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Anne Limelette,
Camille Boulagnon,
Caroline Terrade,
Yohan N'guyen,
Thomas Guillard,
Laurent Andréoletti,
Roselyne Garnotel,
Béatrice Digeon,
Christophe De Champs, Paul Fornes,
Nicolas Lévêque
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ABSTRACT: The concept of sudden infant death syndrome (SIDS) is defined as the sudden, unexpected death of an infant less than a year old which remains unexplained after in-depth investigations comprising a complete autopsy, biological analyses, and a clinical examination of the circumstances surrounding the death. This definition underlines the importance of finding the cause of this disease in order to improve preventative measures to reduce the number of deaths due to sudden infant death syndrome. Among the causes of SIDS, pediatric infectious diseases may be neglected and must be systematically sought after. We report upon a SIDS death case of a four and a half month-old that occurred during his sleep. Following the absence of an evident cause of death a scientific autopsy was performed. The histological examination of pulmonary tissue revealed broncolitic lesions associated with numerous micro-abscesses. The post mortem microbiological analyses revealed evidence of an infection by the respiratory syncytial virus complicated by a bacterial infection due to Haemophilus influenzae. The case underlines the necessity of a multidisciplinary approach to researching SIDS, involving both clinicians and biologists, in order to determine the causes of these deaths.
Annales de biologie clinique. 06/2013; 71(3):299-304.
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ABSTRACT: Viral detection in heart tissues has become a central issue for the diagnosis and the pathogenesis exploration of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses were detected and semi-quantified for the first time using a new technology based on PCR assays coupled to mass spectrometry analysis (PCR-MS) and in comparison by referenced real-time PCR ((RT)-qPCR) assays in 67 explanted heart samples of 31 IDCM adult patients. PCR-MS identified single or mixed Enterovirus (EV) and Parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas (RT)-qPCR assays identified viral infections in 26 (38.8%) samples corresponding to 16 (51.6%) of the patients. PCR-MS results correlated well with EV and PVB19 detection by (RT)-qPCR assays (kappa tests= 0.85 [0.72-1.00; 95%] and 0.82 [0.66-0.99; 95%], respectively). Levels of EV RNA (median value=550 [178-3200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median value= 486 [80-1157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and were correlated with those obtained by (RT)-qPCR assays (r(2)=0.57 P=0.002 and r(2)=0.64, P<0.001, for EV and PVB19 respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology that was capable to simultaneously identify 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semi-quantify common virus in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.
Journal of clinical microbiology 05/2013; · 4.16 Impact Factor
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ABSTRACT: Standardized one-step real-time RT-PCR assay detected enterovirus RNA in cardiac biopsy samples from 4 of 20 patients suffering from idiopathic dilated cardiomyopathy (IDCM). The median viral load was 287 copies per microgram of total extracted nucleic acids, with positive- to negative-strand RNA ratios ranging from 2 to 20. These results demonstrate enterovirus persistence in the heart of IDCM patients, characterized by low viral loads and low positive- to negative-RNA ratios.
Journal of clinical microbiology 07/2012; 50(10):3378-80. · 4.16 Impact Factor
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ABSTRACT: In March 2009, a new strain of influenza A/H1N1 virus was identified in Mexico, responsible for a pandemic. Worldwide, more than 13,500 patients died, most often from acute respiratory distress syndrome. Because sudden death cases were rare, involving mostly young apparently healthy persons, influenza A/H1N1 (2009)-related deaths may be misdiagnosed, which can raise medico-legal issues. Case history: we report on an unexpected out-of-hospital death involving a young male with no past medical history and no vaccination. Fever was his only symptom. Laboratory tests: histology showed patchy necrotic foci with mononuclear inflammation in the lungs. The heart was histologically normal, but virological analyses using molecular biology on frozen myocardial samples showed high virus load. In conclusion, this case report shows that influenza A/H1N1 (2009) virus can be a cause of sudden cardiac death in the young and demonstrates the importance of quantitative virological analyses for the diagnosis of myocarditis.
