Sudden death of an infant with 'an early epileptic encephalopathy'.

This article reports an autopsy case of sudden death of an infant with an infrequent encephalopathy involving epileptic episodes. The infant was a 1-year and 10-month-old boy, who had a history of the first convulsive seizures in the third month after birth. The clinical diagnosis was described as 'an early infantile epileptic encephalopathy with suppression-bursts' (Ohtahara syndrome). On a winter day, he was collapsed following a high fever and was already dead on the arrival at a hospital. The body was small for the age and poorly nourished. The autopsy and postmortem magnetic resonance imaging scan (MRI) of formalin-fixed brain revealed advanced unsymmetric brain atrophy with cortical dysplasia, which were prominent in the left temporal and right occipital lobes, and sclerotic atrophy of the parahippocampal gyri, additionally showing a feature of the olivo-ponto-cerebellar atrophy. However, the cause of death was pathologically and microbiologically determined as bacterial bronchopneumonia following pulmonary infection of the influenza A virus. In sudden death cases of physically handicapped infants, the investigation of viral infection in consideration of an epidemiological survey is important even when the death can be pathomorphologically explained.

Intranuclear ubiquitin immunoreactivity of the pigmented neurons of the substantia nigra in fatal acute mechanical asphyxiation and drowning.

To evaluate the significance of immunohistochemical staining of ubiquitin (heat shock protein) in the midbrain for the medico-legal diagnosis of fatal asphyxiation and drowning, we investigated forensic autopsy cases of fatal mechanical asphyxia (n = 18), manual/ligature strangulation (n = 9), hanging (n = 4), aspiration/choking (n = 5) and drowning (n = 16). These were compared to control groups (n = 30) consisting of fatalities from brainstem injury (n = 12) and acute myocardial infarction (n = 18). Ubiquitin was clearly demonstrated in the nuclei of pigmented substantia nigra neurons, showing two intranuclear staining patterns: a type of inclusion (possibly Marinesco bodies) and a diffuse staining. The diffuse staining was significantly more frequently observed in cases of drowning. The percentage of total ubiquitin positive neurons was frequently higher in strangulation (5.1-28.4%, mean 17.0%), aspiration/choking (5.3-32.0%, mean 17.6%) and drowning (7.0-34.1%, mean 19.8%), but relatively low in hanging (5.1-12.7%, mean 8.6%), brainstem injury (0-10.4%, mean 5.0%) and acute myocardial infarction (1.5-16.9%, mean 8.3%). These observations suggest that intranuclear ubiquitin immunoreactivity of the pigmented substantia nigra neurons in the midbrain was induced by a fatal severe stress on the central nervous system in asphyxiation and drowning.

Intranuclear ubiquitin immunoreactivity in the pigmented neurons of the substantia nigra in fire fatalities.

To evaluate the significance of immunohistochemical staining of ubiquitin (heat shock protein) in the midbrain for medico-legal investigation of death in fires, we examined forensic autopsy cases of fire fatalities (n = 35) in comparison with controls (n = 27; brain stem injury, acute myocardial infarction and carbon monoxide poisoning other than fire fatality). There were two intranuclear staining patterns in the nuclei of pigmented substantia nigra neurons: a type of inclusion (possible Marinesco bodies) and a diffuse staining. Percentage of nuclear ubiquitin positivity (Ub-positive %) in fire fatalities (2.7-44.7%; mean, 18.5%) was significantly higher than in brain stem injury (n = 9; 0-10.4%; mean, 4.5%) and myocardial infarction (n = 14; 1.5-14.6%; mean, 6.9%), independently of blood carboxyhemoglobin (COHb) levels. Age-dependent increase in Ub-positive % was observed in lower COHb (< 60%) cases. The intranuclear diffuse ubiquitin staining was not observed in cases of high blood cyanide level (> 1.0 microg/ml). These observations showed that intranuclear ubiquitin immunoreactivity of the pigmented substantia nigra neurons in the midbrain was induced by severe stress in fires.

Immunohistochemical investigation of pulmonary surfactant-associated protein A in fatal poisoning.

