Case report of a fatal intoxication by Nucynta.

Tapentadol (Nucynta) is a centrally acting opioid analgesic prescribed for the treatment of moderate to severe acute pain. Its efficacy is believed to be due to µ-opioid receptor agonist activity and inhibition of norepinephrine reuptake resulting in increased norepinephrine concentrations. There is only one other case in the literature relating to the toxicity of this agent or report of a fatality. This case report documents a case in which tapentadol was identified as the cause of death. The tapentadol concentration found in the heart blood submitted in this case was more than 20 times the upper limit of the therapeutic range. Possible mechanisms of death include respiratory depression, central nervous system depression, and serotonin syndrome. Based on the scene investigation and autopsy findings in this case, the medical examiner determined that the cause of death was narcotic (Nucynta) intoxication and the manner of death was undetermined.

Quantitative Immunohistochemistry of Desmosomal Proteins (Plakoglobin, Desmoplakin and Plakophilin), Connexin-43, and N-cadherin in Arrhythmogenic Cardiomyopathy: An Autopsy Study.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder related to mutations in desmosomal proteins. The current study tests the hypothesis that immunohistochemical staining for desmosomal proteins is of diagnostic utility by studying autopsy-confirmed cases of ARVC. METHODS AND RESULTS: We studied 23 hearts from patients dying suddenly with ARVC. Control subject tissues were 21 hearts from people dying from non-cardiac causes (n=15), dilated cardiomyopathy (n=3) and coronary artery disease (n=3). Areas free of fibrofatty change or scarring were assessed on 50 sections from ARVC (24 left ventricle, 26 right ventricle) and 28 sections from controls. Immunohistochemical stains against plakoglobin, plakophilin, desmoplakin, connexin-43, and N-cadherin were applied and area expression analyzed by computerized morphometry. Desmin was stained as a control for fixation and similarly analyzed. The mean area of desmin expression was similar in controls and ARVC (86% vs. 85%, p=0.6). Plakoglobin expression was 4.9% ± 0.3% in controls, vs. 4.6% ± 0.3% in ARVC (p=0.3). Plakophilin staining was 4.8% ± 0.3% in controls vs. 4.4% ± 03% in ARVC (p=0.3). Desmoplakin staining was 3.4% in controls vs. 3.2 ± 0.2% in ARVC (p=0.6). There were no significant differences when staining was compared between right and left ventricles (all p > 0.1). For non-desmosomal proteins, the mean area of connexin-43 staining showed no significant difference by presence of disease. CONCLUSIONS: The small and insignificant decrease in junction protein expression in ARVC suggests that immunohistochemistry is not a useful tool for the diagnosis.

Distribution of biventricular disease in arrhythmogenic cardiomyopathy: an autopsy study.

Arrhythmogenic cardiomyopathy is a rare cardiomyopathy characterized by fibrofatty replacement primarily of the right ventricular myocardium. It is a major cause of sudden death in the young and in athletes. There are few autopsy studies of the ventricular distribution of the disease. Fifty cases of sudden cardiac death with fibrofatty replacement in either ventricle from a single medical examiner's office were studied. Distribution of disease as determined grossly and microscopically was correlated with activity at time of death, race, and presence of inflammation. Extent of disease was right ventricular in 6 cases (12%; age, 25 ± 5 years), biventricular in 25 (50%; age, 36 ± 3 years), and left ventricular in 19 (38%; age, 37 ± 3 years) (P = .13). Inflammation was present in 44% of biventricular arrhythmogenic cardiomyopathy versus 74% of left ventricular arrhythmogenic cardiomyopathy and 83% of right ventricular arrhythmogenic cardiomyopathy (P = .06). Arrhythmogenic cardiomyopathy, when presenting with sudden death, is usually biventricular. There is a trend that univentricular involvement occurs at an earlier age and that right ventricular involvement shows more inflammation, suggesting different stages of disease.

[Frequency of acute plaque ruptures and thin cap atheromas at sites of maximal stenosis].

BACKGROUND: There have been few autopsy studies relating sites of thin cap atheroma (TCFA) to sites of acute plaque rupture in culprit arteries, and sites of maximal narrowing in non-culprit arteries. OBJECTIVE: We aimed to quantify and locate the frequency of TCFA related to the sites of maximal stenosis in atherosclerotic plaques. METHODS: We studied 88 hearts in victims of sudden death dying with coronary thrombus overlying acute plaque rupture. Thin cap atheromas were defined as fibrous cap < 65 microns overlying a necrotic core. Percent luminal narrowing was determined at the sites of plaque rupture and thin cap atheromas. RESULTS: There were 81 men and 7 women, mean age 50 years +/- 9 SD. The plaque rupture was the site of maximal luminal narrowing in 47% of culprit arteries. TCFAs were present in 67 hearts (83%). Of these, 49 (73%) demonstrated TCFAs in the culprit artery; 17 (25%) in the culprit artery only, 32 (48%) in the culprit artery and in a non-culprit artery, and 18 (27%) only in a non-culprit artery. In non-culprit arteries, TCFAs represented the maximal site of stenosis in 44% of arteries. The acute rupture site is the site of maximal luminal narrowing in the involved vessel in 47% of hearts from patients dying with acute plaque rupture. CONCLUSION: These data may suggest that luminal narrowing is not a reliable marker for TCFA.

