Comparative histologic studies of the origin of petechial thymus hemorrhage

Systematic histological investigations were carried out on the thymus with regard to the incidence and genesis of petechial thymus hemorrhages in 145 cases of death (fetuses from pregnancy terminations and stillbirth, mature and immature neonates, SIDS cases, other baby deaths, deaths during infancy and childhood). Petechial thymus hemorrhages were most frequently found in SIDS cases (87%). Even though distinguishable, a distribution pattern similar to that of thymus hemorrhages in SIDS cases (including hemorrhages mainly in the cortical zone of the lobes) could be detected in the group of fetuses from pregnancy terminations and stillbirth, as well as in mature and immature neonates. Histologically, deaths in babies and infants without extrinsic suffocation showed a different histological bleeding pattern (irregular hemorrhages of varying size in the cortex and medulla of the lobes). In violent extrinsic suffocation of babies and infants, thymus hemorrhages were much rarer and less pronounced in quantitative terms. Acute and subacute or chronic forms of asphyxia, the cause of death and the duration of the death struggle are discussed as pathogenetic factors to explain the different patterns of the findings.     

Morphometrical investigations into alterations of the wall thickness of small pulmonary arteries after birth and in cases of sudden infant death syndrome (SIDS)

In 1973 Naeye was the first to demonstrate that, in cases of SIDS, the small pulmonary arteries have more smooth muscle than in controls and suggested that this is a consequence of chronic alveolar hypoxia. Seventy-five cases have been investigated morphometrically in order to obtain quantitative data on the alterations of wall thickness of the small pulmonary arteries after birth and in cases of SIDS. The investigations comprise seven cases of stillbirth, 19 cases of newborn, 33 cases of SIDS and 16 controls. In each case the thickness of the media, the external diameter of the artery and the media area have been measured planimetrically for 90 arteries ranging between 50 μm and 500 μm. A media index was calculated as the ratio of the thickness of the media to the diameter of the artery. Using this index a thickening of the media of the small pulmonary arteries, corresponding to the situation in fetal and neonatal life, has been confirmed for cases of SIDS. The normal postnatal changes in the small pulmonary arteries, media thinning and enlargement of the lumen, could not be observed in SIDS cases in the first year of life.     

Cytomegalic inclusion disease of the salivary glands in sudden infant death syndrome

The parotid gland and/or the submandibular gland in SIDS cases (180 from Berlin und 75 cases from Hamburg) were examined by means of HE staining, immunohistochemical analysis, in situ hybridization and electron microscopy. The SIDS cases were taken from the last 10 years; the age of the children ranged from 2 weeks to 1 year. Typical cytomegaly inclusion bodies were recognized in 10% (18 cases from Berlin; more girls than boys) and 7% (6 cases from Hamburg; more boys than girls). Our files indicate that the frequency of CMV infection was not age-dependent within the first 12 months of life. Using immunohistochemical analysis and in situ hybridization, virus substances were detected in cytomegal cells as well as in morphologically uninfected cells. The literature on the clinical and epidemiological aspects of cytomegaly indicates that a localized CMV infection of the salivary glands does not sufficiently explain the sudden death of these infants; however, it should be emphasized that cytomegaly can influence the immunological status of the organism.     

Delayed death in sudden infant death syndrome: a San Diego SIDS/SUDC Research Project 15-year population-based report

A fraction of SIDS cases have death delayed by successful CPR, yet they have not been compared to SIDS cases which were found dead or not successfully resuscitated. Our aims were to: (1) determine the percent of SIDS cases in the San Diego SIDS Research Project database for whom death was delayed by CPR and subsequent life support; (2) compare demographics, circumstances of death and autopsy findings of delayed death SIDS cases (delayed SIDS) with those whose deaths were not delayed (non-delayed SIDS); (3) examine the evolution of pathologic changes in delayed SIDS as a function of survival interval. A retrospective 15-year population-based study of 454 infant deaths attributed to SIDS revealed 29 delayed SIDS cases (Group I) and 425 non-delayed SIDS cases (Group II). Group I cases were significantly older than Group II cases (mean age 132 days vs. 102 days and p<0.0001). Eighty-nine percent of the Group I cases were discovered between 08.00 and 19.59 h; none were found between 00.00 and 07.59 h, compared to 38% of the Group II cases. Group I infants were found significantly more often away from home (at daycare, or at the home of a relative, friend, or baby sitter) than Group II infants (45% vs. 25%, p<0.05). There were no differences between groups with regard to gender, gestational age, type of delivery, bed sharing, URI within 48 h of death, ALTEs, a history of referral to child protective services, body position when placed or found, or face position when found. Pathologic changes were semiquantitatively evaluated; findings were characteristic of anoxic-ischemic injury that generally became more severe with increasing survival intervals. Anoxic-ischemic brain injury was the immediate cause of death in all delayed SIDS cases. Aspiration of gastric contents was identified in Group I cases surviving less than 48 h and was the likely etiology of acute bronchopneumonia occurring in 83% of the Group I cases. We did not identify factors that would reliably predict which SIDS cases might be discovered soon enough to allow earlier and more effective CPR and survival without permanent brain injury.     

