Papers by Lara Chalabreysse
Circulation, Jan 16, 2003
Sudden death is a possible consequence of arrhythmogenic right ventricular cardiomyopathy/dysplas... more Sudden death is a possible consequence of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Prevalence of ARVC/D in unexpected sudden cardiac death (USCD), however, remains imprecise, as do circumstances of death and ARVC/D-associated gross and microscopic findings, especially His bundle anomalies. We reviewed 14 000 forensic autopsies required by judicial authorities from January 1980 to January 1999 in a 2 000 000-resident area. Age, gender, and circumstances of death were recorded. Hearts were examined macroscopically and microscopically. In this series, the ARVC/D group accounted for 200 consecutive cases (10.4%) of USCD, including 108 males and 92 females (average age 32.5 and 34.5 years, respectively). Nearly one third of deaths occurred during the fourth decade of life. Circumstances of death were various, but 75.6% occurred during everyday life events (at home, 63.1%; in the street, 6.6%; or at work, 6.1%); only 7 cases (3.5%) occurred during sports activit...
Interactive cardiovascular and thoracic surgery, 2007
Microscopic thymoma was first described in 1976 and remains in the latest WHO classification (200... more Microscopic thymoma was first described in 1976 and remains in the latest WHO classification (2004). It defines an epithelial proliferation, with <1 mm in diameter, usually multifocal, that preferentially occurs in patients suffering from myasthenia gravis without a macroscopically evident tumour. A series of 87 thymectomies realised in myasthenic patients between 1992 and 2005 was reviewed. We describe three cases of microscopic thymoma: two male and one female with an average age of 41.6 years. All patients suffered from myasthenia gravis positive for acetylcholine receptor antibodies without any tumour detectable on chest tomodensitometric examination. Thymectomy was performed in all cases, enlarged to the mediastinal fat in one. Microscopic examination revealed three type-A microscopic thymoma, one multifocal, associated with lymphoid hyperplasia in two cases. After surgery, all patients had clinically improved. In summary, chest computed tomography is unable to detect micros...
Interactive cardiovascular and thoracic surgery, 2004
The purpose of the present study was to analyze the histological aspects of the saphenous veins a... more The purpose of the present study was to analyze the histological aspects of the saphenous veins after the use of the Symmetry aortic connector in off pump coronary artery bypass surgery (OPCAB). Nineteen consecutive patients who underwent OPCAB surgery and who received one proximal saphenous vein anastomosis using the St Jude aortic Symmetry connector system were evaluated. In each patient one small segment of the saphenous vein was cut before the use of the Symmetry connector (V0), then another segment after (V1). All segments were stored in an acetone-formaldehyde-alcohol solution before examination. Examination of the V0 segments showed non-specific media fibrosis. In V1, 11 segments presented with a complete alteration of the endothelial layer (58%) and 8 with severe lesions (more than 80%). Among all the V1 segments, 8 had a dissection of the media (42%) and one presented with a wall thrombus. These results suggest that the use of the aortic connector can be associated with dif...
The Journal of Heart and Lung Transplantation, 2010
BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term surv... more BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR). METHODS: Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60. Agilent microarrays were then used to highlight differentially expressed genes between isografted and allografted rat aortas. Further investigation of a selected candidate gene was performed on human coronary arteries. RESULTS: 1829, 2582 and 1925 genes (fold changes Ͼ2 or Ͻ2 and p values Ͻ0.05) were differentially expressed at day 8, 25 and 60 respectively between isografs and allografts. Seventeen candidate genes were selected according to significant differential expression at day 60. These rat candidate genes were then validated by quantitative real time polymerase chain reaction (Q-PCR). One of these candidate genes, T-Cadherin (T-Cad) was further investigated, using immunohistochemistry (IHC), in human coronary arteries showing CAV compared to classical atherosclerosis present in ischemic cardiomyopathy (ICM) and normal coronary arteries present in dilated cardiomyopathy (DCM). Results showed an over expression of T-Cad in CAV and classical atherosclerosis compared to normal coronary arteries. CONCLUSIONS: T-Cad was found to be over expressed in CAV. T-Cad could potentially act as a trigger for smooth muscle cells (SMCs) proliferation and vascular remodelling observed in CAV leading to a diffuse narrowing of the arterial lumen.
