31 research outputs found
Analysis of mRNA from human heart tissue and putative applications in forensic molecular pathology.
No full textThe usefulness of post-mortem mRNA analysis and its potential applications in forensic casework is currently of interest, especially because of several factors affecting the quality of RNA samples that are not practically predictable. In fact, post-mortem RNA degradation is a complex process that has not been studied systematically. The purpose of this work is to establish whether RNA analysis from post-mortem heart tissue could be used as a forensic tool to investigate the cause of death, with special regard to those cases where a cardiac disease is suspected as the manner of death. We analysed heart tissue from 16 individuals with normal cardiac function, 9 with long post-mortem intervals (L-PMI) and 7 from organ donors with very short PMIs (S-PMIs). Right ventricle tissue was homogenised, and the RNA was isolated and reverse transcribed. The resulting cDNA was used in real-time PCR reactions to quantify the gene expression of beta-glucuronidase (GUSB), Nitric Oxide Synthase 3 (NOS3), Collagen 1 (COL1A1) and Collagen 3 (COL3A1). The percentage of samples with high-quality RNA was higher in samples with S-PMI (7 out of 7) than in samples with L-PMI (4 out of 9, p<0.05). No differences in PMI time or cause of exitus were found between samples with degraded or non-degraded RNA in the L-PMI group. When comparing mRNA levels in samples with non-degraded RNA, we found similar values between the L-PMI and S-PMI groups for GUSB, COL1A1 and COL3A1. The NOS3 gene expression in the L-PMI subgroup was less than half that in the S-PMI. These results suggest that high-quality mRNA can be extracted from post-mortem human hearts only in some cases. Moreover, our data show that mRNA levels are independent from the PMI, even though there are mRNAs in which the expression levels are very susceptible to ischemia times. Clear knowledge about the relationship between mRNA integrity and expression and PMI could allow the use of several mRNAs as forensic tools to contribute to the determination of the cause of death with special regard to cardiovascular diseases
Autopsy investigation and bayesian approach to coronary artery disease in victims of motor-vehicle accidents
No full textAnalysis of the arrhythmogenic substrate in human heart failure
No full textThe mechanism of sudden cardiac death in patients with heart failure (HF) is uncertain. Both electrical instability and structural remodelling could be factors that lead to fatal arrhythmias. We sought to analyse the expression of the sodium (SCN5A) and potassium (KCND3) channels as well as the fibrosis content in the ventricles of human HF and of non-diseased hearts under different post-mortem intervals
State of the art in forensic investigation of sudden cardiac death.
No full textThe sudden death of a young person is a devastating event for both the family and community. Over the last decade, significant advances have been made in understanding both the clinical and genetic basis of sudden cardiac death. Many of the causes of sudden death are due to genetic heart disorders, which can lead to both structural (eg, hypertrophic cardiomyopathy) and arrhythmogenic abnormalities (eg, familial long QT syndrome, Brugada syndrome). Most commonly, sudden cardiac death can be the first presentation of an underlying heart problem, leaving the family at a loss as to why an otherwise healthy young person has died. Not only is this a tragic event for those involved, but it also presents a great challenge to the forensic pathologist involved in the management of the surviving family members. Evaluation of families requires a multidisciplinary approach, which should include cardiologists, a clinical geneticist, a genetic counselor, and the forensic pathologist directly involved in the sudden death case. This multifaceted cardiac genetic service is crucial in the evaluation and management of the clinical, genetic, psychological, and social complexities observed in families in which there has been a young sudden cardiac death. The present study will address the spectrum of structural substrates of cardiac sudden death with particular emphasis given to the possible role of forensic molecular biology techniques in identifying subtle or even merely functional disorders accounting for electrical instability
Fatal injection of ranitidine: a case report
Get PDFABSTRACT: INTRODUCTION: Ranitidine hydrochloride (Zantac(R)), a histamine-2-receptor antagonist, is a widely used medication with an excellent safety record. Anaphylactic reaction to ranitidine is an extremely rare event and a related death has never been described in the literature. CASE PRESENTATION: We present the clinical history, histological and toxicological data of a 51-year-old man with negative anamnesis for allergic events, who died suddenly after the intravenous administration of one phial of Zantac(R) 50 mg prescribed as a routine post-surgical prophylaxis for stress ulcer. CONCLUSION: Although the incidence of anaphylactic reactions related to ranitidine is low, caution needs to be exercised on administration of this drug. In addition, further study is needed to define strategies for the prevention of adverse drug reactions in hospitalized patients
Autopsy investigation and Bayesian approach to coronary artery disease in victims of motor-vehicle accidents
No full textBACKGROUND: Each year, 1.2 million people die worldwide as a result of motor-vehicle accidents (MVA), representing a tremendous burden to healthcare. The aim of this study was to define the prevalence of coronary disease and its possible role in motor-vehicle accidents.