Journal of Forensic Sciences 05/2012; · 1.23 Impact Factor
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ABSTRACT: Human Herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis in immunocompromised or immunocompetent patients. However the physiopathological mechanisms of HHV-6 related acute myocarditis and the involvement of subsequent HHV-6 reactivation phases in the development of chronic cardiomyopathies remain to be assessed.
To describe a case of fatal HHV-6 chronic myocarditis in an immunocompetent adult.
Case report and detailed histological and viral diagnoses by combination of histology/immunohistochemistry and polymerase chain reaction techniques on cardiac tissues.
Histopathological analysis of ventricular tissues showed large interstitial and scarring fibrotic areas with a moderate mononuclear cell infiltrate compatible with histological aspect of chronic myocarditis. Detection of both HHV-6 by real-time PCR and viral glycoproteins in mononuclear and endothelial cells by immunohistochemistry evidenced an ongoing cardiac HHV-6 replication with viral late protein synthesis activity.
This case report indicates that HHV-6 can establish a chronic active myocarditis leading to heart failure in immunocompetent subjects.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2011; 52(2):142-5. · 3.12 Impact Factor
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ABSTRACT: Post-mortem biochemistry, also called thanatochemistry, has proved useful in forensics for estimating the time since death and assessing the cause of death. Ketoacidosis is a frequent complication of diabetes mellitus which can be lethal, with possible medicolegal implications. However, interpretation of biochemical analyses is difficult because of post-mortem blood alterations involving glucose metabolic pathways. Vitreous humor is better preserved than blood after death, and therefore is preferentially used in thanatochemistry. However, both the lack of experience of most biochemists with this matrix in clinical practice, and the paucity of post-mortem studies make interpretation of post-mortem analyses difficult. This review examines the recent advances in the knowledge of glucose metabolism in vitreous humor, and the methods used for the post-mortem diagnosis of diabetic complications.
Clinical Chemistry and Laboratory Medicine 06/2011; 49(8):1265-70. · 2.15 Impact Factor
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ABSTRACT: In 1965, Kerley pioneered histomorphometry of bone as an aging method. The technique has been modified by several authors, and some have used computer-assisted image analysis. Undecalcified bone sections used in these methods are obtained with a diamond wafer saw or by grinding the sections manually or automatically with abrasive paper. In the present study, we examined the application of histomorphometry to decalcified bone sections, routinely obtained in every pathology lab, from paraffin blocks cut with a standard microtome. This study was divided into two parts: in the first, we tested different decalcifying methods to determine the most appropriate for femoral bone; in the second part, we used computer-assisted histomorphometry to estimate age at death in 29 samples of femoral bone. We measured intact osteon density (N.On), fragmented osteon density (N.On.Fg) and percentage of lamellar bone surface per unit area (Lm.B.Ar) in the cortex of the femoral midshaft, on four or 20 fields per section. We found that 20% nitric acid solution at room temperature proved to be the best decalcifying method, with a mean decalcification duration of 1 week. Fragmented osteon density was found to be the morphometric feature most closely correlated with age, followed by intact osteon density; Lm.B.Ar. did not increase accuracy. The best accuracy (4.1 +/- 3.5 years) was obtained for individuals under the age of 70 when measurements of 20 fields were used for the analysis. For all individuals, the inaccuracy was 6.1 +/- 6.2 years and 8.1 +/- 8 years, with 20 and four fields respectively. The present study shows that decalcification of bone sections can be used for age estimation at death. This procedure is particularly useful in case of mass disaster as it is easily done in any pathology department.
Journal of Forensic Sciences 10/2009; 54(6):1231-7. · 1.23 Impact Factor
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ABSTRACT: Ventricular assistance device (VAD) implantation provides large ventricular core biopsies available for pathological assessment. We present here the pathological data from 60 apex removed during a 7-year-period in a single institution.
