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Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.

Exposure to metals and trace elements (TE) is universal and can cause toxicity in case of excessive exposure. We evaluated the concentrations and tissue distribution of 39 TE using high-resolution ICP-MS after total mineralization by microwave in twenty autopsied French subjects. We found a globally homogeneous distribution of TE in the body, with some accumulations in agents, involved in respiratory pathologies and classified as carcinogens, in the lungs. The liver, an organ of metabolism, appeared to concentrate Co, Fe, La, Mn, Mo, Pb and Zn. Fe seemed to accumulate in the spleen, the organ of hematopoiesis. The kidney showed high concentrations of some TE, which can cause nephrotoxicity. The use of microwave mineralization and high-resolution ICP-MS allowed accurate quantification and a very high sensitivity, without spectral interferences. The results obtained in this study could be used to support the interpretation of post-mortem metal concentrations in tissues.

A manner of death may be ruled undetermined by the forensic pathologist when there is insufficient information about the circumstances surrounding the death to make a ruling. The aim of our study was to retrospectively analyze a series of autopsy cases that were classified as undetermined manner of death after complete investigations. In all, 48 cases were examined. In 23 cases (48%), the cause of death was determined. The most frequent cause of death was toxic death (n = 11). More than one manner of death was deemed conceivable for most cases (n = 39). The most frequent and the most probable manner of death was accident (n = 37). Homicide was not excluded in about 23% of the cases. Our study showed that the manner of death may remain undetermined despite an established cause of death, and even when two or more conceivable causes of death are considered. Our study pointed out that undetermined manner of death covers a wide range of situations and that homicide may be underestimated.

The aim of our study was to highlight the epidemiological difference in adult sudden death between males and females. The type of pathologies found in adult victims of sudden death was compared to control cases in order to determine the most significant pathologies involved in sudden death. Among all autopsies performed between 1995 and 2009, 534 adult cases of sudden death and 154 cases who violently died were respectively selected. For each case, a complete autopsy was carried out, including systematic histological examination of all major organs. The sudden death population was composed of 369 males and 165 females. There was no statistical difference regarding age between males and female. Sudden death took place more often at home in women than in men (p 0.0001). A stressful event was more frequently found in men than in women (p = 0.03). Deaths caused by cardiovascular diseases were more frequent in males than in females, especially Coronary Artery Disease (CAD) (p 0.0001). Cardiomyopathy was more often the cause of death in women, particularly Arrythmogenic Right Ventricular Cardiomyopathy (ARVC). Cardiac pathologies were found in 45% of the control cases. CAD and ARVC were statistically more frequent in the sudden death group than in the control group. According to our study, profile of sudden death is different between males and females. Those data seem to be important for clinicians involved in prevention programs of sudden death, as they can adapt their screening according to the gender.

Determination of the manner of death is a major issue in forensic practice. Differentiating the injuries caused by falls from a low height from injuries due to the deliberate application of a blunt object can be difficult. A few studies suggested the use of certain criteria, such as the hat brim line rule, to help in differentiating between falls and blows. Unfortunately they are not consistent. All autopsy cases from a 16-year period (1996–2012) were analyzed retrospectively. Three groups were defined: homicide cases (n = 31), sudden natural deaths involving a fall (n = 103), and accidental fall cases (n = 30). The three groups were statistically compared across a wide range of parameters including general characteristics, presence, and characteristics of different types of wounds (lacerations, deep bruises, fractures, intracranial trauma, and defense injuries) as well as their respective anatomical site. There were marked differences in wounds between homicide and fall cases, e.g., wounds were more numerous and larger in homicides. We did not confirm the hat brim line rule as a reliable discriminating parameter. A simple and highly effective multivariate model was found, which included the presence of lacerations, deep bruises, and intracranial trauma. This study underlines the importance of autopsy findings in providing an indication of the manner of death. Conversely, the limitations of the hat brim line rule have been highlighted.

