RESUMEN
INTRODUCTION: Sudden unexplained death account for one-third of all sudden natural deaths in the young (1-35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long-QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide setting. METHODS: DNA for genetic testing was available for 44 cases of sudden unexplained death in Denmark in the period 2000-2006 (equaling 33% of all cases of sudden unexplained death in the age group). KCNQ1, KCNH2, and SCN5A were sequenced and in vitro electrophysiological studies were performed on novel mutations. RESULTS: In total, 5 of 44 cases (11%) carried a mutation in 1 of the 3 genes corresponding to 11% of all investigated cases (R190W KCNQ1, F29L KCNH2 (2 cases), P297S KCNH2 and P1177L SCN5A). P1177L SCN5A has not been reported before. In vitro electrophysiological studies of P1177L SCN5A revealed an increased sustained current suggesting a LQTS phenotype. CONCLUSION: In a nationwide setting, the genetic investigation of an unselected population of sudden unexplained death cases aged 1-35 years finds a lower than expected number of mutations compared to referred populations previously reported. We therefore conclude that the prevalence of mutations in the 3 major LQTS associated genes may not be as abundant as previously estimated.
Asunto(s)
Muerte Súbita Cardíaca/etiología , Canales de Potasio Éter-A-Go-Go/genética , Canal de Potasio KCNQ1/genética , Síndrome de QT Prolongado/genética , Mutación , Canal de Sodio Activado por Voltaje NAV1.5/genética , Adolescente , Adulto , Factores de Edad , Análisis de Varianza , Autopsia , Niño , Preescolar , Estudios de Cohortes , Análisis Mutacional de ADN , Muerte Súbita Cardíaca/epidemiología , Dinamarca , Canal de Potasio ERG1 , Técnicas Electrofisiológicas Cardíacas , Canales de Potasio Éter-A-Go-Go/metabolismo , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Células HEK293 , Humanos , Lactante , Canal de Potasio KCNQ1/metabolismo , Síndrome de QT Prolongado/metabolismo , Síndrome de QT Prolongado/mortalidad , Masculino , Potenciales de la Membrana , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Técnicas de Placa-Clamp , Linaje , Fenotipo , Síndrome de Romano-Ward/genética , Síndrome de Romano-Ward/mortalidad , Transfección , Adulto JovenRESUMEN
BACKGROUND: Inherited disease may be causative in many young sudden unexpected death cases. Autopsy is essential in the counselling of the bereaved, as the family of the victim may be at risk too. In a nationwide setting operating under the same set of laws, we hypothesized that regional differences exist in the investigation of young persons dying suddenly and unexpectedly. METHODS AND RESULTS: All deaths in persons aged 1-35 years in Denmark in 2000-2006 were included. Death certificates were read independently by two physicians. External examination as well as autopsy status was retrieved. Significant regional differences were found regarding external examinations and autopsy frequencies. Ratios of conducted external examinations varied between 63% and 93% (p = 0.004). Autopsy ratios varied between 60% and 88% (p = 0.001). In urban areas, external examinations and autopsies were more often conducted than in rural areas. In East Denmark, there were more external examinations resulting in a forensic autopsy, and there was a higher overall autopsy rate compared to West Denmark. CONCLUSION: Despite operating under the same set of laws, we document significant regional differences in forensic investigations of young persons suffering a sudden unexpected death. This is probably not unique for Denmark although no data exist to confirm that. The results are worrying and call for a revision of the way these deaths are handled. Mandatory autopsy in sudden unexpected death in young persons is warranted as a thorough investigation of the death may help the clinician in guidance of the relatives in relation to hereditary diseases.
