Blood and liver monoamine oxidases in fatal alcoholic intoxication]

Biochemical studies of monoamine oxygenases (MAO) were studied in albino rats and in subjects dead from ethanol poisoning, alcoholic cardiomyopathy, and coronary heart disease. Experiments demonstrated that chronic alcoholization leads to increase in the levels of both types of MAO (A and B), the longer the alcoholization, the more pronounced the increase. Intake of high ethanol doses in the course of regular alcohol abuse involves a drop in MAO activity (by 1.9-2-2 times). Study of MAO helps detect chronic alcoholization and differentiate it from coronary heart disease and alcoholic cardiomyopathy and thus make an objective conclusion about the cause of death and thanatogenesis.     

118例心源性猝死分析

心源性猝死(sudden cardiac death,SCD)在成人猝死的死因中占首位,本文对1998-2005年陕西地区发生的118例SCD案例进行统计分析,结果显示男性是女性的5.9倍,其中冠心病占55.1%,心肌炎占17.8%,心肌病占9.3%,先天性心脏病、瓣膜病、主动脉夹层瘤破裂各占2.5%,其他疾病占4.5%。说明SCD多发于男性,冠心病仍是SCD的主要基础疾病,心肌炎是青少年SCD的主要原因,心肌病是青壮年SCD的危险因素,无结构异常的心脏病也同样严重威胁生命健康。     

178例心源性猝死法医组织病理学诊断分析

目的探讨心源性猝死(SCD)的病理特点与鉴别要点。方法对四川华西法医学鉴定中心2000—2005年尸检出的178例SCD死亡案例进行回顾性分析,主要对其病因、年龄、诱因及病理改变进行分析。结果本组资料显示冠心病、心传导系统病变、心肌炎、心肌病等在SCD中占有较大比例。冠心病猝死是中老年人SCD的最主要原因,青壮年人SCD的病因以非冠心病为主。如传导系统病变、心肌炎、心肌病。在儿童的SCD中先天性心脏病、传导系统病变及心肌炎占主导地位。结论不同的病因,其病理特点不同,其病理变化是法医学鉴定的主要依据。     

The importance of biochemical studies for practical forensic-medical expert examination

Sudden death along with differential diagnosis of deaths from coronary heart disease and alcoholic cardiomyopathy is a challenging problem in practical forensic medicine. Relevant investigations demonstrated the possibility to address it using a battery of biochemical methods, such as measurement of blood glucose level in heart cavities, lactate dehydrogenase activity in myocardium, etc.     

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.     

Stressful events as a trigger of sudden death: a study of 43 medico-legal autopsy cases

The reports relating emotional stress to sudden death are largely anecdotal. In addition to experimental and electrophysiological studies, an opportunity for a better understanding of possible stress-related sudden death (SSD) may be provided by medico-legal autopsies. The goal of our autopsy study was to analyze cardiovascular pathologic findings in cases of SSD and if possible identify mechanisms by which the stressful event (SE) could be the cause. Forty three cases were studied (29 males and 14 females). In all cases, the SE and the death were witnessed. The age range was 22 to 90 years in males (mean, 52) and 30 to 92 years in females (mean, 64). Death occurred in all cases without premonitory symptoms. In 20 cases, death occurred during the SE and in the other 23 cases occurred within 2 h of the event. SE included fear, 15 cases; altercation, 21 cases; sexual activity, 3 cases; police questioning or arrest, 4 cases. According to police reports, in 40 cases (90%), the victims had no previous clinical history of cardiovascular disease. At autopsy, the heart weight in males ranged from 255 to 1000 g with a mean of 517 g and in females the range was 250–700 g with a mean of 417 g. In only 3 cases, gross and microscopic examination of the heart was normal. In 2 of the remaining 40 cases the subjects died of subarachnoid hemorrhage. In 38 cases, a cardiac cause of death was found as follows: coronary heart disease, 27 cases; cardiomyopathy, 6 cases; aortic valvular stenosis, 2 cases and right ventricular dysplasia, 3 cases. A coronary artery thrombosis was found in 8 cases of sudden coronary death. Post myocardial infarction fibrosis was present in 25 cases (92%) of sudden coronary death. In conclusion, it appears from our autopsy study that SSD occurs primarily in those individuals with severe heart disease, especially coronary heart disease.     