The most frequent specific lesions were ischemic myocardial damage. Nonspecific pathological features were quite as frequently observed and correspond either to dilated cardiomyopathies, chronic ischemic cardiopathies, or miscellaneous conditions. Myocarditis represented 10 out of the 60 cases. The pathological data changed the clinical diagnosis in four cases: 1 case of juvenile hemochromatosis featuring as myocarditis and three cases of myocarditis featuring as dilated cardiomyopathies.
Apex pathological analysis provides definite diagnosis and contributes to determine the cases which the cardiac disease have a possibility to recover under VAD.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 02/2009; 19(2):112-6. · 1.63 Impact Factor
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ABSTRACT: Background: In recent clinical studies, growth factors have been used in both cardio-vascular and plastic surgery. We showed in a previous study that local administration of bFGF (basic Fibroblast Growth Factor), VEGF (vascular endothelial growth factor) and RGTA (regenerating agent), at the Latissimus Dorsi Muscle (LDM)-epicardial interface in a model of dynamic cardiomyoplasty, improved the vascularization and the trophicity of the LDM. In this study we compared two different methods of growth factor administra-tion. Methods: Right and left LDM flaps were performed in 24 sheep and left "in situ" in the thoracic wall. To create an ischemic environment, the serratus major was removed and the fascia was burned by electrocoagulation. Two different methods of growth factors admini-stration were used: topically on the LDM surface through a multiperforated catheter for weekly administration over a 1-month period, or intramuscularly (IM) during the proce-dure. Basic fibroblast growth factor (n=12) and regenerating agent (n=12) a synthetic mole-cule which potentiates the effect of heparin binding growth factors, were administered. E-ach animal has been operated on both right and left sides: one side treated by one of the two factors, and the other as the control group. At three months, angiographic, histologic and histomorphometric studies were performed. Results: Hypervascularization due to the development of new vessels has been demonstra-ted by angiographic studies of the animals treated with growth factors. Histomorphometric and histologic studies showed a significant increase in the number of capillaries and arterio-les (100 fields/muscle) in the groups treated with bFGF (IM: 661.4 ± 43.2, catheter: 631.6 ± 72.1) and RGTA (IM: 563.1 ± 80.6, catheter: 574.8 ± 44.3), in comparison with the control group: 388.5 ± 74.3. The atrophy score was lower in the group treated with bFGF (IM: 0.91 ± 0.14, catheter: 0.87 ± 0.23) and RGTA (IM: 0.85 ± 0.33, catheter: 1.13 ± 0.38) than in the control group (1.65 ± 0.37). Conclusions: RGTA and bFGF increase muscle vascularization and avoid muscle atrophy in an experimental model of LDM flap. A single intramuscular injection during surgery which is as efficient as weekly administration through a catheter, is the simpler and the bet-ter method for growth factor administration. Key words: Latissimus dorsi muscle flap – cardiomyoplasty – growth factors – heart failure.
Basic Appl Myol. 01/2006; 16:9-15.
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ABSTRACT: A 37-year-old female patient had a cardiac transplantation for dilated cardiomyopathy. She was sensitized by two pregnancies showing anti-human leukocyte antigen I and II antibodies. The pretransplantation crossmatch was negative, but she developed acute humoral rejection characterized by vascular C4d deposits, arteriolitis, and intravascular leukocyte accumulation and adhesion in venules. Although C4d deposits disappeared in 4 weeks, she had persistent endothelial cell activation (endothelial expression of ELAM-1, VCAM-1, or human leukocyte antigen class II) throughout the 6 months of follow-up. Although she received intensive immunosuppression, she presented three episodes of acute cellular rejection during that period of time. This case shows that C4d deposits represent a sensitive marker of acute humoral rejection in cardiac transplantation. Therefore, C4d immunofluorescence should be more frequently assessed in endomyocardial biopsies.