Journal of Dental Research, 2011
Dental agenesis is either syndromic or non-syndromic. Here, we describe a familial case with Carv... more Dental agenesis is either syndromic or non-syndromic. Here, we describe a familial case with Carvajal/Naxos syndrome associating woolly hair, palmoplantar keratoderma, and biventricular dilated cardiomyopathy. In addition to these signs, all three affected family members had hypo/oligodontia ranging from absence of the lower left second molar to 15 missing teeth, the typical pattern of oligodontia being absent 2nd premolars and absent 2nd and 3rd molars. Mutation screening in the desmoplakin gene (DSP) revealed a de novo missense mutation (c.1790 C&gt;T, p.Ser597Leu) changing a serine residue conserved in all vertebrates. In addition, this variation was absent from 100 control DNA samples. There were no mutations in the plakoglobin gene. This familial case report and two other previous reports demonstrate that autosomal-dominant mutations in the DSP gene are associated with hypo/oligodontia in the setting of Carvajal/Naxos syndrome. This study suggests that dentists discovering oligo/hypodontia should screen for woolly hair and palmoplantar keratoderma because of the probable cardiac involvement with an inherent high risk of severe cardiomyopathy. In addition, this study reveals the role of desmosomes in the development of teeth and suggests that other genes encoding proteins of the desmosome could be involved in oligo/hypodontia.
Heart Rhythm, 2005
OBJECTIVES To quantify and study the distribution of innervation of the left atrium and the pulmo... more OBJECTIVES To quantify and study the distribution of innervation of the left atrium and the pulmonary veins in humans. BACKGROUND Damage to cardiac nerves has been hypothesized as the explanation for successful radiofrequency ablation of atrial fibrillation. METHODS From January 2003 to September 2003, histologic and quantitative studies of innervation of the left atrium and the pulmonary veins was performed in 43 consecutive necropsied adult hearts (30 men and 3 women; mean age 45.5 Ϯ 12.4 years). The left atrium was sectioned in 1-cm slices from left to right, with the plane of section perpendicular to the long axis of the heart. Sections of the pulmonary veins at their ostia and sections 1 cm away of this structure also were obtained. Nerve fiber density was counted manually for each case and expressed as the mean number per slice. RESULTS Numerous epicardial nerve fibers and ganglia having distinct patterns of distribution in the left atrium were found. Nerve density was significantly higher at the ostia of the four pulmonary veins than in their distal part (7.1 Ϯ 2.1 vs 5.2 Ϯ 1.3 for left upper pulmonary vein; 6.3 Ϯ 1.5 vs 5.2 Ϯ 1.7 for right upper pulmonary vein; 7.4 Ϯ 2 vs 5.9 Ϯ 2 for left lower pulmonary vein; 6.7 Ϯ 1.8 vs 3.9 Ϯ 1.3 for right lower pulmonary vein). The left superior vein was significantly more innervated than the right inferior vein (12.3 Ϯ 3 vs 10.6 Ϯ 1.4). Gradients of innervation were found from right to left (9.8 Ϯ 4.6 vs 18.5 Ϯ 6.6, P Ͻ .05) and from the front to the rear of the atrium (17.2 Ϯ 6.4 vs 20.7 Ϯ 6.5, P Ͻ .05). The same heterogeneous distribution was observed at the myocardial level but with thinner nerve fibers, making quantification difficult. Only very thin nerve fibers were present in the endocardium. CONCLUSIONS The human left atrium exhibits several gradients of innervation at discrete sites. These findings may have clinical implications for radiofrequency ablation of atrial fibrillation.
Objective: We investigated whether ischemic preconditioning (PC) may modify mitochondrial permeab... more Objective: We investigated whether ischemic preconditioning (PC) may modify mitochondrial permeability transition (MPT) pore opening. Methods: In protocol 1, New Zealand White rabbits underwent either no intervention (sham group) or 10 min of ischemia followed by 5 min of reperfusion, preceded (PC) or not (C; control) by one episode of 5 min of ischemia and 5 min of reperfusion. Rabbits
In a vulnerable plaque (VP), rupture often occurs at a site of high stress within the cap. It is ... more In a vulnerable plaque (VP), rupture often occurs at a site of high stress within the cap. It is also known that vessels do not become free of stress when all external loads are removed.