To evaluate the immunohistochemical distribution of pulmonary surfactant-associated protein A (SP-A) in fatal poisoning in relation to the effects of drugs and poisons on respiratory function, 42 forensic autopsy cases were examined by scoring the staining intensity. The highest scores of SP-A staining, with dense granular deposits (aggregates) in the intra-alveolar space, were observed in fatalities from pancuronium bromide (muscle relaxant) injection and petroleum (butane) gas inhalation. Poisoning with organophosphate pesticides and arsenic (ingestion) showed a second grade SP-A score. However, The SP-A scores were relatively low in ethanol and sedative-hypnotic intoxication. Carbon monoxide intoxication showed a varied degree of SP-A score, and the aggregated SP-A score tended to be higher in cases of lower blood carboxyhemoglobin concentration. A varied SP-A score was also observed in methamphetamine fatalities, in which the score was relatively low in cases with a higher serum drug level. Increase of SP-A was not always associated with the intra-alveolar effusion or hemorrhages. The above-described observations suggested that the immunohistochemical score of SP-A may be a possible indication for intensity and duration of drug/poison-dependent respiratory distress.

Fatal traumatic rupture of an aortic aneurysm of the sinus of Valsalva: an autopsy case.

This report describes an autopsy case of a rare type of aortic sinus of Valsalva aneurysm, which caused fatal rupture from a blunt chest impact. A 51-year-old male was hit in the chest with a fist, lost consciousness after about 15min and died after approximately 7h. The postmortem examination revealed a large saccular aneurysm of the right coronary sinus bulging on the right atrium, which had a full laceration causing pericardial hematoma (cardiac tamponade). A related chest wall injury was observed in the right outer mammary region. A rare type of bulging onto the right atrium and subsequent sclerosis of the right coronary artery appeared to have greatly contributed to the fatal rupture.

Post-mortem urinary myoglobin levels with reference to the causes of death.

To evaluate pathophysiological significance of post-mortem urinary myoglobin levels in determining the cause of death, we investigated 210 forensic autopsy cases, partially in comparison with serum levels. Post-mortem serum myoglobin levels were extraordinary high in most cases possibly due to post-mortem change. Urinary myoglobin levels did not correlate with the serum levels, showing possible post-mortem elevation in cases of a prolonged post-mortem period over 48h. A high (>1000 ng/ml), moderate (100-1000 ng/ml), slight (50-100 ng/ml) and not significant (<50 ng/ml) elevation of urinary myoglobin were observed in 26, 43, 31 and 110 cases, respectively. Half the highly elevated cases were those with a survival time over 24h. In cases of minor muscle injury such as head trauma, elevation of urinary myoglobin level was closely related to longer survival. In acute/subacute deaths with a post-mortem interval within 48h, a significant difference was observed in relation to the blood carboxyhemoglobin (COHb) levels of fire victims: myoglobinuria over 100 ng/ml was more frequently and markedly observed in cases with COHb below 60% than over 60%, suggesting muscle damage in fatal burns. Similar elevation was observed in heat stroke victims, and also in some cases of acute and subacute death from polytrauma, asphyxiation, drowning, electricity and spontaneous cerebral bleeding, but not in myocardial infarction. Thus, it was suggested that high post-mortem urinary myoglobin levels in acute and subacute death cases may be a possible indicator of antemortem massive skeletal muscle damage as well as exertional muscle hyperactivity or convulsive disorders associated with hypoxia.

[Radiographic examination of skeletalized remains of an abandoned infant: a case report with special reference to odontological findings].

A homeless couple confessed that they had buried their baby, who died at the age of three months, in the graveyard two years earlier. The recovered infantile remains had been already completely skeletonized and dismembered. However, the maxilla and mandibula of the average matured infants, the age of the body was estimated to be 1 to 2.5 months old on the basis of the degree of calcification of deciduous teeth.

Immunohistochemistry of pulmonary surfactant-associated protein A in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a fatal complication in severe traumas and diseases. Although the contribution of pulmonary surfactant abnormality to the pathogenesis of ARDS has been clinically fairly well investigated, the histopathological evidence has not been established. The aim of this study was to clarify the immunohistochemical distribution of surfactant-associated protein A (SP-A) for early diagnosis of ARDS with special regard to hyaline membrane (HM) formation. Two-hundred-and-ten autopsy cases of prolonged death from various traumas and diseases were investigated. ARDS were observed in 23 cases, showing speckled SP-A immunostaining. During the early, exudative phase of ARDS, characteristic SP-A distribution showed intense staining in the intra-alveolar massive aggregates and thick 'peeling'-like substances accompanied with a lot of granular staining. During the proliferative phase, localized accumulation of granular SP-A and macrophages containing dense granular SP-A became predominant. During the final fibrotic phase, SP-A staining in HMs became weak, and disseminated granular staining was observed in the alveolar spaces. These findings provide morphological evidence of the increase of SP-A during the early phase of ARDS, including some molecular alteration and its decrease during the late phase. Characteristic SP-A distribution in the exudative phase appeared to be especially useful for early histopathological diagnosis of respiratory distress, even prior to the appearance of typical HMs.

