Nontraumatic Convexal Subarachnoid Hemorrhage Accompanied by Sylvian Hematoma: An Autopsy Case of Ruptured Distal Middle Cerebral Artery Aneurysm.

We describe an autopsy case of nontraumatic convexal subarachnoid hemorrhage (cSAH) accompanied by sylvian hematoma. A woman in her 50s was found dead in her house. On autopsy, massive cSAH accompanied by sylvian hematoma was observed. Because of the absence of subarachnoid hemorrhage (SAH) in the basal cistern, initial suspicion was that of a traumatic SAH. After a detailed investigation, a ruptured cerebral aneurysm of the distal middle cerebral artery was found in the hematoma, and the cSAH in this case was confirmed to be endogenous. Convexal subarachnoid hemorrhages typically result from traumatic injury, whereas endogenous cSAHs are exceedingly rare. Autopsy findings of a sylvian hematoma with SAH may result from endogenous hemorrhage from ruptured aneurysm of the distal middle cerebral artery. Detailed investigation of the hematoma may help identify the culprit lesion and help arrive at the correct postmortem diagnosis.

Pilsicainide Poisoning: An Autopsy Case and Review of Literature.

We describe an autopsy case of fatal poisoning due to accidental overdose of pilsicainide, which is a Vaughan Williams class IC antiarrhythmic drug (a pure sodium channel blocker). A man in his 50s was found dead in his home at approximately noon. He had ischemic heart disease and insomnia, and had previously demonstrated improper prescription drug adherence. The autopsy revealed old coronary artery bypass grafting and mild fibrosis of myocardium, but no acute myocardial infarction was found in microscopic examination. Toxicological analysis also identified a high blood concentration of pilsicainide (femoral vein blood, 14.9 µg/mL), more than 15 times higher than reported therapeutic levels. The blood concentrations of other drugs were at therapeutic levels, and no alcohol was detected. We concluded that the cause of death was pilsicainide poisoning, based on the results of the autopsy and the toxicological examination. This is the first autopsy report of fatal poisoning due to pilsicainide as a single agent.

An Autopsy Case of Injuries Caused by Automobile Dragging for a Distance of 3.4 km Without Thoracoabdominal Organ Injuries.

Dragging injuries caused by automobiles involved in an accident are occasionally reported; however, those without injury to the thoracoabdominal organs are rare. We present an autopsy case of a man in his 20s found dead on the road after being dragged by a passenger automobile for a distance of 3.4 km. The accident caused fatal dragging injuries but no thoracoabdominal injuries. The victim appeared to be drunk and was lying on the road in front of the parked automobile. Dragging injuries are a unique type of traffic accident that sometimes result from limited and poor visibility due to darkness, rain, or fog. In particular, lying on the road in a drunken state is a specific risk factor for dragging injuries. The dragging distance, road-surface properties, strength of pressure applied by the underbody of the automobile, and the victim's posture are considered to affect the distribution and degree of dragging injuries. Based on autopsy findings and eyewitness testimonies, we discuss the injury mechanism and attempt to reconstruct the accident.

Comprehensive behavioral study of C57BL/6.KOR-ApoEshl mice.

Background: Apolipoprotein E (ApoE) is associated with Alzheimer's disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral abnormalities in ApoE-deficient (Apoeshl) mice, which have been described as AD mouse models. Spontaneously hyperlipidemic mice were discovered in 1999 as ApoE-deficient mice due to ApoE gene mutations. However, behavioral abnormalities in commercially available Apoeshl mice remain unclear. Accordingly, we aimed to investigate the behavioral abnormalities of Apoeshl mice. Results: Apoeshl mice showed decreased motor skill learning and increased anxiety-like behavior toward heights. Apoeshl mice did not show abnormal behavior in the Y-maze test, open-field test, light/dark transition test, and passive avoidance test. Conclusion: Our findings suggest the utility of Apoeshl mice in investigating the function of ApoE in the central nervous system.

Component-specific reduction in perineuronal nets in senescence-accelerated mouse strains.

