Yoshihisa Seto

Association of plasma triglyceride-rich lipoprotein remnants with coronary atherosclerosis in cases of sudden cardiac death

Among the risk factors for coronary atherosclerosis, elevated LDL-C level is best known. The action of lipoprotein lipase on triglyceride-rich lipoproteins produces remnant lipoprotein particles enriched in cholesterol and apolipoprotein E (apo E). Apo E serves as the ligand for uptake of remnant lipoproteins via the LDL-receptor or the remnant receptor. In this study, postmortem plasma total cholesterol, triglycerides (TG), VLDL-C, HDL-C, lipoprotein (a) [Lp(a)] and remnant-like lipoprotein particles (RLP)-cholesterol, RLP-TG, apolipoproteins B, C III and E were measured, together with LDL-C to assess their potential contribution to the severity of coronary and aortic atherosclerosis of the 197 cases of sudden death (132 cardiac death and 65 non-cardiac death). In all cases, the severity of coronary atherosclerosis was determined at postmortem pathological examination. RLP-cholesterol (RLP-C) and LDL-C concentrations were significantly higher in cases with advanced coronary atherosclerosis compared with those without coronary atherosclerosis; respective median values were 13.5 vs 8.4 mg/dl (P < 0.001) and 140 vs 115 mg/dl (P < 0.05). RLP-C levels were more strongly correlated with the severity score of coronary atherosclerosis than LDL-C.

The possible role of remnant-like particles as a risk factor for sudden cardiac death.

Abstract Postmortem plasma lipid and lipoprotein levels were analyzed in two groups of Japanese subjects who died suddenly and unexpectedly due to cardiac (n = 93) or non-cardiac (n = 26) causes. No individuals in either group had a significant medical or cardiac history. In this study, we measured plasma total cholesterol, triglycerides, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, and especially triglyceride-rich lipoprotein remnants. Triglyceride and apo E-rich remnant-like particles (RLP) were studied as a possible risk factor for sudden cardiac death in relation to the progression of coronary atherosclerosis. The receiver-operating characteristic curve (ROC) analysis showed that RLP-TG was the most significant risk factor for sudden cardiac death among the lipids and lipoproteins and RLP-C was the best predictor for coronary atherosclerosis. HDL-C and LDL-C levels were within normal limits in the majority of the cases and did not appear to relate to the sudden cardiac death. Apo E phenotyping was performed for the detection of the genetic background in the lipid metabolism. The frequency of the Apo E3/3 (wild type) phenotype, which closely relates with the remnant metabolism, was significantly reduced in the sudden cardiac death group. Our study on the postmortem plasma lipid analysis suggested that RLP-C and RLP-TG are the best risk predictor for coronary atherosclerosis and sudden cardiac death, respectively.

“dead in Hot Bathtub” Phenomenon: Accidental Drowning or Natural Disease?

AbstractSudden death in a hot bathtub occurs frequently in Japan, particularly among elderly people. This retrospective report describes the epidemiologic circumstances and physical findings at autopsy. In total, 268 victims were found unconscious or dead during tub bathing. After postmortem examination, the manner of death was judged as natural cause in 191 (71.2%) and accidental drowning in 63 (23.5%) cases. Mean age (SD) was 72.1 (15.2) years with no significant difference between males and females. A seasonal difference was evident: the winter displayed the highest frequency. Drowning water inhalation, which was confirmed in 72% of victims, was absent in the others. The most common observations on postmortem examination were cardiac ischemic changes and cardiomegaly. Water inhalation signs were evident in a significantly fewer victims exhibiting these factors. In contrast, inhalational findings were observed more frequently in victims with other backgrounds such as alcohol intake, mobility disturbance, and history of epilepsy. Annual mortality in Japan from accidental drowning in persons aged older than 75 years is 33 deaths per 100,000 population. However, this number may be considerably underestimated as pathologists tend to regard lack of water inhalation as indicating a natural cause of death. Confusion in diagnosis remains consequent to the accidental and natural aspects of “dead in hot bathtub” phenomenon.

Fatal subarachnoid hemorrhage complicating actinomycotic meningitis

Actinomycosis is caused by Gram-positive Actinomyces species that are part of the normal oral flora with low virulence. We describe a rare case of sudden death of a 48-year-old man with actinomycotic basilar meningitis that was complicated by fatal subarachnoid hemorrhage. Autopsy revealed meningitis at the basilar region of the brain, and histological examination revealed characteristic bacterial aggregates with extensive leukocyte infiltration and severe vasculitis of arteries of this region. Rupture of an artery by severe arteritis was thought to be the cause of the subarachnoid hemorrhage. The probable primary source of infection was found in the left lung. To the best of our knowledge, the complication of subarachnoid hemorrhage has not been reported previously in actinomycotic meningitis.