Previous population-based studies have identified increased suicide rates among cancer patients. Available post mortem data on the contribution of cancer to completed suicide are limited, however. This study examines forensic autopsy data in order to assess whether cancer is significantly more frequent in a suicide population compared with a control population. In total, 232 cases were included in both the suicide and the control groups. Based on a complete standard histological examination, cancer was significantly more often found in the suicide group than in the control one (8.6% vs. 3.9%, p=0.03). The multivariate analysis also showed that the presence of cancer increased the risk of suicide. Moreover, cancer was not known to the deceased in 70% of cases, while the most frequent mental disease found in cancer-related suicide cases was depression (75%). In the 20 cancer-related suicide cases analysed herein, it was difficult to ascertain whether malignancy was the only motive for committing suicide, as cancer could be considered to be either a major causative factor for suicide or an incidental finding. Therefore, further research is warranted with the help of the psychological autopsy method to investigate the link between suicide and cancer further.

Impaired arginine vasopressin (AVP) synthesis and release by the neurohypophyseal system, which includes the neurohypophysis and magnocellular neurons of the paraventricular and supraoptic nuclei, have been postulated in septic shock, but changes in this system have never been assessed in human septic shock, and only partially experimentally. We investigated AVP synthesis and release by the neurohypophyseal system in 9 patients who died from septic shock and 10 controls, and in 20 rats with fecal peritonitis-induced sepsis and 8 sham-operation controls. Ten rats died spontaneously from septic shock, and the others were sacrificed. In patients with septic shock, as in rats that died spontaneously following sepsis induction, AVP immunohistochemical expression was decreased in the neurohypophysis and supraoptic magnocellular neurons, whereas it was increased in the paraventricular magnocellular neurons. No significant change was observed in AVP messenger RiboNucleic Acid (mRNA) expression assessed by in situ hybridization in either paraventricular or supraoptic magnocellular cells. This study shows that both in human and experimental septic shock, AVP posttranscriptional synthesis and transport are differently modified in the magnocellular neurons of the supraoptic and paraventricular nuclei. This may account for the inappropriate AVP release in septic shock and suggests that distinct pathogenic mechanisms operate in these nuclei.

The forensic community does not agree on the need to perform histological examination at forensic autopsy. The aim of our study was to determine the usefulness of systematic standard histology in forensic autopsies. A prospective study was carried out on 428 autopsy cases for which standard histological examination was systematic. Mechanism of death not shown by gross anatomic findings was discovered by histology in about 40% of the cases. Cause of death was established by only histology in 8.4% of the cases. Microscopic findings affected the manner of death in 13% of the cases. Histology provided complementary information about prior medical condition of the deceased in about 49% of the cases. Traumatic lesions were better documented by histology in about 22% of the cases. According to the results of our study, systematic standard histology for the main organs should be used in routine forensic autopsies.

The macroscopic study of cranial sutures is one of the methods that may be used in forensic anthropology to estimate age at the time of death. The present study aims at assessing the value of a microscopic analysis of the fronto-sphenoidal suture (FSS) sampled at autopsy, to determine both the physiological mechanisms responsible for the FFS closing during ageing and its value in the estimation of age at the time of death. We assessed the vascular capital as well as the apoptosis of conjunctive cells intervening as parameters in the physiological mechanism involved in cell ageing, in a population of individuals, whose gender and age was known. The FSS analysis was performed after decalcification and standard histological study, respectively with immunohistochemistry (Factor Von Willebrand antibody) VWF and (TdT-mediated dUTP nick end labelling) TUNEL method and caspase-3 immunohistochemical expression. In this study we found a significant reversed correlation between the degree of vascular expression of VWF and age at the time of death. There was also a significant positive correlation between the degree of apoptosis in the conjunctive cells of the FSS and age at the time of death. According to these results, suture closing during ageing can be explained by these two combined mechanisms of conjunctival apoptosis and vascular involution. Thus, the findings justify the study of closing sutures to estimate age at the time of death. Besides, it also enabled us to establish linear regressions. The vascular expression of the VWF enables to estimate an individual's age at the time of his death more or less at about 1.55 years, offering an interesting perspective both in forensic pathology and anthropology.