With increased life expectancy, age-related diseases are a significant health concern in Western societies. Animal models (e.g., rodents) have been used to understand age-related changes in brain function-particularly through the senescence-accelerated mouse (SAM) strain. Previous reports have shown that the senescence-accelerated mouse propensity (SAMP)8 and SAMP10 strains have learning disabilities. In this study, we analyzed the prefrontal cortex, which is involved in cognitive function. We aimed to clarify the changes in parvalbumin-positive interneurons (PV-positive neurons), which are related to cognitive function, and perineuronal nets (PNNs), which are special extracellular matrix molecules formed around them. We performed histological analysis of PV-positive neurons and PNNs in the prefrontal cortex to elucidate the mechanism of behavioral abnormalities in SAMP8 and SAMP10 strains. Expression of Cat-315-positive PNN was not confirmed in the prefrontal cortex of SAMP10 mice. However, the density of AB1031-positive PNN, tenascin-R-positive PNN, and brevican-positive PNN decreased in the prefrontal cortex of SAMP8 and SAMP10 mice compared to that of the senescence-accelerated mouse resistance (SAMR1) mice. In addition, the density of PV-positive neurons was lower in SAMP8 mice than in SAMR1 mice. These mice, which exhibited behavioral and neuropathological phenotypes with age, showed different PV-positive neurons and PNNs in the prefrontal cortex compared with the SAMR1 mice. We believe that the results of this study will be useful for elucidating the mechanisms of age-related decline in cognitive and learning functions using SAM.

Chronic Inhibition of Aggressive Behavior Induces Behavioral Change in Mice.

Suppression of anger is more common than its expression among Asian individuals. Emotional suppression is considered an unhealthy emotional regulation. Most studies on emotional suppression have concluded that suppression adversely affects social outcomes, with approximately 5% of the world's population suffering from emotional disorders. However, anger suppression has not received academic attention, and details of the effects of chronic anger suppression on the central nervous system remain unclear. In this study, we performed the resident-intruder test to investigate the effect of chronic suppression of aggressive behavior in mice using a behavioral test battery and to clarify whether suppression of this aggressive behavior is stressful for mice. Mice chronically inhibited aggressive behavior and lost weight. Mice with inhibited aggressive behavior showed a reduced percentage of immobility time during the tail suspension test as well as no changes in activity, anxiety-like behavior, muscle strength, or temperature sensitivity. This study provides scientific evidence for the effects of chronic aggressive behavior inhibition on the body and central nervous system.

The prevention of home-cage grid climbing affects muscle strength in mice.

Experimenters and treatment methods are the major contributors to data variability in behavioral neuroscience. However, home cage characteristics are likely associated with data variability. Mice housed in breeding cages spontaneously exhibit behavioral patterns such as biting into the wire grid and climbing on the grid lid. We aimed to clarify the effect of covering the stainless steel wire grid lid in commonly used home cage with Plexiglas to prevent climbing on muscle strength in mice. Furthermore, we investigated the effects of climbing prevention on activity and anxiety-like behavior, and the impact of climbing prevention during the postnatal development period and adulthood on muscle strength. Muscle strength, anxiety-like behavior, and locomotor activity were assessed by a battery of tests (wire hang, suspension, grip strength, rotarod, elevated-plus maze, and open field tests). Mice prevented from climbing the wire grid during postnatal development displayed lower muscle strength than those able to climb. Moreover, mice prevented from climbing for 3 weeks following maturity had weakened muscles. The muscle strength was decreased with 3 weeks of climbing prevention in even 1-year-old mice. In summary, the stainless steel wire grid in the home cage contributed to the development and maintenance of muscle strength in mice.

Ryanodine receptors are involved in the improvement of depression-like behaviors through electroconvulsive shock in stressed mice.

