these, acute combined drug intoxication due to the use of multiple drugs accounted for 76% of the deaths. Most of these victims were found to have gastrointestinal and cardiovascular diseases. Cases of psychotropic drug-related deaths had especially poor medical conditions. In addition, tests were positive for blood alcohol in 23% of the cases.Conclusion: The descriptive results revealed several factors that may be related to psychotropic drug-related deaths. To prevent drug abuse, several factors were deemed to be important, including improvements in the medical state of an individual, the avoidance of social isolation, and from a medical standpoint, the management of prescription drugs by medical personnel. Keywords: forensic autopsy, epidemiology, psychiatric drugs, drug abuse, dependency factor

A fire is an important cause of mass disasters, involving various forensic issues. Before dawn on an early morning, 16 male visitors in their twenties to sixties were killed in a possibly incendiary fire at a ‘private video parlor’ consisting of small compartments in a building. The main causes of death as determined by forensic autopsy were acute carbon monoxide (CO) intoxication for all of the 15 found-dead victims, and hypoxic-ischemic encephalopathy following acute CO intoxication for a victim who died in hospital. Burns were mild (

Postmortem CT (PM-CT) is useful to investigate the viscera in situ before opening the body cavities at autopsy. The present study involved a virtual morphometric analysis of thoracic and abdominal great vessels with regard to the cause of death as a possible index of terminal circulatory status in forensic autopsy cases, using PM-CT data of forensic autopsy cases within 3 days postmortem (n = 93). Perimeters and cross-sectional areas of the aorta and vena cava depended on the age and/or gender of subjects; however, when the vessel flattening index (vFI) was calculated as the ratio of the cross-sectional area (a) to the estimated circle area having the same perimeter (l), using the formula vFI = 4πa/l(2), the vFI showed distinct differences among the causes of death without significant postmortem time dependence. The index was low for each vessel in fatal bleeding, while the vFI of the abdominal aorta and inferior vena cava was low in hyperthermia (heatstroke), but higher in drowning, hypothermia (cold exposure) and sudden cardiac death. These CT findings provide quantitative data as supplementary indicators to reinforce autopsy findings for interpreting terminal circulatory status.

Postmortem CT (PMCT) is useful to investigate air/gas distribution and content in body cavities and viscera. The present study investigated the procedure to estimate total lung air/gas content and aeration ratio as possible indices of terminal respiratory function, using three-dimensional (3-D) PMCT data analysis of forensic autopsy cases without putrefactive gas formation (within 3 days postmortem, n =75), and analyzed the volumetric data with regard to the cause of death. When 3-D bilateral lung images were reconstructed using an image analyzer, combined lung volume was larger in drowning ( n =12) than in alcohol/sedative-hypnotic intoxication ( n =8) and sudden cardiac death (SCD; n =10), and intermediate in other cases, including mechanical asphyxiation ( n =12), fire fatalities due to burns ( n =6) and carbon monoxide intoxication ( n =7), fatal methamphetamine abuse ( n =7), hyperthermia (heatstroke; n =6) and fatal hypothermia (cold exposure; n =7). Air/gas content of the lung as detected using HU interval between −2000 and −400 (‘effective' lung aeration areas) and between −2000 and −191 (total lung aeration areas) as well as the ratios to total lung volume (‘effective' and total lung aeration ratios, respectively) was higher in mechanical asphyxiation, drowning, fatal burns and hypothermia (cold exposure) than in SCD, and was intermediate in other cases. ‘Effective' and total lung aeration ratios may be useful for comparisons between specific causes of death to discriminate between hypothermia (cold exposure) and drug intoxication, and between SCD and other causes of death, respectively. These findings provide interesting insights into potential efficacy of PMCT data analyses of lung volume and CT density as well as lung air/gas content and aeration ratio with regard to the cause of death, as possible indicators of terminal respiratory function, as part of virtual autopsy of the viscera in situ.