Self-inflicted fatal shotgun wound from a homemade weapon

A case of suicide, a male shot in the abdomen using a homemade weapon, is described herein. Postmortem examination revealed bleeding into the thoracic and abdominal cavities, a collapsed liver and other organs with numerous pellets. The contact-shot wound was not noticed during the initial investigation at the scene, but it was elucidated during autopsy. A simple launcher had been assembled from pipes of a clothes rack frame made for home use. The deceased had once owned a shotgun, but his firearm license had been relinquished 5 years prior. A shotgun shell that he had kept was used. Presumably, the injuries from the homemade weapon were not noticed initially because of strict gun control rules in Japan.

Cytokine Elevation in Sudden Death With Respiratory Syncytial Virus: A Case Report of 2 Children

Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis and pneumonia in young children worldwide. Premature birth, bronchopulmonary dysplasia, congenital heart disease, and Down syndrome are risk factors for high mortality and prolonged morbidity after RSV infection. Conversely, many previously healthy, full-term children are also admitted to the hospital because of RSV, and some of them experience severe sequelae or die due to the virus. Various complications of RSV infection have been reported, such as encephalopathy, encephalitis, and cardiomyopathy. However, the pathogenesis of serious cases in children without an underlying disease has not been elucidated. In this report, we present 2 RSV-related deaths of children who were born at full-term and developed normally up to the age of 19 months. Their cardiopulmonary arrests occurred within half a day after the onset of symptoms, such as cough and high fever. Many postmortem examinations were performed to investigate their unexpected deaths. Histopathological examinations revealed extensive bronchiolitis and mild pneumonia accompanying airway obstruction. Immunostaining revealed the presence of the virus mainly in bronchial epithelia, but not in alveoli. Complete brain edema was prominent, and encephalopathy was developing. Blood tests revealed that the IL-6 level was elevated more than >200-fold above normal, despite a normal C-reactive protein level. Because IL-6 may reflect the severity of bronchial epithelial damage and contribute to brain edema, an extreme elevation of IL-6 may predict the risk for sudden death in children with RSV infection.

EPITOPE ANALYSIS OF MONOCLONAL ANTIBODIES TO HUMAN GC GLOBULIN (VITAMIN D-BINDING PROTEIN)

Gc globulin, also called vitamin D‐binding protein, is human 56 kD plasma protein. Antigenic epitopes of the protein recognized by 12 different monoclonal antibodies (MoAbs), including the previously prepared MoAb E12 of which binding to Gc is inhibited by actin, were analyzed in relation to the functional domains of the protein. To map the epitopes recognized by the respective antibody, the reactivities of the MoAbs were tested by immunoblotting against the recombinant Gc fragments expressed in E. coli cells, and then a competitive ELISA was performed. The results showed that the antibodies were classified into at least six groups. Furthermore, in addition to E12, actin inhibited the reactivity of MoAb 21, of which the epitope was located within residues Asp320 to Glu379, in an ELISA in the presence of the ligand. This result must indicate that this antibody‐binding site is near the site that interacts with actin. In contrast, no inhibitory effect by 25‐hydroxyvitamin D to any antibodies was observed. Furthermore, all antibodies, including E12 and 21, reacted with membrane‐bound Gc of lymphocytes by an immunofluorescence study, suggesting that Gc is unlikely to bind to the plasma membrane in its interaction with actin.

Fatal Staphylococcus aureus bacteremia in the Felty syndrome: a maltreatment-suspected case.

Familial neglect was suspected when an older deceased female was found to have large decubitus ulcers and weight loss. Postmortem examinations including histopathology and bacterial culture revealed systemic Staphylococcus aureus infection as the cause of death. The victim might have exhibited Felty syndrome, which is characterized by complications of splenomegaly and neutropenia in the underlying rheumatoid arthritis. As a result of neutropenia, the affected individual was susceptible to skin ulcer formation and sepsis. The manifestation of pressure ulcers as abuse biomarkers should also be explored from interaction with intrinsic disease factors.

An Autopsy Case of Traumatic Sinus Thrombosis

A 38-year-old male slipped accidentally and fell from a height of 4.6 m, and was admitted to a hospital. A radiograph indicated a linear fracture of the parietal bone across the sagittal sutura, and a computed tomography scan of the head showed severe subdural hematoma on both parietal sides, so an operation was performed to remove the hematoma. Five hours after the operation, brain death due to a cerebral herniation occurred, and he died six days later. Autopsy revealed a linear fracture of the parietal bones, which crossed obliquely the sagittal sutura. A slightly lacerated wound of the dura mater was seen on the sagittal sutura, from where the latter half of that point to the left and right transverse sinuses were occluded completely with thrombosis. The brain was markedly swollen. From these findings, the victim was considered to have died from acute cerebral swelling due to traumatic thrombosis of the superior sagittal sinus.

Experimental Studies on Concentration-Time Profiles of Ethanol and Acetaldehyde in Various Organs

The present study was designed to measure the ethanol and its toxic metabolite acetaldehyde concentrations in post-mortem tissue specimens of corpse from whom no quantity of the blood could be collected. Another purpose was to discuss the toxic effects of ethanol and/or acetaldehyde on the various organs.