Evaluation of the distribution of nicotine intravenous injection: an adult autopsy case report with a review of literature.

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

Case Report of an Autopsy of a Child Who Died in a Drum-Type Washing Machine Tub: Pathophysiology Resulting in Death and Assessment of Previous Literature.

The patient was a 5-year-old boy who was found in a state of cardiorespiratory arrest in the tub of a washing machine without water with the door closed. The autopsy findings included severe facial congestion and petechiae of the facial skin and palpebral conjunctiva. Several organs exhibited congestion. Hemorrhagic spots were seen on the serous membranes of various organs, with particularly marked hemorrhagic spots seen on the lungs. The heart contained fluid blood without soft clots. There were no findings indicative of marked trauma, intoxication, or hyperthermia. The examination results suggested that asphyxia had occurred in this case. However, there were no findings indicative of cervical compression, oronasal obstruction, or the presence of a foreign body in the respiratory tract. Image analysis showed the child could make postural changes inside the washing machine tub. Consequently, impaired thoracic movement and postural asphyxia were considered unlikely to have occurred. The results of blood gas analysis showed no evidence of marked hypercapnia. We, therefore, concluded that the cause of the child's death was asphyxia due to hypoxia caused by being in a closed space, that is, a washing machine tub.

Immunohistochemical detection of respiratory syncytial virus at autopsy.

BACKGROUND: Respiratory syncytial virus (RSV) infection can be fatal in infants <1 year after birth. Morphological findings associated with infant death, however, are insufficient, and screening procedures are problematic. The aim of the present study was to establish a postmortem diagnosis of RSV pathogenicity. METHODS: Serial forensic autopsies of 55 infants who suddenly died ≤1 year after birth due to viral pneumonia (n = 18), bacterial pneumonia (n = 12), or other diseases and trauma (n = 25) were assessed. Causes of viral pneumonia determined on immunochemical screening and histological staining of airway effusions consisted of RSV (n = 8) and other viruses (n = 10). RESULTS: Bronchial epithelial and inflammatory cells in the interstitium around bronchioles and alveoli were immunopositive for RSV. Bronchial epithelium was more frequently positive for RSV (5/8, 62.5%) than for bacterial pneumonia and other causes of death (7/47, 14.9%); and intra-alveolar sites were also more frequently positive for RSV pneumonia (3/8, 37.5%) than for bacterial pneumonia and other causes of death (4/47, 8.5%). Screening immunoassays and immunohistochemical staining for RSV can serve as an index of RSV infection when serum antibody titers, viral identification and polymerase chain reaction (PCR) are not informative. Peribronchiolar interstitial RSV positivity was similar between RSV pneumonia (7/8, 87.5%) and other causes of death (34/47, 72.3%). CONCLUSIONS: RSV was the cause of death in only eight infants because RSV infection was difficult to diagnose. Therefore, more deaths associated with RSV need to be investigated. Bronchial epithelium and intra-alveolar cells that are RSV immunopositive might augment RSV pathogenicity in viral pneumonia.

Effects of postmortem positional changes on conjunctival petechiae.

The present study aimed to determine whether postmortem period, physical constitution, cause of death, and cardiopulmonary resuscitation are associated with positional changes in the postmortem appearance of conjunctival petechiae. We retrospectively investigated serial forensic autopsies from 6 h to 6 days postmortem (n = 442; male, 303; female, 139; median age, 62 years; range, 0-100 years). The causes of death were sharp instrument injury, blunt force trauma, fire, intoxication, asphyxia, drowning, hypothermia, hyperthermia, acute heart failure, and natural causes. Of these, 28 (male, n = 18; female, n = 10) were aged ≤5 years. Palpebral conjunctival petechiae were initially assessed at autopsy in supine bodies, then reassessed in prone bodies after 30 min. Among 414 bodies, 291 (70.2%) and 123 (29.7%) who were aged between 6 and 100 years, and 18 (64.2%) and 10 (35.7%) aged <5 years at the time of death, were discovered in the supine and prone positions, respectively. The amounts of petechiae increased within 1.5 days postmortem, but not in those discovered in the prone position. The rates at which petechiae increased were higher in supine overweight bodies (BMI ≥ 25.0) and in those who were discovered supine and had died of asphyxia or drowning (37.5%). Cardiopulmonary resuscitation for bodies discovered in the supine and prone positions did not statistically affect the occurrence of petechiae. Several postmortem factors can cause hypostatic blood redistribution that manifests as increased amounts of petechiae in the palpebral conjunctivae.