METHODS AND RESULTS: We examined consecutive cases of non-hospital sudden death autopsies in the area of West Quebec during the period of 2002-2006, and we focused on those victims of MVA. Severe coronary artery disease (CAD) was defined as a narrowing of ≥ 75% of a cross-sectional area or the presence of acute plaque events in major epicardial coronary arteries. From a total cohort of 1260 autopsies, MVA were responsible for 123 deaths, 100 of whom were men and 23 were women. Significant CAD was documented in approximately 37% of these cases. In individuals older than 60 years, the prevalence of significant CAD and ischemia were 86.2% and 19.8%, respectively. A percentage of 40% of the coronary patients showed erratic driving before the accident, as observed by witnesses. Statistical analysis showed that an individual affected by CAD has 9% probability of suffering a motor-vehicle accident.
CONCLUSIONS: The prevalence of severe CAD and acute myocardial ischemia is very high among individuals who have suffered a MVA. Our data suggest the hypothesis that acute CAD could be the cause of accidents in a large group of the drivers affected by coronary disease. For these reasons CAD could be investigated in drivers above 50 years old, as a possible preventive measure and determinant of individual risk stratificatio
Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation
No full textCardiac arrhythmias are associated with abnormal channel function due to mutations in ion channel genes. Epilepsy is a disorder of neuronal function also involving abnormal channel function. It is increasingly demonstrated that the etiologies of long QT syndrome and epilepsy may partly overlap. However, only a few genetic studies have addressed a possible link between cardiac and neural channelopathies. We describe a family showing the association between Brugada syndrome and epilepsy in which a known mutation in the SCN5A gene (p.W1095X, c.3284G>A) was identified. We suggest that this mutation can be responsible for cardiac and brain involvement, probably at different developmental age in the same individual. This observation confirms the possibility that SCN5A mutations may confer susceptibility for recurrent seizure activity, supporting the emerging concept of a genetically determined cardiocerebral channelopathy
A neutron tomographic system developed at the Rome research reactor
No full textA third-generation neutron tomographic system, mainly used for nondestructive evaluation on small hydrogenated samples, has been recently set up at the ENEA TRIGA RC II research reactor in Rome, Italy. This reactor operates at a nominal power of 1 MW and produces a thermal beam of about 2 × 105 cm-2 s-1 with a collimation ratio L/D of about 30. The object to be examined is viewed by a Thomson CSF neutron image intensifier coupled to a cooled CCD (Charge Coupled Device) camera equipped with a sensitive array of 192 × 165 pixels, each acting as an equivalent elementary neutron detector. The entire set of projections (usually 120) needed for the examination is acquired in about 90 min, as the system operates in a rotate-only configuration with parallel beam. The reconstruction software used is a development of the Donner Package for Reconstruction Tomography, specifically modified in order to deal with third-generation algorithms using the projection images produced by the CCD camera. At present, the total reconstruction time to obtain the full set of 165 slices of 192 × 192 pixels each is about 60 min on a standard Solbourne SPARC 4 multi-user workstation. © 1994
Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series
No full textEpilepsy affects approximately 3 % of the world’s population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17 % of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24 % of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy
Genetic analysis, in silico prediction, and family segregation in long QT syndrome
Get PDFThe heritable cardiovascular disorder long QT syndrome (LQTS), characterized by prolongation of the QT interval on electrocardiogram, carries a high risk of sudden cardiac death. We sought to add new data to the existing knowledge of genetic mutations contributing to LQTS to both expand our understanding of its genetic basis and assess the value of genetic testing in clinical decision-making. Direct sequencing of the five major contributing genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, was performed in a cohort of 115 non-related LQTS patients. Pathogenicity of the variants was analyzed using family segregation, allele frequency from public databases, conservation analysis, and Condel and Provean in silico predictors. Phenotype-genotype correlations were analyzed statistically. Sequencing identified 36 previously described and 18 novel mutations. In 51.3% of the index cases, mutations were found, mostly in KCNQ1, KCNH2, and SCN5A; 5.2% of cases had multiple mutations. Pathogenicity analysis revealed 39 mutations as likely pathogenic, 12 as VUS, and 3 as non-pathogenic. Clinical analysis revealed that 75.6% of patients with QTc≥500 ms were genetically confirmed. Our results support the use of genetic testing of KCNQ1, KCNH2, and SCN5A as part of the diagnosis of LQTS and to help identify relatives at risk of SCD. Further, the genetic tools appear more valuable as disease severity increases. However, the identification of genetic variations in the clinical investigation of single patients using bioinformatic tools can produce erroneous conclusions regarding pathogenicity. Therefore segregation studies are key to determining causality.European Journal of Human Genetics advance online publication, 26 March 2014; doi:10.1038/ejhg.2014.54