肾上腺结核猝死的法医学鉴定

通过两例肾上腺结核猝死的案例观察发现：肾上腺和肾上腺以外器官的结核病变均表现为不典型的慢性陈旧性的病理学特征。提示在法医学鉴定中,对患过结核病和“不明死因”猝死尸体剖验时肾上腺的组织病理学检验尤为重要     

Cytomegalovirus-induced pneumonia and myocarditis in three cases of suspected sudden infant death syndrome (SIDS): diagnosis by immunohistochemical techniques and molecularpathologic methods

Immunohistochemical and molecularpathologic techniques have improved the diagnosis of myocarditis as compared with conventional histologic staining methods done according to the Dallas criteria. Additionally, immunohistochemistry and in situ-hybridization are able to demonstrate viral infection, e.g. cytomegaloviruses in salivary glands and lungs, locations both known to be involved in cytomegalovirusinfection. However, in many cases of proved cytomegalovirusinfection the cause of death remains unclear. We report on three children younger than 1-year of age, who died suddenly without prodromal symptoms. Their deaths were attributed to SIDS (sudden infant death syndrome). In situ-hybridization, immunohistochemical (LCA, CD45R0, CD68, MHC-class-II-molecules, E-selectine) and molecularpathologic investigations (PCR), however, suggested that death was caused by a cytomegalovirus-induced pneumonia or myocarditis. In the future, these methods should be used for investigating cases with suspicion of SIDS.     

Periventricular fatty metamorphosis in neuroglia--a morphologic substrate in SIDS

In 7 of 15 cases of sudden infant death syndrome (SIDS), distinct periventricular fatty metamorphosis of the neuroglia could be demonstrated by a histological staining technique. None of the six children (under 1 year of age) used as a control group whose cause of death was not SIDS showed this morphological change. Thin-layer chromatographic analysis of the lipids accumulated in the glial cells in SIDS established a high amount of esterified cholesterol whereas the content of esterified cholesterol in the control group was low. We presume that fatty metamorphosis of the neuroglia represents the morphological substrate of a metabolic disorder of the sensitive, immature glia of the periventricular white cerebral matter caused by various kinds of damage.     

Thymus and adrenal glands in elder abuse

Endogenous glucocorticoid-induced thymic involution is generally considered to be an important finding for determining child abuse. The present study investigated the weight of the thymus and the adrenal glands in elder abuse cases to identify a potential marker for elder abuse. There was no significant difference in the thymus and the adrenal weight between elder abuse and control cases. However, the elder abuse cases in which the duration of abuse was less than 3 months showed a significant increase in the adrenal weight in comparison to control cases. In such cases, histopathological findings showed a loss of intracellular light granules from the zona fasciculata, which might indicate a loss of cholesterol due to the overproduction of glucocorticoid. These results might imply that the elderly, who were maltreated for less than 3 months, were in the early phase of a long-term stress state during which stress-induced overproduction of glucocorticoid was observed in adrenal glands as indicated by Selye. Our results suggest that an increase in adrenal weight may be a potential marker for elder abuse of relatively short periods, especially less than a few months.     

