Immunohistochemical examination of the lungs in infant death cases using antibodies against milk components

To examine the use of immunohistochemical staining with antibodies against milk components for detection of aspirated milk on lung sections, eighteen infant death cases were investigated. Immunostaining was performed with anti-human alpha lactalbumin, anti-human IgA, anti-human milk fat globulin 1, and anti-cow whey antibody. Reactivity with each antibody was examined, and semi-quantitative examinations were performed to compare the amount of aspirated milk using anti-human alpha lactalbumin antibody. Materials in the alveoli or bronchioli on lung sections suspected to be aspirated milk showed the most sensitive and clearest reaction with anti-human alpha lactalbumin antibody. Of the eighteen cases, ten cases showed positive reaction with this antibody. The amount of aspirated milk varied widely in each case. In conclusion, immunohistochemical staining with antibodies against human milk components, especially anti-human alpha lactalbumin antibody, can detect small amounts of milk. Using this method, we were able to compare the relative amount of aspirated milk among cases.     

Unexpected death due to intestinal obstruction by a duplication cyst in an infant

An 11-month-old female infant died at home after being diagnosed as having gastroenteritis. Autopsy examination revealed a distended distal ileum filled with a large amount of watery contents, and a 3 cm x 3 cm x 4 cm cyst at the ileocecal part of the cecum that was histologically consistent with a duplication cyst. The cause of death was determined to be acute dehydration due to intestinal obstruction caused by a duplication cyst. This case indicates that intestinal obstruction by a duplication cyst should be recognized as a cause of unexpected death in infants.     

Histologic thyroid gland findings in the newborn infant and infant, with special reference to sudden infant death

The morphological picture of the thyroid gland, the only endocrine organ with a follicle structure, allows a limited conclusion to be drawn with respect to the functional state in spite of any physiological variability. The thyroid of the newborn shows total colloid release and collapse of the follicles. The regular structure of the thyroid will be rebuilt within several weeks after birth. Total colloid absorption can be found in cases of stress-activated thyroids as well as in cases of death due to freezing. A histological examination was done on 88 thyroids of fetuses, newborns and infants. About 70% of the results on 27 cases of sudden infant death syndrome (SIDS) may be interpreted as a morphological correlate of a premortal chronic or recurrent stress reaction. The value of these results is discussed.     

Sudden death due to an unrecognized cardiac hydatid cyst: three medicolegal autopsy cases

Echinococcosis is a human infection caused by the larval stage of Echinococcocus granulosus. The most common sites of infection are the liver and the lungs. Cardiac hydatid cysts are very rare, even in regions where hydatic cysts are endemic (the Mediterranean, South America, Africa, and Australia). It has been reported that cardiac involvement is seen in about 0.5-3% of human echinococcosis cases. Three cases of cardiac hydatid disease that caused sudden death and which were histopathologically diagnosed are reported. Cardiac echinococcosis is rare, but due to its insidious presentation and affinity to cause sudden death, it is important that it be identified in the histopathological examination.     

Immunohistochemical techniques improve the diagnosis of myocarditis in cases of suspected sudden infant death syndrome (SIDS)

Immunohistochemical techniques have improved the diagnosis of myocarditis. In a post mortem study, eight specimens in each case of the formalin-fixed and paraffin-embedded hearts of 20 suspected cases of sudden infant death syndrome (SIDS) were investigated with traditional hematoxylin-eosin staining and immunohistochemical methods. The hematoxylin-eosin stained specimens were examined for myocarditis according to the Dallas criteria; only in one case was a myocarditis diagnosed. The subsequent definition of the major histocompatibility complex class II antigens (HLA-DP,DQ,DR and HLA-DR), known to be enhanced in cases of myocarditis, the quantification of leucocytes with leucocyte common antigen (LCA) and characterization and quantification of T-lymphocytes using a specific marker (CD-3) allowed the definite diagnosis of myocarditis in three additional cases, six cases were found with moderate changes and ten cases without signs of inflammation.     

A case of sudden infant death due to massive hemorrhage in primitive neuroectodermal tumor.

A case of the sudden death of a 14-month-old girl due to massive hemorrhage in a primitive neuroectodermal tumor (PNET) is presented along with a review of the relevant literature. PNET is a rare, malignant brain neoplasm occurring predominantly in children.     

Morphologic variations in 180 cases of sudden infant death and 180 controls.

