青壮年猝死综合征心肌细胞内纤维连接蛋白免疫组化观察初探

本文应用免疫组化ＬＳＡＢ法首次对５例青壮年碎死综合征和１１例非心性死亡对照组进行心肌细胞内纤维连接蛋白的研究。发现青壮年猝死综合征５例中有３例心肌细胞内纤维连接蛋白阳性。１１例非心性死、对照组心肌细胞内纤维连接蛋白均呈阴性。说明上述３例青壮年猝死综合征的心肌细胞已发生不可逆损伤，实属早期心肌梗死。该研究为青壮年猝死综合征的死因研究提供了一个新的方向和手段。     

PKC在青壮年猝死综合征心肌组织中的变化

目的探讨蛋白激酶C（PKC）与青壮年猝死综合征之间的关系。方法取30例青壮年猝死综合征、20例正常对照心脏标本的左右心室肌、窦房结、房室结组织,通过免疫组化学染色,应用图像分析软件对PKC分布及强度变化进行定量检测分析,并进行统计学处理。结果青壮年猝死者心肌细胞PKC平均灰度值及面积代数和显著高于正常对照组（P〈0.05）;其中青壮年猝死者窦房结中的PKC平均灰度值大于房室结（P〈0.05）。结论PKC作为体液调节的途径之一,参与青壮年猝死发病过程,并起到保护性作用。PKC可以作为诊断青壮年猝死的一项参考指标。     

离子通道病所致的心源性猝死与死后基因检测技术

心脏疾病引起的猝死占人类各类疾病所致猝死的首位.多数心源性猝死案例通过尸体解剖、病理组织学检验可以明确死因为心源性疾病,但尚有少数案例虽经过详细检验并高度怀疑为心源性猝死,但仍不能明确检测到可说明死因的心脏疾病.随着现代分子生物学技术的进步,发现此类猝死者中相当一部分属于先天性心肌细胞离子通道疾病所致,主要包括Brugada综合征、长QT综合征、儿茶酚胺敏感性多形性室性心动过速、短QT综合征等.本文对此类疾病的分子遗传学、心电图所见、临床表现和猝死机制以及死后基因检测技术在死因鉴定中的作用进行了详细的阐述,以期为法医学实践中先天性心肌细胞离子通道疾病所致猝死原因的鉴定提供指导.     

青壮年猝死综合征的研究现状

青壮年猝死综合征（SMDS）是法医学研究的难点之一，其猝死机制尚未阐明。本文从SMDS的流行病学、心脏组织免疫学、心脏电生理、基因学等方面的研究进行综述，以期望为进一步研究获得启示。     

HSP70在青壮年猝死综合征心肌组织中的变化

目的探讨热休克蛋白70（HSP70）在青壮年猝死综合征形成机制中的作用,及其早期诊断作用。方法取30例青壮年猝死、20例正常对照心脏标本的左右心室肌、窦房结、房室结组织,通过免疫组化学染色,应用图像分析软件对HSP70分布及强度变化进行定量检测分析,并进行统计学处理。结果青壮年猝死者心肌传导系统内HSP70表达高于正常对照组,且具有统计学意义（P〈0.05）。其中青壮年猝死者右心室肌HSP70的表达显著低于其他部位心肌组织（P〈0.05）。结论HSP70作为一种应激反应的介质参与青壮年猝死综合征的发生过程,并对心脏起到保护性作用。HSP70可作为青壮年猝死综合征诊断的参考指标。     

浅析青壮年猝死综合征的法医学鉴定

正青壮年猝死综合征是指青壮年男性原因不明的突然死亡,在法医实践中并不罕见,但其发生原因及死亡机制尚无统一的认识。近年来,我国也有多例这类死亡的报道。笔者根据自己的法医学经验,参考一些法医学资料,对青壮年猝死综合证发生的原因、病理特点、发病的临床表现以及法医学鉴定时应注意的事项分析如下,以供同道参考。     

南粤地区青壮年猝死综合征的流行病学调查

<正> 青壮年猝死综合征(sudden manhood death syn—drome,SMDS)[1,2]是一类迄今死因不明、主要累及青壮年男性的猝死综合征。为探究其发病的危险因素、猝死机制和公益性防治策略,本文作者在对东莞地区外来工的SMDS的流行病学特征进行初步调查的基础上[3],进一步对南粤地区SMDS的流行病学因子进行调查,现将结果报道如下。     