Human Pathlogy 04/2004; 35(3):385-8. · 2.88 Impact Factor
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ABSTRACT: Tracheal reconstruction after extensive resection remains a challenge in thoracic surgery. The goal of this experimental study was to analyze the long-term evolution of tracheal replacement using an autologous aortic graft.
In 21 sheep, a 5-cm segment of the cervical trachea was replaced by a segment of the descending thoracic aorta that was reconstructed to a prosthetic graft. Because of the airway collapse reported in a previous series, a permanent (n = 13) or temporary (n = 8) stent was systematically placed in the lumen of the graft. Clinical, bronchoscopic, and histologic examinations were performed up to 3 years after implantation.
All animals survived the operation with no paraplegia. In the group with a permanent stent, three complications occurred: one stent displacement, one laryngeal edema, and one infection. Stent removal was tolerated after 6 months in the group with a temporary stent. Histologic examination showed a progressive transformation of the arterial segment into first extensive inflammatory tissue with a squamous epithelium, and after 6 to 36 months well-differentiated tracheal tissue including a continuous mucociliary epithelium and regular rings of newly formed cartilage.
An autologous aortic graft used as a substitute for extensive tracheal replacement in sheep remained functional for periods up to 3 years. The progressive transformation of the graft into a structure resembling tracheal tissue seems to be a key factor in long-term patency. The mechanism of this regenerative process and the possibility of using arterial homografts, which would make clinical application easier, remain to be evaluated.
The Annals of Thoracic Surgery 06/2003; 75(5):1572-8; discussion 1578. · 3.74 Impact Factor
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Pediatrics International 05/2003; 45(2):219 - 219. · 0.63 Impact Factor
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Pediatrics International 05/2003; 45(2):219. · 0.63 Impact Factor
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ABSTRACT: A growing number of people are involved in recreational physical activity. It is therefore not uncommon for a medical examiner to encounter sports-related sudden deaths and to be faced with the legal implications. The authors examined the clinical and cardiac pathologic patterns in 31 persons who died suddenly during sports activities and underwent autopsy at the Institute of Forensic Medicine of Paris between 1991 and 2001. Twenty-nine male subjects, ranging in age from 7 to 57 years (mean 30 years) and two female subjects, 8 and 60 years old, died suddenly during sports activities. The sports involved were various, with running the most frequent: 13 cases. Cardiomyopathies (10 cases) and coronary artery disease (9 cases) were the most frequent causes of deaths. Despite the severity of lesions, only 4 subjects had a known cardiovascular disease. In conclusion, with regard to prevention, efforts should be continued to improve the sensitivity and specificity of diagnostic tools and screening strategies. In this regard, medicolegal autopsies should be systematically performed in cases of sudden death during sports activities, because they provide accurate and useful information for a better knowledge of sports-related mortality.
American Journal of Forensic Medicine & Pathology 04/2003; 24(1):9-16. · 0.88 Impact Factor
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ABSTRACT: Dynamic cardiomyoplasty consists of wrapping the electrostimulated latissimus dorsi muscle (LDM) around the failed heart. Partial ischemia followed by atrophy of the middle and distal part of the LDM were observed in 30% of clinical cases after LDM flap elevation from its origin. In the current study, we hypothesized that local administration of growth factors at the LDM/epicardial interface could improve muscle vascularization and trophicity.
In 24 sheep, dynamic cardiomyoplasty was performed using the left LDM. A multiperforated catheter was positioned at the LDM/epicardial interface for a weekly administration, during a 1-month period, of the following factors: basic fibroblast growth factor (bFGF, n = 6), vascular endothelial growth factor (VEGF, n = 6), and regenerating agent (RGTA, n = 6). Six sheep injected with phosphate-buffered saline (used for dilution of the growth factors) were used as a control group. At 3 months, angiographic, histologic, and histomorphometric studies were performed.
