Association between serum catecholamine levels and VNTR polymorphism in the promoter region of the monoamine oxidase A gene in forensic autopsy cases.

Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected.We examined the frequencies of MAOA-uVNTR alleles in these cases and investigated the effects of the MAOA-uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA-uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA-uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA-uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA-uVNTR polymorphism influences serum Adr and DA levels only in females.

An autopsy case of cerebral hemorrhage in an HIV-infected patient with suspected HIV-associated cerebrovascular disease.

A male in his late 30s was found dead in his home. He was diagnosed with human immunodeficiency virus (HIV) about six years prior. The HIV infection was well controlled before his death. He was 166 cm in height and 75 kg in weight. Aside from discoloration of the skin on the right lower patellar, there were no obvious injuries. His brain weighed 1456 g. A cut surface of the brain revealed left thalamic hemorrhage. Histologically, infiltration of phagocytic cells was observed in the bleeding site. Thalamic hemorrhage was considered to be his cause of death in this case. Due to the effects of anti-HIV therapy, the mortality rate from HIV infection has decreased and the causes of death of HIV-infected persons have changed. HIV-infected persons have been suggested to be associated with cerebrovascular disease, especially juvenile ischemic stroke. Patients with acquired immunodeficiency syndrome (AIDS) have an increased risk of cerebrovascular disease. Possible mechanisms of cerebrovascular disease in HIV-infected individuals include coagulopathy, secondary effects of embolism and central nervous system infection, and direct vascular disease due to HIV. At the time of autopsy, his post-mortem interval was estimated to be approximately two weeks. Therefore, it was difficult to clarify histologically the cerebrovascular disorder that caused his cerebral hemorrhage. In recent years, anti-HIV therapy has reduced the number of AIDS-related deaths, but deaths in HIV-infected people from cardiovascular disease are increasing. This case is considered to be a valuable forensic autopsy case of an HIV-infected patient who actually died due to cerebral hemorrhage in Japan.

The effect of tea catechins on the forensic identification of urine: Urine camouflage to evade drug tests.

BACKGROUND: We encountered a urine sample suspected of being mixed with tea, submitted by a suspect attempting to camouflage illegal drugs. Although urine should turn reddish-pink during a urea test with p-Dimethylaminocinnamaldehyde (DAC), this suspect's sample exhibited a blue coloration when tested with DAC. AIM: Our aim was to examine the influence and mechanism of green tea on various urine identification tests. RESULTS: Our examination revealed that DAC forms a compound with the urea in urine, resulting in a reddish pink coloration with a molecular weight of 217. However, it has been reported that DAC binds to polyphenols such as catechin. In the case of catechin, DAC binds to the C8 position, forming a compound that exhibits the highest absorption at 640 nm and appears blue. we investigated the effect of urine from volunteers who had consumed a large amount of catechin on the urea test with DAC. Additionally, we carried out quantitative analysis of catechin in urine by LC-MS/MS after enzymatic treatment with ß-glucuronidase. The concentration of urinary excreted catechin reached its peak approximately 3 to 4 h after ingestion. During the DAC test, urine samples collected 3 to 4 h after catechin ingestion displayed a bluish pink color, but not the blue color observed in the original suspect sample. CONCLUSION: This study investigated the impact of catechin on urine tests, revealing that a blue color in the DAC test indicates a high likelihood of camouflage by the suspect.

Urinary phenylacetylglutamine as a possible biomarker for central nervous system disorders in forensic autopsy cases.

Phenylacetylglutamine (PAG) is a metabolite that is excreted in human urine. Phenylalanine is metabolized to phenylacetic acid, which is then amide-bonded to glutamine to form PAG. We are currently studying PAG as a urinary biomarker in forensic autopsy cases. MATERIALS AND METHODS: Urine samples were collected from 188 forensic autopsy cases and the urinary PAG concentration was analyzed quantitatively using GC-MS. Urinary creatinine (Cr) concentration was also analyzed by GC-MS. For statistical analysis, the JMP Pro 15.0.0 software program was used. The relationship between urine PAG/Cr (the ratio of each concentration), sex, age, postmortem interval (PMI), survival duration, and cause of death was statistically analyzed. RESULTS AND DISCUSSION: The median (range) of PAG/Cr was 0.12 (0.002-3.26). The PAG/Cr ratio showed no significant relationship to sex or survival duration. Regarding the cause of death, traumatic brain injuries had a significantly higher ratio than intoxication (p=0.023). Cerebrovascular disease, such as cerebral hemorrhage and subarachnoid hemorrhage, did not differ significantly from any cause of death group. However, when traumatic brain injuries and cerebrovascular accidents are combined as one cause of death group, the PAG/Cr value of CNS damages was significantly higher than that of intoxication (p=0.062). CONCLUSION: Urinary PAG/Cr might be a biomarker not only for traumatic brain injuries but also for antemortem CNS damages.