BACKGROUND: Electroconvulsive therapy (ECT) is effective for treating depression. However, the mechanisms underlying the antidepressant effects of ECT remain unknown. Depressed patients exhibit abnormal Ca2+ kinetics. Early stages of the intracellular Ca2+ signaling pathway involve the release of Ca2+ from the endoplasmic reticulum (ER) via Ca2+ release channels. OBJECTIVE: We considered that depression may be improved via ECT-induced normalization of intracellular Ca2+ regulation through the Ca2+ release channels. The current study aimed to investigate the effects of ECT on two Ca2+ release channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). METHODS: A mouse depression-like model subjected to water immersion with restraint stress was administered electroconvulsive shock (ECS) therapy. Their depression-like status was behaviorally and histologically assessed using forced swimming tests, novelty-suppressed feeding tests, and by evaluating neurogenesis in the hippocampal dentate gyrus, respectively. A RyRs blocker, dantrolene, was administered prior to ECS, and the changes in depression-like conditions were examined. RESULTS: The protein expressions of RyR1 and RyR3 significantly increased in the hippocampus of the mouse model with depression-like symptoms. This increase was attenuated as depression-like symptoms were reduced due to ECS application. However, pre-injection with dantrolene reduced the antidepressant effects of ECS. CONCLUSIONS: A significant increase in RyRs expression in a depression-like state and exacerbation of depression-like symptoms by RyRs inhibitors may be caused by RyRs dysfunction, suggesting overexpression of RyRs is a compensatory effect. Normalization of RyRs expression levels by ECS suggests that ECT normalizes the Ca2+ release via RyRs. Thus, normalizing the function of RyRs may play an important role in the therapeutic effect of ECT.

An autopsy case of a primary aortoenteric fistula: a pitfall of the endoscopic diagnosis.

A primary aortoenteric fistula (PAEF), defined as a communication between the native aorta and the gastrointestinal tract, is a rare cause of gastrointestinal bleeding. The preoperative diagnosis of PAEF is extremely difficult. Consequently, PAEF may cause sudden and unexpected death. We present an autopsy case of a 68-year-old man who died of massive gastrointestinal bleeding due to a PAEF. Autopsy revealed a pinhole rupture located on the third part of the duodenal mucosa and fistulized into the adjacent abdominal aortic aneurysm (AAA). Our case indicates that the aortoenteric fistula can result in fatal gastrointestinal bleeding. Consequently, a PAEF should be included in the differential diagnosis of gastrointestinal bleeding.

Analysis of oseltamivir active metabolite, oseltamivir carboxylate, in biological materials by HPLC-UV in a case of death following ingestion of Tamiflu.

An HPLC-UV method was established for determination of oseltamivir carboxylate, an active metabolite of oseltamivir, in biological materials. Oseltamivir carboxylate and floropipamide (internal standard) were extracted by using a mixed mode cation exchange extraction cartridge. The recovery yields of oseltamivir carboxylate from spiked blood at concentrations 0.1microg/ml and 1.0microg/ml were 103.8+/-16.9% and 95.0+/-4.3%, respectively. Linearity was obtained in the concentration from 0.1 to 3.0microg/ml. The detection limit was 0.04microg/ml (S/N=3). This method was applied to a case of death from falling after ingestion of a Tamiflu capsule containing 75mg of oseltamivir. Concentration of oseltamivir carboxylate in the femoral blood was 0.4microg/ml. The highest concentration in all specimens was in the liver at 18.3microg/g. In all brain samples, the concentrations were not higher than the quantification limit (0.1microg/g).

Scuba-diving related deaths in Okinawa, Japan, from 1982 to 2007.

We reviewed the autopsies of scuba-diving related deaths (SDRDs) that were collected from April 1982 until March 2007. In the period under consideration, a total of 40 SDRDs were registered, out of which 34 were males and 6 females. Ages ranged from 19 to 65 years, with the average of 41.5 years (SD=12.9). Divers over the age of 40 accounted for 60% of all fatalities. The major cause of death was drowning (62.5%), followed by disease (28.5%). The average age for drowning and disease-related deaths was 38.6 (SD=12.8) and 48.7 years (SD=10.1), respectively. Of the 40 fatalities, 24 were beginners who had little or no experience. In this study, we compared SDRDs in the first term, from April 1982 to March 1995, and in the second term, from April 1995 to March 2007. The average age in the first and second terms was 35.4 and 45.2 years, respectively; the average age for the second term was 10 years older than the first. Of those in the first term, 13.3%, and of those in the second term, 40.0%, died from complications arising from already existing conditions. This study revealed that the onset of diseases during diving frequently causes fatal accidents, especially for older divers.

