Fatal injection of ranitidine: a case report

ABSTRACT: 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

Analysis of the arrhythmogenic substrate in human heart failure

The 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

Autopsy investigation and Bayesian approach to coronary artery disease in victims of motor-vehicle accidents

BACKGROUND: 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

Analysis of mRNA from human heart tissue and putative applications in forensic molecular pathology.

The 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

Genetic analysis, in silico prediction, and family segregation in long QT syndrome

The 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