Asunto(s)
Autopsia/estadística & datos numéricos , Causas de Muerte , Muerte Súbita/patología , Adolescente , Adulto , Niño , Preescolar , Muerte Súbita/epidemiología , Dinamarca/epidemiología , Femenino , Humanos , Incidencia , Lactante , Masculino , Adulto JovenRESUMEN
BACKGROUND: Incidence of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) differs among studies and non-autopsied cases are difficult to assess. OBJECTIVES: To investigate causes of sudden death in infancy in a nationwide setting. Validate the use of the ICD-10 code for SIDS (R95) in the Danish Cause of Death registry. DESIGN: A retrospective analysis of all infant deaths (< 1 year of age) in Denmark in 2000-2006. All death certificates and autopsy reports were read. RESULTS: We identified 192 SUDI cases (10% of total deaths, 0.42 per 1000 births) with autopsy performed in 87% of cases. In total, 49% of autopsied SUDI cases were defined as SIDS (5% of all deaths, 0.22 per 1000 births); Cardiac cause of death was denoted in 24% of cases. The Danish Cause of Death Registry misclassified 30% of SIDS cases. CONCLUSIONS: A large proportion of infant deaths are SUDI, and the majority of these are caused by cardiac disease or SIDS. Autopsy is not always performed and valuable information is subsequently lost. Cause of Death registry data is not accurate in describing SIDS.
Asunto(s)
Causas de Muerte , Clasificación Internacional de Enfermedades , Registros , Muerte Súbita del Lactante/epidemiología , Autopsia , Certificado de Defunción , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Muerte Súbita del Lactante/clasificaciónRESUMEN
AIMS: The aim of this investigation was to study the incidence of sudden cardiac death (SCD) in persons aged 1-35 years in a nationwide setting (5.38 million people) by systematic evaluation of all deaths. METHODS AND RESULTS: All deaths in persons aged 1-35 years in Denmark in 2000-06 were included. Death certificates were read independently by two physicians. The National Patient Registry was used to retrieve information on prior medical history. All autopsy reports were read and the cause of death was revised based on autopsy findings. We identified 625 cases of sudden unexpected death (10% of all deaths), of which 156 (25%) were not autopsied. Of the 469 autopsied cases, 314 (67%) were SCD. The most common cardiac cause of death was ischaemic heart disease (13%); 29% of autopsied sudden unexpected death cases were unexplained. In 45% of SCD cases, the death was witnessed; 34% died during sleep; 89% were out-of-hospital deaths. Highest possible incidence rate of SCD in the young was 2.8 per 100 000 person-years including non-autopsied cases of sudden unexpected death. Excluding those, the incidence rate declined to 1.9 per 100 000 person-years. CONCLUSIONS: A total of 7% of all deaths in the young can be attributed to SCD, when including non-autopsied cases (autopsy ratio 75%). The incidence rate of SCD in the young of 2.8 per 100 000 person-years is higher than previously reported.
Asunto(s)
Muerte Súbita Cardíaca/epidemiología , Adolescente , Adulto , Distribución por Edad , Autopsia , Causas de Muerte , Niño , Preescolar , Certificado de Defunción , Dinamarca/epidemiología , Humanos , Incidencia , Lactante , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Studies on incidences of sports-related sudden cardiac death (SrSCD) are few and data are needed for the discussion of preparticipation screening for cardiac disease. OBJECTIVE: We sought to chart the incidence and etiology of SrSCD in the young in Denmark (population 5.4 million) and to compare this to the incidence of sudden cardiac death (SCD) in the background population. METHODS: All 5,662 death certificates for decedents in the period 2000 to 2006 in the age group 12 to 35 years in Denmark were read independently by 2 physicians to identify cases of SCD. Information from autopsy reports, selected hospital records, and multiple registries was used to identify cases of SCD and SrSCD. SrSCD was defined as SCD occurring during or within 1 hour after exercise in a competitive athlete. The size of the athlete population was estimated from national survey data. RESULTS: Fifteen (range 0 to 5 per year) cases of SrSCD were found, 8 of which had antecedent symptoms. The incidence rate was 1.21 (95% confidence interval [CI]: 0.68 to 2.00) per 100,000 athlete person-years. The most common autopsy findings were arrhythmogenic right ventricular cardiomyopathy (n = 4), sudden unexplained death (n = 4), and coronary artery disease (n = 2). The incidence of SCD in the general population age 12 to 35 was 3.76 (95% CI: 3.42 to 4.14) per 100,000 person-years. CONCLUSION: In Denmark, SrSCD is a rare occurrence and the incidence rate is lower than that of SCD in the general population. This may imply a low value of preparticipation screening of athletes in Denmark.