Annals of Diagnostic Pathology, 2015
Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneum... more Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia, with typical high-resolution computed tomography (HRCT) features and histologic pattern of usual interstitial pneumonia (UIP); its main differential diagnosis is fibrotic nonspecific interstitial pneumonia (F-NSIP). Usual interstitial pneumonia was mainly described from lung biopsies, and little is known on explants. Twenty-two UIP/IPF explants were analyzed histologically and compared with previous open lung biopsies (OLBs; n = 11) and HRCT (n = 19), when available. Temporospatial heterogeneity and subpleural and paraseptal fibrosis were similarly found in UIP/IPF explants and OLB (91%-95%). Fibroblastic foci were found in 82% of OLBs and 100% of explants, with a higher mean score in explants (P = .023). Honeycombing was present in 64% of OLBs and 95% of explants, with a higher mean score in explants (P = .005). Almost 60% of UIP/IPF explants showed NSIP areas and 41% peribronchiolar fibrosis; inflammation, bronchiolar metaplasia, and vascular changes were more frequent in UIP/IPF explants; and Desquamative Interstitial Pneumonia (DIP)-like areas were not common (18%-27%). Numerous large airspace enlargements with fibrosis were frequent in UIP/IPF explants (59%). On HRCT, honeycombing was observed in 95% of the cases and ground-glass opacities in 53%, correlating with NSIP areas or acute exacerbation at histology. Six patients had combined IPF and emphysema. Lesions were more severe in UIP/IPF explants, reflecting the worsening of the disease. Usual interstitial pneumonia/IPF explants more frequently presented with confounding lesions such as NSIP areas, peribronchiolar fibrosis, and airspace enlargements with fibrosis sometimes associated with emphysema.
Cardiovascular ultrasound, 2006
Aortic valve decalcification by ultrasound was given up. We evaluated a new ultrasound microhandp... more Aortic valve decalcification by ultrasound was given up. We evaluated a new ultrasound microhandpiece (Dissectron Penstyle) to rehabilitate this alternative treatment. We used under magnifying lenses the ultrasound microhandpiece to decalcify 30 explanted aortic valves. In the cases with embedded calcifications the thin top of the probe could be introduced into the thickness of the leaflet preserving covering layers. The leaflets were totally decalcified and flexible, and surrounding structures were preserved as assessed by histological examination. This new approach of ultrasonic aortic valve decalcification gives good in vitro results which allow to consider a clinical evaluation of this procedure.
AJR. American journal of roentgenology, 2002
Malignant pleural mesothelioma is a rare primary tumor of the pleura, strongly linked to asbestos... more Malignant pleural mesothelioma is a rare primary tumor of the pleura, strongly linked to asbestos exposure [1]. The microscopic features have been characterized according to three main groups, including the epithelioid, sarcomatoid, and biphasic forms [1]. Malignant ...
European Journal of Heart Failure Supplements, 2003
ABSTRACT We investigated whether ischemic preconditioning (PC) may modify mitochondrial permeabil... more ABSTRACT We investigated whether ischemic preconditioning (PC) may modify mitochondrial permeability transition (MPT) pore opening. In protocol 1, New Zealand White rabbits underwent either no intervention (sham group) or 10 min of ischemia followed by 5 min of reperfusion, preceded (PC) or not (C; control) by one episode of 5 min of ischemia and 5 min of reperfusion. Rabbits were pretreated by either saline or the MPT pore inhibitor cyclosporin A (CsA), or its non-immunosuppressive derivative Cs29 (10 mg/kg, IV bolus). Hearts were harvested and mitochondria isolated for further assessment of Ca(2+)-induced MPT using a Ca(2+)-sensitive micro-electrode. In protocol 2, C and PC hearts underwent 30 min of ischemia and 4 h of reperfusion. They were pretreated either by saline, CsA or Cs29, as in protocol 1. Infarct size was assessed by triphenyltetrazolium, and apoptosis by TUNEL staining. In protocol 1, the Ca(2+) overload required to induce MPT pore opening was significantly higher in PC than in C hearts. CsA and Cs29 significantly increased the Ca(2+) overload required for MPT pore opening. In protocol 2, mean infarct size averaged 25% of the risk region in CsA/Cs29 treated hearts versus 15% in PC and 55% in controls (P&lt;0.05 vs. C, P=ns vs. PC). Cardiomyocyte apoptosis was significantly reduced by PC and cyclosporin treatment with a mean apoptotic index of less than 2% in either group versus more than 11% in controls. This suggests that delayed opening of MPT pore may play a major role in ischemic PC.
