Cardiovascular Pathology. 004. Pathomorphological and CT-angiographical characteristics of coronary atherosclerotic plaques in cases of sudden cardiac death

Objective. The goal of this study was to present the pathological and radiological patterns of "vulnerable" atherosclerotic plaques in cases of sudden cardiac death. Method. This retrospective study was performed on forensic cases for which the cause of death was attributed to coronary artery disease. A complete autopsy was performed in all cases, along with either post-mortem CT-angiography, toxicological analyses and/or biochemistry. Results. 89 cases were selected (mean age 55±11.6 years; 75 men and 14 women). In 96.6% of cases a CT-angiography was performed. Acute coronary lesions were found in 60 cases (mean age 53±11.1 years), which included plaque erosion in 26 cases (mean age 47±8.3 years) and ruptures or intraplaque hemorrhage in 33 cases (mean age 58±10.4 years). Erosions were most frequently found in the left ascending artery (61.5 %), while only 36% of ruptures were observed in this artery. Chronic coronary pathology was described in 30 cases (mean age 58±10.4 years). CT-angiographies performed prior to the autopsy enabled an initial evaluation of coronary artery perfusion. Conclusion. In the face of decreasing clinical autopsy rates, postmortem studies on forensic autopsies, including modern radiological examinations, allow for a more thorough understanding of the clinical picture of disease which can result in sudden cardiac death.

Postmortem imaging: real or virtual?

Since the earliest years after the discovery of X-rays, radiological images have been used successfully for answering medico-legal and forensic questions. The possibility to evaluate the inside of a body without actually opening it has been appreciated and used in forensic pathology since then. However, the introduction of modern cross-sectional imaging techniques into post-mortem investigations has created controversial discussions among the medico-legal community. Terms like "Virtual Autopsy" and "Necro-Radiology" have led to confusion and controversy concerning the role of radiological techniques in forensic case work. Regardless, the use of those techniques in post-mortem investigations is increasing, especially the one of Muti-Detector Computed Tomography (MDCT). But also other imaging techniques such as Postmortem Angiography and Magnetic Resonance Imaging are increasingly applied. This presentation shall give an overview over the different techniques of postmortem imaging. It will critically explain their advantages and limitations in forensic death investigations compared to conventional autopsy. The role of postmortem imaging shall be discussed in order to distinguish between real state of the art and virtual reality.

Simulit, un modèle de simulation pour la planification hospitalière. [Simulit, a simulation model for hospital planning].

The aim of this computerized simulation model is to provide an estimate of the number of beds used by a population, taking into accounts important determining factors. These factors are demographic data of the deserved population, hospitalization rates, hospital case-mix and length of stay; these parameters can be taken either from observed data or from scenarii. As an example, the projected evolution of the number of beds in Canton Vaud for the period 1893-2010 is presented.

Análisis comparativo de trestraducciones al castellano delcuentoVom Fischer und seiner Frau

El presente trabajo analiza hasta qué punto el paso del tiempo y la evolución de la lengua pueden afectar a las traducciones que derivan de un mismo original. Esta comparación se ha realizado a partir del cuento Vom Fischer und seiner Frau, recogido por los hermanos Grimm en su antología.