Immunohistochemical investigation of pulmonary surfactant-associated protein A in fire victims.

To evaluate the forensic pathological significance of the immunohistochemical distribution of pulmonary surfactant-associated protein A (SP-A) in determining the cause of death in fires, 57 fire victims were examined by scoring the staining intensity. The highest SP-A score with dense granular deposits (aggregates) in the intra-alveolar space was frequently observed in cases with a lower blood carboxyhemoglobin (COHb) level (<60%). The SP-A score was relatively low in carbon monoxide intoxication due to causes other than fires. High SP-A scores showed a relation to the serum level and in part related to the bloody exudate in the lower airway. These observations suggested that the increase in SP-A in fire victims may be mainly related to pulmonary alveolar injury due to the inhalation of hot air and/or irritant gases rather than hypoxia.

Immunohistochemical investigation of a pulmonary surfactant in fatal mechanical asphyxia.

We evaluated the usefulness of pulmonary surfactant protein A (SP-A) as a practical diagnostic marker of fatal mechanical asphyxia in forensic autopsy cases. A total of 27 cases of asphyxia were examined histologically and immunohistochemically and compared with a control group consisting of 16 cases of poisoning (n = 9) and peracute death (n = 7). Both groups showed histological findings of local atelectasis and local emphysema, congestion, intra-alveolar and interstitial edema in most cases and pulmonary hemorrhages in some cases. The mechanical asphyxia group showed a significantly increased intensity of SP-A staining in the intra-alveolar space accompanied by many massive aggregates in approximately 60% of cases, which was not found in the control group. These structures may be interpreted as aggregates of pulmonary surfactant released from the alveolar wall due to enhanced secretion caused by strong forced breathing or over-excitement of the autonomic nervous system by mechanical asphyxia. The results of our investigation suggest the practical usefulness of the immunohistochemical detection of SP-A in distinguishing mechanical asphyxia from other types of hypoxia.

Immunohistochemical distribution of C-reactive protein in the hepatic tissue in forensic autopsy.

Previously, we examined the expression of C-reactive protein (CRP) in hepatic tissues in fatal injuries (injury deaths) immunohistochemically, and classified the CRP distribution into three patterns: diffuse (D-) pattern, diffuse with strong positivity in the hepatic lobules; periportal (PP-) pattern, characterized by positive cells in the periportal region of some lobules; focal (F-) pattern, showing small islands of positive cells in some lobules. There was a relationship between the CRP distribution and the survival time. In this study, we further analyzed the deaths including those due to other than fatal injuries (non-injury deaths), and a study of a total of 314 deaths from various causes was performed. Generally, non-injury deaths showed findings similar to those in injury deaths. PP- and/or F-patterns were observed in 43.7% of cases having a short survival time (<6 h), but found in only 3% of those surviving longer (>6 h), showing that such findings are suggestive of a short survival time. D-pattern was found more frequently in non-acute deaths (60.4%), than in acute deaths (10.9%). In acute deaths, D-pattern was found in some cases showing extensive tissue injuries, such as burns and polytrauma, and inflammative predisposition. Immunohistochemical findings also showed some correlation with the serum CRP level. Our data suggest that hepatic CRP immunohistochemistry may be a useful tool for elucidating the dying process.

Immunohistochemistry of pulmonary surfactant apoprotein A in forensic autopsy: reassessment in relation to the causes of death.

To reassess the immunohistochemical distribution of pulmonary surfactant apoprotein A (SP-A) in relation to the causes of death, 282 forensic autopsy cases were reviewed. The most intense and dense granular immunostaining of intra-alveolar SP-A was observed in the hyaline membrane syndrome from various traumas, protracted death from drowning, and perinatal aspiration of amniotic fluid. Similar granular staining pattern was found in fatal poisoning by a muscle relaxant and organophosphate pesticides. An evident increase of intra-alveolar granular staining was noted in most fatalities from mechanical asphyxia and drowning, and some cases of fire death. SP-A staining was usually very weak or sparse in alcohol intoxication, poisoning by hypnotics and also carbon monoxide poisoning. These findings suggest that the amount of intra-alveolar granular SP-A staining may be a possible indicator of severity and duration of respiratory distress (agony) from peripheral (non-central nervous system) origin and alveolar damage.