Interactive cardiovascular and thoracic surgery, 2004
The purpose of the present study was to analyze the histological aspects of the saphenous veins a... more The purpose of the present study was to analyze the histological aspects of the saphenous veins after the use of the Symmetry aortic connector in off pump coronary artery bypass surgery (OPCAB). Nineteen consecutive patients who underwent OPCAB surgery and who received one proximal saphenous vein anastomosis using the St Jude aortic Symmetry connector system were evaluated. In each patient one small segment of the saphenous vein was cut before the use of the Symmetry connector (V0), then another segment after (V1). All segments were stored in an acetone-formaldehyde-alcohol solution before examination. Examination of the V0 segments showed non-specific media fibrosis. In V1, 11 segments presented with a complete alteration of the endothelial layer (58%) and 8 with severe lesions (more than 80%). Among all the V1 segments, 8 had a dissection of the media (42%) and one presented with a wall thrombus. These results suggest that the use of the aortic connector can be associated with dif...
La Presse Médicale, 2007
Un patient âgé de 66 ans, qui avait fumé 30 paquetsannées, recevait une corticothérapie orale, du... more Un patient âgé de 66 ans, qui avait fumé 30 paquetsannées, recevait une corticothérapie orale, du méthotrexate, et du léflunomide pour une polyarthrite rhumatoïde. Le facteur rhumatoïde et les anticorps anti-peptide cyclique citrulliné étaient positifs. Une radiographie thoracique systématique a montré l'apparition d'une dizaine de nodules pulmonaires bilatéraux. À la tomodensitométrie, le nodule le plus volumineux, situé dans le lobe supérieur gauche, avait des contours spiculés (figure 1) ; il existait également des lésions emphysémateuses centrolobulaires des sommets, sans trappage aérique en expiration. L'examen clinique ne décelait pas de nodule rhumatoïde sous-cutané. Le patient avait une arthrite des 2 poignets et d'un coude. La fibroscopie bronchique était normale, et la recherche de mycobactérie était négative. La tomographie par émission de positons montrait une fixation modérée de la majorité des nodules pulmonaires. Il existait un trouble ventilatoire obstructif chronique, modéré, stable, et non réversible sous bronchodilatateur. Le
Lung Cancer, 2002
Background: Chest physicians have a limited experience of primary pulmonary sarcomas, which repre... more Background: Chest physicians have a limited experience of primary pulmonary sarcomas, which represent a particular entity among rare intrathoracic neoplasms. Design: Retrospective review of medical records. Purpose: To study patients with primary sarcomas of the lung diagnosed in our pathology department in order to define their clinical characteristics, treatment, and prognosis. Patients: The study group consisted of 12 patients, with a mean age of 53 years. Results: The main symptoms were chest pain, and cough. Imaging findings consisted of: eight single peripheral opacities, three single parahilar opacities, and one lobar actelectasis. The histologic diagnoses confirmed in all cases by detailed immunohistochemical study were leiomyosarcoma , monophasic synovial sarcoma (2), one case each of malignant peripheral nerve sheath tumor (MPNST), epithelioid sarcoma, and malignant fibrous histiocytoma. Thoracic surgery done in nine cases consisted of six lobectomies with further parietal resection in two cases, and three pneumonectomies. Four patients received chemotherapy and two patients had radiation therapy postoperatively. Follow up available on 12 patients ranged from 3 to 144 (mean 42) months. Long term survival up to 3 years was observed in five patients. Median overall survival was 48 months. Overall 5-year survival rate was 38%. Conclusions: Primary sarcomas of the lung are a rare and aggressive malignancy. Treatment and prognosis do not differ from other soft tissue sarcomas. #
Journal of the American College of Cardiology, 2003
Journal of the American College of Cardiology, 2004
