Death following administration of 1,250 mg chloroquine in porphyria cutanea tarda

The death of a 23-year-old female patient is reported. She was being treated for porphyria cutanea tarda (p.c.t.) and was mistakenly given a single dose of 1250 mg chloroquine (instead of the intended dose of 125 mg). The course differed from the typical course of chloroquine toxification, which involves cardiac arrhythmias as the main complication (reported in adults only after much higher doses); in spite of intensive care, this patient died 13 days after the ingestion of chloroquine, in a coma caused by irreversible, acute decompensation of the liver. Forensic autopsy and histological and toxicological investigations confirmed the clinical findings. Starting from the chloroquine's pharmacological mechanism of effect in p.c.t., the severe hepatotoxic effect of this drug in the present case is explained. The authors give a serious warning against exceeding the dose of chloroquine now usually recommended for the treatment of the p.c.t., which is 125-250 mg twice weekly. The presence of chronic porphyria hepatica, at least in its clinically manifest form, (= p.c.t.), should be considered a contraindication for chloroquine in prophylaxis and treatment of other illnesses (e.g. malaria and rheumatism).     

氯喹类药物在新型冠状病毒肺炎治疗中的试用及其法医毒理学研究进展

氯喹类药物是一类历史悠久的处方药,临床常用于抗疟疾及结缔组织病的治疗。2019年12月以来,在我国各地和世界多国发生了由2019新型冠状病毒(2019 novel coronavirus,2019-nCoV)引起的新型冠状病毒肺炎(corona virus disease 2019,COVID-19)疫情。由于缺乏针对COVID-19的药物,导致该病迅速蔓延且死亡率较高,因此亟待快速筛选抗2019-nCoV的特效药物,已批准使用的抗疟药磷酸氯喹被证实具有抗2019-nCoV的作用,并被纳入诊疗指南。但对磷酸氯喹引起急性中毒甚至死亡的风险意识也应同时加强,当前临床推荐剂量较以往治疗疟疾用药剂量偏大、疗程偏长,多地已要求临床密切监测不良反应。本文从法医学的角度,对氯喹类药物的药理作用、中毒与毒理作用机制、体内代谢与分布及法医学鉴定要点进行综述,以期为法医学实践及临床工作提供帮助。     

乙酰甲胺磷中毒血液灌流血药浓度的动态检测

目的探索乙酰甲胺磷中毒在血液灌流(HP)过程中血药浓度的变化规律及终末浓度。方法采用医院急诊病例病人股静脉血,通过气相色谱法分析血浆中的乙酰甲胺磷含量。结果经血液灌流后血浆中乙酰甲胺磷浓度迅速下降,并呈现出灌流前血药浓度越高下降速度越快的特性。结论血液灌流法能迅速降低血液中乙酰甲胺磷浓度,其下降的速度受制于乙酰甲胺磷的初始浓度和灌流开始时间等。     

Chloroquine as a poison in murder. Report of fatalities after criminal or suicidal chloroquine administration

Presented is a case of murder by means of chloroquine, committed on a 36-year-old male. The wife of the deceased had confessed to have secretely administered chloroquine-containing tablets to her husband. She was lawfully sentenced to life-imprisonment. The toxicological findings of this case are compared to the results of two chloroquine suicide cases and discussed in the context of the referring literature. An additional case where chloroquine intoxication was doubtful is introduced because of the unusual circumstances under which it occurred.     