A 54-year-old man was found dead with a bottle containing a brownish fluid near him. A toxicological screening was carried out in blood, urine, and stomach content. Only dichlorvos (2,2 dichlorovinyl 0-0 dimethylphosphate or DDVP) was found. A simple and rapid method, using DDVP-D 6 as an internal standard, was developed for the determination of DDVP by gas chromatography/mass spectrometry (GC/MS). The method was linear from 1 to 10 mg/L. Intraday and interday precisions were all

In this study, we evaluated the potential direct role of enterovirus (EV) cardiac infections in the pathogenesis of myocardial infarction (MI).Enteroviruses (Picornaviridae) have been suspected to play a role in the development of acute MI.The presence of EV ribonucleic acid (RNA) sequences and capsid viral protein 1 (VP1) and the virus-mediated focal disruption of dystrophin were retrospectively investigated by reverse transcriptase-polymerase chain reaction and immunohistochemistry assays in endomyocardial tissues of patients who died suddenly of acute MI by comparison with similar samples of control patients matched for gender, residence area, and year of death.Enterovirus infection markers were detected in 20 (40%) of 50 patients who died suddenly of MI, 2 (4%) of 50 matched subjects without cardiac disease (p0.001), and 4 (8%) of 50 matched patients exhibiting a noncoronary chronic cardiopathy (p0.001). All of the EV RNA-positive patients exhibited VP1, which provided evidence of viral protein synthesis activity. The VP1 gene sequences amplified after cloning from myocardial or coronary samples of 8 of the MI patients and showed a strong homology with sequences of coxsackievirus B2 and B3 serotypes. Moreover, in the endomyocardial tissue of these 8 patients, immunohistochemical analyses demonstrated that there was disruption of the sarcolemmal localization of dystrophin in the same tissue areas that were infected by coxsackieviruses.Our findings demonstrate a significantly higher proportion of active coxsackievirus B cardiovascular infections in patients who suddenly died of MI compared with matched control subjects, suggesting that these EVs may significantly contribute to the pathogenesis of acute MI by a focal disruption of the dystrophin-glycoprotein complex.

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.

An original liquid chromatography method with photodiode-array detection (DAD) is presented for the determination of strychnine in blood. This sensitive method allows the use of only 0.1 ml of sample. The strychnine was isolated from blood using a liquid-liquid extraction procedure and chloroquine as an internal standard. The limits of detection (LOD) and quantification were 0.06 and 0.5 mg/l, respectively. The recovery was 94% and the coefficients of variation (CV) ranged from 5.9 to 10.8%. A fatal case of strychnine poisoning is presented, with a lethal blood concentration of 25 mg/l.

A new rapid and sensitive high-performance liquid chromatography method has been developed for the screening and determination in human plasma of the 11 most commonly prescribed nontricyclic antidepressants and two metabolites: fluoxetine, norfluoxetine, sertraline, paroxetine, citalopram, fluvoxamine, moclobemide, mirtazapine, milnacipram, toloxatone, venlafaxine, desmethyl venlafaxine, and viloxazine. It involves liquid-liquid extraction procedures followed by liquid chromatography coupled to photodiode-array UV detection with three fixed wavelengths (220, 240, and 290 nm). Compounds were separated on a 5-microm Hypurity C18 (ThermoHypersil) analytic column (250 x 4.6 mm i.d.) using a gradient of acetonitrile-phosphate buffer pH 3.8 at a flow rate of 1.0 mL/min. The total analysis time was only 18 min per sample. Extraction recoveries were in the 74-109% range for 11 compounds but were of only 59% for moclobemide and less than 10% for toloxatone. Calibration curves were linear in the 25 to 1000 ng/mL range for all compounds, all of them with coefficients of determination (r2 values) > or = 0.999. Limits of detection (LODs) ranged from 2.5 to 5 ng/mL except for toloxatone (10 ng/mL). Intraassay and interassay precision and accuracy were studied at two concentration levels (50 and 500 ng/mL). The intraassay coefficients of variation (CVs) for all compounds were < or = 7.6%, and all interassay CVs were below 11.5% except for milnacipram (14.8%). The intraassay and interassay accuracies for all compounds were found to be within 88.4% and 105.9% at 50 ng/mL and within 87.2% and 100.5% at 500 ng/mL. The performance of the method allows the therapeutic drug monitoring of the most prescribed nontricyclic antidepressant drugs as well as its use in toxicologic screening.