Hemoperitoneum due to rupture of a subserosal vein overlying a uterine leiomyoma.

Uterine leiomyoma is the most common tumor in women of reproductive age, but rarely does it lead to fatal hemoperitoneum. We present an autopsy case in which the cause of death was massive hemoperitoneum due to rupture of a subserosal vein overlying a uterine leiomyoma. We report the case of a 28-year-old Japanese woman who had tuberous sclerosis and was gravida 0, para 0. She had a uterine leiomyoma leading to dysmenorrhea. Autopsy revealed a pinhole-sized rupture of a subserosal vein superficial to the leiomyoma that resulted in fatal hemoperitoneum. Rupture of a subserosal vein overlying a uterine leiomyoma may cause sudden and unexpected death.

Global hypomethylation of peripheral leukocyte DNA in male patients with schizophrenia: a potential link between epigenetics and schizophrenia.

Genetic and epigenetic factors can potentially alter susceptibility to psychiatric disorders such as schizophrenia. In order to explore the effect of epigenetics on the pathogenesis of schizophrenia, we examined the global methylation level of leukocyte DNA from 210 patients with schizophrenia (124 males and 86 females) and 237 healthy subjects (108 males and 129 females). Methylated deoxycytidine (mC) content in peripheral leukocyte DNA was measured by high performance liquid chromatography (HPLC). We confirmed in the healthy subjects our previous finding that there are sex-dependent differences in mC content (males>females; beta=0.319, p<0.001), in addition to the effect of age (beta=-0.141, p=0.022). We therefore used multiple regression to analyze the data from all subjects by sex, with age as a co-variant. In males, a tendency was observed toward lower mC content in patients than in controls (beta=-0.115, p=0.075), with a significant effect of age (beta=-0.212, p<0.001). This difference was more prominent in younger individuals. In females, no effect of age or disease status on mC content was observed. These results established that there is significant sex-dependent difference in the mC content of human peripheral leukocyte DNA, and raise the possibility that alterations in DNA methylation state are present in patients with schizophrenia.

A two-rider motorcycle accident involving injuries around groin area in both the driver and the passenger.

This paper presents a two-rider motorcycle accident in which both riders received injuries around the groin area. In medico-legal autopsies, injuries around the groin area in victims of motorcycle accidents are usually regarded as a "fuel tank injury." Although fuel tank injuries are one of the most useful and important characteristics in determining injuries that have been found to be exclusive to the driver, our study reveals that passengers can also suffer from injuries around the groin area. To distinguish the driver from the passenger, we need to carefully consider each injury in both riders. In addition, we present bilateral traumatic testicular dislocation in the driver. We consider traumatic testicular dislocation as one of the important findings of fuel tank injuries in motorcycle accidents.

[Autopsy case of aspirin intoxication: distribution of salicylic acid and salicyluric acid in body fluid and organs].

A 52 year-old woman ingested approximately 300 tablets (325 mg) of aspirin in a suicide attempt. We analyzed the concentrations of salicylic acid (SA) and salicyluric acid (SUA) in body fluids and organs using a modified previous high-performance liquid chromatographic method. The concentrations of SA in heart and femoral blood were 1.1 mg/mL and 1.3 mg/mL, respectively; the results were far higher than the lethal level. The concentration of SA was 0.3-0.4 mg/g in brain, 0.9-1.4 mg/g in lung, 0.6-0.8 mg/g in liver and 0.9 mg/mL in kidney.

An experimental study of postmortem decomposition of methomyl in blood.

