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.

Distinguishing true from pseudo hematoma in the cervical spinal canal using postmortem computed tomography.

Spinal cord injury is difficult to detect directly on postmortem computed tomography (PMCT) and it is usually diagnosed by indirect findings such as a hematoma in the spinal canal. However, we have encountered cases where the hematoma-like high-attenuation area in the cervical spinal canal was visible on PMCT, while no hematoma was observed at autopsy; we called it a "pseudo hematoma in the cervical spinal canal (pseudo-HCSC)." In this retrospective study, we performed statistical analysis to distinguish true from pseudo-HCSC. The cervical spinal canal was dissected in 35 autopsy cases with a hematoma-like high-attenuation area (CT values 60-100 Hounsfield Unit (HU)) in the spinal canal from the first to the fourth cervical vertebrae in axial slices of PMCT images. Of these 22 had a hematoma and 13 did not (pseudo-HCSC). The location and length of the hematoma-like high-attenuation and spinal cord areas were assessed on reconstructed PMCT images, true HCSC cases had longer the posterior hematoma-like area and shorter the spinal cord area in the midline of the spinal canal (P < 0.05). Furthermore, we found that true HCSC cases were more likely to have fractures and gases on PMCT while pseudo-HCSC cases were more likely to have significant facial congestion (P < 0.05). We suggest that pseudo-HCSC on PMCT is related to congestion of the internal vertebral venous plexus. This study raises awareness about the importance of distinguishing true HCSC from pseudo-HCSC in PMCT diagnosis, and it also presents methods for differentiation between these two groups.

[Cyanamide-ethanol reaction induced shock: report of a case and literature review].

Cyanamide is a known alcohol deterrent, and it may cause severe cyanamide-ethanol reaction if a patient consumes high amounts of alcohol during treatment. We report a rare case of cyanamide-ethanol reaction-induced shock in a 73-year-old man who was taking cyanamide for the treatment of alcohol dependence. The patient complained of acute onset of dyspnea after drinking. On arrival, he was in a state of shock. We immediately started hydration and administered 0.3 mg adrenaline by intramuscular injection. However, the patient's general condition did not improve. We could rescue him only after a high dose of adrenaline was administered by continuous intravascular injection. In general, in the treatment of cyanamide-ethanol reaction-induced shock, adrenaline or noradrenaline should be used instead of dopamine. Some cases of severe cyanamide-ethanol reactions have been recently reported in Japan. We performed a literature review and have discussed these cases in the text.

Quantitative analysis of respiratory viral distribution in forensic autopsy cases.

Respiratory viruses can cause fatal systemic infections; therefore, post-mortem diagnosis is essential in forensic autopsy cases. However, little is known regarding the distribution of respiratory viruses in the body. In this study, we investigated the anatomical distribution of respiratory viruses in 48 forensic autopsy cases suspected of viral infections at our institute. Fast Track Diagnostics (FTD) Respiratory Pathogens 21 was used as a screening test for 20 respiratory viruses in nasopharyngeal swabs. In cases with positive results for virus detection by the screening test, the detected viruses were quantified in body fluid and organ specimens by virus-specific real-time reverse transcription polymerase chain reaction (RT-PCR) and digital PCR. Viruses were detected in 33 cases, with the viral distribution and load differing among the cases. Since various respiratory viruses were detected from the nasopharyngeal swab and its viral load was higher than those of other body fluid specimens, the nasopharyngeal swab was suggested as a useful specimen for the post-mortem detection of respiratory viruses. Viruses were detected in almost all specimens including the serum in six cases. Considering the viral distribution in the body, pathological findings, and ante-mortem symptoms, these cases were presumed to be systemically infected, having died in the acute infection phase. In conclusion, the anatomical distribution of respiratory viruses can help indicate ante-mortem systemic conditions and the cause of death.

Kinetics and distribution of benzalkonium compounds with different alkyl chain length following intravenous administration in rats.

Benzalkonium chloride is widely used in disinfectants. Several toxicological and fatal cases have been reported; however, little is known about its kinetics and distribution. We investigated the kinetic characteristics and distribution of benzalkonium cation (BZK) based on the length of the alkyl chains C12, C14, and C16. Rats were treated intravenously with BZK solution (dose, 13.9 mg/kg) containing equal amounts of the three homologues. Kinetic parameters in the blood were assessed, and BZK distribution in the blood and tissues was examined both in rapid intravenous (IV) and drip intravenous (DIV) administrations. BZK concentrations were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). BZK with longer alkyl chains showed lower elimination tendencies and remained in the blood for a longer duration. Concentrations of BZK were higher in the heart, lung, spleen, and kidney than those in the blood, and lower in the brain and fat. In both the IV and DIV groups, the lung, liver, spleen, and fat samples showed higher concentrations of the longer alkyl chains (BZK-C12 < -C14 < -C16), and the opposite trend was observed in the kidney (BZK-C16 < -C14 < -C12). Only the heart and muscle samples displayed the homologues in ratios comparable to the original administered solutions. Differences between IV and DIV groups could be identified by comparing concentrations of BZK homologues in the heart, lung, spleen, and kidney samples. We found that the kinetics and distribution of BZK were influenced by the alkyl chain length, and analysing each BZK homologues in blood and tissue samples may provide useful information.