Rpe65-Gene Transfer Using an Integration-Deficient Lentiviral Vector

Purpose: We previously demonstrated efficient retinal rescue of RPE65 mouse models (Rpe65-/- (Bemelmans et al, 2006) and Rpe65R91W/R91W mice) using a HIV1-derived lentiviral vector encoding for the mouse RPE65 cDNA. In order to optimize a lentiviral vector as an alternative tool for RPE65-derived Leber Congenital Amaurosis clinical trials, we evaluated the efficiency of an integration-deficient lentiviral vector (IDLV) encoding the human RPE65 cDNA to restore retinal function in the Rpe65R91W/R91W mice. Methods: An HIV-1-derived lentiviral vector expressing either the hrGFPII or the human Rpe65 cDNA under the control of a 0.8 kb fragment of the human Rpe65 promoter (R0.8) was produced by transient transfection of 293T cells. A LQ-integrase mutant was used to generate the IDLV vectors. IDLV-R0.8-hRPE65 or hrGFPII were injected subretinally into 1 month-old Rpe65R91W/R91W mice. Functional rescue was assessed by ERG (1 and 3 months post-injection) and cone survival by immunohistology. Results: An increased light sensitivity was detected by scotopic ERG in animals injected with IDLV-R0.8-hRPE65 compared to hrGFPII-treated animals or untreated mice. However the improvement was delayed compared to integration-proficient LV and observed at 3 months but not 1 month post-injection. Immunolabelling of cone markers showed an increased number of cones in the transduced area compared to control groups. Conclusions: The IDLV-R0.8-hRPE65 vectors allow retinal improvement in the Rpe65R91W/R91W mice. Both rod function and cone survival were demonstrated even if there is a delay in the rescue as assessed by scotopic ERG. Integration-deficient vectors minimize insertional mutagenesis and thus are safer candidates for human application. Further experiments using large animals are now needed to validate correct gene transfer and expression of the RPE65 gene as well as tolerance of the vector after subretinal injection before envisaging a clinical trial application.

In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death.

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods.

Reduction of respiratory motion artifacts for free-breathing whole-heart coronary MRA by weighted iterative reconstruction.

PURPOSE: To combine weighted iterative reconstruction with self-navigated free-breathing coronary magnetic resonance angiography for retrospective reduction of respiratory motion artifacts. METHODS: One-dimensional self-navigation was improved for robust respiratory motion detection and the consistency of the acquired data was estimated on the detected motion. Based on the data consistency, the data fidelity term of iterative reconstruction was weighted to reduce the effects of respiratory motion. In vivo experiments were performed in 14 healthy volunteers and the resulting image quality of the proposed method was compared to a navigator-gated reference in terms of acquisition time, vessel length, and sharpness. RESULT: Although the sampling pattern of the proposed method contained 60% more samples with respect to the reference, the scan efficiency was improved from 39.5 ± 10.1% to 55.1 ± 9.1%. The improved self-navigation showed a high correlation to the standard navigator signal and the described weighting efficiently reduced respiratory motion artifacts. Overall, the average image quality of the proposed method was comparable to the navigator-gated reference. CONCLUSION: Self-navigated coronary magnetic resonance angiography was successfully combined with weighted iterative reconstruction to reduce the total acquisition time and efficiently suppress respiratory motion artifacts. The simplicity of the experimental setup and the promising image quality are encouraging toward future clinical evaluation. Magn Reson Med 73:1885-1895, 2015. © 2014 Wiley Periodicals, Inc.

Postmortem magnetic resonance imaging of the heart ex situ: development of technical protocols.

Postmortem MRI (PMMR) examinations are seldom performed in legal medicine due to long examination times, unfamiliarity with the technique, and high costs. Furthermore, it is difficult to obtain access to an MRI device used for patients in clinical settings to image an entire human body. An alternative is available: ex situ organ examination. To our knowledge, there is no standardized protocol that includes ex situ organ preparation and scanning parameters for postmortem MRI. Thus, our objective was to develop a standard procedure for ex situ heart PMMR examinations. We also tested the oily contrast agent Angiofil® commonly used for PMCT angiography, for its applicability in MRI. We worked with a 3 Tesla MRI device and 32-channel head coils. Twelve porcine hearts were used to test different materials to find the best way to prepare and place organs in the device and to test scanning parameters. For coronary MR angiography, we tested different mixtures of Angiofil® and different injection materials. In a second step, 17 human hearts were examined to test the procedure and its applicability to human organs. We established two standardized protocols: one for preparation of the heart and another for scanning parameters based on experience in clinical practice. The established protocols enabled a standardized technical procedure with comparable radiological images, allowing for easy radiological reading. The performance of coronary MR angiography enabled detailed coronary assessment and revealed the utility of Angiofil® as a contrast agent for PMMR. Our simple, reproducible method for performing heart examinations ex situ yields high quality images and visualization of the coronary arteries.