Previous studies suggested substantial postmortem interference with pulmonary CT findings. The present study evaluated postmortem CT (PM-CT) morphology of the lung, compared with histology, in autopsy cases of sudden cardiac death without recovery from cardiac arrest (SCD, n=22) with regard to the posture at the time of death and postmortem interference from a forensic pathological viewpoint. In witnessed cases (n=5), a case of SCD in a prone position had anterior consolidation with weak hypostatic opacification in the posterior about 18 h later. Among unwitnessed deaths (n=17), 8 cases of death lying prone, sitting facedown and lying laterally had possible gravity-dependent opacity about 15-38 h postmortem. Hypostatic opacification with 'niveau' formation was not evident in more than half of the cases (n=15). Histological findings for ground glass opacification and consolidation on PM-CT varied by case, involving intraalveolar edema and hemorrhages, accompanied by marked congestion; however, possible postmortem hypostatic opacification mostly represented intraalveolar edema. CT morphology of acute pulmonary congestion in SCD may often remain without serious postmortem interference in cases without clinical intervention involving massive fluid infusion, suggesting plain PM-CT findings of the lung to be useful for investigating the death process when combined with histology; however, the possible influence of the hydration status of the lungs at the time of death should be assessed by evaluation of CT and autopsy findings.

Motion sickness medications such as Travelmin® prescribed in Japan include diphenhydramine (DPH), dyphylline, diphenidol, and/or caffeine. Herein, we report a patient who died due to rhabdomyolysis after ingesting a DPH containing motion sickness medication. A Japanese male in his 30 s reported missing after going out for a drive early in the morning was found dead in his car in the evening of the same day. An autopsy showed moderate edema, congestion, and several petechiae in both lungs. The brain was congested and edematous with no atherosclerosis of cerebral arteries. The prostate and both testes were slightly edematous. Gastric contents included approximately 15 mL of dark-brown fluid without tablets or food residue. Toxicological examination showed that blood DPH levels in all tissues were between 4.90 and 7.27 μg/mL, which represented toxic to lethal levels. DPH (μg/mL) levels were approximately 3–9 times higher in the prostate (73.42) and testes (left, 28.23; right, 30.09) than those in all regions of the brain (range 7.75–12.33). Blood dyphylline, diphenidol and caffeine levels in reproductive organs reached high, but not toxic levels. In conclusion, DPH, dyphylline, diphenidol, and caffeine levels were higher in reproductive organs such as the prostate and testes than in the central nervous system and heart. As we determined in this case, motion sickness medications might accumulate in reproductive organs. Thus, further examination of tissue biodistribution of DPH, dyphylline, diphenidol, and caffeine is necessary to assess their potential long-term effects in these sites.

Recently in Japan, there have been scattered cases of suicide by inhalation of hydrogen sulfide (H2S), produced by mixing domestic chemicals containing sulfur and hydrochloric acid. We report four cases of such fatalities with regard to the pathological and toxicological findings. Two cases were male and female suicide victims (cases 1 and 2; about 2 days and 30 h postmortem, respectively), and the other two were a female suicide victim and her husband (cases 3 and 4; about 3 days postmortem). Partial greenish discoloration was observed on the skin in three cases (cases 1, 3, and 4), and also in the airways and lungs and on the brain surface in one case (case 3). The most evident pathology was marked pulmonary and cerebral edema in all cases. Concentrations of H2S and the metabolite thiosulfate (TS) in the blood varied by case (0.66–85.0 and 0.00–369 μg/ml, respectively), and similar distributions were seen in the viscera; these concentrations were markedly high in a case of visceral discoloration (case 3). Both H2S and TS contents in the skin and muscle were higher at the sites of discoloration in individual cases. A control study demonstrated an unexpected increase of TS contents along with H2S production due to putrefaction as well as higher TS content than H2S. It was difficult to discriminate putrefaction using H2S and TS measurements, especially in gastric contents, bone marrow, heart, liver, kidney, spleen, pancreas, and intestine. However, vitreous body, pericardial fluid, and lung tissue showed different findings compared with putrefactive changes, and may be used as supplementary or alternative samples. These findings suggest the significant contribution of postmortem exposure to H2S gas to the pathological and toxicological findings, depending on the circumstances, and the importance of systemic toxicological analysis for determining death due to H2S intoxication.

