A retrospective study of unexpected deaths with alcohol use disorder from Japanese forensic autopsy cases.

BACKGROUND: Alcohol use disorder (AUD) is an important target for prevention of alcohol-related problems. In this study, we analyzed forensic autopsy cases to reveal the characteristics of the living conditions and death situations of individuals with AUD. METHODS: We retrospectively investigated 486 cases with a history of alcohol consumption for which a forensic autopsy was performed from 2012 to 2021 in Yamaguchi prefecture. Judgement of AUD was made using DSM-5. Various factors were compared statistically between AUD and non-AUD cases. RESULTS: Of the 486 cases, 225 (46.2%) were judged to be AUD, including 89 (18.3%) with advanced AUD, 33 (6.8%) were judged not to be AUD, and a judgement could not be made in the remaining cases. AUD was associated with alcohol consumption prior to death. Only 14.3% of the advanced-AUD cases was in treatment for alcohol dependence. The rates of interpersonal, health, financial and legal problems, receipt of public assistance and an extremely cluttered or hoarding house status were higher in all AUD and advanced AUD cases. Living alone, smoking and BMI were also associated with AUD. CONCLUSIONS: Many cases of alcohol-related deaths may have AUD, and persons with AUD who undergo a forensic autopsy commonly have multiple socioeconomic factors that may be associated with isolation that is involved in exacerbation of AUD. Further studies of these associations are needed because early diagnosis and treatment of AUD and support for the patient may lead to reduction of alcohol-related deaths.

Practices and Awareness Regarding an Infant's Sleep Environment among Japanese Caregivers: A Cross-Sectional Survey.

Preventing sudden, unexpected infant death related to sleep, especially suffocation and sudden infant death syndrome, remains challenging globally. To evaluate factors associated with an unsafe sleep environment (SE) for infants in Japan, this cross-sectional study investigated the current status of practices and awareness among caregivers about a safe SE. Two hundred and fifty-four caregivers of infants in Yamaguchi Prefecture participated. Among the caregivers, 96.0% could not thoroughly practice a safe SE, although 65.0% had knowledge about a safe SE. More unsafe SE practices were significantly associated with 8- to 11-month-old infants than with 0- to 3-month-old infants, using the same practice as for an older child than with accessing information or a familiar person than with mass media as the most useful source of information. The differences in having knowledge were not associated with their practice. Many caregivers obtained information about an infant's SE from mass media and a familiar person. They preferred education via a face-to-face method by medical experts to raise awareness about a safe SE. Thus, efforts need to be developed in Japan in which experts who directly attend to caregivers can truly educate them to ensure that caregivers are continuously aware of the importance of an SE.

An autopsy case of acetyl fentanyl intoxication caused by insufflation of 'designer drugs'.

We present a fatal case of intoxication due to insufflation of acetyl fentanyl. His blood concentration of acetyl fentanyl was 270ng/mL, and the manner of death was classified as an accident. This is the first report of an autopsy case of acetyl fentanyl delivered by insufflation, rather than intravenous administration. He had been snoring loudly for at least 12h prior to death, and transport to a hospital during this time and treatment with naloxone may have saved his life. In this sense, it can be said that his death was preventable. This case reemphasizes the risk of death associated with drug overdose and the narrow range of acetyl fentanyl between the effective dose (ED50) and lethal dose (LD50). The case should also raise awareness among medical professionals of the effectiveness of naloxone and the need to establish a comprehensive system for toxicological analysis while keeping the possibility of use of 'designer drugs' in mind.

[Relationship between alcohol consumption and external causes of death based on the forensic autopsy cases in Yamaguchi].

We analyzed forensic autopsy cases to assess the relationship between alcohol consumption and external causes of death. We divided 605 autopsy cases which had been performed from 2000 to 2011 at our department into Alcohol group (n = 172, 28.4%) and Non-alcohol group (n = 433, 71.6%) according to whether alcohol could be detected in the deceased's blood. The individuals' sex and age, season when the death occurred, cause of death, type of death and circumstances of death were analyzed. Alcohol group had a significantly higher ratio of males and younger ages (both p < 0.05). There was no significant between-group difference regarding the seasons when the deaths occurred. Alcohol group had significantly greater rates of spinal injuries, abdominal injuries, traffic accidents, and accidental drowning. "Bicycling" was revealed as a related factor of the traffic accidents only in Alcohol group. In contrast, "accident on the expressway," "riding a motorcycle," and "a passenger in a vehicle" were related factors only in Non-alcohol group. We concluded that the factors of male gender and middle-to-senior age are responsible for the increased risk of external causes of death after alcohol consumption, and that alcohol consumption is one of the risk factors for accidental death. In Japan, drunk-driving-related accidents have shown a downward trend whereas bicycling-related accidents have shown an upward trend, and similar results were obtained in the present study. The low awareness of drinking-induced pitfalls may be responsible for drinking-related bicycle accidents.