Methomyl (S-methyl-1-N-[(methylcarbamoyl)oxy]thioacetimidate) is a carbamate pesticide. It has been noted that in some cases of methomyl poisoning, methomyl is either not detected or detected only in low concentrations in the blood of the victims. However, in such cases, methomyl is detected at higher concentrations in the vitreous humor than in the blood. This indicates that methomyl in the blood is possibly decomposed after death. However, the reasons for this phenomenon have been unclear. We have previously reported that methomyl is decomposed to dimethyl disulfide (DMDS) in the livers and kidneys of pigs but not in their blood. In addition, in the field of forensic toxicology, it is known that some compounds are decomposed or produced by internal bacteria in biological samples after death. This indicates that there is a possibility that methomyl in blood may be decomposed by bacteria after death. The aim of this study was therefore to investigate whether methomyl in blood is decomposed by bacteria isolated from human stool. Our findings demonstrated that methomyl was decomposed in human stool homogenates, resulting in the generation of DMDS. In addition, it was observed that three bacterial species isolated from the stool homogenates, Bacillus cereus, Pseudomonas aeruginosa, and Bacillus sp., showed methomyl-decomposing activity. The results therefore indicated that one reason for the difficulty in detecting methomyl in postmortem blood from methomyl-poisoning victims is the decomposition of methomyl by internal bacteria such as B. cereus, P. aeruginosa, and Bacillus sp.

Investigation of an anatomically variant isolated bicuspid pulmonary valve: A case report.

INTRODUCTION: We provide a discussion of the anatomical characteristics of the bicuspid pulmonary valve (BPV) in this paper. We performed an autopsy of an isolated BPV found in the heart of a deceased individual. The deceased was a man in his 60s and had no previous history of cardiovascular disease. The heart weighed 260 g and had mild right ventricular hypertrophy. The pulmonary valve had a fish-mouth-like shape that was convex to the pulmonary trunk and both cusps were thickened and hardened. The anterior and left semilunar cusps of the pulmonary valve were fused. Post-stenotic dilatation was noted. CONCLUSIONS: In comparing the present case with previous reports, we found that, in human BPVs, cusps are fused in at least 2 patterns.

The stability of organophosphorus insecticides in fresh blood.

We investigated the stability of 14 organophosphorus insecticides: dichlorvos, fenitrothion, cyanophos, malathion, phenthoate, methidathion, dimethoate, thiometon, isoxathion, diazinon, trichlorfon, EPN, acephate and sulprofos, in fresh blood. The organophosphorus compounds, except for sulprofos, decomposed over time at 37 degrees C, with varying decomposition speed for each compound. Methyl phosphate types (dichlorvos) decomposed most rapidly, followed by methyl thiophosphate types (fenitrothion and cyanophos) and methyl dithiophosphate types (methidathion, dimethoate and thiometon). Methyl thiophosphate types decomposed faster than ethyl thiophosphate types (isoxathion and diazinon). Of the five methyl dithiophosphate type insecticides (malathion, phenthoate, methidathion, dimethoate and thiometon), the compounds with a carboxylic ester bond (malathion and phenthoate) decomposed faster than the others. Compounds left standing at 37 degrees C decomposed faster than those left standing at 4 degrees C. Temperature has a great effect on the decomposition of organophosphorus insecticides in blood. However, the order of the decomposition speeds of each compound was approximately the same at different temperatures. In cases of suspected organophosphate poisoning, it should be considered that the blood concentration of the compound might decrease during the postmortem interval.

Stage and region dependent expression of a radial glial marker in commissural fibers in kindled mice.

Amygdala kindling is regarded as a model of temporal lobe epilepsy in humans because of many points of similarity. In amygdala kindling, bilateralization of epileptic seizures follows from the accumulation of stimulation and commissural fibers may play a role in this process. However, new progenies of cells following amygdala kindling have not been reported and the precise nature of how bilateralization occurs is not clear. In the present study, we aim to clarify the emergence of radial glia during the progress of amygdala kindling in mouse brain. For this purpose, immunohistochemical staining for 3CB2, which is a specific marker of radial glia, was employed. Immunoreactivity for 3CB2 was observed in the forceps minor, radiation of trunk and forceps major regions at Clonus 3 and more strongly at Clonus 5. In the forceps major, the cingulate gyrus showed immunopositive staining at Clonus 3, but the corpus callosum and alveus hippocampi showed staining only at Clonus 5. In the fimbria hippocampus, the anterior commissure posterior showed staining at Clonus 5. However, the anterior commissure anterior was not stained at the stage progressed to Clonus 5. These findings indicate stage and region dependent expression of progenitor cells in commissural fibers and suggest that these changes may accompany the formation of new circuits in seizure progression during amygdala kindling.