Evaluation of diagnostic tools applied in the examination of sudden unexpected deaths in infancy and early childhood

During the period between 1984 and 1999, 309 cases of sudden unexpected death in infancy and early childhood (0-3 years) were investigated at the Institute of Forensic Medicine in Oslo. In 73 cases, an explainable cause of death was found. In this non-sudden infant death syndrome (SIDS) group, 42 cases were due to disease, 14 to accidents, 7 to neglect/abuse and 10 cases were due to homicide. In 43 cases, there were pathological findings at the autopsy or suspect features in the history and/or circumstances, which were, however, insufficient to explain death ("borderline" SIDS). In the remaining 193 cases, nothing of significance was detected ("pure" SIDS).The purpose of the present study was to evaluate the importance of the different diagnostic tools used in diagnosing non-SIDS and borderline SIDS cases. The definition of SIDS requires a negative history as well as a negative autopsy result. Thus, the following variables were analysed: circumstances, medical history and autopsy, which included a gross pathological investigation, histology, neuropathology, microbiology, radiology and toxicology. In diagnosing deaths due to disease, histology, neuropathology and microbiology were the most important diagnostic tools. In contrast, information about the circumstances of death and the gross pathological findings at autopsy most often revealed the cause of death in accidents and cases of neglect/abuse and homicide.Following the drop in SIDS rate in Norway after 1989, the share of pure SIDS in proportion to the total population of sudden unexpected deaths in infancy and early childhood has decreased. The increasing proportion of non-SIDS and borderline SIDS cases presents a challenge to improve the quality of the investigation in cases of sudden death in infancy and early childhood.     

Laryngeal basement membrane thickening is not a reliable postmortem marker for SIDS: results from the Chicago Infant Mortality Study.

It has been suggested that laryngeal basement membrane (LBM) thickening is a pathognomonic postmortem marker for sudden infant death syndrome (SIDS) and is not seen in other causes of explained sudden infant death. To test this hypothesis, we evaluated longitudinal sections of the right hemilarynx taken through the midpoint of the true vocal cord from 129 SIDS cases and 77 postneonatal sudden infant death controls. Using a five-point semi-quantitative scale, maximum LBM thickness (LBMT) for SIDS cases and controls was not statistically different (mean, 2.39 + 0.69 and 2.40 + 0.77, respectively). Likewise, scores based on the average thickness along the entire basement membrane (i.e., "average" score), were not found to be different between SIDS cases and controls. Average and maximum LBMT increased with age in both SIDS cases and controls and were not different between SIDS cases and controls within each age interval. Similar trends in the distribution of maximum and average LBMTs were found between black and Hispanic SIDS and controls; the number of white/non-Hispanic infants was too low for meaningful comparisons. Maximum and average LBMTs were not different in SIDS cases and controls exposed to environmental tobacco compared with unexposed infants. The LBMTs also increased significantly with body weight and length in both SIDS cases and controls. Finally, there were no differences in LBMT in infants intubated prior to death compared with those who were not intubated. From these data, we conclude that LBMT is not pathognomonic of SIDS, is present or absent with equal frequency in SIDS and controls, increases with postnatal age, and does not correlate with passive smoke exposure. Therefore, LBMT should not be used to diagnose SIDS.     

A comparison of pulmonary intra-alveolar hemorrhage in cases of sudden infant death due to SIDS in a safe sleep environment or to suffocation

The differentiation of SIDS from accidental or inflicted suffocation may be impossible without corroborating findings from the death scene or autopsy or in the absence of a confession from a perpetrator. Pulmonary intra-alveolar hemorrhage (PH) has been proposed as a potential clue to suffocation, but none of the previous studies on this topic have limited SIDS cases to those who were in a safe sleep environment, in which all were found supine and alone on a firm surface with their heads uncovered. Our aims are to: (1) compare PH in SIDS cases found in a safe sleep environment to a control group comprised of infants whose deaths were attributed to accidental or inflicted suffocation and (2) assess the effect of age, CPR, and postmortem interval (PMI), with regard to the severity of PH in this subset of safe-sleeping SIDS cases. We conducted a retrospective study of all postneonatal cases accessioned by the Office of the Medical Examiner in San Diego County, California who died of SIDS or suffocation between 1999 and 2004. A total of 74 cases of sudden infant death caused by SIDS (34 cases as defined above, comprising 8% of the total SIDS cases), accidental suffocation (37), and inflicted suffocation (3) from the San Diego SIDS/SUDC Research Project database were compared using a semiquantitative measure of pulmonary intra-alveolar hemorrhage. The most severe (grade 3 or 4) PH occurred in 35% of deaths attributed to suffocation, but in only 9% of the SIDS cases. Age, duration of CPR attempts and PMI had no effect on the severity of PH in SIDS. Our results indicate that the severity of PH cannot be used independently to differentiate SIDS from suffocation deaths. Each case must be evaluated on its own merits after thorough review of the medical history, circumstances of death, and postmortem findings.     