Carvedilol attenuates the progression of alcohol fatty liver disease in rats.

BACKGROUND: Hepatosteatosis is an essential step in liver disease progression. However, the mechanisms that mediate the progression of hepatosteatosis and the optimal inhibitor of them remain largely unclear. The sympathetic nervous system (SNS) is responsible for the lipid metabolism and the accumulation of collagen that occurs in an injured liver. Medicines that inhibit this pathway may be a relevant treatment for the hepatosteatosis, and then reduce the liver injury that progresses through the stage of steatosis to fibrosis. METHODS: Using an ethanol-liquid-diet-fed rat model of alcohol fatty liver disease (AFLD), we studied the effects of carvedilol, which can block the SNS completely via ß1, ß2, and α1 adrenergic receptors, on the sympathetic tone, hepatosteatosis, and fibrosis based on histological, immunohistochemical, Western blot, and reverse transcriptase polymerase chain reaction analyses. RESULTS: Carvedilol inhibited the ethanol-induced whole-body and hepatic sympathetic activities based on the serum 3-methoxy-4-hydroxyphenylglycol level and hepatic tyrosine hydroxylase expression. Carvedilol attenuated the hepatosteatosis, as evidenced by reduced hepatic triglyceride level and the accumulation of fatty droplets within hepatocytes, down-regulated fatty acid synthase and sterol regulatory element binding protein-1, and up-regulated peroxisome proliferator-activated receptor-α. No fibrosis signs were shown in our rat model. Carvedilol inhibited ethanol-induced the thickening of zone 3 vessel walls, reduced the activation of hepatic stellate cells (HSCs), and decreased the induction of collagen, transforming growth factor ß1, and tissue inhibitor of metalloproteinases-1. Tumor necrosis factor α (TNF-α) was expressed on the activated HSCs and inhibited by carvedilol based on the immunohistochemical double staining analysis. CONCLUSIONS: Ethanol metabolism-induced lipogenesis may trigger the SNS-activated HSCs feedback loop, and then induct the activated HSCs and the activated HSCs-derived TNF-α, the mediator of lipogenesis, overproduction. Carvedilol may block this feedback loop via antisympathetic activity and demonstrate its preventive role on the development of hepatosteatosis in rat with AFLD.

[Protective effects of d-chlorpheniramine maleate pre-treatment against acute side effects of Irinotecan(CPT- 11)].

It is wellknown that cholinomimetic side effects, such as sedation, abdominal pain, nasal flow and watery eyes, may develop in patients in the early stage of Irinotecan (CPT-11) administration; however, there have been no investigations concerning methods for preventing the development of these side effects. To assess the protective effects of pre-treatment with d-CM on cholinomimetic side effects in the early stage after Irinotecan (CPT-11) administration, we prescribed d- Chlorpheniramine maleate (d-CM) to a group of patients prior to Irinotecan (CPT-11) administration. Twenty members from the group of non-d-CM-treated patients (n=39) and 4 members from the group of treated patients (n=20) complained of side effects. The pre-administration of d-CM significantly reduced the number of patients with side effects (p<0.05). The relative risk (RR) for the frequency of side effects was 0.39 (95% CI; 0.15-0.98), demonstrating that the frequency of side effects was significantly reduced. Based on theses findings, we concluded that the pre-administration of d-CM had protective effects against side effects that might develop in the early stage after Irinotecan (CPT-11) administration.

A fatal case of potential chronic overdoses of prescribed and proprietary remedies.

