Volatile lipophilic substances management in case of fatal sniffing

Death due to inhalation of aliphatic hydrocarbons such as butane and propane is a particularly serious problem worldwide, resulting in several fatal cases of sniffing these volatile substances in order to “get high”. Despite the number of cases published, there is not a unique approach to case management of fatal sniffing. In this paper we illustrate the volatile lipophilic substances management in a case of a prisoner died after sniffing a butane-propane gas mixture from prefilled camping stove gas canisters, discussing the comprehensive approach of the crime scene, the autopsy, histology and toxicology.A large set of accurate values of both butane and propane was obtained by gas chromatography–mass spectrometry analyzing the following post-mortem biological samples: peripheral blood, heart blood, vitreous humor, liver, lung, heart, brain/cerebral cortex, fat tissue, kidney, and allowed an in depth discussion about the cause of death. A key role is played by following the proper sampling approach during autopsy.     

Three sudden deaths in men associated with undiagnosed chronic thyroiditis

Three cases of sudden death associated with undiagnosed chronic thyroiditis are described. All were young or middle-aged men who were found dead, and death appeared to have occurred suddenly. Two of them had not previously experienced any serious medical problems, the third suffered from well-controlled Addison's disease. None had been investigated or treated for thyroid disease previously. Microscopically all showed a severe chronic thyroiditis with parenchymal destruction and reactive hyperplasia of the acinar epithelium. In the first case elevated triiodothyronin (T3), thyroxin (T4) and low thyroid stimulating hormone (TSH) were present, in the second case low T3 and T4 and normal TSH, and in the third an isolated elevation of T3 were found. Anti-thyroid antibodies were found in two cases. The possible causal relationship between silent chronic autoimmune thyroiditis and sudden death is discussed.     

Unnatural causes of sudden unexpected deaths initially thought to be sudden infant death syndrome

The aim of this clinicopathological study was to determine the frequency of infant deaths due to unnatural causes among cases of sudden and unexpected infant death. Nine institutes of legal medicine in Germany that took part in the German study on Sudden Infant Death Syndrome (GeSID), representing 35% of the German territory, investigated in a 3-year period (from 1998 to 2001) 339 cases of infant death that were not expected to be due to unnatural causes from the first external examination. All cases were investigated by complete, standardised, post-mortem examination including death scene investigation, autopsy, histology, toxicology and neuropathology. The frequency of unnatural deaths was 5.0% (n=17). The causes of death were head injury (n=7), suffocation (n=5), poisoning (n=2), neglect (n=2) and septicaemia due to aspiration of a foreign body (n=1). Two deaths were unsuspected accidents and 12 were due to infanticide. In 3 cases, it was not possible to differentiate between accidental death and infanticide. A complete postmortem examination including an analysis of the clinical history, death scene investigation, autopsy, histology, toxicology, and neuropathology is mandatory to differentiate sudden and unexpected deaths due to natural causes (e.g. SIDS) and cases of unnatural death.Contributors at Institutes of Legal Medicine: U. Deml, Friedrich-Alexander-University, Erlangen; A. Freislederer, University Duisburg-Essen, Essen; S. Heide, Martin-Luther-University, Halle; H.-J. Kaatsch, S. Ritz-Timme, Christian-Albrechts-University, Kiel; K.-P. Larsch, A. Fiegut, Medizinische Hochschule Hannover, Hannover; H.W. Leukel, Johann-Wolfgang-Goethe-University, Frankfurt am Main; C. Ortmann, Friedrich-Schiller-University, Jena; R. Penning, Ludwig-Maximilians-University, Munich.     