26例心脏传导系统发育异常猝死的病理学分析

目的研究心脏传导系统发育异常致猝死的病理变化。方法排除外伤、中毒及疾病所致死亡,收集26例不明原因猝死者心脏,采用作者创建的心脏传导系统取材法,常规切片、HE染色和Masson三色染色,光镜观察。结果 26例中见心传导系统有发育不全、结构异常、细胞或组织结构移位和窦房结纤维垫等病变,9例同时具有2~3种类型。16~30岁共21例,占全部样本的80.8%。结论心脏传导系统发育异常可能是不明原因青壮年猝死的重要原因之一。     

青壮年猝死综合征研究现状

青壮年猝死综合征(SMDS)一直是国内外医学界尤其是法医学领域研究的热点,近来对SMDS的发病特点及致病机制等都有广泛而深入的研究,但仍有部分关键问题尚未解决。本文通过文献复习并结合法医检案,分别从分子遗传学、免疫组织化学、冠状动脉结构或功能异常、自主神经调节作用等方面介绍SMDS的研究进展。     

东莞地区外来工青壮年猝死综合征的流行病学研究

目的研究东莞地区青壮年猝死综合征(SMDS)的流行病学特征。方法对东莞市公安局1990～2001年的法医学检案中遴选的284例SMDS案例资料进行回顾性研究。结果分析SMDS猝死者的籍贯、年龄、性别、死亡季节的分布及死亡经过、尸检所见的特征。结论此项研究为下一步进行SMDS的流行病学研究积累了初步资料。     

Impact of Myocardial Infarction and Abnormalities of Cardiac Conduction System on Sudden Cardiac DeathCSCD

Sudden cardiac death (SCD), most commonly seen in coronary heart disease, is a kind of sudden death caused by series of cardiac parameters, which usually combines with myocardial infarction. However, some SCDs (including early myocardial infarction) happen suddenly and cause death in a very short time. In these circumstances, typical morphological changes are lack in macroscopic or microscopic fields, which make such SCDs become the emphasis and difficulty in the present research. SCD caused by myocardial infarction and abnormalities of cardiac conduction system (CCS) is related to atherosclerosis of coronary artery closely. This paper reviews cardiac dysfunction caused by myocardial infarction and diseases of CCS from morphology and molecular biology, and explores potential relationship between them. This paper aims to provide clues to the mechanism of myocardial infarction related sudden death and possible assistance for forensic diagnosis of SCD. © 2017 by the Editorial Department of Journal of Forensic Medicine.     

Is there progress in the autopsy diagnosis of sudden unexpected death in adults?

Sudden death is now currently described as natural unexpected death occurring within 1h of new symptoms. Most studies on the subject focused on cardiac causes of death because most of the cases are related to cardiovascular disease, especially coronary artery disease. The incidence of sudden death varies largely as a function of coronary heart disease prevalence and is underestimated. Although cardiac causes are the leading cause of sudden death, the exact incidence of the other causes is not well established because in some countries, many sudden deaths are not autopsied. Many risk factors of sudden cardiac death are identified: age, gender, heredity factors such as malignant mutations, left ventricular hypertrophy and left ventricle function impairment. The role of the police surgeon in the investigation of sudden death is very important. This investigation requires the interrogation of witnesses and of the family members of the deceased. The interrogation of physicians of the rescue team who attempted resuscitation is also useful. Recent symptoms before death and past medical history must be searched. Other sudden deaths in the family must be noted. The distinction between sudden death at rest and during effort is very important because some lethal arrhythmia are triggered by catecholamines during stressful activity. The type of drugs taken by the deceased may indicate a particular disease linked with sudden death. Sudden death in the young always requires systematic forensic autopsy performed by at least one forensic pathologist. According to recent autopsy studies, coronary artery disease is still the major cause of death in people aged more than 35 years. Cardiomyopathies are more frequently encountered in people aged less than 35 years. The most frequent cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The postmortem diagnosis of cardiomyopathies is very important because the family of the deceased will need counseling and the first-degree relatives may undergo a possible screening to prevent other sudden deaths. In each case of sudden death, one important duty of the forensic pathologist is to inform the family of all autopsy results within 1 month after the autopsy. Most of the recent progress in autopsy diagnosis of sudden unexpected death in the adults comes from molecular biology, especially in case of sudden death without significant morphological anomalies. Searching mutations linked with functional cardiac pathology such as long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now the best way in order to explain such sudden death. Moreover, new syndromes have been described by cardiologists, such as short-QT syndrome and revealed in some cases by a sudden death. Molecular biology is now needed when limits of morphological diagnosis have been reached.     