[Survey of analytical work done for drugs at the emergency and critical care centers equipped with high-performance instruments provided by the Ministry of Health and Welfare (at present: Ministry of Health, Labour and Welfare) in fiscal 1998].

A questionnaire was sent to 73 emergency and critical care centers where high-performance instruments for analyzing drugs and chemicals were provided by the Ministry of Health and Welfare (currently Ministry of Health, Labour and Welfare) in fiscal 1998. 52 centers (71.2%) responded to the questionnaire. Among these, the instruments have been in operation at 36 centers. This means that analytical work has been performed in at least 49.3% (36/73) of facilities with the instruments. A positive correlation was observed between the annual number of patients tested for drugs and chemicals and analytical work hours at the 36 facilities. The results indicated that 150 cases may be tested for drugs and chemicals in a year on the condition that 100 hours a month of analytical work are secured, and 200 or more cases may be tested if 200 hours a month are secured. As for the running costs required for the operation of the instruments, the instrument maintenance and repair cost was estimated at 2 million yen a year, and it was calculated that 100 cases could be handled with a maximum annual supply expense of 1 million yen and 150 cases could be handled with a maximum annual supply expense of 2 million yen. These results suggest that the instrument running cost would be fully covered at nationwide emergency and critical care centers if the additional 5,000 NHI points (1 point = 10 yen) for hospital admission, which is approved for advanced emergency and critical care centers, were applicable to all facilities. Among the 36 facilities, the implementation of analysis varied for each of the 15 toxic substances recommended for analysis by the Japanese Society for Clinical Toxicology. Further research will be necessary to investigate and assess the frequency of analysis requests and combination of simple qualitative and instrumental analyses for each of the 15 substances, in order to evaluate the approach to the 15 substances in analytical work.

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.

[Qualitative and quantitative analysis by analytical instruments of compounds causing acute poisoning].

In generally, the results of screening drugs or poisons by simple analytical techniques or screening kits show the possibility that the group of compounds detected is contained in the specimen. Then, qualitative and quantitative analyses by analytical instruments are required to identify the compound which is the cause of acute poisoning. Gas chromatograph-equipped electron ionization mass spectrometer is the most reliable apparatus of all analytical instruments. When the retention time and EI-mass spectrum of the detected peak by GC/MS analysis coincide with those of the reference standard and the blood level is abnormal, the compound is concluded to be the subject of the cause of acute poisoning. If we do not use GC/MS, we use two or more different analytical instruments or different analytical methods, and then we consider the overall results obtained from each analysis totally to identify the compound. In order to analyze drugs or poisons in biological materials using these instruments, pretreatment procedures are indispensable to identify the compound. The appropriate procedures increase sensitivity and specificity. When treating an acute poisoned patient, the use of analytical instruments tends to be avoided because it requires rapid investigation into the cause of acute poisoning. If the operator is proficient in using analytical instruments and the cause of acute poisoning is the compound that has been analyzed before, results using analytical instruments could give more useful information than using simple but rapid analytical techniques or screening kits. For this purpose, it is important to understand well the characteristics of the equipment to collect many reference standards, and to prepare for emergency analysis.

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.

Haloperidol treatment induces tissue- and sex-specific changes in DNA methylation: a control study using rats.

BACKGROUND: We previously found that there is a subtle difference in the global methylation state of blood leukocyte DNA between male subjects with and without schizophrenia. The aim of the current study was to determine whether this difference was a primary effect of the disease state, or a secondary effect of antipsychotics administered to these patients. METHODS: We examined the methyl cytosine (mC) content of DNA from the leukocytes, brain, and liver of rats using high performance liquid chromatography. A total of 40 male and female rats received for 21 days daily injection of haloperidol or vehicle solution alone. RESULTS: In control rats injected with buffer only, there was a sex-dependent difference in mC content in leukocyte DNA (male > female; P = 0.028, n = 10), similar to our previous observations in human peripheral leukocytes. No difference in mC content between the sexes was observed in the brain or liver in buffer-treated animals. Haloperidol treatment slightly decreased the mC content of leukocytes in male rats, but unexpectedly, increased the mC content of leukocytes in females. We observed a trend toward a higher level of mC in the liver in both sexes following haloperidol treatment, compared to buffer-treated animals. In contrast, haloperidol treatment resulted in a decrease in mC content in the brain in females, and this difference was statistically significant (P = 0.026). CONCLUSION: These results indicate that haloperidol can affect DNA methylation states in the brain, as well as in certain other tissues, and raise the possibility that antipsychotic drugs play a role in the observed disparity in mC content in male subjects with and without schizophrenia.

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.