尿中氯喹定性定量分析方法的研究

建立了人尿中氯喹的定性定量分析方法,2ml尿样用2ml×2环己烷：乙酸乙酯（8：2）提取净化后,60℃水浴室气吹干,残留物定容溶解后,气相色谱分析,氯喹的保留时间为9．44min。方法最低检测限为200ng／ml,回收率为87．0％,RSD＝7．9％（n＝5）,在0～50μg／ml浓度范围内,有良好的线性关系：A＝1778．9＋13686C,r＝0．999。方法同时可用于血中氯喹的分析。附一例应用报告,测得尿中氯喹的含量为0．745mg／ml,血中氯喹的含量为3．68μg／ml。尿液中同时检出氯喹的N－去单已基代谢物。定性结果经质谱法验证。     

Determination of chloroquine and monodesethylchloroquine in hair

Using thin-layer and gas chromatography and mass spectrometry, chloroquine and its major metabolite (monodesethylchloroquine) were identified in hair samples of numerous patients who received this antimalarial drug for several months. In two patients the amounts of chloroquine were, respectively, 310 and 145 mg/kg hair and those of the monodesethylchloroquine 23 and 11 mg/kg. The respective proportions (93 and 7%) are the same in the two subjects. The chloroquine percentage was near those in the spleen or stomach wall after poisoning. Other metabolites in hair are being identified. Hair analysis may provide a good toxicologic and forensic science complement to the blood, urine, and tissues. It may be useful for the control of chloroquine therapy.     

Cardiac concussion: definition, differential diagnosis, and cases presentation and the legal ramification of a misdiagnosis

A cardiac concussion is caused by a sudden, nonpenetrating, localized impact to the chest that is theorized to result in almost simultaneous sudden death from a disruption to the conductive system. The detailed external/internal forensic examination of the body reveals no evidence of structural, pathologic, or histologic signs of trauma to the heart. A cardiac concussion is a rare and often overlooked cause of sudden death. This type of sudden death is typically seen among younger individuals participating in sports involving projectiles and, to a lesser degree, where collisions occur. Cardiac concussions are clinically, pathologically, and chemically different from a cardiac contusion. The objective of this paper will be to define cardiac concussion, differentiate between cardiac concussion and cardiac contusion, and describe the clinical and pathologic features of a 32-year-old white male who died of a cardiac concussion following a collision with a catcher during a softball game. The civil ramification of incorrectly diagnosing the manner of death in cases of death involving a cardiac concussion will also be addressed.     

Spontaneous Coronary Artery Dissection: Case Report and Literature Review

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction and sudden cardiac death. It occurs most commonly in otherwise healthy women during pregnancy or the postpartum period. The true incidence of SCAD is underestimated, as most cases are diagnosed at autopsy. The pathophysiology of SCAD is still not fully understood, and its management can be challenging. This report describes a 35‐year‐old pregnant female who presented with an acute antero‐lateral ST elevation secondary to spontaneous dissection of the left anterior descending artery and the circumflex artery. The diagnosis was established by coronary artery angiography. However, the patient died following cardiac tamponade. The examination of this case represented a starting point for the reviewing of the diagnosis, clinical course, and management of SCAD, and for the placing of this in context with the existing literature. This study highlights the importance of prompt diagnosis and subsequent lifesaving treatment.     

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.     

43例心脏外科手术后死亡医疗纠纷法医学分析

目的 探究心脏外科手术后死亡引起医疗纠纷的原因及特点,重点分析心脏外科手术后病理改变及法医学解剖要点,为心脏外科手术临床诊治及司法鉴定提供病理学证据,为此类案件医疗纠纷防范提供参考.方法 收集中山大学法医鉴定中心2013—2018年受理的心脏外科手术后死亡引发医疗纠纷的法医病理学案件,从死亡原因、病理诊断、手术情况和医...     

Demonstration of a chloroquine fatality after 10-month earth-grave

A 19-year-old woman suspect of a suicidal drug intoxication was exhumed after a 10-month earth-grave, because the police was accused of manslaughter and neglected help by the relatives of the deceased. Toxicologic analysis revealed as the cause of death an acute chloroquine intoxication. An expert opinion had to deal with the question if the woman would have been saved if the police had appeared earlier. Therefore the duration of agonal period after suicidal chloroquine ingestion was important. An estimation of the time since death was possible on the one hand ex-post from the development of cadaveric changes and supravital reactions and on the other hand, based on premortal changes detectable on the body together with the findings of the authorities. Taking into account all evidence the woman was probably already dead at or prior to the arrival of the police (110 min after ingestion), at least this could not be excluded. Chloroquine has to be considered to be useful for fatal poisoning, which is also recommended in some publications on methods to commit suicide.     