Child and elderly victims in forensic autopsy during a recent 5 year period in the southern half of Osaka city and surrounding areas.

To outline the recent features of child and elderly victims from the medico-legal perspective with special reference to abuse and neglect, a retrospective investigation of forensic autopsy cases over a 5 year period (1994-1998) in the southern half of Osaka city and surrounding areas (a population of 1.57 million) was undertaken. Among 646 autopsy cases, there were 53 child cases (under the age of 15 years, about 80% below 6) and 121 elderly cases (65 years old and above). Nearly half of the child deaths and more than half of the elderly deaths were described as accidental. Fire and traffic victims were much more frequent in the elderly. Child victims included those of neonaticide/infanticide (n=6), physical abuse (n=10), unintentional fatal infliction (n=2), neglect (n=2), mutual suicide (n=2), suicide (n=1) and murder (n=3). Child abuse and neglect were domestic maltreatment by the parents. In this series, there was a comparable number of fatalities due to maltreatment in the elderly (n=13) and in children, and non-domestic violence was more frequent in the elderly than domestic violence. Elderly females tended to be battered by their sons or grandsons in domestic violence cases, whereas males were predominantly attacked by younger males in non-domestic violence. The other elderly victims included those of self-neglect (n=2), murder (n=7) and suicide (n=9). Non-domestic homicide of the elderly occurred mainly in the center of the city, whereas domestic maltreatment of children and the elderly was sporadic, although somewhat more frequent in the peripheral zone of the city and the surrounding areas. The above profile of child and elderly abuse suggests a substantial influence of social and familial backgrounds.

Automated determination of carboxyhemoglobin contents in autopsy materials using head-space gas chromatography/mass spectrometry.

To establish a method for the routine analysis of carboxyhemoglobin (COHb) in autopsy materials including those which have undergone postmortem changes, e.g. thermo-coagulation, putrifaction and contamination, an automated head-space gas chromatography/mass spectrometry (GC/MS) analysis was utilized. The procedure consisted of preparation of the sample in a vial and a carbon monoxide (CO) saturated sample, for estimation of hemoglobin content, in another vial, the addition of n-octanol, potassium ferricyanide and an internal standard (t-butanol), GC separation and determination of CO using a GC/MS system equipped with an automated head-space gas sampler. The method was practical not only with the blood and bone marrow aspirates to confirm the findings on the CO-oximeter system, but also with the thermo-coagulated and putrified blood.

Methamphetamine-related fatalities in forensic autopsy during 5 years in the southern half of Osaka city and surrounding areas.

To outline the recent features of methamphetamine-related fatalities from the medico-legal point of view, a retrospective investigation of forensic autopsy cases involving methamphetamine during a 5-year period (1994-1998) in the southern half of Osaka city and surrounding areas (about 1.57 million population) was undertaken. Among 646 autopsy cases, methamphetamine was detected in 15 victims (nine males, six females; 16-71 years of age; most frequently in males in their thirties). Primary scenes of fatal events were concentrated in the middle of the city. About half of them were transferred from emergency medical centers (survival time, up to 30 h). The cause and manner of death were: methamphetamine poisoning (n=4), homicide (n=4), accidental falls and aspiration from drug abuse (n=4), fire death (n=1), myocardial infarction (n=1), and cerebral hemorrhage (n=1) under drug influence. Usually injection scars and fresh puncture sites were found. Blood methamphetamine concentrations were 2.29-17.05 micromol/dl in the fatal poisoning, 0. 44-3.80 micromol/dl in deaths from other extrinsic causes (trauma), and 1.35-2.17 micromol/dl in cardio- and cerebrovascular strokes. Common complications were cardiomyopathy, cerebral perivasculitis and liver cirrhosis/interstitial hepatitis. Fatal and nonfatal methamphetamine poisonings are separately dealt with by the administrative medical examiner's office and in emergency medical centers. Tightly cooperative approaches of clinical and medico-legal experts are required for the effective social and medical management of drug abuse.

A case of serial homicide by injection of succinylcholine.