The incidence of morphologic variations (MVs) was investigated in 180 infants who died unexpectedly and suddenly and in 180 age-matched nonsuddenly deceased infants. The same person (G.M.) performed a full postmortem and histologic examination on all of the infants, none of whom had significant malformations. The test group (TG) consisted of 146 infants whose death was unexplained, whereas group 3 (G3) consisted of 34 infants with adequately determined causes of death. The principal findings in the control group were prematurity, inflammatory and metabolic diseases, tumors, and traumatic lesions. MVs were present in 62% of the TG infants, in 47% of the G3 children, and in 22% of the controls. The differences between the TG and G3 on the one hand and the controls on the other are statistically significant (p < 0.001 and 0.05, respectively). In the TG, anomalies were twice, dysplasias three times, and dysmorphisms four times as common as in controls; in G3, four times as many dysplasias and dystropics were found as in controls. In the TG, 23% of the MVs were multiple as compared with 9% in G3 and 5% in controls. The pattern of distribution was not confined to certain organs. Among the relative high percentage of dysplasias, the large number of neuroblastomas is striking.     

A comparison of respiratory symptoms and inflammation in sudden infant death syndrome and in accidental or inflicted infant death

Upper respiratory infection and pulmonary inflammation are common in sudden infant death syndrome, but their role in the cause of death remains controversial. Controlled studies comparing clinical upper respiratory infection and inflammation in sudden infant death syndrome with sudden infant deaths caused by accidents and inflicted injuries (controls) are unavailable. Our aim was to compare respiratory inflammation and upper respiratory infection within 48 hours of death and postmortem culture results in these two groups. A retrospective analysis of upper respiratory infection and pathologic variables in the trachea and lung of 155 infants dying of sudden infant death syndrome and 33 control infants was undertaken. Upper respiratory infection was present in 39% of sudden infant death syndrome cases and 40% of control cases. Upper respiratory infection was more likely to have occurred in association with more severe lymphocytic interstitial pneumonitis when sudden infant death syndrome cases and control cases were combined ( P=.04). Proximal and distal tracheal lymphocytic infiltration was more severe in control cases than in sudden infant death syndrome cases ( P=.01 and.01, respectively). Lymphocytic infiltrations of the bronchi, bronchioles, and pulmonary interstitium were similar between groups. Bronchial associated lymphoid tissue was more prominent in control cases ( P=.04). Cultures were positive in 80% of sudden infant death syndrome cases, 78% of which were polymicrobial. Among control cases, 89% were positive, with 94% being polymicrobial. This study confirms that microscopic inflammatory infiltrates in sudden infant death syndrome are not lethal.     

心肌病猝死者心肌连接蛋白43的免疫组化染色观察

目的探讨心肌病猝死者心肌连接蛋白43(Cx43)染色变化及其与猝死的关系。方法运用免疫组化和图像分析技术,分2组(A和B组)检测20例心肌病猝死者心室肌的Cx43染色情况;并与14例非心肌病猝死者(C组)的检测结果对照。结果扩张型心肌病(DCM)猝死组(A组,11例)心肌Cx43染色明显减弱,阳性着色斑点大小不等、深浅不一、分布不均,有的呈散在颗粒状;其它类型的心肌病猝死组(B组,9例)亦见类似变化;非心肌病猝死的对照组(C组,14例)未见明显变化。定量检测并经统计分析发现,Cx43蛋白染色阳性的面积,A组与B组和C组的差异有非常显著性意义(P<0.01),B组与C组的差异无显著性意义(P>0.05);而平均光密度各组之间的差异无显著性意义(P>0.05)。结论心肌病猝死者心肌Cx43免疫组化染色明显减弱,尤以扩张型心肌病明显;心肌病猝死者心肌Cx43变化可能与其猝死有一定关系。     

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

Emotional, physiological and physical stress is associated with increased rates of cerebrovascular events and sudden deaths. The pathophysiology of stress-induced cardiomyopathy is not well understood. Proposed mechanisms for catecholamine-mediated stunning in stress cardiomyopathy include epicardial vasospasm, microvascular dysfunction, hyperdynamic contractility with midventricular or outflow tract obstruction, and direct effects of catecholamines on cardiomyocytes. Studies show evidence of significant heritable influences on individual responses to adrenergic stimulation. Data from such studies may be of help for a more accurate comprehension of clinical and morphological alterations of the heart. Irrespective of the cause, patients with the classic stress-induced cardiomyopathy morphology deserve special attention because this extensive distribution of wall motion abnormalities has implications for potential associated complications. Cardiac response may be significantly coupled to genetic differences at candidate loci that encode components of catecholamine biosynthesis, storage, and metabolic pathway. Given the role of the sympathetic nervous system in responses to acute stress, it is reasonable to explore whether genetically determined alterations in catecholamine system functions contribute to acute and chronic cardiovascular disorders such as stress-induced cardiomyopathy.     