A 33-year-old man was found in a state of cardiopulmonary arrest. He was transported to an emergency hospital but was pronounced dead. He had suffered from depression for about 8 years and had attempted suicide repeatedly. A search by the police found 645 empty Press Through Package (PTP) sheets. They had included neuroleptics, antidepressants, hypnotics, proprietary antitussives containing caffeine, proprietary cold remedies containing caffeine, and other unidentified drugs. An autopsy showed higher rectal temperature (38 degrees C), severe pulmonary edema (left: 681 g, right: 821 g), and a large amount of urine in the bladder (about 760 mL). Toxicological analyses using gas chromatography-mass spectrometry (GC/MS) and high performance liquid chromatography (HPLC) demonstrated that doses of clomipramine hydrochloride (a tricyclic antidepressant), chlorpromazine (a phenothiazine), and caffeine (a methylxanthine derivative) were within the toxic range (0.68, 0.64, and 34.24 [microg/mL], respectively). Histological examination showed centrilobular necrosis of the liver with small fat droplets. We concluded that he had died of pulmonary edema due to combined drug intoxication including proprietary antitussives and cold remedies. Furthermore, there was a strong possibility that he had habitually taken overdoses of those drugs. Herein, the risk of misuse of prescribed and proprietary drugs, especially for people with psychological problems, should be reemphasized.

Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes.

Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ-hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256 % while that of normal control was 1.745 %. Macrophages and T cells-but no natural killer cells-had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6 % of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7+/- 7.0 % of T cells and 62.7+/- 32.3 % of macrophages (mean+/- SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. Enterovirus RNA was detected in beta-cell positive islets in one of the three patients by in situ-hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.

Energy consumption during prosthetic walking and wheelchair locomotion by elderly hip disarticulation amputees.

OBJECTIVE: To investigate the differences in energy consumption by patients with hip disarticulation between prosthetic walking and wheelchair locomotion. DESIGN: : The subjects consisted of seven amputees, all older than 60, with unilateral hip disarticulation. Energy consumption when walking with prosthesis and when propelling a wheelchair, each at the respective comfortable movement speed, was measured by means of a portable telemetric system. RESULTS: The average comfortable movement speed for prosthetic walking was 30.5 m/min, which was much slower than the 63.1 m/min average for wheelchair locomotion (P < 0.01). The average oxygen cost value for prosthetic walking was 0.639 ml/kg/m, and the average for wheelchair locomotion was 0.175 ml/kg/m, indicating that oxygen cost was significantly higher for prosthetic walking than for wheelchair locomotion (P < 0.01). CONCLUSIONS: The results of this research clearly showed that the efficiency of prosthetic walking for elderly hip disarticulation amputees was very low. When the subject is judged not to be a candidate for practical prosthetic walking after a careful multidisciplinary evaluation, wheelchair locomotion may be an alternative to prosthetic walking as a realistic goal.

Measurement of force to obstruct the cervical arteries and distribution of tension exerted on a ligature in hanging.

We experienced suicidal hanging cases without a ligature in front of the neck. We conducted several anatomical autopsies and the magnetic resonance imaging (MRI), and studied the dynamics behind hanging by applying an apparatus to cadaver and creating a dummy. MRI revealed that the vertebral artery protrudes diagonally upward from the second vertebra to the first one. We also found that this area was not covered with any bony tissue. The average length between the first and second transverse processes was 2 cm. We measured the minimum required force to obstruct the blood stream in both carotid and vertebral arteries exerting 130 mmHg. The required force was 6 kg for the carotid artery and 7 kg for the vertebral artery. Compared to the reported cases, there was not a significant difference in the force to obstruct the carotid artery, however, that of the vertebral artery was lower than the force reported so far. With an experiment of pressure sensitive plastic-sheet, we learned the lateral sides of the neck are compressed more. The results obtained from this study show that the complete and fatal obstruction of the carotid and the vertebral arteries may easily occur when the ligature transects at the lower part of mandible angle.

A study of monoamine neuronal systems of schizophrenic patients: using forensic autopsy brains.

Studies on autopsy brains of mental illnesses are essential for psychiatric research. Brain materials from forensic autopsy cases have been valuable research resource. We introduced some characteristic neuronal structures of schizophrenic post-mortem brains and normal controls detected using both forensic and pathological autopsy cases and immunohistochemical method. Dopamine-related neuronal structures in schizophrenic cases were investigated by using immunohistochemistry for tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC) and phenylethanolamine-N-methyltransferase (PNMT). At the level of the striatum, the number of AADC-positive, but TH-negative neurons (D-neurons) reduced in schizophrenics compared with controls. In the brainstem structures, we described some morphological findings characteristic to catecholaminergic neurons of the ventral tegmental area of schizophrenic cases and reduction of the number of medullary catecholaminergic neurons. These results might be in accordance with recent reports describing neural stem cell dysfunction in schizophrenic brains. The authors also introduced the first systematic psychiatric brain bank in Japan, the Fukushima Psychiatric Brain Bank, constructed in 1997, and mentioned the necessity for arrangement of brain bank systems to further promote the psychiatric brain research.