Congestion bleedings of the face and cardiopulmonary resuscitation--an attempt to evaluate their relationship

OBJECTIVES: Are any other factors besides the factor "cause of death" involved in the development of petechial hemorrhages (PET) of the head? The significance of the cause of death is well known, other factors have been rarely investigated in medical literature. Do they include cardiopulmonary resuscitation (CPR), as has been claimed in several forensic publications? MATERIALS AND METHODS: (a) 473 consecutive autopsy cases (without strangulation) evaluated by one examiner, which were appropriate for this investigation; (b) analysis of 181 cardiac deaths (investigated by all physicians of our institute). RESULTS: Petechiae were found in 13.3% of all cases and were clearly dependent on the cause of death, up to 20% were found in burn victims, intensive-care patients and cardiac fatalities. Petechiae were more frequently observed in the middle age groups (>20%) than in old persons (<10%). The number of PET cases increased with body mass but was lower in extremely obese persons, a greater number of cases with PET was also observed with increasing heart weight. PET were observed in 11% of the deaths without CPR compared to 19% with CPR. This difference was predominantly caused by the subgroup "acute coronary death", especially if victims younger than 60 years were considered, whereas in many other causes of death no difference in the prevalence of PET with or without CPR could be observed. CONCLUSION: Besides the cause of death, other factors (age, body mass and possibly even heart weight) influence the development of petechiae. The hypothesis that CPR alone produces PET is not confirmed by our experience.     

脑钠尿肽作为心功能评价指标在法医学上的应用价值

脑钠尿肽(brain natriuretic peptide,BNP)是临床上广泛应用反映心功能的主要指标,近来研究表明,脑钠尿肽对法医病理学心功能障碍导致的心源性猝死的认定也有帮助.本文就脑钠尿肽的结构、分子生物学特征以及在临床和实验研究中的进展加以综述,探讨其作为功能学指标在法医学方面的应用价值,认为运用免疫组织化...     

Diagnostic value of post-mortem examination of the cardiac conduction system

Introduction (Aim)

Sudden unexplained death (SUD) is a common problem in forensic pathology. In many of these cases, the autopsy findings, toxicological examinations and patient history are inconclusive. Many studies suggest that in such cases, the cardiac conduction system (CCS) should be histologically examined. We decided to determine the diagnostic value of histological examination of the CCS.

Methods

We reviewed autopsy files from the period 2005–2007 and selected those cases in which the CCS had been sampled. These were divided into two groups, the first comprising cases with an obvious cardiac pathology (e.g. severe coronary disease, myocardial infarction, significant myocardial hypertrophy/dilatation, valvular disease, etc.) and the second comprising cases without obvious cardiac pathology (i.e. fatal injuries, intoxications and deaths unexplainable by routine procedures). The CCS was sampled according to a detailed protocol and examined under a light microscope. On the basis of the findings of histological examination of CCS, we formed subgroups of the aforementioned main groups.

Results

We analyzed 118 cases, of which 83 were males and 35 females. In 57% of cases, autopsy revealed gross pathological abnormalities of the heart. In 10 (15%) of them, examination of the CCS showed significant pathological changes (narrowing of the nodal artery and its branches, moderate to severe interstitial fibrosis, calcifications in the central fibrous body impinging upon CCS). In some, especially those with no acute findings, CCS disease can be considered to have been the cause of fatal arrhythmias. In 43% of cases, autopsy revealed no gross abnormalities of the heart, while histological examination of the CCS disclosed significant pathological changes in 4 (8%). Among them, CCS disease was regarded as the cause of death in one case and as a possible cause in another case.

Conclusion

As with other similar studies, our study showed that examination of the CCS can provide valuable information on the cause of death. We therefore consider that examination of the CCS should be performed in all SUD cases, especially those in which the cause of death cannot be established by routine procedures. Although we had only 1 confirmed cause of death linked to CCS disease and one possible, we had 14 cases with significant pathological CCS changes. This leads us to the conclusion that post-mortem examination of the CCS is of diagnostic value.     

Iatrogenic deaths following treatment for hypertrophic obstructive cardiomyopathy: case reports and an approach to the autopsy and death certification

Hypertrophic cardiomyopathy (HCM) is a disease process which results in a large, heavy heart, with hypertrophy of the interventricular septum (IVS) and left ventricle. HCM accounts for a significant number of cases of sudden cardiac death each year, most infamously in young athletes. The prevalence of the disease has increased over the past several years due to advances in clinical diagnosis and molecular genetic studies. Over this same period, new forms of treatment also have emerged. One such treatment is alcohol septal ablation (ASA). ASA is a procedure performed by a cardiologist, via cardiac catheterization, by injecting pure ethanol into selected arteries which supply the IVS, resulting in a targeted myocardial infarction. This infarct then retracts and forms a scar, decreasing the outflow obstruction and improving the patient's clinical symptoms.The authors report 2 cases of death following ASA treatment of HCM. The first, a 56-year-old male, had his ASA procedure 10 days prior to death. The second decedent, a 76-year-old female, had her procedure only 30 hours before death. These case reports are followed by a discussion about HCM, including pathology, treatments, and treatment-related pathology, before closing with a discussion about death certification in the cases presented and therapy-related deaths in general.     