Asunto(s)
Muerte Súbita Cardíaca/etiología , Cardiopatías/diagnóstico , Tamizaje Masivo , Deportes , Adolescente , Adulto , Niño , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/patología , Muerte Súbita Cardíaca/prevención & control , Dinamarca/epidemiología , Humanos , Incidencia , Masculino , Medicina Deportiva , Estados Unidos/epidemiología , Adulto JovenAsunto(s)
Fármacos Antiobesidad/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Enfermedad Coronaria/complicaciones , Muerte Súbita Cardíaca/etiología , Efedrina/efectos adversos , Adulto , Cafeína/efectos adversos , Causas de Muerte , Enfermedad Coronaria/patología , Muerte Súbita Cardíaca/patología , Combinación de Medicamentos , Ejercicio Físico , Resultado Fatal , Humanos , MasculinoRESUMEN
Hypertrophic cardiomyopathy (HCM) may have sudden death as its first presentation. This case presentation describes a 25-year-old man with post-mortem finding of previously unknown left ventricular hypertrophy. Genetic analysis revealed a mutation in the myosin-binding protein C (MYBPC3). Autopsy combined with molecular genetic screening for mutations may give the relatives certainty of cause of death and the opportunity for genetic screening for diagnosis and treatment as well as prevention of sudden cardiac death.
Asunto(s)
Cardiomiopatía Hipertrófica Familiar/patología , Muerte Súbita Cardíaca/etiología , Adulto , Autopsia , Proteínas Portadoras/genética , Causas de Muerte , Resultado Fatal , Humanos , Masculino , MutaciónAsunto(s)
Enfermedades Cardiovasculares/etiología , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Tejido Conectivo/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/complicaciones , Humanos , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen , UltrasonografíaRESUMEN
We surveyed our data over a 15-year period to determine the prevalence of cardiomyopathy diagnoses in our database and characterized the cases in regards to demographic and clinicopathological data. Furthermore we evaluated implications for screening. The data were acquired through our computerized database containing autopsy reports. Only cases with typical anatomical and histological features were included. The total number of autopsies in the studied period was 7,185 of which 32 suited the following criteria: 14 arrythmogenic right ventricular cardiomyopathies (ARVC), 8 hypertrophic cardiomyopathies (HCM), 8 dilated cardiomyopathies (DCM) and 2 other cardiomyopathies. Symptoms of cardiac disease were present in 8 ARVC, 3 HCM and 7 DCM cases. Symptoms of cardiac disease, including suspected sudden cardiac deaths, were present in the families of 5 cases. In two of these families the illnesses were discovered as a result of testing after autopsy. We underscore that these diseases are difficult to diagnose as the presenting symptoms are elusive. We found the circumstances around death to be extremely varied, and found that new hereditary cases could be discovered after autopsy. This places an intriguing perspective on the integration of standardized screening protocols with participation from forensic institutes.
Asunto(s)
Cardiomiopatías/mortalidad , Adolescente , Adulto , Anciano , Cardiomiopatías/genética , Niño , Bases de Datos Factuales , Dinamarca/epidemiología , Patologia Forense , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Miocardio/patología , Tamaño de los Órganos , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Information about the expression of atherosclerosis in different arteries is important. The impact of cardiovascular risk factors is artery-related, and the assessment of arterial structure and function in peripheral arteries are increasingly used as surrogate markers for coronary atherosclerosis and the risk of developing heart attack. METHODS: In an autopsy study, we analyzed the coronary, carotid and superficial femoral arteries from 100 individuals (70 men; 20 to 82 years of age) of which 27 died from coronary atherosclerosis. Microscopic sections (n=4756) were analyzed blindly using a modification of the histological classification endorsed by the American Heart Association (AHA). RESULTS: We found distinct artery-dependent patterns of atherosclerosis with a high prevalence of foam cell lesions and lipid core plaques in the carotid arteries. The femoral arteries were least affected by atherosclerosis, foam cell lesions were rare, and the development of advanced atherosclerosis was strongly age-dependent and dominated by fibrous plaques. Plaques were most common in the left anterior descending coronary artery and the carotid bifurcation. In coronary (versus noncoronary) death, lipid core plaques were more prevalent in all arteries. CONCLUSIONS: The initiation, speed of development, and phenotypic expression of atherosclerotic plaques are artery-related. Foam cell lesions are frequent in the carotid arteries, probably explaining the dynamics in carotid intima-media thickness. Atherosclerosis develops slowly in femoral arteries, and severe atherosclerosis is dominated by fibrous plaques. The higher prevalence of lipid core plaques in all arteries in coronary death indicates a systemically more vulnerable expression of atherosclerosis in these individuals.