Assessment of cervical venous blood flow and the craniocervical venus valve using ultrasound sonography.

Severe congestion with petechiae and/or small hemorrhages over a wide area consisting of the subcutaneous and mucous level of the head and neck is observed in most cases of strangulation and positional asphyxial death. Congestion present above the strangulation mark is accepted as a vital reaction. Although the congestion results from a disturbance of cervical venous flow, only a few reports concerning a relationship between venous flow and posture were found in the literature. We assessed the physiological situation of cervical venous return and movement of the craniocervical venous valve for many types of valve with respect to posture using color-duplex ultrasound sonography (US). We measured the Doppler wave of cervical veins consisting of internal jugular vein (IJV), external jugular vein (EJV) and vertebral vein (VV) and the motion of IJV valves in three positions on a seat which could be manually moved through +90 degrees to -90. The diameter of IJVs and EJVs were thicker in a head-down position, moderate in a supine position and flat in a sitting position. The diameter of VVs was thick in a sitting position, moderate in supine position and unclear in an upside-down position because of difficulty in scanning owing to very slow velocity and deep lying position. The velocities were high in a sitting position, but very slow and intermittent in an upside-down position. The EJV which is markedly congested in some cardiac tamponade cases and drains mainly the facial superficial region is very important in legal medicine but has not often observed in previous reports. We confirmed that cervical venous return (IJV, EJV, VV) changes its route according to the posture. The motion of IJV valves was very complicated and varied in three positions, even after the Doppler wave and the motion of valve became stable. Asphyxia and strangulation should be studied taking the complex venous structure into consideration. We could not find any consistent explanation for venous valve motion and further studies on the valves are necessary to understand the venous reflux in some diseases in legal medicine.

Successful prosthetic fitting of elderly trans-femoral amputees with Intelligent Prosthesis (IP): a clinical pilot study.

The objective of the study was to compare the Physiological Cost Index (PCI) and walking speeds during walking in two elderly trans-femoral amputees when using knee joints which emphasized stance-phase control and Intelligent Prosthesis, and to provide some bibliographic observations on factors behind their success in improving walking ability despite their age. It was a within-subject comparison. The subjects comprised two patients, aged 75 and 81 years, with trans-femoral amputations. On admission subjects were subjected to one-leg cycling test driven by their non-amputated leg in order to evaluate their physical fitness. The PCI and speed during free level walking was measured using their original knee joints. The knee joint was then changed to IP and the subjects received prosthetic walking training programs using it. The PCI and speed measurements were taken during free level walking on completion of the training program. Both subjects showed a decreased PCI and an increased free walking speed when using the IP compared with the original knee joints. It was concluded that elderly trans-femoral amputees who are judged to be in good physical condition appear to merit the application of knee joints with superior swing phase control functions such as IP, regardless of their age.

Comparison of different microprocessor controlled knee joints on the energy consumption during walking in trans-femoral amputees: intelligent knee prosthesis (IP) versus C-leg.

The purpose of this study was to investigate the characteristic differences between the IP and C-Leg by making a comparative study of energy consumption and walking speeds in trans-femoral amputees. The subjects consisted of four persons with traumatic trans-femoral amputations aged 17 - 33 years who had been using the IP and were active in society. Fourteen able-bodied persons served as controls. First the energy consumption at walking speeds of 30, 50, 70, and 90 m/min was measured when using the IP. Then the knee joint was switched to the C-Leg. The same energy consumption measurement was taken once the subjects were accustomed to using the C-Leg. The most metabolically efficient walking speed was also determined. At a walking speed of 30 m/min using the IP and C-Leg, the oxygen rate (ml/kg/ min) was, on average, 42.5% and 33.3% higher (P< 0.05) than for the able-bodied group. At 50 m/min, the equivalent figures were 56.6% and 49.5% (P< 0.05), while at 70 m/min the figures were 57.8% and 51.2% (P<0.05), and at 90m/min the figures were 61.9% and 55.2% (P<0.05%). Comparing the oxygen rates for the subjects using the IP and C-Leg at walking speeds of 30 m/min and 90 m/min it was found that subjects who used C-Leg walked somewhat more efficiently than those who used IP. However, there was no significant difference between the two types at each walking speed. It was also determined that the most energy-efficient walking speed for subjects using the IP and C-Leg was the same as for the controls. Although the subjects in this study walked with comparable speed and efficiency whether they used the IP or C-Leg, the subjects' energy consumption while walking with the IP and C-Leg at normal speeds were much lower than previously reported. This study suggested that the microprocessor controlled knee joints appeared to be valid alternative for improving walking performance of trans-femoral amputees.

