Age-dependent morphologic findings of the thyroid in sudden infant death

Age (eight days to 12 months) and degree of colloid depletion or colloid content of the follicles (normal, partially depleted, depleted) were correlated on the basis of 176 thyroid investigations in cases of sudden infant death syndrome (SIDS). In the 176 SIDS cases, a resting thyroid gland with normal colloid content could only be found in 14%, whereas partially depleted follicles were found in 35% and depleted follicles in 51%. 60% of all cases showed a large degree of epithelial desquamation up to collapse of all follicles. A marked capillary hyperemia was found in 48%. 80% of the cases showed a normal colloid content in the first month of life, and colloidfree follicles should not be detected in any case. An increased incidence of thyroid activation was obtained in the total number of cases only from the second month of life. The histomorphological appearance of the thyroid gland thus corresponds to that of healthy infants only in the first month of life. The question as to why there is an evidently raised thyroid activity in the subsequent months of life in SIDS cases is discussed.     

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.     

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.     

Delimitation of the time of death by immunohistochemical detection of thyroglobulin

To improve the possibilities to delimit the time of death after longer laytime it was examined if this is possible by immunohistochemical detection of thyroglobulin. The results show that in our examination material the colloid and the follicular cells of the thyroid glands of up to 5-day-old corpses produce a positive immunoreaction towards thyroglobulin in all cases whereas none of the corpses older than 13 days show such a reaction. This means that in case of a negative immunoreaction the time of death can be assumed to lie more than 6 days before the autopsy. The fact that a negative immunoreaction occurrs consistently after 13 days leads to the conclusion that when thyroglobulin has been stained in a specimen, the death of the respective person must lie a maximum of 12 days earlier, whereby these time-limits may change in considerably different surrounding conditions.     

Delimitation of the time of death by immunohistochemical detection of thyroglobulin

To improve the possibilities to delimit the time of death after longer laytime it was examined if this is possible by immunohistochemical detection of thyroglobulin. The results show that in our examination material the colloid and the follicular cells of the thyroid glands of up to 5-day-old corpses produce a positive immunoreaction towards thyroglobulin in all cases whereas none of the corpses older than 13 days show such a reaction. This means that in case of a negative immunoreaction the time of death can be assumed to lie more than 6 days before the autopsy. The fact that a negative immunoreaction occurs consistently after 13 days leads to the conclusion that when thyroglobulin has been stained in a specimen, the death of the respective person must lie a maximum of 12 days earlier, whereby these time-limits may change in considerably different surrounding conditions.     

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.     

Pulmonary siderophages and unexpected infant death

It has been proposed that the presence of siderophages in the lungs of infants who die unexpectedly should be considered a marker of a previous hypoxic event, which may preclude a diagnosis of sudden infant death syndrome. The authors retrospectively reviewed all infant deaths (<1 year old) going to autopsy at the Denver Office of the Medical Examiner from January 1999 to January 2001. Lung sections were stained with Prussian blue, and siderophages were counted in 20 high-power fields per lobe sampled. Cell counts were performed by two independent pathologists who were blinded to history and cause of death, with good reproducibility. Iron stain results were then categorized by average number of siderophages per 20 high-power field (category 1 = <5, category 2 = 5-100, category 3A = 100-500, category 3B = >100 in a single lobe, category 4 = >500). The results were subsequently correlated to case history, autopsy findings, and cause/manner of death. Forty-three cases were reviewed. The causes of death included sudden infant death syndrome (16), asphyxia (5), undetermined (6), and other (16). Those deaths were categorized by the above criteria as follows: category 1. (32), category 2. (6), category 3. (4), and category 4. (1). All sudden infant death syndrome deaths were in category 1. Categories 1 and 2 also included deaths in which hypoxia might have been present before death because of such factors as pneumonia and congenital heart disease. Categories 3 and 4 included a known homicidal asphyxia in which repeated episodes of intentional smothering were documented, 2 probable asphyxias, 1 nonaccidental trauma, and 1 undetermined. All 5 cases had questionable circumstances surrounding the death of the infant. Pulmonary siderophages were described in only 1 of the 43 autopsy reports. It was concluded that pulmonary siderophages can be markedly increased in cases of repeated asphyxia. Siderophages may also be increased in cases where hypoxia may have been present for another reason, but not to the same degree. Siderophages are not increased in sudden infant death syndrome. Because iron-laden macrophages often are not recognized on routine examination with hematoxylin and eosin staining, iron stains may be helpful in the evaluation of infant deaths. If siderophages are present in increased amounts without an obvious explanation, further investigation is warranted.     