Myocardial Cx43 expression in the cases of sudden death due to dilated cardiomyopathy

PURPOSE: Probing into myocardial connexin (Cx) 43 expression in the cases of sudden death due to dilated cardiomyopathy (DCM) and relationship between Cx43 expression and sudden death. METHOD: Myocardial Cx43 was detected with immunohistochemical staining in the cases of 11 sudden death caused by DCM and 14 cases of control group who died of violent reasons and other diseases, which were autopsied in our department from 1997 to 2003. RESULT: Of 11 cases of DCM, there were 10 men and 1 woman with ranging in age from 7 to 49 years old (x (37.8) years old for 9 adult cases). Of 14 cases in the control group, there were 10 men and 4 women with ranging in age from 11 to 53 years old (x (29.9) years old for 11 adult cases). Myocardial Cx43 expression was obviously decreased in DCM group. Positive dyeing spots were different in size, distribution, color and disparity, some of them were distributed in the form of particle. Obvious change had not been observed in the cases of control group or with only slight changes in coloring degree and expressive area. The quantitative data showed that there was significant difference between two groups (p=0.0075) about Cx43 expressive area, but there was no difference between the left and right ventricles (p>0.05) in each group itself. And there was not difference between the two groups about average optical density of expression. CONCLUSION: Myocardial Cx43 expression is obviously reduced in the patients with DCM who die suddenly. The alteration of quantity and distribution of myocardial Cx43 expression is probably related to sudden death of the patients with DCM.     

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.     

Histologic findings in the esophagus in infancy. A contribution to the question of gastroesophageal reflux in sudden infant death

In 53 mortalities (1 stillbirth, 2 neonates, 7 cases up to 5 years of age and 43 SIDS cases), systematic histological investigations were carried out on the esophagus. The results comprised a topography of epithelial defects and inflammatory wall changes. In the SIDS cases, focal epithelial defects could be detected in 14% and fresh inflammatory infiltrates in 7% without preferential localization. There were also lymphocytic reactions of varying extent (62%), but mainly in the upper one-third of the esophagus. Similar findings were found in the 10 non-SIDS cases. The results pattern is discussed with regard to its pathological relevance. It appears to be doubtful that the inflammatory changes are the result of reflux, as reflected in morphological terms.     

Simultaneous sudden infant death syndrome: a proposed definition and worldwide review of cases.

Epidemiologic studies of sudden infant death syndrome (SIDS), the leading cause of death of infants during the postperinatal period (7-365 days), have mainly focused on the deaths of single infants. Simultaneous sudden infant death syndrome (SSIDS), the death of a pair of twins occurring at the same time, has received limited attention within the medical community. To the authors' knowledge, this article is the first to describe the 41 SSIDS cases cited in the world literature from 1900 to 1998 by the location of death, a summary of the circumstances surrounding the deaths, and evaluation of these cases in terms of a proposed definition of SSIDS. This evaluation critiques whether the 41 pairs of SSIDS cases adhere to a newly proposed definition of SSIDS. Twin infant deaths must meet all three criteria to be considered SSIDS. The study found that only 12 pairs of twins met all three criteria (29.2%), nine pairs met two criteria (21.9%), alternative cause of death was offered in five pairs of twins (12.1%) and in the remaining 15 pairs (36.6%), only limited information was available; therefore, no conclusions could be reached.     