Radiological lung transparency depends on the air contents involved in respiratory function. The present study quantitatively investigated postmortem lung air distribution in forensic autopsy cases (n=135) using computed tomography (CT) to analyze cardiopulmonary pathophysiology in the death process, involving emphysema, congestion and edema. Combined analyses of the CT morphology and attenuation value (Hounsfield unit, HU) of the bilateral lungs, with reference to histopathology, could categorize CT findings (10-90 percentile mode/mean HU values) with regard to the causes of death as follows: (I) hyperaeration (mode/mean HU below -760/-560: emphysema) for obstructive pulmonary disease, starvation and hypothermia (cold exposure); (II) mostly normal aeration with partial ground glass opacification (mode/mean HU, -850 to -360/-700 to -380: partial congestion and edema), consisting of subtype II-a with peri-bronchial/-vascular opacity for mechanical asphyxia, drowning and fire fatality, and subtype II-b with decreased vascularity for gunshot head injury, cerebrovascular disease and hemopericardium; (III) hypoaeration to airless with predominant hypostatic ground glass opacification (mode/mean HU, -870 to 0/-720 to -200: mottled hypostatic congestion and edema) for blunt head/neck injury, intoxication, hyperthermia (heat stroke) and congestive heart failure; (IV) hypoaeration to airless with predominant hypostatic consolidation (mode/mean HU, -790 to 0/-520 to -70: intense hypostatic congestion with edema) for acute ischemic heart disease; and (V) airless to consolidated (mode/mean HU over -420/-370: segmental or multiple patchy consolidations with edema) for pneumonia. Mode HU represents the major alveolar status, while the mean HU reflects the whole lung air contents. CT data analysis is useful for quantitative evaluation of pulmonary pathology as a supplementary procedure.

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.

The aim of the present study was to examine the factors that contribute to the postmortem lung weight in acute fire fatalities (n=149) including those with lower (60%) and higher (60%) blood carboxyhemoglobin (COHb) levels (n=94 and 55, respectively). The control groups consisted of acute myocardial infarction/ischemia (AMI, n=99) and mechanical asphyxiation (n=85). For all cases (n=333), the lung and heart weights were independent of the postmortem time (4.5-72 h) and charring of the body. The combined weight of both lobes of the lung showed a significant gender difference (malesfemales, P0.001), negative regression with respect to age (R=0.167, P0.01) and positive regression with respect to heart weight (R=0.316, P0.001). The gender difference was also significant for each cause of death even after being corrected using body height measurements. When the lung-heart weight ratio was estimated to diminish the influence of possible cardiogenic factors, the gender difference was insignificant for each cause of death among the non-elderly (60 years of age). However, for elderly fire fatalities (60 years of age), there was a gender difference (malesfemales) for the lower COHb group (P0.05) and higher COHb group (P0.001). A significant age-dependent difference (non-elderlyelderly) in the lung-heart weight ratio was observed for fire fatalities with a lower COHb and AMI among males and for fire fatalities with a higher COHb among females. Such gender- and/or age-dependent influences were not significant for fatal mechanical asphyxiation. These findings suggest that a person's heart weight may be a possible contributory factor to an increase in the lung weight in acute death, and that gender- and/or age-dependent susceptibilities may be additional factors that contribute to fire fatalities and AMI. In addition, elderly females appear to be most susceptible among fire casualties, and extreme cardiomegaly may also be a potential fatal risk factor.

The aim of the present study was to investigate the differences in postmortem blood biochemistry between fresh-, saltwater drowning and acute myocardial infarction/ischemia (AMI) (n=11, n=15 and n=23, respectively; postmortem interval

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.