Diagnostic meaning of urinary ethyl glucoside concentrations in relationship to alcoholic beverage consumption.

Incidents and accidents often involve the drinking of alcoholic beverages. We investigated compounds that indicate the consumption of alcoholic beverages even after ethanol (EtOH) becomes undetectable in blood and urine. Ethyl glucoside (EG) has been isolated as a possible drinking marker, and a GC-MS/MS method for EG isomers has been developed. EG isomers in several alcoholic beverages were analyzed. In sake, only αEG was observed in high concentrations. In wine and beer, both α and ßEG were detected. Whisky, however, did not contain EG. EtOH and EG concentrations were analyzed in urine up to 48 h after ingestion. Maximum EtOH concentrations were reached in 1-2 h and was mostly eliminated in 6 h. Maximum EG concentrations were reached in 3-6 h, gradually decreased, and remained low after 24 h. After drinking sake, the αEG concentrations were much higher than that of other alcoholic beverages. After drinking wine or beer, ßEG was detected, but lower than αEG. Also, αEG was detected in urine after drinking whisky that contained no EG. This suggested that αEG may be synthesized in vivo. Disaccharide-degrading enzymes such as α-glucosidase are present in the human small intestine. It was considered that αEG was synthesized when alcohol was consumed with certain foods, such as carbohydrates. In actual forensic autopsy cases, EtOH and EG isomer analysis provided useful information regarding drinking history. In conclusion, it is considered that urinary EG isomers can be used as drinking markers that complement EtOH analysis.

Giant intracranial arteriovenous malformation as a possibility of epileptic seizures in a case of drowning.

A male in his late 50s had been complaining of headaches and dizziness for 25 years. He also had episodes of losing consciousness, but had not sought treatment because of financial hardship. He was found in the ocean. Autopsy revealed foamy liquid leaking from his nose and mouth, and pleural effusions. The trachea and bronchi contained the same foamy liquid. The lungs were swollen and edematous, and leaked a large amount of foamy liquid. His cause of death was diagnosed as drowning. In the brain, the veins on the frontal lobe and the temporal pole, each on the right cerebral hemisphere, were dilated. A vascular lesion measuring 5 × 5 × 8 cm was found on the bottom of the right frontal lobe, and was located between the right middle cerebral artery and those veins. This vascular lesion extended to the brain parenchyma, and the basal ganglia of the right cerebrum was displaced outward and upward. The vascular lesions in the brain showed blood vessels of various sizes and shapes, and some of the vessel walls were thickened. The vascular lesion on the right frontal lobe was diagnosed as an arteriovenous malformation (AVM). According to the police investigation, the harbor where his body was found was a place he often came for fishing and walking. The possibility of suicide cannot be ruled out. Moreover, it was considered that his AVM might have rendered him unconscious, causing him to fall into the ocean.

A large interhemispheric glioependymal cyst associated with partial defect of the corpus callosum in an elderly man.

Interhemispheric cysts are congenital, and usually present symptoms during childhood. However, they are occasionally detected in adults. These cystic lesions are sometimes associated with defects of the corpus callosum. Although defects of the corpus callosum by themselves do not present clinical symptoms, they are often accompanied by other brain malformations. A man in his late 60s was found dead at the scene of a fire. At autopsy, his brain weighed 1223 g and had a large interhemispheric cyst, measuring 5.5 × 4.5 × 4.0 cm in size. The cyst contained clear fluid but was not connected to the ventricular system. On slices of the cerebrum, the corpus callosum did not connect the right and left cerebral hemispheres, and the right lateral ventricle was dilated. By the existence of the cyst, compressed by the cyst, the hemispheres were displaced on either side. Histologically, the cerebral parenchyma around the cyst was slightly edematous but structurally normal. Immunohistochemically, both glial fibrillary acidic protein and podoplanin were expressed in the cystic components. Thus, the cystic lesion was diagnosed as a glioependymal cyst. In this case, because the cyst was located at the interhemispheric space between the right and left frontal lobes, the individual experienced no obvious symptoms, despite its large size. The individual's brain malformations included the partial defect of the corpus callosum and the cyst. The dilation of the right lateral ventricle was considered to result from the location of the cyst. Under the influence of the cyst, the third ventricle was displaced downward, and one or both of the interventricular foramen were obstructed. The decedent had burns over his whole body. Burns to the epiglottis and soot in the airway were also observed. Volatile hydrocarbons, such as benzene and styrene, were detected in the blood. The percentage of carboxyhemoglobin levels in a total of hemoglobin levels were 19-25%. Therefore, the individual's cause of death was established as death by fire.