Epidemiology of sudden infant death (sudden infant death syndrome, SIDS) in the Lübeck area. Catamnestic studies of 155 observed cases from 1971 to 1981

The 155 cases of SIDS investigated at the Institut für Rechtsmedizin of the Medizinische Hochschule in Lübeck (northern part of the Federal Republic of Germany) between 1971 and 1981 have been analysed retrospectively under epidemiological aspects. The incidence was 2.17 cases of SIDS/1,000 live-born babies, 63.9% were male, 79.3% of the infants died during the first 6 months of life with a clear peak in the 2nd month. There was no seasonal accumulation; 68.4% of the infants died between 8.00 p.m. and 8.00 a.m., in 75% the socio-economic factors were inconspicuous, but we observed a significantly higher incidence of infants from mothers younger than 25 years. In 58% of our cases no signs of illness or changed behaviour had been observed during the 48 h before death. The results of our study are compared with the literature and discussed with special regard to a possible prevention.     

Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases

Tolperisone (Mydocalm) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10 g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0 mg/l, 14 mg/l and 19 mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.     

Birth and death in a new land attitudes to infant death in colonial Australia

The goldrush colony of Victoria, Australia, was a favoured destination for aspirational emigrants from nineteenth-century Britain. Yet the persistence of high rates of infant mortality blighted the happiness of many first and second generation immigrant families alone in a new land. Drawing on birth, death and inquest records this paper interrogates the experience of infant death amongst the poorest families in the capital city popularly known as ‘Marvellous Melbourne’ during the second half of the nineteenth century. Although few infants died alone, the familial and community networks in which they were enmeshed were not always committed to their survival. While the paper argues that there was a hierarchy of value which determined the degree to which the death of a child would be welcomed or mourned, it also contests popular notions that evil baby farmers and unfeeling mothers were a major cause of infant death.     

Unexpected death in persons with symptomatic epilepsy due to glial brain tumors: a report of two cases and review of the literature.

Two cases of unexpected death in persons with epileptic seizures due to a brain tumor are presented which encompassed an astrocytoma WHO grade II and an anaplastic astrocytoma WHO grade III. A 35-year-old man was found somnolent and disoriented at home. A computed tomography (CT) scan revealed a tumor of the right frontal lobe suggestive for an oligodendroglioma. During an angiographic examination the patient experienced an epileptic seizure. Some weeks later, the man was found dead in front of his house with a fresh bite mark of the tongue. Neuropathological examination revealed an astrocytoma WHO grade II of the right frontal lobe. A 47-year-old man plunged into a swimming-pool and was found submerged some minutes later. After resuscitation he survived comatose for 8 days but finally died due to severe hypoxic brain damage. He had been operated on a brain tumor of the temporal lobe 1 year before the accident. Neuropathological examination revealed residual tumor tissue at the operation site corresponding to an anaplastic astrocytoma WHO grade III. Although rare, death in persons with epileptic seizures due to brain tumors is an important mechanism of death encountered by the forensic pathologist.     

Sudden infant death syndrome and hypertrophy of the palatine tonsil: reports on two cases.

Two cases of sudden infant death syndrome (SIDS) with hypertrophy of the palatine tonsil were reported. The pathogenesis of the SIDS has been clarified (Guilleminault et al., Pediatrics, 68 (1981) 354-360). According to this theory, it is due to a central impairment of the breathing control during sleep, which is particularly pronounced in predisposed subjects. The present cases suggest that the hypertrophied palatine tonsil might contribute as a predisposing factor to the emergence of a SIDS by mechanical impediment to breathing by narrowing of the upper airway.     

Screening of milk aspiration in 105 infant death cases by immunostaining with anti-human alpha-lactalbumin antibody.

To determine the frequency and degree of milk aspiration in infant death cases, immunohistochemical examinations were performed on lung sections from 41 sudden death cases and 64 in-hospital death cases using anti-human alpha-lactalbumin antibody. Milk aspiration to some degree was detected in more than half of the sudden death cases and in about one-third of the in-hospital death cases. A semi-quantitative examination of the amount of aspirated milk was subsequently performed in the positive cases. The amount of aspirated milk in the sudden death cases was significantly higher than that in the in-hospital death cases. The frequency distribution of the amount of aspirated milk was similar in shape in both groups. In most cases, a very small amount of aspirated milk was detected. The aspirated milk was assumed to be a result of occasional gastroesophageal reflux or cardiopulmonary resuscitation. However, in five cases, much larger amounts of aspirated milk were found. In these cases, milk aspiration may have been an important part of the cause of death. We concluded that slight milk aspiration is not rare in infant death cases, and that in a few cases, the aspiration is lethal. An immunohistochemical screening test is available to perform a postmortem diagnosis in these cases.