We have investigated postmortem serum CRP levels in 408 forensic autopsy cases consisting of 216 acute and 192 non-acute death cases having postmortem interval of less than 48 h. CRP ranged from 0.03 to 66.13 mg/dl with the median of 0.28 mg/dl. In 362 traumatic death, survival time and the presence of severe infection were the major factors contributing to CRP elevation, while postmortem interval, age, gender, hepatic injury and liver cirrhosis was not. In almost all the immediate deaths (15/16) CRP remained at a low level (

Serum uric acid (UA) and creatinine (Cr) mainly derive from skeletal muscle tissues. Although, remarkable postmortem stability of the serum levels has been reported, there appears to be very poor knowledge of the diagnostic value in investigation of death, except for uremia. The aim of the present study was to evaluate postmortem serum UA and Cr levels using 395 forensic autopsy cases, in comparison with blood urea nitrogen (BUN), for investigation of the pathophysiology of death with special regard to the causes of death involving possible skeletal muscle damage, e.g. due to hypoxia, heat or agonal convulsions. Cr and BUN showed relatively good topographic stability in the cadaveric blood, whereas, UA was often much higher in the right heart blood than in the left heart and peripheral blood, independent of postmortem intervals. Moderate to marked elevation of Cr and BUN accompanied with hyperuricemia was observed in delayed death. In the acute death cases (survival time30 min), UA, especially in the right heart blood, showed a considerable elevation in mechanical asphyxiation and drowning. The Cr level in fire victims with a lower carboxyhemoglobin (COHb) level (60%) was significantly higher than in those with the possible fatal level (60%). A similar elevation of Cr was observed in fatalities from heat stroke and methamphetamine (MA) poisoning. The observations suggested that hyperuricemia in acute death may be indicative of advanced hypoxia and that elevated Cr level may reflect the skeletal muscle damage, especially due to thermal influence.

Toxicological analysis is indispensable in forensic autopsy laboratories, but often depends on the limitations of individual institutions. The present study reviewed routine drug screening data of forensic autopsy cases (n=2996) during an 18.5-year period (January 1996-June 2014) at our institute to examine the efficacy of the procedures and findings in autopsy diagnosis and interpretation. Drug screening was performed using on-site immunoassay screening devices and gas chromatography/mass spectrometry (GC/MS) in all cases, followed by re-examination using GC/MS and liquid chromatography/tandem mass spectrometry (LC/MS/MS) at a cooperating institute in specific cases in the last 4 years. GC/MS detected drugs in 486 cases (16.2%), including amphetamines (n=160), major tranquilizers (n=72), minor tranquilizers (n=294), antidepressants (n=21), cold remedies (n=77), and other drugs (n=19). Among these cases, fatal intoxication (n=123) involved amphetamines (n=73), major tranquilizers (n=37), minor tranquilizers (n=86), antidepressants (n=3), and cold remedies (n=9); most cases involved self-administration, alleged suicide and accidental overdose, while homicide was not included. These drugs were also identified in other manners of death, including homicide (n=40/372), suicide (n=34/226), accidental falls (n=27/129), and natural death (n=72/514). In these cases, on-site immunoassay screening of drugs of abuse showed negative findings in 2440 cases (81.4% in all cases), while GC/MS detected other drugs in 218 cases (7.3% in all cases), including several antipsychotic drugs, acetaminophen and salicylic acid. Further analysis using LC/MS/MS detected low concentrations of benzodiazepines in 32 cases, and also anti-diabetic and hypertensive drugs in a case of fatal abuse. These observations indicate the efficacy of systematic routine toxicological analysis to investigate not only the cause of death but also the background of fatalities in forensic autopsy. The provision of extensive drug screening is needed for forensic and social risk management, considering the marked diversity of medical and illicit drugs.

This report describes an autopsy case of a rare type of aortic sinus of Valsalva aneurysm, which caused fatal rupture from a blunt chest impact. A 51-year-old male was hit in the chest with a fist, lost consciousness after about 15 min and died after approximately 7 h. The postmortem examination revealed a large saccular aneurysm of the right coronary sinus bulging on the right atrium, which had a full laceration causing pericardial hematoma (cardiac tamponade). A related chest wall injury was observed in the right outer mammary region. A rare type of bulging onto the right atrium and subsequent sclerosis of the right coronary artery appeared to have greatly contributed to the fatal rupture.