Sudden death after isobutane sniffing: a report of two forensic cases

The intentional inhalation of a volatile substance (“sniffing”) causing euphoria and hallucinations is an under-recognised form of substance abuse in children and adolescents with a high morbidity and mortality. Sudden death can be caused by cardiac arrhythmia, asphyxia or trauma. Two fatal cases of isobutane sniffing of cigarette lighter refill containing isobutane are reported. Toxicological investigations revealed the presence of isobutane in the heart blood and brain tissue of both cases (case 1: heart blood 0.1 μg/g, brain tissue 2.3 μg/g; case 2: heart blood 4.6 μg/g, brain tissue 17.4 μg/g) and the presence of its metabolite 2-methyl-2-propanol in the heart blood of both cases (0.5 and 1.8 μg/g, respectively). The histological investigations of the inner organs showed similar results in both victims. Autopsy findings, results of the histological and immunohistochemical investigations, toxicological findings and analytical procedures are discussed.     

Association between sudden unexpected deaths in bathtubs and ambient temperature among elderly Japanese adults: A time-series regression study

BackgroundSudden unexpected deaths in bathtubs among elderly Japanese adults occur predominantly during the cold season. This study investigated the relationship between these deaths and bathing day temperature among elderly adults in Tokyo.MethodsData for 1408 cases of bath-related deaths from January 1 to December 31, 2015 were obtained from the Tokyo Medical Examiner’s Office. We excluded 409 cases for the following reasons: criminal death, injury-related death, suicide, intoxication, non-sudden death, not bathtub-related death, out-of-bathroom death, subject aged under 65 years, undetermined bathing date, institutional housing, and bathing not at subject’s home. Ultimately, 999 cases were analyzed. Daily mean temperature data were collected. A time-series regression study was performed to estimate the influence of sex, age, and bathing day temperature. Monthly changes in the population bathing in a bathtub were considered in the model.ResultsThe relative risk (RR) of sudden unexpected death in a bathtub was 1.381 for males (95% confidence interval [CI]: 1.218–1.564) compared to females. The RRs were 4.182 (95% CI: 3.523–4.986) and 9.382 (95% CI: 7.836–11.273) among those aged 75–84 years and ≥85 years, respectively, compared to among those aged 65–74 years. The RR increased to 1.092 (95% CI: 1.082–1.102) as the daily mean temperature decreased by 1 °C.ConclusionSudden unexpected death in a bathtub correlated with bathing day temperature among elderly Japanese adults, and extremely low temperature, male sex, and older age increased the risk of such death. Our findings provide insight into preventing sudden unexpected deaths in bathtubs.     

Performance enhancing drugs (doping agents) and sudden death – a case report and review of the literature

The case of sudden cardiac death of a 23-year-old body builder who used anabolic steroids combined with other performance enhancing drugs is reported. Postmortem investigations revealed cardiac hypertrophy, acute cellular necrosis and interstitial fibrosis of the myocardium. The side-effects and interactions of the substances used are discussed. Received: 4 November 1997 / Received in revised form: 3 March 1998     

Unclassified sudden infant death associated with pulmonary intra-alveolar hemosiderosis and hemorrhage

The significance of severe pulmonary intra-alveolar hemosiderosis in sudden infant death is controversial in forensic pathology. We report a previously healthy 9-month-old female infant who died suddenly and unexpectedly after being placed and then found prone in her crib. Her gestation and delivery were uncomplicated, and she had no history of anemia, hemoptysis, chest trauma, or chronic lung disease. Autopsy revealed diffuse severe pulmonary congestion and severe multifocal intra-alvedar hemorrhage. Metabolic and toxicological screening, microbiologic cultures, and vitreous chemistry were noncontributory. A diagnosis of SIDS had been made by the medical examiner. Subsequent semiquantitative assessment of the severity of pulmonary intra-alveolar hemosiderosis prompted consideration of other disorders, including a heretofore undescribed lethal infantile variant of idiopathic pulmonary hemosiderosis, but none could be confirmed. Therefore, we assigned a study diagnosis of unclassified sudden infant death. We recommend that a diagnosis of SIDS not be made in cases with unexplained large numbers of intra-alveolar PS. We also recommend that quantitative assessment of lung sections stained for iron be undertaken in cases with numerous intra-alveolar macrophages in order to accumulate data that might allow diagnostic correlations with the circumstances of death and autopsy findings.     

