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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 noncold 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 coculture, 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.

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.

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.

Highlights •We investigated the tissue water contents of the lungs, brain, kidneys, and spleen. •We evaluated the relationship between tissue water content and cause of death.