The laryngeal cartilages undergo age changes, including mineralization and ossification. Keen and Wainwright defined, in male and female subjects, recognizable stages of radiopacity of the thyroid, cricoid, and arytenoid cartilages. The present study analyzed quantitatively the degree of laryngeal radiopacity to determine whether radiography of the larynx can be used routinely in forensic pathology to estimate age at death. In each of 82 subjects, the larynx was removed during forensic autopsy and subjected to radiography in an anteroposterior orientation. Each radiograph was independently scored by two observers. For each case, the degree of laryngeal radiopacity was evaluated according to the classification of Keen and Wainwright. There was a positive correlation between the total score of laryngeal radiopacity and age (correlation coefficient = 0.74). It was concluded that this method is simple, fast, and nondestructive and has a good reproducibility between observers. Because there was a wide interindividual variability in the same age class, this method must be associated with more accurate methods.

This article describes the case of a sudden death in a 45-year-old female consecutive to acute and extensive arterial dissection in a context of Ehlers-Danlos syndrome type IV. The interest of this case report is that autopsy findings led to the suspicion of a clinical diagnosis prompting as carrying out a genetic testing which definitively confirms the diagnosis, opening the way to genetic council for family members. Criteria for this disease diagnosis and full methodology are described, that may help forensic practitioners.

A retrospective study was carried out on 58 fatalities due to stab or incised wounds. The frequency of bone or cartilage lesions was analysed according to the number of wounds, the circumstances of death and the anatomical site. Our findings showed that bone/cartilage lesions were present in about 53% of the cases. Cartilage lesions were more frequent than bone lesions. The mean number of wounds in the group with bone/cartilage lesions was statistically higher than the mean number of wounds in the group without lesions (P=0.0068). The main cause of death was thoracic injury in the groups with and without bone/cartilage lesions. In case of skeletal remains, only bone or cartilage lesions allow to diagnose stab or incised wounds. The discovery of these lesions, often of small size, justifies a complete and careful examination of skeletal remains with the help of stereomicroscopy.

A retrospective study was carried out on 93 autopsy cases who died after a fall from a height. For each case, following parameters were reported: age, sex, manner of death, estimated height of fall, ground type, estimated site of primary impact, type of laryngeal and hyoid bone trauma, presence of associated local trauma in the neck and cephalic region. Mean age of the studied population was about 33 years. Sex ratio (men/women) was 1.8. Mean height of fall was about 15 m. Manner of death was, respectively, suicide and accident in 70 and 23 cases. The type of ground was concrete in 94% of the cases. The site of primary impact was, respectively, head, front of the body, back of the body, feet/lower limbs, and lateral body in 31, 26, 19, 12, and 5 cases. Cervical soft tissue bruising without laryngohyoid fractures was found in 5 cases. Laryngohyoid fractures were found in 5 cases. These fractures could be explained by direct impact of the neck structures against the ground. The mechanism of these fractures could also be indirect fractures due to high muscle strains on the hyoid bone or thyroid cartilage due to cervical hyperflexion or hyperextension or secondary to mandible or cervical vertebral column fractures.