Increase of pulmonary density of macrophages in sudden infant death syndrome

A 1996 cytodensitometric study found increased cellular density in the pulmonary parenchyma of infants who died of sudden infant death syndrome (SIDS). The present study clarifies these results in quantifying the density of immunohistochemical subtyped inflammatory cells. Histomorphometry was used to compare the density of macrophages, granulocytes and T and B lymphocytes in the lungs of two groups of infants. From the post-mortem records of infant deaths between 1983 and 1995, 29 (mean age = 5 months) were randomly selected including 16 cases of SIDS and 13 who died of other non-pulmonary causes. Densities of immunoreactive cells were measured under blind conditions in the parenchyma. The mean density of macrophages was significantly higher in cases of SIDS compared with the controls (P = 0.0318), but there were no differences for the lymphocytes and the granulocytes. These morphometrical results must be interpreted within the methodological limits of this study, especially the non-uniform level of lung inflation between selected subjects. However, the differences in level of inflation are not sufficient to explain the observed increase of macrophage density. Indeed, the mean values of alveolar surface area, which represent an indirect measure of lung inflation, are not significantly different between the two groups. Increase of pulmonary macrophage density in SIDS agrees with three non-exclusive hypotheses: (1) an abnormal inflammatory reaction by expression of Th1 helper cell phenotype activation; (2) consequence of passive smoking; and (3) post-agonal mechanisms. Bacterial superantigens produced by toxigenic bacteria in the respiratory tract could play a role as a trigger factor that initiates a fatal cascade with overproduction of cytokines leading to death. The significant increase of pulmonary macrophage density would be the morphological expression of this potential mechanism of death.     

Oronasal blood in sudden infant death.

Oronasal secretions are observed frequently in sudden infant death syndrome (SIDS), but overt blood is uncommonly reported. The literature on oronasal blood in sudden infant death is limited. The goal of this study was to determine the frequency of oronasal blood in sudden infant deaths and to examine possible causative factors. Oronasal blood was described in 28 (7%) of 406 cases of sudden infant death. Oronasal blood could not be attributed to cardiopulmonary resuscitation in 14 cases, including 10 (3%) of 300 cases of SIDS, 2 (14%) of 14 accidental suffocation cases, and 2 (15%) of 13 undetermined cases. Eight of the 10 infants in cases of sudden infant death were bedsharing: 5 with both parents, 2 between both parents. The infant in 1 SIDS case was from a family that had had three referrals to Child Protective Services. Oronasal blood not attributable to cardiopulmonary resuscitation occurs rarely in SIDS when the infant is sleeping supine in a safe environment. Bedsharing may place infants at risk of suffocation from overlaying. Oronasal blood observed before cardiopulmonary resuscitation is given is probably of oronasal skin or mucous membrane origin and may be a sign of accidental or inflicted suffocation. Sanguineous secretions that are mucoid or frothy are likely of remote origin, such as lung alveoli. The use of an otoscope to establish the origin of oronasal blood in cases of sudden infant death is recommended.     

Variable Presentations of Lethal Colloid Cysts

Four cases of colloid cysts that led to death are reported to demonstrate their nonspecific and protean presentations at autopsy: a 27‐year‐old man with severe occipital headache, blurred vision, drowsiness and vomiting; a 44‐year‐old man with recent memory disturbance; a 54‐year‐old man with head and neck pains, tiredness, urinary incontinence, confusion, and drowsiness; and a 66‐year‐old man with severe frontal headache, gait disturbance, vomiting, and syncope with a previous episode of confusion and disorientation. Each death was due to an occult colloid cyst obstructing the foramen of Monro causing acute hydrocephalus. Nonspecific manifestations may mean that the diagnosis of colloid cyst is only made at the time of autopsy. The possibility of rare cases being familial may necessitate medical review of family members. Forensic evaluation should identify how a colloid cyst was related to the mechanism of death and whether there are any features that were associated with precipitate decline.     

Toxicology and sudden infant death

One hundred thirty cases of sudden infant death occurring in Wayne County, Michigan, (population 2.7 million) were analyzed for possible drugs. The toxicological protocol has been outlined. Six cases were found to be positive, and in five of these the drugs found had been prescribed for a variety of illnesses. In one case methadone was found in the blood of an infant whose mother was undergoing methadone treatment for drug addiction, the drug being transmitted through breast milk. In none of the 102 cases of sudden infant death syndrome (SIDS) included in the study did the toxicological results affect the diagnosis. In our study, toxicological analyses never contradicted an initial diagnosis of SIDS, and, therefore, we feel that this diagnosis should be made promptly based on investigative and autopsy findings.     