To evaluate pathophysiological significance of post-mortem urinary myoglobin levels in determining the cause of death, we investigated 210 forensic autopsy cases, partially in comparison with serum levels. Post-mortem serum myoglobin levels were extraordinary high in most cases possibly due to post-mortem change. Urinary myoglobin levels did not correlate with the serum levels, showing possible post-mortem elevation in cases of a prolonged post-mortem period over 48h. A high (>1000 ng/ml), moderate (100-1000 ng/ml), slight (50-100 ng/ml) and not significant (

We report a case of self-decapitation by suicidal hanging from a river bridge and discuss the decapitation mechanism, reviewing the literature. The torso and the head of the victim, respectively, were found apart in a river approximately 100 m and 600 m, respectively, downstream from the bridge in two days. Morphological, serological and DNA analyses confirmed their identity. Torn ligaments between the atlas and axis accompanied by fractures in the axis at the partes interarticulares were indicative of a traction force combined with anteroflexion of the head by falling from a height, and the radial pressure due to a strong, single twisted nylon rope with a slip knot was considered to have contributed considerably to the subsequent skin laceration with wavy marginal abrasions. In the reviewed literature, cervical spine fractures were described only in two of six cases, suggesting head movement at the time of decapitation.

To outline the recent features of methamphetamine-related fatalities from the medico-legal point of view, a retrospective investigation of forensic autopsy cases involving methamphetamine during a 5-year period (1994-1998) in the southern half of Osaka city and surrounding areas (about 1.57 million population) was undertaken. Among 646 autopsy cases, methamphetamine was detected in 15 victims (nine males, six females; 16-71 years of age; most frequently in males in their thirties). Primary scenes of fatal events were concentrated in the middle of the city. About half of them were transferred from emergency medical centers (survival time, up to 30 h). The cause and manner of death were: methamphetamine poisoning (n=4), homicide (n=4), accidental falls and aspiration from drug abuse (n=4), fire death (n=1), myocardial infarction (n=1), and cerebral hemorrhage (n=1) under drug influence. Usually injection scars and fresh puncture sites were found. Blood methamphetamine concentrations were 2.29-17.05 micromol/dl in the fatal poisoning, 0. 44-3.80 micromol/dl in deaths from other extrinsic causes (trauma), and 1.35-2.17 micromol/dl in cardio- and cerebrovascular strokes. Common complications were cardiomyopathy, cerebral perivasculitis and liver cirrhosis/interstitial hepatitis. Fatal and nonfatal methamphetamine poisonings are separately dealt with by the administrative medical examiner's office and in emergency medical centers. Tightly cooperative approaches of clinical and medico-legal experts are required for the effective social and medical management of drug abuse.

We report a case of suspected fatal physical abuse in which the cause of death was proved to be pulmonary embolism. A patient with mental retardation presenting aggressive behavior was admitted to a psychiatric hospital and was treated with major tranquilizers. She suddenly died subsequent to an angina-like attack. For several days before her death, she had been confined to her bed because of very low physical and mental activity. Bruises and abrasions were observed on the extremities, suggesting the recent restraints. There was no positive evidence of physical abuse. At autopsy, the cause of death was elucidated to be pulmonary embolism originating from thrombi in the left popliteal vein. This case indicates the risk of pulmonary embolism in immobilized patients in psychiatric hospitals.

Postmortem CT (PM-CT) is useful to investigate the viscera in situ before opening the body cavity at autopsy. The present study investigated heart and lung volumes in situ with regard to the cause of death as possible indexes of terminal cardiopulmonary dysfunction by means of PM-CT data analysis of forensic autopsy cases within 3 days postmortem (n=70). Estimated heart volume was larger in sudden cardiac death (SCD; n=10) and fatal methamphetamine abuse (n=5) than in other groups, including mechanical asphyxiation (n=12), drowning (n=11), acute alcohol/sedative-hypnotic intoxication (n=8), fire fatality (n=12), hyperthermia (heatstroke; n=6) and fatal hypothermia (cold exposure; n=6). Estimated combined lung volume was larger in drowning, smaller in fire fatality due to carbon monoxide intoxication and SCD, and intermediate in other groups. Volume ratio of the lung to heart was higher in drowning, lower in SCD, and intermediate or varied in other groups; high and low ratios can indicate predominant/antecedent pulmonary and cardiac dysfunctions, respectively. These findings provide quantitative data that are not available at conventional autopsy or by routine two-dimensional CT morphology to assess three-dimensional gross heart and lung morphologies for interpreting terminal cardiopulmonary pathophysiology, detecting significant difference between SCD and other causes of death, especially mechanical asphyxiation and drowning.