Angiographic studies of the animals treated with growth factors demonstrated hypervascularization due to the development of new vessels. Histomorphometric and histologic studies showed a significant increase in the number of capillaries and arterioles (100 fields/muscle) in the groups treated with bFGF (443.0 +/- 101.2, p < 0.01), RGTA (293.2 +/- 29.3, p < 0.05), and VEGF (246.5 +/- 45.9, p < 0.05), as compared with the control group (81.5 +/- 11.4). A significantly lower atrophy score was observed in the groups treated with bFGF (1.4 +/- 0.18, p < 0.05), RGTA (1.59 +/- 0.17, p < 0.05), and VEGF (1.96 +/- 0.14, NS), as compared with the control group (2.48 +/- 0.16).
Local administration at the heart/muscle interface of growth factors increases muscle vascularization and avoids muscle atrophy in an experimental cardiomyoplasty model, both of which are advantageous to the contracting LDM. The local growth factors delivery system used in this study appears efficient, easy to implant, and manipulate and safe.
The Annals of Thoracic Surgery 02/2003; 75(2):549-54. · 3.74 Impact Factor
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ABSTRACT: Although cardiac transplantation has been performed for complete removal of ventricular tumors, complete surgical resection with ventricular reconstruction is desirable. Thus patients with benign tumors would probably be cured, and those with malignant tumors would have a better prognosis. In this study extensive and complete surgical resection of ventricular tumors is followed by anatomic and functional ventricular reconstruction with a dynamic cardiomyoplasty procedure.
Seven patients (mean age, 32.7 years) underwent complete resection of ventricular tumors. Histologic types were distributed as follows: fibroma in 2 patients and sarcoma, lymphosarcoma, hemangioma, lipoma, and metastatic angiosarcoma, respectively, in the remaining 5 patients. Six of the patients were considered candidates for heart transplantation because of the extent of tumor invasion. Surgery consisted of 4 steps: (1) tumor resection; (2) coronary artery resection (when invaded by the tumor) and coronary artery bypass grafting; (3) valvular reconstruction (when possible) or replacement; and (4) ventricular wall reconstruction with a pericardial patch for closure of the ventricular defect (neoendocardium) covered by the electrostimulated latissimus dorsi muscle flap (neomyocardium).
All patients survived surgical intervention, but 2 late postoperative deaths are reported. Among the surviving patients, early complications played a major role in their postoperative course and consisted of arrhythmias, atrioventricular block necessitating a dual-chamber pulse generator, respiratory insufficiency, and heart failure. Two patients were assisted postoperatively with an intra-aortic balloon pump. On postoperative follow-up (mean, 72.4 +/- 8.5 months), an improvement in the patients' functional status was observed. Patients moved from a mean New York Heart Association functional class of 2.8 to a mean functional class of 1.2.
The excellent long-term evolution without recurrence, ventricular dysfunction, and/or thromboembolic complications implies that cardiomyoplasty could be recommended as an alternative to heart transplantation for the therapy of large ventricular tumors.
Journal of Thoracic and Cardiovascular Surgery 06/2002; 123(5):889-94. · 3.41 Impact Factor
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ABSTRACT: Thoracic calcifications are found in the following locations: mediastinum, lung, pleura, cardiovascular system, and thoracic wall. The calcifications of the mediastinum include mostly inflammatory lesions and malignant neoplasms. Pulmonary calcifications are mainly inflammatory lesions and metastases of osteosarcomas. Where the cardiovascular system is concerned, the most common calcifications are those of the heart relating to tumors or surgery. Calcifications of the aortic wall and valve calcifications can be found. In the thoracic wall there are calcifications of the bone and of soft tissues. The knowledge of shape and location is very useful for the diagnosis of the underlying disease. Calcifications in the thorax are frequently manifestations of previous infectious processes. Less often, they may be due to neoplasms, metabolic disorders, or previous medical therapy.
Critical reviews in computed tomography 02/2002; 43(1):9-37.