The epidemiology of sudden infant death syndrome in Finland in 1969-1980

SIDS cases were defined by examining all death certificates, in which sudden deaths were expected to be found from the years 1969-80 from the Central Statistical Office of Finland. The age limits were 28-364 days. If the death certificate did not give enough information as to whether the cause of death was explained or unexplained, autopsy records and microscopic specimens were examined. If the death was sudden, but no autopsy was done, no microscopic specimens were taken, or there were some slight findings which could have partly explained the death were classified as borderline cases. The mean annual incidence of SIDS in Finland was 0.41/1000 livebirths in 1969-80. In 1969-74 and 1975-80 the incidences were 0.31 and 0.51, respectively. The increasing tendency of SIDS was partly due to more borderline cases in the first period and partly due to more twins, and infants with small birth weight, dying of SIDS in the second period. Deaths at weekends and sleeping with parents in the second period were more common than in the first study period. In the SIDs group the young maternal age, low social class, family type unmarried couple or single mother, maternal anemia during pregnancy were more common than in the control group. Mothers of SIDS infants had more previous children and fewer visits and later first visit to prenatal clinics than control mothers. The duration of gestation was shorter and the mean birth weight and length were smaller in the SIDS case than in the control group. Twins were more common among SIDS infants than in the common population. The most important risk factor of SIDS was maternal smoking during pregnancy. The epidemiological results conform with the hypoxia hypotheses.     

Ethanol-oxidizing enzymes of the adrenal glands in acute alcoholic intoxication

Complex morphological-and-histological examinations of the adrenal glands were performed on actual forensic-medical samples in acute alcoholic intoxication (AAI), i.e. 107 death cases of men and women, aged 17 to 60, due to mechanical trauma, lethal ethanol intoxication and somatic complications of chronic alcoholism. A differentiated distribution of ethanol-oxidizing enzymes was defined, i.e. of alcohol-dehydrogenase and acetyl-dehydrogenase in the structural-and-functional zones of the adrenal cortex and medullary substance. A differential activity of enzymes was established that correlated with the level of exogenous alcoholemia. Sets of morphological signs related with examinations of the adrenal glands, which enabled a differential diagnosis of death causes in AAI, were specified.     

Histochemical changes in the hypothalamus, hypophysis, and adrenal glands observed in ethanol poisoning

A comprehensive morphological-and-histochemical study of neuroendocrinal internals in cases of ethanol poisonings was undertaken. Actual forensic medical materials were used (62 cadavers) to make morphometry examinations of the hypothesis and adrenal glands. Besides, the distribution of alcohol dehydrogenase and acetaldehyde dehydrogenase was investigated in the mediatory differential brain sections, i.e. cerebellum, locus coeruleus, dorsal raphe nucleus, hypothalamus and adrenal glands. A differential distribution of ethanol-oxidizing enzymes as well as their changes in ethanol lethal poisoning were established; additionally, a variety of morphological signs were defined, which enable the differential diagnosis of a death reason in acute alcoholic intoxication.     

No association of IL-10 promoter SNP −592 and −1082 and SIDS

Sudden infant death syndrome (SIDS) constitutes a considerable percentage of infant death of unknown etiology. The genetically controlled pathway of cytokine mediated response to inflammation is presumed to play a role in SIDS. The A allele of SNP ?592 of the promoter region of the anti-inflammatory cytokine IL-10 has been suggested to be associated with SIDS. Herein we investigated whether we could confirm this finding by SNP genotyping a series of 123 cases of SIDS and 406 control cases. We did not find a correlation between the A allele or an A allele containing genotype of IL-10 promoter SNP ?592 and SIDS which is in contrast to previous studies. Also, in concordance with previous work, no association of the A allele or A allele containing genotypes of IL-10 promoter SNP ?1082 and SIDS was found.     

Incidence and forensic value of liver cell hydrops in external asphyxia and sudden infant death

A histological examination was carried out in 108 cases of asphyxia, 28 cases of SIDS, and 33 cases with other causes of death to assess the occurrence of liver-cell hydrops. In almost all cases of violent suffocation of newborns and children up to 10 years of age hydrops of the hepatocytes were found, whereas these results could be verified only exceptionally after violent suffocation of adults. Eighteen cases or 64.3% of SIDS showed a diffuse distribution of liver-cell hydrops over each liver lobule. Liver-cell hydrops seems to represent a frequent morphological equivalent of acute oxygen deficiency in asphyxia in childhood and is a common finding in SIDS.     