Fatality due to acute fluoride poisoning in the workplace.

We report a case of a 65-year-old worker who suffered a third-degree skin burn to 5% of his total body surface area as a result of being splashed in the face with hydrofluoric acid (HF). He died shortly thereafter without having received adequate first aid. His serum fluoride concentration was markedly increased at 6.38 mg/dl with hypocalcemia and hyperkalemia. We concluded that he died of HF poisoning. In this case he might have managed to avoid death if he had not been working alone and if he had received adequate first aid on the scene as soon as possible. We re-emphasize the need for the immediate initiation of first aid on the scene and the distribution of information on the risks of HF to workers.

Analysis of two types of novel alleles in the DXS10011 locus.

A population study of the short tandem repeat locus DXS10011 was carried out in a sample of 104 unrelated Japanese individuals (56 males, 48 females). Thirty-six different alleles were distinguished. The power of discrimination was 0.933 (male) and 0.997 (female). Sequence analysis of alleles was examined for 34 samples. The sequence structures of the alleles were classified into three types: A, B and C. Type A had a regular repeat structure of the repeat region: (GAAA)(n). Types A and B differed in the base sequence of the repeat region. As an A (adenine) insertion in 5' upstream of (GAAA)(n) repeat unit was type C, this type was differentiated from type A.

Sequence analysis of two de novo mutation alleles at the DXS10011 locus.

We have detected two unusual alleles at the DXS10011 locus in two paternity trio cases. In one case, one allele of the daughter was found not to have been derived from the mother but the other allele was shared with the father. In the other case, the mother and the son shared no bands. Paternity in both cases was established using conventional polymorphic markers in addition to DNA markers (probabilities: >0.999999). Sequencing showed that the two de novo alleles of the children acquired a single unit (GAAA).

Effect of an Intelligent Prosthesis (IP) on the walking ability of young transfemoral amputees: comparison of IP users with able-bodied people.

OBJECTIVE: To make a comparative study of energy expenditure and walking speeds between able-bodied people and young Intelligent Prosthesis (IP) users and to demonstrate the effect of IP on the walking ability of young amputees. DESIGN: The test subjects were eight young traumatic transfemoral amputees. Fourteen able-bodied persons served as controls. All amputees used an IP, and they had all undergone a prosthetic rehabilitation program for 8 wk. IP users, who had completed the rehabilitation program, were instructed to walk at speeds of 30, 50, 70, 90, and 110 m/min. Measurements of energy expenditure while walking were taken. The most metabolically efficient waking speed was also determined. RESULTS: On average, the IP users experienced an oxygen uptake that was 24.1% and 24.2% higher than those for the controls at speeds of 70 and 90 m/min, respectively. It was also determined that the most metabolically efficient walking speed for the IP users was the same as for the controls. CONCLUSIONS: This study showed that young IP users who undergo an adequate prosthetic rehabilitation program can achieve remarkably improved walking performance. Young IP users could walk at the normal speeds of able-bodied people, with only around a 24% increase in energy expenditure.

A case of delayed shock due to dissection of the hyperplastic coronary artery after balloon angioplasty and stenting.

A 42-year-old obese woman with a history of liver cirrhosis and diabetes mellitus was admitted because of chest pain. Coronary balloon angioplasty and stenting were performed on the left anterior descending artery (LAD), which was 90% stenotic. She developed moderate shock about 6h later, and about 15 h after the procedure, she died from excessive bleeding from the right femoral artery because of removal of the catheter sheath by herself. Autopsy disclosed haemorrhagic cardiac tamponade and extensive haemorrhage into the epicardial adipose tissue, however, neither coronary perforation nor myocardial rupture was recognized. Histological examination of the dilated coronary segment revealed extensive dissection with an eccentric intimal thickening and the disruption of the adventitia. It was thought to be the origin of the haemorrhage. Although coronary dissection is a well-known complication during cardiac catheterization procedures, this report describes a rare fatal case with delayed onset of shock due to coronary dissection caused by balloon angioplasty and stenting in the presence of eccentric hyperplasia of the vessel wall.