Flotation tests on the lungs and gastrointestinal tract to investigate aeration are classic procedures to examine the life of a newborn after birth; however, there are arguments about the reliability. The present study investigated serial forensic autopsy cases of newborn infants without marked decomposition (n = 4) with regard to air/gas distribution in the lungs and gastrointestinal tracts by means of postmortem CT (PM-CT) as well as macromorphology and histology, compared with intrauterine and aborted fetuses (n = 3). No gas was detected in the lungs or gastrointestinal tracts in all of three intrauterine fetal deaths. Gas was diffusely detected in the lungs of a newborn fatality attributed to smothering after birth; however, two neonatal fatalities had poor lung gas contents due to marked congestion with edema and diffuse atelectasis. In a case of unsuccessful cardiopulmonary resuscitation following possible birth asphyxia, pulmonary aeration was evidently localized on CT morphology, despite a larger amount of bowel gas, and was also uneven in histology, showing a membranous immunostaining pattern of pulmonary surfactant on the intra-alveolar surfaces of expanded alveoli. The combined use of PM-CT is useful to demonstrate air/gas distributions in the lungs and gastrointestinal tract for interpretation of spontaneous breathing after birth in newborn fatalities.

Previous studies showed significant differences in postmortem urea nitrogen (UN), creatinine (Cr) and uric acid (UA) levels in heart blood depending on the causes of death, including acute death. In addition, the levels in pericardial fluid approximated the clinical serum reference ranges, and their elevations may be assessed based on clinical criteria. The present study investigated difference between blood and pericardial levels of these markers. Medicolegal autopsy cases (n=556, within 48h postmortem) of the following causes of death were examined: injury (n=136), asphyxiation (n=50), drowning (n=39), fire fatalities (n=99), hyperthermia (n=11), hypothermia (n=8), poisoning (n=26), delayed traumatic death (n=44) and natural diseases (n=143). When serum UN, Cr and UA levels were compared with the pericardial levels, there was an equivalency for delayed traumatic death and chronic renal failure, although each level was markedly elevated. Parallel increases in serum and pericardial UA and/or Cr levels were also observed for hypothermia and gastrointestinal bleeding. However, in drowning cases, the left cardiac and pericardial UN levels were lower than the right cardiac and peripheral levels, suggesting the influence of water aspiration. Significant elevations in serum and pericardial Cr and UA levels with a higher serum/pericardial UA ratio for fatal methamphetamine intoxication suggest progressive skeletal muscle damage due to advanced hypoxia/acidosis. Similar findings were often observed for other acute and subacute deaths. These findings suggest that a comparison between blood and pericardial nitrogenous compounds would be useful for investigating the cause and process of death.

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

Ubiquitin (Ub) is involved in neurodegeneration and various stress responses in the brain. The present study investigated the Ub-immunoreactive structures in the midbrain of methamphetamine (MA) abusers as a marker of drug-induced neurodegeneration. Medico-legal autopsy cases were examined: fatal MA intoxication (n=14), other fatalities of MA abusers (n=23) including those due to injuries, asphyxiation, drowning, fire and natural diseases, and control groups (n=260). In the motor nervous systems, MA abusers showed a mild increase in the diffuse-type nuclear Ub-positivity in the pigmented neurons of the substantia nigra, depending on the blood MA level and irrespectively of the immediate causes of death. The intranuclear inclusion-type Ub-positivity of the nigral neurons and the granular 'dot-like' Ub-immunoreactivity area in the crus cerebri (cortico-spinal tracts) were usually low in MA abusers, and any increases were related to the immediate causes of death and the age of subjects. Acute MA fatality showed a higher neuronal Ub-positivity in the midbrain periaqueductal gray matter (PGM), which is involved in processing pain, fear and anxiety, and regulation of respiration and circulation. These findings suggest dysfunction of the nigral dopaminergic neurons and PGM neurons in the midbrain in MA abuse, which may account for the clinical symptoms.