Relationship of ischemic heart disease to sudden death

A clinicopathological synthesis is presented of the relationship of ischemic heart disease to sudden cardiac death. The immediate pathophysiological process responsible for sudden cardiac death is a lethal arrhythmia, usually ventricular fibrillation. Although significant coronary atherosclerosis is present in most cases of naturally occurring sudden death, available evidence indicates that several mechanisms can be operative in the pathogenesis of the fatal event. These are (1) acute myocardial infarction in a minority of cases; (2) myocardial ischemia, without infarction, which is initiated either by (a) an exertion-induced increase in myocardial oxygen demand or (b) an acute coronary event often involving plaque degeneration and platelet aggregation; and (3) a primary arrhythmia, usually resulting from altered electrical conduction in the setting of a previous myocardial infarction.     

过敏性和冠心病猝死者心肌组织中肥大细胞类胰蛋白酶、脑利钠肽的表达

目的探讨肥大细胞类胰蛋白酶、脑利钠肽(brain natriuretic peptide,BNP)在过敏性猝死和冠心病猝死鉴别诊断中的意义。方法选取山西医科大学法医病理学教研室2010—2015年尸检案例心肌标本共30例,分为颅脑损伤致死组、过敏性猝死组、冠心病猝死组,每组各10例。采用免疫荧光染色和Western印迹法分析各组心肌组织肥大细胞类胰蛋白酶和BNP的表达。结果过敏性猝死组、冠心病猝死组心肌组织内肥大细胞类胰蛋白酶免疫荧光染色均出现阳性染色;三组间两两比较,表达差异均具有统计学意义(P0.05)。冠心病猝死组心肌组织内BNP的表达量高于过敏性猝死组、颅脑损伤致死组(P0.05),过敏性猝死组与颅脑损伤致死组之间差异无统计学意义(P0.05)。结论联合检测心肌组织内肥大细胞类胰蛋白酶、BNP有望为过敏性猝死和冠心病猝死的法医学鉴别诊断提供帮助。     

病毒性心肌炎和扩张性心肌病中Dystrophin蛋白的表达

目的探讨病毒性心肌炎和扩张性心肌病的发病机制及相互关系,从而提高心性猝死法医学鉴定的可靠性和准确性。方法对17例对照(包括正常心脏、冠心病、高血压性心脏病等),25例病毒性心肌炎和28例扩张性心肌病的心肌组织进行改良的病理学dystrophin免疫组织化学研究。结果dystrophin蛋白在对照组,病毒性心肌炎组和扩张性心肌病组中阳性表达率分别为100%,88%,57%,三组表达差异有显著性(P<0.05),且在病毒性心肌炎和扩张性心肌病组间表达有显著差异(P<0.05),经Spearman等级相关分析呈显著负相关(r=-0.526)。结论病毒性心肌炎和扩张性心肌病心肌中细胞骨架蛋白均有破坏,且随着由病毒性心肌炎进展为扩张性心肌病,dystrophin蛋白表达逐渐降低,说明在病毒性心肌炎和扩张性心肌病的发病机制中可能与dystrophin的被破坏有关,病毒感染并破坏心肌细胞骨架蛋白并最终导致心肌细胞坏死,心功能受损,从而使病毒性心肌炎进展为扩张性心肌病。     

Diagnostic role of organ-specific isoforms of lactate dehydrogenase in blood plasma

Changes in plasm isoenzymic spectrum of lactate dehydrogenase (LDG), a glycolytic enzyme, were studied in death of cardiovascular diseases, ethanol poisoning and a mechanical injury. The tests used electrophoresis in 1% solution of agarose. Isoenzymic composition differed between the groups with acute coronary failure, chronic coronary heart disease, alcohol cardiomyopathy and a mechanical injury. Ethanol poisoning caused two types of characteristic shifts in LDG isoenzymic spectrum. Nomograms were designed for practical application in forensic medical expertise of sudden death.     