Organ distribution of endogenous p-cresol in hemodialysis patients.

BACKGROUND: p-Cresol concentrations are high in the blood of hemodialysis (HD) patients. However, its organ distribution has not yet been investigated in detail. We herein report the distribution of p-cresolin HD patients from forensic autopsy cases. METHODS: p-Cresol was measured in the blood, urine, lungs, liver, and kidneys from 4 HD and 4 non-HD cases. Samples were extracted with p-cresol-d8 (internal standard), derivatized,and injected on the GC-MS. RESULTS AND DISCUSSION: The total urinary p-cresol/Cr was 79.73 ng/ml in HD cases,which was 16-fold higher than that in non-HD cases. p-Cresol in the blood and kidneys were 30-fold higher or more at 11.92 and 13.08 µg/mL(g), respectively. p-Cresol in the liver and lungs were approximately 20-fold higher at 4.82 and 9.99 µg/g, respectively. p-Cresol was markedly increased in not only the blood, but also the urine and organs of HD cases. The distribution of p-cresol in the blood, urine, and organs differed between HD and non-HD cases. In HD cases, the percentages of conjugated (C) and protein-bound conjugated (PC) urinary p-cresol were 57 and 41%, respectively. C and PC p-cresol was 66% and 25% in the kidneys, respectively, and similar results were obtained in the lungs. J. Med. Invest. 66 : 81-85, February, 2019.

VNTR polymorphism in the monoamine oxidase A promoter region and cerebrospinal fluid catecholamine concentrations in forensic autopsy cases.

Monoamine oxidase A (MAOA) plays important roles in the metabolism of catecholamines and modulates adrenergic, noradrenergic, and dopaminergic signaling. A polymorphic promoter variable number tandem repeat (VNTR) locus (MAOA-uVNTR) is located approximately 1.2 kb upstream from MAOA exon 1. Functional studies revealed that MAOA-uVNTR affects gene expression. In the present study, we examined the frequencies of MAOA-uVNTR alleles in Japanese autopsy cases, in which amphetamines or psychotropic drugs were not detected. In total, 87 males and 35 females were evaluated and investigated for the possible effect of MAOA-uVNTR polymorphisms on cerebrospinal fluid (CSF) catecholamine concentrations. In males, there was no significant association between MAOA-uVNTR polymorphisms and CSF adrenaline (Adr), noradrenaline (Nad), or dopamine (DA) levels. In contrast, females who were homozygous for the 3-repeat allele (i.e., 3/3 genotype carriers) had higher CSF levels of Adr (p = 0.024) and DA (p = 0.035) than individuals who were heterozygous or homozygous for the 4-repeat allele (3/4 and 4/4, respectively). We found no significant association between MAOA-uVNTR polymorphisms and CSF Nad levels in females. Thus, the results of the present study indicated that MAOA-uVNTR polymorphism influences CSF Adr and DA levels in females.

Diagnostic meaning of blood p-cresol concentration in forensic autopsy cases.

In some forensic autopsy cases there are high concentrations of p-cresol in the blood. In vivo, p-cresol is the only isomer yielded by intestinal bacteria and is excreted into urine. We investigated the diagnostic meaning of p-cresol in the blood of forensic autopsy cases. Blood samples from 110 autopsy cases within 48 h of the postmortem interval (PMI) and 10 healthy adults were examined. Blood with p-cresol-d8 as an internal standard was analyzed using a GC-MS/MS method. Using acid and heat deproteinization, free (F) and conjugated (non-protein bound: C; protein bound: PC) p-cresol were individually analyzed. The p-cresol concentrations were 1.39 ±â€¯0.86 µg/ml [mean ±â€¯SD] and 1.18 (0.19-18.80) µg/ml [median (range)] in healthy adults and autopsy cases, respectively. The p-cresol showed no significant relationship to age, sex, fasting duration, survival duration, or PMI. No significant differences were found between causes of death. Significantly higher levels of C p-cresol were found in cases with atherosclerosis in the basilar or renal arteries, or stenosis in the coronary artery. Significantly higher levels of p-cresol except F were found in cases with hyalinosis of the kidney. Cases with low BMI also showed significantly higher p-cresol concentrations. The 22 cases of abnormally high total p-cresol were investigated. It was considered that high concentrations of p-cresol could be an indicator of certain diseases and physical conditions that effect the production, absorption, metabolism, circulation, and excretion of p-cresol. Measuring the levels of p-cresol may provide valuable information about the antemortem physical conditions.