Asunto(s)
Aterosclerosis/patología , Enfermedades de las Arterias Carótidas/clasificación , Enfermedades de las Arterias Carótidas/patología , Enfermedad de la Arteria Coronaria/clasificación , Enfermedad de la Arteria Coronaria/patología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , American Heart Association , Enfermedades de las Arterias Carótidas/mortalidad , Causas de Muerte , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Arteria Femoral/patología , Células Espumosas/patología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Distribución por Sexo , Túnica Íntima/patología , Túnica Media/patología , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: This study was performed to identify the substances used in deliberate self-poisoning and to investigate the epidemiological characteristics of these cases, with the goal of improving prevention of suicides. MATERIALS AND METHODS: The material is made up of 121 cases of deliberate self-poisoning examined at the Institute of Forensic Medicine, University of Aarhus, during the years 1994-2003. The cases were subjected to a forensic autopsy and a toxicological screening for alcohol, drugs, carbon monoxide, cyanide and pesticides. RESULTS: This material included only 12% of the cases of deliberate self-poisoning in the area serviced by the Institute. 70% were caused by legal drugs and 17% by carbon monoxide. A total of 52 different substances were found. In one third of the cases, two or more substances were found in a lethal concentration. Analgesics and antidepressants were the most common of these. The wide range of substances used was subject to change during the period of investigation. In addition, 40 different substances in therapeutic or only slightly increased concentrations were found. In most cases, the deceased was unemployed, living alone, suffering from a psychiatric disease and addicted to legal or illegal drugs or alcohol. In half the cases, there had been a previous suicide attempt. CONCLUSION: It is recommended that only small amounts of drugs be prescribed to persons in danger of committing suicide, as identified by the above-mentioned characteristics.
Asunto(s)
Intoxicación/epidemiología , Suicidio/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos/envenenamiento , Antidepresivos/envenenamiento , Autopsia , Intoxicación por Monóxido de Carbono/epidemiología , Intoxicación por Monóxido de Carbono/prevención & control , Dinamarca/epidemiología , Prescripciones de Medicamentos , Femenino , Medicina Legal , Humanos , Hipnóticos y Sedantes/envenenamiento , Masculino , Persona de Mediana Edad , Intoxicación/prevención & control , Estudios Retrospectivos , Factores Socioeconómicos , Prevención del SuicidioRESUMEN
The Armanni-Ebstein phenomenon is a vacuolization of the cells of the proximal kidney tubules in diabetic coma. It has been believed to represent glycogen. In the present examination of 14 cases of diabetic coma, high contents of lipids, probably triglycerides, were demonstrated in the vacuoles by histological staining. Only weak positive reactions were found in diabetic controls. In both alcoholic and nonalcoholic-nondiabetics, no lipid was found. The sensivity was very high, but it was difficult from the present material to ascertain the level of specificity. The authors suggest the term fatty kidney in diabetics.
RESUMEN
Lemierre syndrome is a rare clinical entity involving oropharyngeal infection and anaerobic bacteremia, followed by jugular vein septic thrombophlebitis with embolization and metastatic abscess formation in the lungs, liver, and other organs. Even though it occurs less frequently than in the pre-antibiotic era, it is still important both as a pathologist and as a clinician to recognize the typical presentation because of its lethal potential. Three clinically undiagnosed cases with lethal outcomes are described. All three cases presented as unexpected death, and all were autopsied at the Institute of Forensic Medicine, University of Aarhus.
RESUMEN
Meckel's diverticulum is an uncommon cause of intestinal obstruction in adult life. Rarely Meckel's diverticulum is complicated by a mesodiverticular band, which is believed to be a remnant of a vitelline artery. When this abnormality occurs it is associated with high mortality. We present a case of a 48-year-old man with increasing abdominal pain and vomiting for 3 days. Meckel's diverticulum was not taken into diagnostic consideration, and the man died. Autopsy revealed a Meckel's diverticulum with a mesodiverticular band and intestinal obstruction. Histological examination of cross sections of the mesodiverticular band showed the presence of an artery. Because of the high mortality of this rare anatomic anomaly in adults, we find the case of interest.