Investigation of cardiac troponins in postmortem subjects: comparing antemortem and postmortem levels

The limitations of autopsy in the diagnosis of death due to ischemic heart disease are well known. In the living, a simple reliable biochemical assay for cardiac troponins is used in the diagnosis of acute myocardial ischemia. Several studies have investigated the use of biochemical assays for cardiac troponins in postmortem subjects as a means to distinguish between a cardiac and anoncardiac cause of death. All of these studies, however, rely upon assigning subjects to "cardiac" or "noncardiac" death on the basis of a postmortem examination. As postmortem examination does not always accurately distinguish between these two groups, this approach is intrinsically flawed.Our study compares antemortem and postmortem cardiac troponin levels in five subjects. The antemortem samples were retrieved from the hospital biochemistry laboratory after each subject's death. The postmortem samples for each subject were taken from different sites and at different times during the early postmortem period.Erratic results bearing little or no relation to the antemortem cardiac troponin level were obtained for all subjects. Four of the five subjects had raised antemortem troponin levels, although only one had a cardiac cause of death.From this, we conclude that postmortem blood is not a suitable substrate for standard biochemical assays of cardiac troponins, which are designed for use on serum taken from living patients. In addition, the results of our study support the view that elevated cardiac troponins are a marker of serious morbidity and are not specific for cardiac injury as the primary cause of morbidity or mortality.     

Sarcomeric gene mutations in sudden infant death syndrome (SIDS)

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(?) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype.     

遗传性心律失常猝死的分子解剖研究现状及展望

遗传性心律失常所致猝死的死因鉴定是法医病理学领域亟待解决的难题之一。近年来心律失常易感基因/突变的发现和高通量组学技术的推广,使得利用分子遗传学方法筛查猝死的遗传学病因（即＂分子解剖＂）成为可能。本文通过汇总心律失常分子遗传研究的进展,综述传统遗传分析和近期全基因组关联性研究（GWAS）筛查的结果,为心源性猝死的＂分子解剖＂研究提供候选基因列表;并进一步比较针对不明原因猝死所开展的回顾性＂分子解剖＂筛查的结果,探讨新技术在该领域的应用前景。这一综述有助于更好的认识心律失常所致猝死的分子机制,并为借助新一代遗传分析技术进行分子解剖提供有益参考。     

Spinal epidural haematoma after blunt trauma to the neck and hyperflection of the cervical spine

Spinal epidural haematomas (sEDH) can be regarded as rare events, in principle a spontaneous and a traumatic aetiology can be distinguished. Spontaneous spinal epidural haematomas can arise, e.g. from vascular malformations, coagulopathies, etc. On the other hand, traumatic sEDH are related to, e.g. spinal trauma or intraoperative vascular injuries. With regard to clinical significance, spinal epidural haematomas accompanied by transient mild neurological symptoms up to lethal outcomes have been observed. We report on a 53-year-old male alcoholic who was found in the kitchen of his asylum in a grotesquely fixed body position, with his head and cervical spine in a maximum anteflected position. A general practitioner had ruled for a non-natural manner of death due to "broken neck" and alcohol intoxication, therefore, the prosecution authorities called for a medicolegal autopsy. At autopsy, paravertebral soft tissue haemorrhage in between the shoulder blades was disclosed. Furthermore, a spinal epidural haematoma, extending from the foramen magnum down to the middle portion of the thoracic spine was found. No fractures of vertebrae nor lesions of spine ligaments or bleedings of intervertebral discs were found. Blood alcohol concentration was determined 1.92 g/l and urine alcohol concentration was 1.76 g/l. Further morphological findings were cerebral oedema and cardiac hypertrophy; the urinary bladder was found filled to bursting. Neuropathological investigations confirmed the presence of the spinal epidural haematoma and assigned lethal significance to this finding. There were no histological signs of axonal injury. Reconstruction revealed that when sitting on a chair in a drunk condition, the individual's upper part of the body had fallen backwards in the corner and subsequently got stuck with maximum anteflection of the head and cervical spine, causing rupture of vessels and spinal epidural haematoma. Acute respiratory failure caused by impairment of the phrenic nerve following spinal epidural haematoma with potential synergism of alcohol intoxication was ascertained as the cause of death.