An unusual case of suicide by methanol ingestion.

A female in her late teens purposely ingested alcohol fuel containing methanol to commit suicide, which she admitted on social media. She was found in distress by her parents and died at the hospital some hours later. Autopsy revealed swelling of the brain and edematous and congestive lungs. No other trauma or unusual findings were revealed at autopsy. Methanol was detected upon routine screening for alcohols by headspace gas chromatography with flame-ionization detection. To confirm the presence of methanol and its metabolite formic acid, a method with detection by mass spectrometry was used. Methanol and formic acid were quantitated in body fluids and tissues by headspace gas chromatography with flame-ionization detection. Formic acid was converted to isopropyl formate by reaction with isopropanol and concentrated sulfuric acid. Acetonitrile was used as the internal standard. The methanol and formic acid concentrations were analyzed in peripheral blood, heart blood, cerebrospinal fluid, liver, kidney, spleen, pancreas, lung, muscle, and fat. Successful confirmation and quantitation of methanol and formic acid, a methanol metabolite, in postmortem specimens was achieved on an uncommon case of suicide by methanol ingestion.

Association between cytochrome P450 2D6 polymorphisms and body fluid methamphetamine concentrations in Japanese forensic autopsy cases.

Methamphetamine (MA) is an illicit stimulant that affects the central nervous system. Cytochrome P450 2D6 (CYP2D6) plays an important role in MA metabolism. Numerous allelic variants confer substantial variation in CYP2D6 activity among individuals. In the present study, we examined the frequencies of CYP2D6 alleles, including CYP2D6*1, *2, *4, *5, *10, *14A, *14B, *18, and *36, and multiplication, in 82 forensic autopsy cases of MA abusers and 567 autopsy cases in which MA was not detected (controls). Ultrarapid metabolizer (UM), extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) phenotypes were predicted from CYP2D6 genotypes. Of MA abusers, 64 subjects were predicted to be EM, 17 were IM, and 1 was UM. No MA abuser had the predicted PM phenotype. No significant differences in CYP2D6 phenotype frequencies were found between MA abusers and controls. MA and amphetamine (AMP) concentrations were measured in the right heart blood, left heart blood, peripheral external iliac blood, urine, pericardial fluid, and bone marrow of MA abusers. MA concentrations in urine and bone marrow were significantly higher in IM than in EM. AMP concentration was not associated with CYP2D6 phenotype in any body fluid. These results suggest that the MA concentration in body fluids is influenced by CYP2D6 phenotypes in the Japanese population.

DRD2/ANKK1 gene polymorphisms in forensic autopsies of methamphetamine intoxication fatalities.

Dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) gene polymorphisms have been associated with responses to psychotropic drugs and addiction. We analyzed two DRD2/ANKK1 polymorphisms, Taq1A and -141C Ins/Del, in 37 fatal methamphetamine (MA) intoxication cases and 235 control cases in which MA and psychotropic drugs were not detected. The association among polymorphism, cause of death, and cerebrospinal fluid (CSF) dopamine concentration was evaluated. The Taq1A polymorphism distribution in the fatal MA intoxication cases differed from in the controls (P = 0.030) with a significantly high A1/A1 + A1/A2 genotype frequency. No significant associations were observed between -141C Ins/Del polymorphisms and MA intoxication cases or between DRD2/ANKK1 polymorphisms and CSF dopamine concentrations. Our findings suggest that the DRD2/ANKK1 Taq1A polymorphism is associated with susceptibility to fatal MA intoxication.

Subarachnoid hemorrhage in a Japanese cocaine abuser: Cocaine-related sudden death.