The abstract of this paper was presented at the 14th Meeting of the International Association of Forensic Sciences, Tokyo in 1996. We report a bizarre criminal case of suspected serial homicide by injection of a muscle relaxant (succinylcholine). Five victims were found buried in a rural area. In two victims showing moderate decomposition (about three months after death), intense pulmonary oedema with pleural effusion was observed. Evidence of a puncture site was found in one of the victims. Succinylcholine could not be detected in the victims, but was identified in a syringe found near the corpses. The 40-mg ampule dose of succinylcholine administered intramuscularly to the victims, possibly causing prolonged apnea, was considered to be at least around the minimum lethal dose, although the combined effect of the sedation with hypnotics also used was not negligible.

Pulmonary surfactant-associated protein A levels in cadaveric sera with reference to the cause of death.

Pulmonary surfactant-associated protein A (SP-A) is an exclusively lung specific protein, and is considered to leak into the blood stream in alveolar septal damage. In this study we examined the serum SP-A level in forensic autopsy materials using an enzyme immunoassay with monoclonal antibodies to assess the postmortem level in relation to the cause and mode of death. Although a gradual postmortem degradation should be taken into consideration, topological relationship of serum level seemed to be fairly stable (arterial> or =venous blood in most cases), indicating no evident influence of postmortem diffusion. Significant elevation of serum SP-A (76.7-250 ng/ml in left heart blood) was observed in hyaline membrane diseases from various causes independent of the postmortem intervals (<30 h). However, mean SP-A levels in postmortem heart blood were usually low in asphyxia including hanging, strangulation and choking (left, 25.5 ng/ml; right, 22.3 ng/ml), polytrauma (left, 13.1 ng/ml; right, 9.0 ng/ml) and stab wound to the neck (left, 34.1 ng/ml; right, 29.4 ng/ml). Prominent elevation was noted in a case of fatal strangulation with complication of idiopathic interstitial pneumonia, and also in some deaths due to drowning, burns in fires, blunt and gunshot chest injuries. These findings indicated that postmortem elevation of serum SP-A levels was associated with alveolar septal damage due to inflammation, mechanical and physical stresses, which caused leakage of SP-A into the bloodstream.

Sudden infant death attributed to peracute pulmonary infection: two autopsy cases.

This report describes two autopsy cases of sudden infant death attributed to peracute pulmonary infection in which possible causative microorganisms could be identified despite only minor pathological findings. Both babies were 5-month-old boys, who had no symptomatic disorders and were found dead in bed. Their main macropathology was inflated heavy lungs with patchy bleedings. One case showed a pulmonary histopathological finding suggestive of viral infection, and adenovirus DNA was detected from the intrabronchial fluid. In the second case, pulmonary histopathology was a feature of early inflammatory reaction involving focal necrosis with some neutrophil infiltration and many intra-alveolar macrophages containing gram-positive cocci, and Staphylococcus aureus was identified in venous blood culture. These findings significantly support the presence of pathogenic microorganisms in sudden infant death.

Dental identification in routine forensic casework: clinical and postmortem investigations.

The aim of this study was to examine the factors which may disturb dental identification of unknown human remains and the practical value of dental evidence in routine forensic casework, including the changes due to dental treatment and postmortem interference. In the investigation of changes due to dental treatment on 696 patients' dental history at two clinics, increase of the number of dental restorations was the greatest in the initial 1-2 years. This finding suggests that dental treatments performed in early period after initial examination contributes more to forensic dental identification than those performed afterwards. The lower anterior teeth (incisors and canines) remained relatively unchanged for years compared with other teeth. The molars appeared to be more frequently restored at a relatively younger age and more frequently missing in the elderly. The investigation of 260 unknown remains in 971 forensic autopsy cases during a period of seven years (1992-1998) at our institute indicated the particular usefulness of dental evidence in cases where the candidates were identified from some other evidence, and usually in cases having a postmortem period corresponding to the obligatory preservation term for the clinical dental records and radiographic films. There were non-identity in the status of dental treatments between ante-mortem dental findings due to additional treatments received after the last day of examination recorded in the corresponding clinical dental records. Postmortem damage from decomposition and fire was more frequently observed in the anterior teeth. These observations indicate that precise documentation of dental evidence including postmortem deterioration and the establishment of a well-organized dental database of missing persons together with a suitable screening system is required to more effectively utilize dental evidence in routine forensic casework.