Diagnostic role of acute microscopic changes in myocardium

Forensic medical diagnosis of death from coronary heart disease, acute ethanol poisoning, alcoholic cardiomyopathy, closed cardiac injuries, mechanical injuries incompatible with life which may be directly caused by acute cardiac failure, requires identification and evaluation of diagnostic complexes of acute myocardial changes. The diagnostic significance of such complexes of myocardial changes is characterized for the first time. A method for evaluation of such changes, addressed to expert histologists, is presented.     

Poor results in attempting to demonstrate the cause of death by examination of the conduction system of the heart in cases of sudden death

A microscopic examination of the proximal part of the conduction system in the heart was undertaken in seven cases of sudden death due to coronary arteriosclerosis; the same technique was applied to 31 control cases. A few infiltrations of mononuclear cells were demonstrated in relation to the conduction system in cases of sudden death as well as in controls. In one case severe narrowing of the sinus node artery was found without particular arteriosclerosis of the coronary arteries.     

青壮年猝死综合征心传导系统及心肌HHF35免疫组化研究

为了探讨青壮年猝死综合征（SMDS）的死亡原因与心性猝死之间的关系，作者对SMDS、冠心病、非心血管疾病死亡（正常对照）三组共23例心脏标本进行H．E和HHF35免疫组化观察．结果：9例SMDS中，8例心传导系统及心肌细胞出现小灶性HHF35阴性缺染区，而H．E染色未发现明显梗死灶；冠心病组7例均出现不同程度的心肌细胞缺染，呈广泛大面积分布；对照组心肌细胞、心传导系统及血管壁里均匀一致的阳性染色．表明部分SMDS死前已有早期心肌缺血或梗死等病变，其死亡原因应为急性心功能不全而致猝死．     

缝隙连接、连接蛋白与冠心病猝死

缝隙连接(gapjunction,GJ)构成细胞之间的跨膜水相通道,协调细胞间化学及电信息的交流。心脏上缝隙连接的主要功能是为心肌细胞间的电冲动提供低压传导通路,并维持心肌的协调运动。近年来的研究显示,心肌细胞(特别是心室肌工作细胞)上构成缝隙连接的连接蛋白含量、分布及功能的异常与各种心律失常的产生和持续关系密切。这很可能为临床及法医实践中,诊断冠心病猝死心肌早期病变提供一个新的思路。     

Asymmetric septal hypertrophy of the heart. New findings concerning the possible etiology of sudden deaths in five males

This report describes certain interesting postmortem findings in the hearts of five subjects who died suddenly, silently, and unexpectedly, and in whom the only significant abnormality at autopsy was asymmetric septal hypertrophy (ASH) of the heart. Deep clefts, cystic faults, and dilated vascular channels were not only seen within the septal myocardium in all the hearts, but also within the left ventricular free walls of two hearts. The septal myocardium and the left ventricular free walls of two hearts and the A-V node and His bundle of one heart demonstrated mural and luminal thrombi of several dilated vascular channels. In another heart, foci of cardiocytic myofibrillar degeneration were seen, especially close to narrowed small coronary vessels. Fetal dispersion and fibrosis of the A-V node and His bundle were evident in one heart. These abnormalities in the conducting system and the ventricular myocardium suggest that the hearts of subjects with ASH are not only excellent anatomic substrates for lethal arrhythmias, but also are bound to be hemodynamically impaired. We believe that conditions such as hypoxia, increased oxygen demand by the heart or abnormal sympathetic stimulus may easily trigger fatal arrhythmias in such individuals, thereby causing sudden death.     