6例甲状腺功能亢进性心脏病猝死法医学分析

目的分析甲状腺功能亢进性心脏病(以下简称甲亢性心脏病)猝死案例,探讨其死亡的一般情况及法医病理学特点,为此类案件的法医病理学鉴定提供参考。方法收集中国医科大学法医学院2001—2016年6例甲亢性心脏病猝死案例,回顾性分析基本信息(性别与年龄)、临床表现、病史、解剖所见和组织病理学所见、生物化学检测指标、死亡原因。结果 6例案例多具有明确的甲状腺功能亢进病史,并表现出不同程度的心血管病症状;均具有明显的死亡诱因;甲状腺病理学检验符合弥漫性毒性甲状腺肿的表现;心脏质量均增加,心腔扩张,心肌肥大,灶状坏死;死后心包液的生物化学检测可作为甲亢性心脏病猝死的辅助手段。结论对甲亢性心脏病猝死案例进行诊断时应参考临床病史、尸体检验、组织病理学检验、死后毒(药)物检验等结果综合判定,必要时进行死后甲状腺和心功能的生物化学检测。     

Death of an infant involving benzocaine

This report describes the death of a four-month-old Hispanic male which may be related to benzocaine toxicity. A toxicological evaluation revealed benzocaine at a concentration of 3.48 mg/L, and postmortem methemoglobin of 36% (normal 0.4-1.5). Methemoglobinemia is a complication of benzocaine toxicity. In light of the toxicology findings, the coroner investigated the source of the benzocaine and discovered that the child was treated with Zenith Goldline Allergen Ear Drops containing 0.25% w/v benzocaine and 5.4% w/v antipyrine. There was an admission by a caregiver that on the day prior to the child's death, he had been treated with three times the prescribed dose. Blood benzocaine concentrations in nine other unrelated cases were determined and concentrations ranged from <0.05-5.3 mg/L (mean 1.48 mg/L). Seven of the nine cases were positive for drugs of abuse, and one additional case was described as a known drug user. Methemoglobin in these benzocaine positive cases ranged from 6-69%; however, methemoglobin concentrations in postmortem cases are frequently elevated and should be interpreted with caution. The unknown significance of the benzocaine, and the circumstances of the case raise questions about the ultimate attribution of this death to SIDS.     

Organ weight in 684 adult autopsies: new tables for a Caucasoid population

The weights of normal organs were retrospectively culled for the years 1987-1991 from 684 forensic autopsy cases. All the subjects were Caucasoid adults who died of external causes and showed no pathological changes. The weights of the following organs were available: the heart, the right and the left lung, the liver, the spleen, the pancreas, the right and the left kidney and the thyroid gland. The external parameters used for statistical correlation were the age, the height, the body weight and the body mass index (BMI) of the deceased. The weight of all the organs was shown to correlate with at least one external parameter, with the exception of thyroids in females. Organ weights decreased with age except for the heart and the thyroid, and increased in relation to body height and/or BMI. Except for the heart, the organ weight showed a better statistical correlation with the body height than the BMI. These updated tables of organ weight were compared with the data collected in previous studies. Such tables have to be regularly updated by pathologists in order to keep organ weight as a good criterion to be used in post-mortem diagnosis.     

Histologic findings in the lung in sudden infant death

The lungs of 79 children who had died between the ages of 1 week and 2 years old were histologically examined. 59 of these children could be categorized as cases of Sudden Infant Death because of the history and postmortem findings. In the remaining 20 cases a definite cause of death could be established. This is the same collective on which the histological investigations of the lymphatic tissue has been carried out. Morphological changes which are typical for a virus pneumonia were found in a substantially higher frequency in the cases of Sudden Infant Death than in the control cases. The validity of these findings and their possible significance for the cause of death are discussed.     

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.     

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.     

Forensic medicine aspects of fatal coronary insufficiency with normal coronary arteries

Clinical experiences give examples for the existence of various courses of anginal symptomatology even with cases of sudden heart death demonstrating angiographically normal coronary arteries. Pathogenetically may be considered spasms of regular or little changed coronary arteries, coronary muscle bridges and acute arrhythmias. In cases of recurrent myocardial ischemias an interstitial fibrosis and endocardial fibrosis can be proved histologically in the myocardial supply area. However an acute coronary insufficiency based on rheological and metabolic etiology cannot be found with morphological methods. The results are discussed, considering forensic aspects in cases of competitive causes of death.     

超生反应阶段人骨骼肌对电刺激反应的形态学研究

利用人骨骼肌在死亡早期阶段能对电刺激产生兴奋和收缩的特点，以加大刺激强度为手段，对18例死亡早期阶段（1小时25分至6小时40分）具有超生反应能力的尸检骨骼肌和17例稍晚阶段（10～60小时）不具有超生反应能力的尸检骨骼肌，进行了电刺激损伤的系列形态学对比研究。结果表明，死亡早期阶段的肢体骨骼肌，经电刺激后，能产生整个肌肉或局部肌肉的收缩；在电极周围以及电路中的肌纤维形成大片的极具特点的收缩带、条带状嗜酸性变、高度变形的节段状和盘片状崩解等改变；稍晚期阶段受刺激的肌纤维则未见上述改变。探讨形态学改变的形成机理及意义，为研究死亡早期阶段的电损伤提供形态学基础。     

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.