Chloroquine distribution in postmortem cases

Chloroquine concentrations in blood and tissues were examined in overdose and non-overdose cases to determine appropriate ranges for interpretation. Twenty-nine literature overdose cases and 8 non-overdose literature cases were compared with this laboratory's findings. The results indicate significant postmortem redistribution of chloroquine. Combining this laboratory's results and the literature results indicates that using a liver concentration of 150 mg/kg as a cutoff between overdose and non-overdose concentrations properly identified 30 of the 34 published cases containing liver chloroquine and 19 of the 20 presented cases.     

Suicide with chloroquine combined with maprotiline and trimipramine]

Report on suicide with chloroquine in combination with maprotiline and trimipramine. Chloroquine and his metabolite monodesethylchloroquine could be determined in organs and body fluids. The highest organ-concentrations of chloroquine were found in liver and kidney. The survival time and dose are discussed.     

Cor triatriatum sinistrum: a rare congenital cardiac anomaly presenting in an adult with chronic atrial fibrillation

Cor triatriatum is a rare congenital cardiac anomaly in which the left atrium is divided into proximal (dorsal or upper) and distal (ventral or lower) chambers by a fibromuscular septum. The upper chamber receives the pulmonary veins and the lower chamber contains the atrial appendage and the mitral valve. The 2 chambers communicate through a defect in the membrane. Cor triatriatum is often associated with other congenital cardiac anomalies. Most frequently, the upper chamber communicates with the right atrium through a patent foramen ovale or atrial septal defect, and the clinical symptoms simulate anomalous pulmonary venous return. Less commonly, the foramen ovale communicates with the distal chamber and the clinical features mimic mitral stenosis. When cor triatriatum is the only abnormality, the clinical findings are also similar to mitral stenosis with development of pulmonary hypertension and subsequent right ventricular hypertrophy and atrial enlargement. The diagnosis is usually made in infancy or childhood, and the lack of treatment results in death in 75% of patients.We report the case of a woman who presented much later in life. The patient was a 57-year-old female with a clinical history of chronic atrial fibrillation who presented to the emergency department because of a "funny sensation" in her chest, though she denied chest pain, nausea, vomiting, or diaphoresis. EKG revealed atrial fibrillation with a rapid ventricular response and a tachycardic rate of 157. She had a therapeutic level of digoxin, and cardiac enzymes were normal. The patient was admitted and placed on Cardizem drip. Serial EKGs remained normal and heart rate control was achieved. On hospital day 2, the patient became dyspneic and cyanotic. She went into cardiac arrest and died.Autopsy revealed cardiomegaly (610 g) with 4-chamber dilatation. A septum divided the left atrium into 2 chambers. The defect in the dividing membrane measured 1 cm in diameter. No other congenital defects were noted. The large size of the defect in the membrane likely accounted for the late onset of symptoms that allowed this patient to survive into adulthood without previous diagnosis or surgical intervention (which is usually required in childhood).     

Informed consent issues in the cardiac transplantation evaluation

As consultation-liaison psychiatrists to a cardiac transplantation team, we have observed various informed consent issues that are particularly associated with evaluation for cardiac transplantation. We discuss complicating factors that relate to each component of informed consent and present the defense mechanism of denial as a barrier to making the decision to accept or refuse transplantation. Changes in the evaluation protocol could preclude existing impediments to provision of information and patient autonomy; however, certain intrapsychic issues must be recognized as ongoing clinical realities to be addressed as the doctrine of informed consent continues to evolve.     