A case of sudden death from primary intracranial germinoma complicated by microvascular disease of the heart

A coroner's autopsy conducted on an 11.5-year-old girl, with a history of hypopituitarism, manifesting as growth hormone deficiency associated with short stature, demonstrated the presence of an undiagnosed hypothalamic intracranial germinoma, showing hypophyseal and mesencephalic invasion, together with histological evidence of microvascular (small coronary artery) disease of the heart. The substantive, or primary, cause of her sudden death was clearly the intracranial germinoma, which was acutely haemorrhagic and necrotic. However, it is postulated that there might be an, as yet, undescribed association between this malignancy and the pathogenesis of the coronary microvascular disease; the latter being deemed, in this instance, to be a contributory cause of death.     

Sudden unexpected death due to familial hypertrophic obstructive cardiomyopathy

Hypertrophic cardiomyopathy is a familial condition with a very distinct risk of sudden death in males in certain families. The disease appears to be not uncommon in Sri Lanka. A sudden death in a 26-year-old healthy man is reported: At autopsy the heart was 500 g due mainly to left ventricular hypertrophy, and showed histological changes consistent with cardiomyopathy. Symptomless family members of the deceased were subsequently referred to a cardiologist. Cardiomyopathy was diagnosed in one of them.     

Metastatic calcification of the cardiac conduction system with heart block: an under-reported entity in chronic renal failure patients

Systemic metastatic calcification is a common complication of chronic renal failure. Cardiac involvement is particularly ominous, especially when the cardiac conduction system is affected. Conduction defects, arrhythmias, and sudden death have all been reported with conduction system calcification; however, these are relatively under-reported or unrecognized causes of cardiac morbidity and mortality. We describe a 40-year-old man with Von Hippel-Lindau disease who had been maintained on hemodialysis for two years following bilateral nephrectomies for renal cell carcinoma. The patient presented with symptomatic complete heart block that had progressed from Mobitz type I atrioventricular block. Two months later, while being internally paced, the patient died unexpectedly after a complicated hospital admission. Postmortem revealed extensive vascular, myocardial, and conduction system calcification. Conduction system calcification may cause sudden death in chronic renal failure patients during hospital admission, or unexpectedly while the patient is in the community. Knowledge of this condition is necessary to detect it, as the conduction system is not routinely examined. A routine abbreviated conduction system examination is warranted for patients with systemic metastatic calcification, especially if they have sudden death or a known history of heart block.     

Sudden death resulting from lesions of the cardiac conduction system

Sudden unexpected deaths in young persons with noncontributory histories, autopsy results, and drug screen results are a common problem in forensic pathology. As part of the evaluation of such cases, the cardiac conduction system (CCS) should be studied. To determine the type and incidence of lethal CCS lesions, the authors reviewed their files of sudden unexpected cardiac deaths with particular attention to cases with causes of death in the conduction system. Cases of sudden cardiac death in patients aged < or=40 years during a 10-year period (Michigan) and a 4 year-period (Spain) were selected from the files. From this group, cases were identified in which the cause of death was a lethal change in the CCS. The portions of the heart containing the CCS were excised, and at least one hematoxylin and eosin slide and at least one trichrome or elastic trichrome slide per block were studied. In the two centers, 381 cases of sudden cardiac death were identified. The most common causes of sudden cardiac death were arteriosclerotic narrowing of the coronary arteries, cardiomyopathy, and myocarditis. In 82 cases, there was no identifiable cause of death even after complete gross and microscopic autopsy was performed, a medical history was obtained, and a drug screen was performed. In 11 cases, the CCS contained lesions that were considered lethal: narrowing of the atrioventricular node artery by fibromuscular hyperplasia (7 cases) and atrioventricular node tumors (4 cases). The 11 cases accounted for 2.9% of the 381 cases of sudden cardiac death and 11.8% of the indeterminable cases. It was concluded that examination of the CCS in deaths in which the gross and microscopic autopsy, history, and drug screen fail to provide a cause of death can yield a cause of death in a significant percentage of cases. If heart block was not documented during life and no explanatory lesions were found during routine cardiac examination, examination of the CCS can yield valuable information.