The aim of the present study was to investigate the lung-heart weight ratio in fresh- and saltwater drowning (n=67 and n=75, respectively) as a possible index of cardiopulmonary pathophysiology, in comparison with acute myocardial infarction/ischemia (AMI, n=75) and asphyxiation (n=85). In drowning cases, the total value of the combined lung weight and the amount of pleural effusion was regarded as a possible total lung weight. The median value of the combined/total lung weight was the highest in saltwater drowning, which was followed by freshwater drowning, AMI and asphyxiation, showing a tendency to be mildly increased depending on the heart weight. The lung-heart weight ratio was significantly higher in fresh-/saltwater drownings (3.944+/-1.538 and 4.825+/-2.242, respectively) than in asphyxiation (2.846+/-1.042) and AMI (2.641+/-0.916) (P

This report describes two autopsy cases of sudden infant death attributed to peracute pulmonary infection in which possible causative microorganisms could be identified despite only minor pathological findings. Both babies were 5-month-old boys, who had no symptomatic disorders and were found dead in bed. Their main macropathology was inflated heavy lungs with patchy bleedings. One case showed a pulmonary histopathological finding suggestive of viral infection, and adenovirus DNA was detected from the intrabronchial fluid. In the second case, pulmonary histopathology was a feature of early inflammatory reaction involving focal necrosis with some neutrophil infiltration and many intra-alveolar macrophages containing gram-positive cocci, and Staphylococcus aureus was identified in venous blood culture. These findings significantly support the presence of pathogenic microorganisms in sudden infant death.

Hemorrhages in the root of the tongue have been considered to be a finding associated with asphyxiation. The aim of the present study was to examine the incidence and diagnostic value of the lingual hemorrhages in fire fatalities with reference to the related pathological and toxicological findings, in comparison with asphyxiation and drowning cases. In fire fatalities (n=90), small to marked hemorrhages were observed in 26 cases (28.9%). In the reference groups (asphyxiation and drowning), the hemorrhages were frequently observed in ligature strangulation (n=10/15), manual strangulation (n=5/7) and traumatic asphyxia (n=4/5). In fire fatalities, the hemorrhages were closely associated with a lower blood carboxyhemoglobin (COHb) level, suggesting an influence of fatal burns: n=16/32 (50.0%), n=8/26 (30.8%) and n=2/32 (6.2%), respectively, in cases of COHb30%, 30-60% and60%. These findings suggested possible acute hemodynamic disturbance in the head including brain (cranial congestion) in the dying process due to fires. A careful differentiation from neck compression may be necessary in such cases.

Acute death from caustic ingestion is uncommon. We report an autopsy case of acute fatality from suicidal ingestion of a liquid caustic soda solution with peritoneal leakage due to a stab wound to the stomach. The victim was a 58-year-old man, who died about 1 h after being transported to a hospital emergency care unit. There were corrosive erosions around the mouth and a stab wound in the lower chest. The tongue, pharynx, larynx, esophagus, stomach and the proximal portion of the duodenum were all eroded and edematous. The stab wound perforated the diaphragm and stomach, accompanied by liquefactive corrosion in the left-lower thoracic and left-upper peritoneal cavities. There was a marked elevation of the postmortem serum sodium concentration and alkalosis. The observations suggested peritoneal absorption of leaked caustic soda solution, which may have greatly contributed to the acute fatality despite an intensive clinical life support.