Biodistribution of Insulin Following Massive Insulin Subcutaneous Injection.

A man in his 30s injected insulin several times into his abdomen and was found dead several hours later. Micropathological findings showed alveolar injury with hemorrhaging and cerebral parietal lobe nerve cell edema. Biochemical examinations showed that the blood insulin level was high, significantly so at the insulin injection sites. The blood glucose and C-peptide levels were low. The insulin level in the kidneys was low. In forensic medicine, a postmortem diagnosis of insulin subcutaneous injection is often difficult. When insulin injection is suspected, particularly high insulin levels can be expected at the insulin injection site, rather than in the blood.

Acute abdominal disease with nonspecific symptoms in the elderly: A case series.

Acute stomach disease in elderly patients often lacks characteristic clinical manifestations. Presentations may differ from those in younger patients and are often complicated by concomitant diseases, delayed presentation, and misdiagnosis. Incorrect diagnosis and treatment can lead to medical-related death claims. We investigated eight cases of elderly fatality due to acute abdominal diseases in forensic autopsy cases. Although most fatalities were unwitnessed, possibly due to the characteristics of elderly individuals, recent social backgrounds, and involvement with health care, some cases of possible misdiagnosis suggested that physicians should carefully consider atypical clinical manifestations and the characteristics of elderly individuals when the managing abdominal symptoms, particularly in primary health care. Our investigation of these forensic autopsy cases indicated the particular importance of peritoneal adhesions as an unexpected cause of acute abdomen in the elderly due to strangulation ileus, even among those with no history of abdominal surgery or trauma. Diagnosis of acute stomach symptoms can be difficult in elderly patients. Pathophysiological examination and autopsy analyses can thus contribute to early-stage diagnosis and prevention of acute stomach symptoms in elderly patient populations.

Problems in Social Medicine Related to Alcohol and Deaths: Autopsy Cases in the Southern Part of Osaka City.

PURPOSE: The purpose of this study was to examine the social and medical background of alcohol dependence and to prevent the abuse of alcohol. METHODS: Alcohol and deaths were retrospectively investigated based on the forensic postmortem data of 1694 decedents ≥20 years of age in 2008-2017. Of these, the 999 cases that could be tested for alcohol within 48 h of death were examined. RESULTS: The alcohol-positive and alcohol-negative groups included 179 (17.9%) and 820 (82.1%) cases, respectively. In terms of medical issues, compared with the alcohol-negative group, men in the positive group were mostly in their 40s to 60s, whereas women's age peaked in the 70s. The causes of death included many blunt injuries in men, though there was no difference in women. Underlying diseases were more frequent in men than women, with many of them having heart or liver disease, and the percentage of cases with mental disorders was 16.8% in the alcohol-positive group. In 15 cases of the alcohol-positive group, phenothiazine and barbituric acids were detected in 53.3% and 46.7% of cases, respectively. The incidence of traffic accidents and homicides was higher in the alcohol-positive group than in the alcohol-negative group. CONCLUSION: Measures to address social issues based on risk factors for alcohol and deaths are required.

Morphological and biochemical changes in the pancreas associated with acute systemic hypoxia.

This study aimed to investigate the changes associated with acute systemic hypoxia in the endocrine system, particularly in pancreatic tissues. The investigation was based on macroscopic, pathohistological, biochemical, and molecular biological findings in cell lines and human cadavers. The results showed that cases of death due to asphyxia more frequently showed severe subcapsular/interstitial hemorrhage versus the other causes of death. Histological examination showed that asphyxia cases were associated with severe morphological changes. Although measured insulin levels in the asphyxia were higher compared to other causes of death, no differences were noted for the glucagon and amylase levels with regard to the cause of death. Increased blood insulin levels were not associated with macro- and micromorphological changes, and did not show any association with glucose or cortisol levels. The experiment conducted under hypoxic conditions in cultured cells demonstrated that insulin mRNA expression and insulin protein levels peaked at 10 min after hypoxia exposure. However, there were no changes in either the amylase mRNA or protein levels. Corticosterone level peaked at 120 min after exposure to hypoxic conditions. Overall, acute systemic hypoxic conditions can directly affect the mechanisms involved in pancreatic insulin secretion.