Between Cratylism and Positivism: the Old Poem and What Alice Found There

En aquest article em referiré molt sumàriament a la fi lologia del dinou, mirant de relacionar-la amb tot el joc de paraules en Lewis Carrol, per tal d'establir-hi una trama correcta de (dis)continuïtats. El meu objectiu és considerar el Jabberwocky de Humpty Dumpty en el context de la feina i les descobertes de la moderna fi lologia. F. A. Wolf i J. Grimm condensen bona cosa dels experiments radicals i les troballes que tingueren lloc en aquells moments, que podríem contrastar amb les aventures textuals d'Alícia a l'altra banda de l'espill. Els llibres de l'altra banda necessiten intèrprets i cerquen la versió correcta, original, de la mateixa manera que la interpretació dels mots depèn d'un mètode fi able. Segurament Lewis Carroll com a jove fi lòleg era capaç de jugar bé amb aquelles troballes, entre un món que s'acabava i un altre que començava.

Pathomorphological and CT-angiographical characteristics of coronary atherosclerotic plaques in cases of sudden cardiac death.

The goal of this study was to assess the localization and types of thrombosed plaques in cases of sudden cardiac death attributed to coronary artery disease and to evaluate possible correlations with body mass index (BMI) and increased heart weight. This retrospective study was performed on forensic cases for which the cause of death was attributed to coronary artery disease. A complete autopsy and a multi-phase postmortem computed tomography (CT) angiography (MPMCTA) were performed in all cases. Eighty-five cases were selected (mean age, 55.18 ± 11.04 years; 72 men and 13 women). MPMCTA performed prior to autopsy enabled an evaluation of coronary artery perfusion before dissection of the body and helped therefore to guide sampling for histology. An acute coronary thrombosis was found in 57 cases, which included plaque erosion in 26 cases (mean age, 46.73 ± 8.33 years) and rupture or intra-plaque hemorrhage in 31 cases (mean age, 58.23 ± 10.62 years). Erosions were most frequently found in the left anterior descending artery (61.5 %), while only 35.48 % of ruptures were observed in this artery. Chronic coronary pathology was considered as the main cause of death in 28 cases (mean age, 59.64 ± 9.47 years). Sixty-two of the cases (72.94 %) had a BMI in the overweight category (BMI ≥25), with the highest mean BMI in patients with chronic coronary pathology without acute thrombosis found at autopsy. The heart weight was above the predicted reference values in 52 cases (61.18 %). Our results are in accordance with previously published studies on the spatial distribution of vulnerable plaques. We observed a higher percentage of eroded plaques than previously reported. Patients with coronary erosions were significantly younger than those with plaque rupture or those without an acute coronary thrombosis (p values <0.0001). BMI and heart weight were significantly higher for cases without thrombosis in comparison with those with plaque rupture (p values 0.028 and 0.003, respectively). Our results indicating that increased BMI and overweight hearts are associated with chronic ischemic heart disease are compatible with clinical studies. Performing more postmortem studies on forensic autopsies, including modern radiological examinations with MPMCTA, can enhance the detection of vulnerable plaques in living patients and prevent sudden cardiac death.

Application of contrast media in post-mortem imaging (CT and MRI).

The application of contrast media in post-mortem radiology differs from clinical approaches in living patients. Post-mortem changes in the vascular system and the absence of blood flow lead to specific problems that have to be considered for the performance of post-mortem angiography. In addition, interpreting the images is challenging due to technique-related and post-mortem artefacts that have to be known and that are specific for each applied technique. Although the idea of injecting contrast media is old, classic methods are not simply transferable to modern radiological techniques in forensic medicine, as they are mostly dedicated to single-organ studies or applicable only shortly after death. With the introduction of modern imaging techniques, such as post-mortem computed tomography (PMCT) and post-mortem magnetic resonance (PMMR), to forensic death investigations, intensive research started to explore their advantages and limitations compared to conventional autopsy. PMCT has already become a routine investigation in several centres, and different techniques have been developed to better visualise the vascular system and organ parenchyma in PMCT. In contrast, the use of PMMR is still limited due to practical issues, and research is now starting in the field of PMMR angiography. This article gives an overview of the problems in post-mortem contrast media application, the various classic and modern techniques, and the issues to consider by using different media.