Frequência de rupturas agudas de placas e fibroateromas de capa fina em locais de estenose máxima / Frecuencia de rupturas agudas de placas y fibroateromas de capa fina en locales de estenosis máxima / Frequency of acute plaque ruptures and thin cap atheromas at sites of maximal stenosis

FUNDAMENTO: Poucos estudos de autópsia relacionam locais de fibroateromas de capa fina (FCF) a locais de ruptura aguda de placas em artérias responsáveis, e locais de estreitamento máximo em artérias não responsáveis. OBJETIVO: O objetivo do presente estudo foi quantificar e localizar a frequência de FCF em relação aos locais de estenose máxima em placas ateroscleróticas. MÉTODOS: Estudamos 88 corações em vítimas de morte súbita devido a um tromo coronariano sobreposta a ruptura aguda da placa. Fibroateromas de capa fina foram definidos como capa fibrosa < 65 mícrons sobrepostos a um núcleo necrótico. O percentual de estreitamento luminal foi determinado nos locais de ruptura de placa e fibroateromas de capa fina. RESULTADOS: O estudo foi composto por 81 homens e 7 mulheres com idade média de 50 anos ± 9 DP. A ruptura da placa se deu no local de estreitamento luminal máximo em 47 por cento das artérias responsáveis. Observou-se a presença de FCFs em 67 corações (83 por cento). Desse número, 49 (73 por cento) demonstravam FCFs na artéria responsável; 17 (25 por cento) apenas na artéria responsável, 32 (48 por cento) na artéria responsável e na artéria não responsável, e 18 (27 por cento) apenas em uma artéria não responsável. Em artérias não responsáveis, os FCFs representaram o local máximo da estenose em 44 por cento das artérias. O local da ruptura aguda foi o local do estreitamento luminal máximo nos vasos envolvidos em 47 por cento de corações de pacientes próximos do óbito devido à ruptura da placa. CONCLUSÃO: Esses dados podem sugerir que o estreitamento luminal não é um marcador confiável para FCF.

BACKGROUND: There have been few autopsy studies relating sites of thin cap atheroma (TCFA) to sites of acute plaque rupture in culprit arteries, and sites of maximal narrowing in non-culprit arteries. OBJECTIVE: We aimed to quantify and locate the frequency of TCFA related to the sites of maximal stenosis in atherosclerotic plaques. METHODS: We studied 88 hearts in victims of sudden death dying with coronary thrombus overlying acute plaque rupture. Thin cap atheromas were defined as fibrous cap < 65 microns overlying a necrotic core. Percent luminal narrowing was determined at the sites of plaque rupture and thin cap atheromas. RESULTS: There were 81 men and 7 women, mean age 50 years ± 9 SD. The plaque rupture was the site of maximal luminal narrowing in 47 percent of culprit arteries. TCFAs were present in 67 hearts (83 percent). Of these, 49 (73 percent) demonstrated TCFAs in the culprit artery; 17 (25 percent) in the culprit artery only, 32 (48 percent) in the culprit artery and in a non-culprit artery, and 18 (27 percent) only in a non-culprit artery. In non-culprit arteries, TCFAs represented the maximal site of stenosis in 44 percent of arteries. The acute rupture site is the site of maximal luminal narrowing in the involved vessel in 47 percent of hearts from patients dying with acute plaque rupture. CONCLUSION: These data may suggest that luminal narrowing is not a reliable marker for TCFA.

FUNDAMENTO: Pocos estudios de autopsia relacionan locales de fibroateromas de capa fina (FCF) a locales de ruptura aguda de placas en arterias responsables, y locales de estrechamiento máximo en arterias no responsables. OBJETIVO: El objetivo del presente estudio fue cuantificar y localizar la frecuencia de FCF con relación a los locales de estenosis máxima en placas ateroscleróticas. MÉTODOS: Estudiamos 88 corazones en víctimas de muerte súbita debido a un trombo coronario sobrepuesto a ruptura aguda de la placa. Fibroateromas de capa fina fueron definidos como capa fibrosa < 65 micrones sobrepuestos a un núcleo necrótico. El porcentaje de estrechamiento luminal fue determinado en los locales de ruptura de placa y fibroateromas de capa fina. RESULTADOS: El estudio estuvo compuesto por 81 hombres y 7 mujeres con edad promedio de 50 años ± 9 SD. La ruptura de la placa se dio en el local de estrechamiento luminal máximo en el 47 por ciento de las arterias responsables. Se observó la presencia de FCFs en 67 corazones (83 por ciento). De ese número, 49 (73 por ciento) mostraban FCFs en la arteria responsable; 17 (25 por ciento) sólo en la arteria responsable, 32 (48 por ciento) en la arteria responsable y en la arteria no responsable, y 18 (27 por ciento) sólo en una arteria no responsable. En arterias no responsables, los FCFs representaron el local máximo de la estenosis en el 44 por ciento de las arterias. El local de la ruptura aguda fue el local del estrechamiento luminal máximo en los vasos involucrados en el 47 por ciento de corazones de pacientes próximos al óbito debido a la ruptura de la placa. CONCLUSIÓN: Estos datos pueden sugerir que el estrechamiento luminal no es un marcador confiable para FCF.