Fetal visceral maturation: a useful contribution to gestational age estimation in human fetuses

With regard to the law, estimating fetal age is essential to assess viability (after 20 weeks according to the WHO) and the proposed methods generally use long bone measurements. Here, we evaluated the accuracy of soft tissue maturational stage and compared it with long bone measurements. First, eight kinds of tissues or organs from 448 fetuses with known medical history were studied (macroscopically or histologically). We clearly demonstrated that adrenal glands and skin were very good age indicators, because some characteristics appeared only after 20 weeks. We established a linear regression with a 95% confidence interval of +/- 2.9 weeks. Second, we applied our original formula using femur measurement and we combined soft tissues and bones in a multiparametric regression. The confidence interval was reduced to +/- 2.5 weeks. We conclude that the pathologist must use both histological and anthropometric data to determine fetal age as accurately as possible.     

Cardiac lesions in sudden infant death syndrome

Sequential morphological changes as found in the hearts of 250 sudden infant death syndrome (SIDS) infants are described. Detailed examination of macroscopic and microscopic lesions reveal that all SIDS infants had identifiable lesions at the time of their death. The lesions can best be described as selective focal anoxic muscle fibre necrosis at chronologically different developmental stages. The extent of these lesions vary markedly from case to case, from a minimal muscle fibre eosinophilia through contraction band formation, myocytolysis, stromal condensation to scar formation. The morphological variations in the lesions amongst individual cases can be interpreted as relating to the time interval of the development of the lesions. The intramural and coronary arteries in some cases are also affected showing intimal hyperplasia. Although these sequential morphological aberrations are not specific and typical to SIDS infants only, they were present in all SIDS infants in this series.     

Comparative histologic and hormonal studies of the thyroid gland with special reference to sudden infant death (SIDS)

In 53 cases of death - including 12 cases of sudden infant death syndrome (SIDS) - where blood samples could be taken within 18 h postmortem, the thyroxines T4, FT4, T3 and FT3 were determined (ELISA and RIA). These hormone values were compared with the corresponding histological thyroid findings in 43 cases (11 SIDS, 32 controls). Nearly identical T4 and FT4 mean values were found in both groups which were within the norms. In contrast to the average values of the control group, the T3 and FT3 concentrations of the SIDS group showed an increase of 3.7-fold and 1.9-fold. Accordingly, histological examination of the SIDS group showed highly activated and extensively released follicles whereas normal colloidal-containing follicle structures were observed in nearly all control cases. The present findings indicate that neither postmortem T4 T3 conversion nor intensified agonal hormone secretion is likely to be the only cause of the increasing T3 and FT3 values. In SIDS cases chronic or recurring chronic stress situations are supposed to be the cause for the hormonal and histological thyroid findings. Some differential diagnoses are discussed. Within 18 h after death, increased concentrations of T3 and FT3, together with simultaneous colloid release, represent a diagnosis of SIDS.     

Lactic acid concentrations in vitreous humor: their use in asphyxial deaths in children

Lactic acid concentrations in brain tissue of humans have been shown to increase with an extended agonal period. Infants and children dying from various causes are undergoing different stress conditions terminally and the postulate of this study is that natural death cases and traumatic asphyxia cases are characterized by varying agonal periods, the former being somewhat prolonged with the latter being rather brief. One-hundred-and-two cases of infants and children were examined for vitreous humor lactic acid concentrations. They were divided into two major categories, Sudden Infant Death Syndrome (SIDS) and non-SIDS cases. SIDS was further divided into SIDS without additional findings and SIDS with secondary findings which contributed to death. The non-SIDS category included traumatic asphyxia cases as well as those dying from blunt trauma, known respiratory diseases, and other causes. Categorical mean values and standard deviations were calculated. The vitreous humor lactic acid mean value for traumatic asphyxia was significantly lower than the mean value for SIDS. Also the mean value for known respiratory diseases was statistically lower than the mean value for SIDS with secondary findings. These findings are probably suggestive of agonal time differences and may be a reflection of the various mechanisms of death.