Inferior mesenteric artery laceration associated with blunt abdominal trauma with Casper's sign in a physically abused child: An autopsy case and literature review.

There have been few studies of the death of children secondary to child abuse-related abdominal compression, and the detailed pathophysiology of such deaths is therefore unknown. The autopsy findings of a 3-year-old boy who died of hemorrhagic shock due to non-accidental severe blunt abdominal trauma were compared to those of children who died of other non-accidental abdominal injuries. Old and acute subcutaneous hemorrhages, abrasions, and scars were present all over the subject's body. No superficial injuries were found on the ventral midline, but a minor hemorrhage was found in the subcutaneous fat tissue, as well as in the rectus abdominis muscle. The intraperitoneal space contained 450 mL of blood, including coagulated blood. There was a tear in the transverse mesocolon and a crush injury in the small bowel mesentery. The inferior mesenteric artery was transected 0.5 cm from the aortic root. The transverse colon was necrotic, with hemorrhages in the mucosa. Since various organs were ischemic, the cause of death was determined to be blood loss from the inferior mesenteric artery injuries. Blunt abdominal trauma in children usually causes organ damage and intestinal injury, but because it is caused on the posterior surface of the mesentery, vascular injury should also be considered, and an autopsy should be performed. In the case of child abuse-related deaths, damage to the skin surface may not always be present; therefore, imaging tests, histopathological examinations, and biochemical tests should be performed with a focus on the gross anatomy to determine the cause of death and pathology.

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation.

We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia. Human samples: Autopsies on 205 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, n = 14) or non-cold exposure (controls; n = 191). Cortisol levels were determined in blood samples obtained from the left and right cardiac chambers and common iliac veins using a chemiluminescent enzyme immunoassay. Adrenal gland tissues samples were stained for cortisol using a rabbit anti-human polyclonal antibody. Cell culture: AtT20, a mouse ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature exposure mimicking hypothermia and compared with data for samples collected postmortem for other cases of death. However, no correlation between ACTH concentration and cortisol levels was observed in hypothermia cases. Immunohistologic analyses of samples from hypothermia cases showed that cortisol staining was localized primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the adrenal gland. During both mono-culture and co-culture, AtT20 cells secreted high levels of ACTH after 10-15 minutes of cold exposure, whereas corticosterone secretion by Y-1 cells increased slowly during the first 15-20 minutes of cold exposure. Similar to autopsy results, no correlation was detected between ACTH levels and corticosterone secretion, either in mono-culture or co-culture experiments. These results suggested that ACTH-independent cortisol secretion may function as a stress response during cold exposure.

Pathophysiological significance of clock genes BMAL1 and PER2 as erythropoietin-controlling factors in acute blood hemorrhage.

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

Postmortem water contents of major organs with regard to the cause of death.

The water contents of individual organs are maintained in a narrow range, but altered in morbidity owing to a disturbance of water equilibrium. The present study investigated the tissue water contents of major organs with regard to the cause of death in serial autopsy cases within 3 days postmortem (n = 329; 223 males, 106 females; age range, 1-100 years). Individual tissue water contents differed markedly across organs, but no significant postmortem or survival-period dependence, gender-related difference, or age dependence was observed. However, the lung water contents were higher in drowning cases, especially in saltwater cases (p < 0.05), and in strangulation among the acute mechanical asphyxiation cases. The brain water contents were higher in hypothermia cases (cold exposure) and tended to be higher in hyperthermia cases (heatstroke). The kidney water contents were higher in drowning and acute cardiac cases than in fatal intoxication and fire fatality cases, but tended to be higher in fresh- and bathwater drowning cases than in saltwater cases (p > 0.05). The spleen water contents were higher in bathwater drowning than in saltwater and freshwater cases, but did not differ among other the causes of death. These findings suggest that the postmortem tissue water content of individual organs, especially the lungs and/or kidney, depends on the cause of death and particularly contributes to differentiation between saltwater and freshwater drowning, respectively. This work therefore provides insight into the investigation of varied tissue water imbalances during the death process. In conclusion, we recommend the measurement of tissue water content because it is easy to perform and appears to be useful for evaluating the pathophysiology of systemic circulatory failure.

Toxicological and Biochemical Analyses of an Autopsy Case Involving Oral Overdose of Multiple Antidiabetic and Antihypertensive Drugs.

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