Reaction patterns in selected lymphatic tissues associated with sudden infant death (SID)

In 50 cases of sudden infant death cervical, paratracheal and lung hilar lymph nodes, the thymus and the spleen were investigated by histology and immunohistochemistry (CD 20, 21, 45RO). The cases were divided into 3 groups based on autopsy findings including extensive histology: A – without pathological changes (N = 12), B – with minimal to intermediate inflammation (N = 23) and C – with severe inflammation (N = 15). In accordance with previous results the frequency of “pathological” lymph node changes, such as paracortical lymphoid hyperplasia and variegated hyperplasia of the pulp increased from group A to group C. The B-cell antigens reacted accordingly. A pronounced lymphodepletation of the thymus as a sign of a long lasting stimulation of the T-cell system was also observed increasingly from group A to C. In summary, in none of the cases results obtained were indicative of a defect of the T- or B-cell system. The results in group A seem to indicate that changes in the reaction pattern of the lymphoid tissues could be a more sensitive method of detection of early stages of inflammation than local histology. Received: 14 October 1996 / Received in revised form: 23 December 1996     

Cardiac MRI and CT features of inheritable and congenital conditions associated with sudden cardiac death

Cardiac MRI (CMR) and electrocardiogram (ECG)-gated multi-detector computed tomography (MDCT) are increasingly important tools in the identification and assessment of cardiac-related disease processes, including those associated with sudden cardiac death (SCD). While the commonest cause of SCD is coronary artery disease (CAD), in patients under 35 years inheritable cardiomyopathies such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are important aetiologies. CMR in particular offers both accurate delineation of the morphological abnormalities associated with these and other conditions and the possibility for risk stratification for development of ventricular arrhythmias with demonstration of macroscopic scar by delayed enhancement imaging with intravenous gadolinium.     

Haemorrhagic complication of acute necrotizing pancreatitis presenting with sudden death

Certain complications of acute pancreatitis may lead to death, and of these, haemorrhage caused by rupture of a peri-pancreatic vessel is among the most dangerous. The case reported here was remarkable because the onset of acute necrotizing pancreatitis was completely asymptomatic and the severe haemorrhage of the portal vein that caused the patient's death was only discovered at autopsy. The onset of abdominal pain was immediately followed by death.     

Conduction system abnormalities in alcoholics with asymptomatic valvular disease who suffer sudden death

We examined the cardiac conduction system of three alcohol abusers who died suddenly. Cases 1 and 2 showed mitral valve disorder (mitral valve prolapse and rheumatic valvular disease), while Case 3 showed mild Ebstein's anomaly. On examination of the conduction system, Cases 1 and 2 showed severe fibrofatty infiltration into the conduction system, and we conclude that these findings were probably a complication of alcohol abuse. Both cases also demonstrated severe small artery disease. The conduction system of Case 3 showed an anomalous location of the bundle of His with its fragmentation. These three cases suggest that such considerable conduction system abnormalities may be significant findings in alcohol abusers with valvular disease. We consider that alcohol intake may be one of the direct accelerating factors for arrhythmogenic potential to the abnormal conduction system in alcohol abusers who have asymptomatic valvular disease.     

A case of sudden unexpected infant death involving a homozygotic twin with the thermolabile CPT2 variant,accompanied by rotavirus infection and treatment with an antibiotic containing pivalic acid

We investigated a case of sudden unexpected death involving a 22-month-old male homozygotic twin infant. After both of the twins had suffered from gastroenteritis, one was found dead in his bed, but his brother survived and has since been healthy. Notably, only the deceased had been treated with an antibiotic containing pivalic acid, which may sometimes cause hypocarnitinemia. Postmortem computed tomography and medicolegal autopsy demonstrated severe liver steatosis, and subsequent genetic analysis revealed that the twin had the thermolabile variant of carnitine palmitoyl transferase 2 (CPT2). On the basis of these facts, we concluded that the cause of death had been fatty acid oxidation deficiency accelerated by an antibiotic containing pivalic acid and virus infection in this infant harboring the thermolabile genetic variant of CPT2. Although each factor alone was not fatal, their combination appeared to have resulted in sudden unexpected infant death.     