Fatal and non-fatal methomyl intoxication in an attempted double suicide

A 79-year-old man and his 73-year-old wife attempted double suicide by ingesting methomyl powder. The woman died 19 h after ingestion in spite of intensive care. At autopsy a large number of miliary hemorrhages were found in both thalami of the brain. Her husband, however, recovered after 10 days of treatment. Methomyl (CAS No. 16752-77-5, Lannate) in the biological materials was analyzed by gas chromatography-mass spectrometry. The methomyl concentration was 44 micrograms/g in the wife's serum sample collected 1 h after ingestion, and 0.2 microgram/g in the blood sample collected at autopsy. The methomyl concentration in the husband's blood sample collected 28 h after ingestion was from 0.01 to 0.1 microgram/g. It is suggested that prompt and adequate intensive care including a direct hemoperfusion is necessary to effect the recovery of patients with lethal blood levels of methomyl. The miliary hemorrhages found in the thalami of the brain are suspected to have been caused by asphyxia induced by methomyl intoxication.     

Non-Heart-Beating Organ Donation: A Defense of the Required Determination of Death

The family of a patient who is unconscious and respirator-dependent has made a decision to discontinue medical treatment. The patient had signed a donor card. The family wants to respect this decision, and agrees to non-heart-beating organ donation. Consequently, as the patient is weaned from the ventilator, he is prepped for organ explantation. Two minutes after the patient goes into cardiac arrest, he is declared dead and the transplant team arrives to begin organ procurement. At the time retrieval begins, it is not certain that the patient's brain is dead or that cardiac function cannot be restored. Procurement follows uneventfully, and two transplantable kidneys are retrieved .     

Study by next generation sequencing of sudden cardiac death (SCD)

Sudden cardiac death (SCD) is one of the most common causes of death; most SCD are related to secondary arrhythmias, to structural heart disease, or to primary electrical abnormalities of the heart.A significant number of SCD, especially among young people, are due to genetic heart disorders, both with structural and arrhythmogenic abnormalities. However SCD occurs also in patients with negative clinical history, autopsy is not always conclusive for a diagnosis.Recent technological advances in DNA sequencing, have led to the commercialization of genetic testing now widely available in clinical practice. In particular, next generation sequencing, allows the large-scale and rapid assessment of entire genomes.Analysis of SCD with a NGS panel of 174 genes was performed in our laboratory in order to identify the genetic causes and thus to direct the clinician to an accurate clinical and genetic screening of relatives.Two SDC were studied:Case 1: female, 57, without story of syncope and no previously highlighted cardiac alteration, died post cardiac arrest; negative family history. Autopsy was apparently negative.Case 2: male, 52, who died during a football game; negative family history, neurological episodes occurred before death was reported by close relative. Autopsy was positive for ventricular hypertrophic.In both cases we made a genetic diagnosis.     

青壮年猝死综合征与SCN5A基因突变的相关性

近几年来,国内外青壮年不明原因猝死的报道逐年增多,对其死因的界定是法医工作者深感棘手的问题。随着病因学向分子水平的深入,心脏病研究已用分子遗传学技术证实了一类“原发性心电紊乱”导致的心律失常与SCN5A突变引发的钠通道疾病有关,本文回顾了法医学中青壮年猝死综合征(SMDS)的特征及临床医学中几种疾病的基因型和表型,分析其相关性,期望为进一步研究获得一些启示。     

Sudden death associated with solitary intracavitary right atrial metastatic tumour deposit.

We report a case of cardiac metastasis of primary adrenal cortical carcinoma to the endocardium of the right atrium resulting in an intracavitary mass which we believe caused sudden death by blocking the tricuspid valve orifice. We have been unable to find a similar case previously reported although primary atrial myxoma is well known to be a rare cause of sudden cardiac death by the same mechanism. Modern non-invasive imaging techniques have facilitated recognition of intracavitary cardiac metastases, and with surgical intervention, when feasible, the risk of sudden cardiac death can be reduced.