Cardiac Function and Heart Failure for providing mechanical support to the failing heart in these... more Cardiac Function and Heart Failure for providing mechanical support to the failing heart in these settings. Methods: We retrospectively reviewed all patients who received a Thoratec Single-Lead-Vented-Electric LVAD at our institution between August 1990 and February 2003. Twentyfive patients with viral myocarditis were identified. Twenty-five patients whose primary indication for LVAD was coronary artery disease (CAD) were randomly selected from the same database to serve as a control group. Variables analyzed included patient demographics, duration of LVAD support, preoperative white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) values, percent explanted, success rate of bridge to transplantation, and post-transplant survival rates. Results: The VM group was younger than (35.88+/-16.43 years vs. 58.88+/-4.30 years) (p<0.01) and consisted of a greater proportion of female patients than (36% vs. 8%) (p=0.02) the CAD group. Duration of LVAD support, preoperative WBC and ESR values, and percent explanted were similar between the two groups. Bridge success rates and post-transplant survival rates were also comparable (64% transplanted in VM, 60% transplanted in CAD (p=0.86); 1-and 5-year post-transplant survival rates of 86.67% and 72.80% in VM, 71.43% and 62.50% in CAD, respectively (p=0.34)). Conclusions: These findings suggest that despite the variable clinical course of VM and the potential to rapidly progress to end-stage heart failure, LVAD implantation in these patients yields outcomes similar to those receiving LVADs for CAD. Device support permits decompression of the dilated ventricle, facilitating myocardial recovery and the likelihood of bridging successfully to transplant or explant.
Journal of Molecular and Cellular Cardiology, 2005
The aim of the present study was to determine whether specific inhibition of mitochondrial permea... more The aim of the present study was to determine whether specific inhibition of mitochondrial permeability transition (MPT) by NIM811 at the time of reperfusion following acute myocardial infarction may protect the heart. MPT pore opening appears to be a pivotal event in cell death following acute myocardial infarction. Recently, MPT pore opening has been involved in ischemic preconditioning. In protocol 1, NZW rabbits underwent either no intervention (sham) or 10 min of ischemia followed by 5 min of reperfusion, preceded (preconditioned, PC) or not (control, C) by 5 min of ischemia and 5 min of reperfusion. Additional rabbits were treated by cyclosporin A (CsA) or its nonimmunosuppressive and more specific derivative (NIM811) (10 mg kg -1 , IV bolus), either 10 min before ischemia or 1 min before reperfusion. Hearts were excised and mitochondria isolated for further assessment of Ca 2+ -induced MPT. In protocol 2, animals were randomly assigned into similar experimental groups and underwent 30 min of ischemia and 4 h of reperfusion. Infarct size was assessed by TTC staining, and apoptosis by TUNEL assay. The Ca 2+ overload required to induce MPT pore opening was significantly higher in NIM811, CsA and PC groups than in controls. Both necrotic and apoptotic cardiomyocyte death were significantly reduced by NIM811, CsA and PC. In both protocols, administration of NIM811 at reperfusion provided full protection. These data indicate that specific inhibition of MPT pore opening at reperfusion following acute myocardial infarction provides a powerful antinecrotic and antiapoptotic protection.
The Journal of Infectious Diseases, 2004
The pathological features of Whipple endocarditis, which is caused by Tropheryma whipplei, were h... more The pathological features of Whipple endocarditis, which is caused by Tropheryma whipplei, were histologically evaluated in cardiac valves from 5 patients. We used quantitative image analysis to compare the valvular fibrosis, calcifications, vegetations, inflammation, and vascularization due to Whipple endocarditis with those due to non-Whipple endocarditis and degenerative valves. We also studied the presence of T. whipplei in valves by immunohistochemical analysis, culture, and polymerase chain reaction (PCR). In histologic analysis, Whipple endocarditis was characterized by significant fibrosis, a lack of calcifications, slight inflammation and vascularization, and vegetations of intermediate size. Inflammatory infiltrates consisted mainly of foamy macrophages and lymphocytes. We found that the detection of T. whipplei in cardiac valves, by immunohistochemical analysis, was correlated with the detection of the bacterium by culture and PCR. We report, for the first time, the immunodetection of T. whipplei in a surgically removed arterial embolus. Pathological and immunohistologic analyses may contribute to the diagnosis of Whipple endocarditis.
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Papers by Lara Chalabreysse