Whole-exome sequencing and electrophysiological study reveal a novel loss-of-function mutation of KCNA10 in epinephrine provoked long QT syndrome with familial history of sudden cardiac death

Congenital long QT syndrome (LQTS) is one type of inherited fatal cardiac arrhythmia that may lead to sudden cardiac death (SCD). Mutations in more than 16 genes have been reported to be associated with LQTS, whereas the genetic causes of about 20% of cases remain unknown. In the present study, we investigated a four-generation pedigree with familial history of syncope and SCD. The proband was a 33-year-old young woman who experienced 3 episodes of syncope when walking at night. The electrocardiogram revealed a markedly epinephrine-provoked prolonged QT interval (QT = 468 ms, QTc = 651 ms) but no obvious arrhythmia in the resting state. Three family members have died of suspected SCD. Whole-exome sequencing and bioinformatic analysis based on pedigree revealed that a novel missense mutation KCNA10 (c.1397G＞A/Arg466Gln) was the potential genetic lesion. Sanger sequencing was performed to confirm the whole-exome sequencing results. This mutation resulted in the K_V1.8 channel amino acid residue 466 changing from arginine to glutamine, and the electrophysiological experiments verified it as a loss-of-function mutation of K_V1.8, which reduced the K⁺ currents of K_V1.8 and might result in the prolonged QT interval. These findings suggested that KCNA10 (c.1397G＞A) mutation was possibly pathogenic in this enrolled LQTS family, and may provide a new potential genetic target for diagnosis and counseling of stress-related LQTS families as well as the postmortem diagnosis of SCD.     

A rare case of sudden death due to endomyocardial fibrosis in Italy: A differential diagnosis with other causes of restrictive cardiomyopathy

A 45-years-old Indonesian woman was admitted to the hospital with nausea, vomiting, abdominal pain and tachyarrhythmia. Atrial fibrillation was found at ECG, blood tests showed mild hepatic function alterations. Radiological exams showed bilateral pleural effusions, ascites, hepatomegaly. Systolic and diastolic functions of the left ventricle were found to be strongly compromised at US. Physical conditions and laboratory results worsened rapidly, followed by multi organ failure. Death occurred 28 hours after admission. An autopsy was performed to clarify the cause of death and investigated medical malpractice. External examination showed jaundice skin and at internal examination bilateral pleural and pericardial effusions, ascites, mild cardiomegaly, ventricular endocardial fibrosis, a thrombus in tight junction to the left ventricular wall and hepatic necrosis were observed. Histological investigations revealed a massive endomyocardial fibrosis, detected through Azan-Mallory and Verhoef-Van-Gieson stain, and confirmed the presence of hepatic and renal necrosis. Toxicological and microbiological investigations were negative. The cause of death was a global cardiac dysfunction caused by a restrictive cardiomyopathy in an Indonesian woman affected by an undiagnosed and asymptomatic endomyocardial fibrosis. In this case, autopsy and histopathological investigations were fundamental to diagnose an occult endomyocardial fibrosis, which is an idiopathic disorder of tropical and subtropical regions of the world. The not common incidence of this disease in our country and its unusual clinical onset were at first perceived as a medical malpractice from the relatives. Consequently, the clinical aspects of the case intertwine with the medicolegal implications concerning the undiagnosed disease and the causality with the patient's death.     

Anomalous origin of the right coronary artery from the pulmonary artery: An autopsied sudden death case with severe atherosclerotic disease of the left coronary artery

Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare anomaly. It may contribute to myocardial ischemia or sudden death, although the lesion is usually asymptomatic. We report a sudden death case of a 58-year-old man with ARCAPA coexisting with severe atherosclerotic coronary artery disease. He had been healthy until he complained of chest pain, several days before death, despite the discovery of heart murmur in childhood and suspicion of valvular heart disease. The autopsy revealed not only typical findings of the right coronary anomaly with well-developed collateral circulations but also severe atherosclerotic lesions of the left coronary artery, and ischemic change of the myocardium in the left and right coronary arterial perfusion territory. In addition to the “coronary steal” phenomenon primarily caused by ARCAPA, the reduced flow of both coronary arteries and further increase of “coronary steal” due to atherosclerotic obstructive coronary disease might have contributed to the patient’s death.     