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ABSTRACT: Background: Angiotensin I–converting enzyme inhibition (ACEI) and angiotensin II AT1-receptor blockade are effective at improving survival and limiting cardiac remodeling in the rat model of postischemic heart failure. Whether their combination yields additive/synergistic effects is unknown. Methods and Results: Rats underwent coronary artery ligation and 7 days later were treated orally for 9 months with placebo (controls), 5 mg/kg valsartan, 1 mg/kg enalapril (doses submaximally effective at reducing mortality in the experimental model used), or 5 mg/kg valsartan and 1 mg/kg enalapril combined. Compared with controls, valsartan, enalapril, and their combination decreased mortality by 40% (P = .006), 21% (P = .065), and 33% (P = .032), respectively, but there was no significant difference between the 3 treatments. At the doses used, valsartan, but neither enalapril nor the combination, slightly limited cardiac hypertrophy and fibrosis development and reduced left ventricular end-diastolic pressure as assessed in the surviving animals at 9 months. Conclusions: In experimental chronic heart failure in rats, valsartan reduces mortality similar to other AT1-receptor blockers and a combination of AT1-receptor blockade (valsartan) and ACEI (enalapril) at submaximal doses does not exert additive/synergistic beneficial effects on mortality.
Journal of Cardiac Failure - J CARD FAIL. 01/2001; 7(3):269-276.
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Journal of Cardiovascular Pharmacology - J CARDIOVASC PHARMACOL. 01/1993; 22(2):305-313.
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Emmanuel Martinod,
Gilbert Zakine, Paul Fornes,
Rachid Zegdi,
Alexandre d’Audiffret,
Bertrand Aupecle,
Nathalie Goussef,
Jacques Azorin,
Juan-Carlos Chachques,
Jean-Noël Fabiani,
Alain Carpentier
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ABSTRACT: Tracheal reconstruction after extensive resection remains an unsolved surgical problem. Numerous attempts have been made using tracheal grafts or prosthetic conduits with disappointing results. In this study, we propose a new alternative using an aortic autograft as tracheal substitute. In a first series of experiments, a half circumference of two rings was replaced with an autologous carotid artery patch. In a second series, a complete segment of trachea was replaced with an autologous aortic graft supported by an endoluminal tracheal stent. No dehiscence or stenosis was observed. Microscopic examinations at 3 and 6 months showed the replacement of the aortic tissue by tracheal tissue comprising neoformation of cartilage and mucociliary or non-keratinizing metaplastic polystratified squamous epithelium. Although these results need to be confirmed by a larger series of experiments, they showed that a vascular tissue placed in a different environment with a different function can be submitted to a metaplastic transformation which tends to restore a normal structure adapted to its new function. These remarkable findings offer new perspectives in tracheal reconstruction in human.RésuméLa reconstruction trachéale après résection étendue est un problème chirurgical non résolu. Les nombreuses tentatives d’utilisation de greffes trachéales ou de conduits prothétiques se sont généralement soldées par des échecs. Ce travail expérimental explore une nouvelle voie : le remplacement de la trachée par une autogreffe aortique, modèle qui permet d’étudier le comportement d’un tissu vasculaire en position trachéale sans être confronté aux problèmes immunologiques. Dans une première phase, on a effectué un remplacement trachéal hémi-circonférentiel étendu sur deux anneaux par une autogreffe d’artère carotide. Dans une deuxième série expérimentale, on a réalisé un remplacement segmentaire circonférentiel de la trachée par une autogreffe aortique avec mise en place d’un tuteur endotrachéal. Aucune sténose ni rupture n’a été observée, avec un recul de 6 mois. Les examens histologiques à 3 et 6 mois ont montré une métaplasie tissulaire avec un remplacement du tissu aortique par un tissu comprenant une néoformation de cartilage, un épithélium malpighien et même, en une occasion, un épithélium cilié et sécrétoire. Ces résultats montrent qu’un tissu aussi différencié que l’aorte peut se transformer en un autre tissu différencié, une fois placé dans un environnement différent et soumis à de nouvelles fonctions. Ils ouvrent d’intéressantes perspectives en matière de reconstruction trachéale chez l’homme.
Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie.