This report describes an autopsy case of a rare longitudinal brainstem laceration associated with complex basilar skull fractures. The victim was a 40-year-old male who died immediately after falling from a roof (9.2m in height) of a factory onto a concrete floor. The postmortem examination revealed an incomplete ring fracture of the base of the skull with longitudinal fractures of the sphenoid (clivus of the dorsum sellae turcicae) and occipital bones, cerebral contusions in the frontal and temporal poles, a longitudinal brainstem laceration at the posterior median sulcus of the pons accompanied with multiple contusional hemorrhages in the brainstem and corpus callosum. Related blunt-force injuries were observed in the parieto-occipital region of the head, shoulder and upper back involving the fractures of the cervical and thoracic vertebrae, and sternum and ribs, indicating a huge impact to the occiput and subsequent impression of the vertebral column into the base of the skull due to violent anteroflexion of the neck, which caused the complex basilar skull fractures, contusions and longitudinal laceration of the brainstem.

To evaluate the significance of immunohistochemical staining of ubiquitin (heat shock protein) in the midbrain for medico-legal investigation of death in fires, we examined forensic autopsy cases of fire fatalities (n = 35) in comparison with controls (n = 27; brain stem injury, acute myocardial infarction and carbon monoxide poisoning other than fire fatality). There were two intranuclear staining patterns in the nuclei of pigmented substantia nigra neurons: a type of inclusion (possible Marinesco bodies) and a diffuse staining. Percentage of nuclear ubiquitin positivity (Ub-positive %) in fire fatalities (2.7-44.7%; mean, 18.5%) was significantly higher than in brain stem injury (n = 9; 0-10.4%; mean, 4.5%) and myocardial infarction (n = 14; 1.5-14.6%; mean, 6.9%), independently of blood carboxyhemoglobin (COHb) levels. Age-dependent increase in Ub-positive % was observed in lower COHb (60%) cases. The intranuclear diffuse ubiquitin staining was not observed in cases of high blood cyanide level (1.0 microg/ml). These observations showed that intranuclear ubiquitin immunoreactivity of the pigmented substantia nigra neurons in the midbrain was induced by severe stress in fires.

To evaluate the immunohistochemical distribution of pulmonary surfactant-associated protein A (SP-A) in fatal poisoning in relation to the effects of drugs and poisons on respiratory function, 42 forensic autopsy cases were examined by scoring the staining intensity. The highest scores of SP-A staining, with dense granular deposits (aggregates) in the intra-alveolar space, were observed in fatalities from pancuronium bromide (muscle relaxant) injection and petroleum (butane) gas inhalation. Poisoning with organophosphate pesticides and arsenic (ingestion) showed a second grade SP-A score. However, The SP-A scores were relatively low in ethanol and sedative–hypnotic intoxication. Carbon monoxide intoxication showed a varied degree of SP-A score, and the aggregated SP-A score tended to be higher in cases of lower blood carboxyhemoglobin concentration. A varied SP-A score was also observed in methamphetamine fatalities, in which the score was relatively low in cases with a higher serum drug level. Increase of SP-A was not always associated with the intra-alveolar effusion or hemorrhages. The above-described observations suggested that the immunohistochemical score of SP-A may be a possible indication for intensity and duration of drug/poison-dependent respiratory distress.

In order to investigate the pathophysiology of death due to fires, we examined blood samples of 48 fire victims on CO-oximeter systems and evaluated the oxymetric differences between arterial and venous blood as well as those between the heart and peripheral blood. Post-mortem carboxyhemoglobin (CO-Hb) levels in the left and right heart blood, respectively, ranged from 1.2 to 94.7% and from 0.4 to 90.5%. Marked arterio-venous and centro-peripheral differences were observed in the cases of high CO-Hb (above ca. 70%), suggesting an immediate effect of fatal carbon monoxide (CO) poisoning probably accompanied with acute heart failure. A relatively high oxyhemoglobin level was observed in the cases of low CO-Hb (below ca. 30%). In some cases, reduced hemoglobin levels in the left heart blood were paradoxically somewhat higher than those in the right. These oxymetric profiles may assist to consider the final balance of blood gas in fire victims depending on increased CO, carbon dioxide, and reduction of oxygen in the ambient atmosphere due to combustion, although post-mortem interference should be taken into consideration.