Use of postmortem coronary computed tomography angiography with water-insoluble contrast medium to detect stenosis of the left anterior descending artery in a case of sudden death

A 40-year-old man was found dead on a sidewalk in an expressway parking area one hour after he had entered the area on a motorcycle. A medicolegal autopsy was performed to reveal the cause of this sudden and unexpected death. Postmortem coronary CT angiography after introduction of 5% gelatin–barium emulsion as a radiopaque contrast medium into the heart demonstrated a significant arterial luminal filling defect in the left anterior descending (LAD) coronary artery. Macroscopic and microscopic examinations revealed that a thrombus had become deposited on ruptured plaque within the LAD artery, and that a small amount of the contrast medium was present between the thrombus and the vessel endothelium. These histological findings were consistent with incomplete occlusion of the LAD artery in the 3D reconstructed image. The cause of death in this case was definitively determined to be ischemic heart disease. Postmortem angiography played a role in screening of a vascular lesion that was subsequently verified by histology to have been responsible for sudden and unexpected death.     

A sudden infant death associated with atrial septal aneurysm and abnormality of the connecting site between the inferior vena cava and right atrium

An atrial septal aneurysm (ASA) is a rare cardiac anomaly characterized by varicose bulging of the atrial septum (oval fossa) into the left or right atrium. Pathogenesis and clinical significance of ASA are controversial. We report an autopsy case of a huge undiagnosed ASA with abnormality of the connecting site between the inferior vena cava and the right atrial ostium in a 2-month-old Japanese female who died suddenly and unexpectedly. She was born at 36 weeks 4 days (body weight 3,110 g). No abnormality was detected during pregnancy or delivery. The postnatal growth was normal with no cardiac problem detected at the 1-month checkup. The ASA bulged off in a mass to the left atrium (width, 0.8 cm; excursion ratio, 53%), reaching close to the inflow site of the right pulmonary vein, with dilation of the pulmonary vein. The connecting site between the inferior vena cava and the right atrium was atypically located 1.6 cm away from the atrioventricular groove. Although most cases of ASA in an infant resolve physiologically as the infant grows, the infant in the present case is thought to have had an exceptional pathological ASA, possibly causing supraventricular arrhythmia. The abnormality of the connecting site between the inferior vena cava and the right atrium might have affected the development and continuation of the ASA.     

Real-time quantitative PCR assay for the detection of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>: no association with sudden infant death syndrome

Helicobacter pylori infection is known to be one of the most common chronic infectious diseases in humans. Recently, a hypothesis was proposed that H. pylori infection could be a frequent cause for sudden infant death syndrome (SIDS). We have investigated this postulated association by examining formalin-fixed paraffin-embedded gastric tissues of a retrospective cohort of 94 SIDS cases: The presence of H. pylori was inferred from a newly developed real-time quantitative PCR assay with SYBR Green I detection. This assay is based on the amplification of the single-copy H. pylori–specific glmM gene. Accuracy and precision were verified using a plasmid containing a 977-bp fragment of this glmM gene. The assay was very sensitive, and as few as 30 template copies per PCR reaction could be detected even in the presence of excess human DNA. The assay was validated on mucosal biopsy samples of patients with known H. pylori infections. Interfering effects due to SIDS gastric tissue were excluded. Only two (2.1%) of the SIDS samples yielded H. pylori DNA copy numbers and only beyond the lowest standard concentration. These results could be confirmed independently by immunohistochemistry using an H. pylori–specific antibody. Thus, an infection by H. pylori is very rare in cases of SIDS, and thus the postulated association of H. pylori infection and SIDS cannot be confirmed.This work was supported by grants from IMF (Innovative Medizinische Forschung, BA 2 1 01 05), Münster University Hospital, Germany, and the Ministry of Education and Science of Germany (01 ED 9401).