Based on a prospective case-control study of forensic autopsies, the causes of cocaine (COC)-related sudden death (SD) are cardiovascular events in 62.0% of cases, cerebrovascular events in 14.0%, and others. A forensic autopsy of a male in his early forties revealed subarachnoid hemorrhage (SAH) at the base of the brain. A cerebral arterial aneurysm was not detected even though hemorrhage was clearly observed in the anterior cerebral artery (ACA) bifurcation area. The brain weighed 1488 g and was edematous. We histopathologically examined the left-ACA, right-ACA, and anterior communicating artery (Acom). Thickening of the internal vessel wall was observed as a pathological change. The internal elastic lamina of the right-ACA, near the peripheral part of Acom, was meandered with a jagged appearance. A toxicology examination detected COC and its metabolites, particularly benzoylecgonin, in blood and urine samples. Therefore, the present case was regarded as a non-fatal intoxication case, but also a COC-related death. Ethanol was also detected, indicating that COC was taken in combination with alcohol. The cause of COC-related death in the present case was SAH. COC use is known to induce aneurysmal SAH; however, whether an aneurysm had formed in the present case was unclear. Meander, extension, and degeneration of the internal elastic lamina of the right-ACA were observed near the bifurcation from the Acom. This area corresponded macroscopically with that considered to be the bleeding point from the blood vessel. Therefore, the present case was diagnosed as COC-related SD.

Tissue Distribution of Suvorexant in Three Forensic Autopsy Cases.

Suvorexant (Belsomra®) is a relatively new insomnia medication that has been available in USA and Japan since 2014. It is a dual orexin receptor antagonist that promotes sleep by inhibiting the binding of orexin neurons to the OX1R and OX2R receptors. In this report, we describe the detection and quantitation of suvorexant from the postmortem specimens of three separate autopsy cases handled by our department. Suvorexant was identified by fast gas chromatography/mass spectrometry during routine screening, and quantitated by a fully validated liquid chromatography-tandem mass spectroscopy method. Quantitation was achieved by positive electrospray ionization in the selected reaction monitoring mode. Monitored transitions were m/z 451 > 186 for quantitation and m/z 451 > 104 for qualification. To our knowledge, this is the first instance of suvorexant being quantitated from actual autopsy cases. It is likely that this compound will be encountered more often by the forensic toxicology community going forward.

Giant intracranial arteriovenous malformation as the focus of epileptic seizures.

A man in his late thirties was found in a supine position in the hallway of his house. He had been diagnosed with epilepsy at approximately 20 years old. Since stopping treatment, epileptic events occurred more frequently and his condition deteriorated in the past 2 years. Autopsy revealed that head injuries were found on the left side of his head. A fracture from the left parietal bone to the anterior cranial fossa was also detected. A subdural hemorrhage (hematoma) spanned a wide range. A subarachnoid hemorrhage was also identified in the left parietal region. His brain weighed 1603 g, was edematous, and showed right uncal herniation. In the right cerebral hemisphere, a thick, enlarged blood vessel ran from the sagittal sinus. An egg-sized tumorous lesion of blood vessels was found on the bottom of the frontal lobe. This vascular lesion had formed between the sagittal sinus and right anterior cerebral artery. Pathologically, veins and arteries were found together, and, thus, this case was diagnosed as an arteriovenous malformation (AVM). No other pathological and toxicological findings were observed. Subdural hematoma, the cause of death, occurred from the fall to the floor. An epileptic seizure may have been the cause of the fall. AVM on his brain was considered to be the focal lesion of epileptic seizures.

Basal subarachnoid hemorrhage by rupture of arteriovenous malformation at the cerebellopontine angle.

A man in his late forties had lived as a recluse for more than ten years. He was found dead in his room. At autopsy, subarachnoid hemorrhage (SAH) was detected at the base of the brain, which weighed 1333 g. The cerebellar tonsil was swollen. The cerebral ventricle was enlarged and filled with blood. A hematoma was observed in the upper part of the left side of the cerebellar hemisphere. The location and size of SAH in this case indicated that the rupture of a cerebral aneurysm (CA) had occurred; however, CA was not detected. A mass of blood vessels buried in the hematoma was observed at the left cerebellopontine angle (CPA). The vascular lesion showed round-shaped blood vessels as well as flat-shaped vessels with the appearance of veins, but with elastic fibers indicative of arteries. The lesion was considered to be the nidus and was 5-8 mm in size. Feeding arteries appeared to be from the anterior inferior cerebellar artery (AICA). However, the draining vein and anastomotic parts of the artery and vein were not confirmed. Based on these histopathological features, this vascular lesion was diagnosed as arteriovenous malformation (AVM). A differential diagnosis between AVM at CPA and CA is needed in order to identify the source of non-traumatic SAH.

Volatile Hydrocarbon Analysis in Blood by Headspace Solid-Phase Microextraction: The Interpretation of VHC Patterns in Fire-Related Incidents.

A headspace solid-phase microextraction (HS-SPME) technique was used to quantitate the concentration of volatile hydrocarbons from the blood of cadavers by cryogenic gas chromatography-mass spectroscopy. A total of 24 compounds including aromatic and aliphatic volatile hydrocarbons were analyzed by this method. The analytes in the headspace of 0.1 g of blood mixed with 1.0 mL of distilled water plus 1 µL of an internal standard solution were adsorbed onto a 100-µm polydimethylsiloxane fiber at 0°C for 15 min, and measured using a GC-MS full scan method. The limit of quantitation for the analytes ranged from 6.8 to 10 ng per 1 g of blood. This method was applied to actual autopsy cases to quantitate the level of volatile hydrocarbons (VHCs) in the blood of cadavers who died in fire-related incidents. The patterns of the VHCs revealed the presence or absence of accelerants. Petroleum-based fuels such as gasoline and kerosene were differentiated. The detection of C8-C13 aliphatic hydrocarbons indicated the presence of kerosene; the detection of C3 alkylbenzenes in the absence of C8-C13 aliphatic hydrocarbons was indicative of gasoline; and elevated levels of styrene or benzene in the absence of C3/C4 alkylbenzenes and aliphatic hydrocarbons indicated a normal construction fire. This sensitive HS-SPME method could help aid the investigation of fire-related deaths by providing a simple pattern to use for the interpretation of VHCs in human blood.

Association between cerebrospinal fluid dopamine concentrations and catechol-O-methyltransferase gene polymorphisms in forensic autopsy cases of methamphetamine abusers.

Methamphetamine (MA) is an illicit psychostimulant that stimulates the release of catecholamines from sympathetic nerve terminals and is widely abused worldwide. Since catechol-O-methyltransferase (COMT) metabolizes catecholamines and mediates adrenergic, noradrenergic, and dopaminergic signaling responses, we investigated the effects of the COMT polymorphisms rs4633 and rs4680 on cerebrospinal fluid (CSF) catecholamine concentrations in autopsies of subjects who died of drug intoxication. 28 MA abusers and 22 fatal psychotropic drug intoxication cases were evaluated. No correlations were identified between rs4633 or rs4680 polymorphisms and CSF concentrations of adrenaline (Adr), noradrenaline (Nad), or dopamine (DA) in fatal psychotropic cases. However, among MA abusers, DA concentrations in the CSF were significantly higher in those with the T allele (CT and TT) of rs4633 than in CC genotype carriers (p=0.004). Moreover, among MA abusers, DA concentrations were significantly higher in those with the A allele (GA and AA) of rs4680 than in GG genotype carriers (p=0.017). In subsequent haplotype analyses of MA abusers, a strong correlation was identified between two COMT haplotypes and CSF DA concentrations (p=0.002). However, the CSF concentrations of Adr and Nad were not associated with COMT genotypes or haplotypes. The present results indicate that rs4633 and rs4680 polymorphisms influence CSF DA concentrations and MA toxicity in MA abusers.

An unexpected death due to massive ascites and a giant mucinous ovarian cystadenoma.

A female in her thirties fell face down in her room. She was motionless when her sister found her. She was transported to the hospital by ambulance and was in a state of cardiopulmonary arrest on admission. She did not respond to resuscitation. Her abdomen had started to swell 3years before her death. An autopsy was performed to clarify the decedent's cause of death. She was 172cm tall and weighed 146kg. Her maximum abdominal girth was 172.1cm. A subcutaneous hemorrhage measuring 4.5cm in diameter was observed in the epigastric region. The abdominal cavity contained brownish ascites (54.1L). The left ovary was markedly swollen, and the combined weight of the uterus and right ovary was more than 13.0kg. A left ovarian tumor consisting of serous and mucinous cysts was detected. There were no metastatic lesions in the peritoneum or other organs. She might have suffered circulatory disturbance caused by the ascites and ovarian tumor. Moreover, being in a prone position would have resulted in an increase in intra-abdominal pressure, further exacerbating her circulatory problems. Therefore, her cause of death was considered to be circulatory failure caused by significant ascites and a large ovarian tumor.