Biomedical subjects
Publications and source records attributed to Paul Fornes.
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BACKGROUND: Expression of inducible heme-oxygenase (HO-1) has been shown to be increased in various inflammatory disorders, which may confer a protective role. The aim of our study was to assess pulmonary expression of HO-1 after ischemia/reperfusion (I/R) of the lower limbs in rats. MATERIALS AND METHODS: We compared three groups of rats (n = 5/group): one Sham group, and two I/R groups (aorta cross-clamped for 2 h followed by 2 h of reperfusion), one of which pre-treated with Zn-protoporphyrin (Zn-PP), a competitive inhibitor of HO (50 micromol/kg, i.p.). At the end of experiment, lungs were harvested for determination of HO activity and HO-1 expression by Western blot and immunohistochemistry. Lung injury was assessed by bronchoalveolar lavage, histological study, and determination of the lung Evans Blue dye content, an index of microvascular permeability. RESULTS: I/R of the lower limbs was responsible for acute lung injury (ALI), characterized by neutrophilic infiltration (87 +/- 20 x 10(3) neutrophils/mm(3), Sham group versus 191 +/- 38 x 10(3) neutrophils/mm(3), I/R group; P < 0.002) and an increase in lung Evans blue dye content: (74 +/- 6 microg/g, Sham group versus 122 +/- 48 microg/g, I/R group; P < 0.05). Pre-treatment with Zn-PP further increases the Evans Blue content (122 +/- 48 microg/g, I/R group versus 179 +/- 23 microg/g Zn-PP group P < 0.05) and the neutrophilic infiltration. Pulmonary heme-oxygenase activity, and HO-1 content were increased after I/R. (10.5 +/- 12 pmol bilirubin/mg protein/h, Sham group versus 101.2 +/- 66 pmol bilirubin/mg protein/h, I/R group; P < 0.02). Immunohistochemistry revealed that the expression of HO-1 was mainly localized to inflammatory cells. CONCLUSIONS: ALI following I/R of the lower limbs in rats is associated with an increase of pulmonary expression of HO-1, inhibition of this expression increase the severity of ALI.
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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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
We investigated in mice whether atherosclerosis exacerbates the development of post-ischemic heart failure and alters the beneficial effects of long-term angiotensin II type 1 receptor blockade in this model. ApoE-deficient (ApoE(-/-)) and C57BL/6J (C57) mice with myocardial infarction (coronary ligation) received vehicle (C57 and ApoE(-/-)) or irbesartan (Ir, 50mg/kg/d orally, C57-Ir and ApoE(-/-)-Ir). Ten months post myocardial infarction, survival rates were similar in C57 (58%) and ApoE(62%). Atherosclerosis induced no significant alteration in blood pressure, cardiac output (fluospheres), total peripheral resistance, or shortening fraction (echocardiography) but increased renal resistance (+50%, P<0.05). Chronic Ir treatment significantly improved survival to a similar extent in both C57-Ir (85%) and ApoE(-/-)-Ir (86%). It also decreased blood pressure to a similar extent in both strains (-16% and -18%, both P<0.05). In C57-Ir mice, Ir did not modify cardiac output or total peripheral resistance, but it decreased renal resistance (-28%, P<0.001) and left-ventricular weight (-28%, P<0.05). In ApoE(-/-)-Ir mice, Ir limited atherosclerotic lesions (-13%, P<0.05), increased cardiac output (+28%, P<0.05) and shortening fraction (+24%, P<0.05), and decreased total peripheral resistance (-33%, P<0.01), renal resistance (-61%, P<0.001), and left-ventricular weight (-27%, P<0.001). In conclusion, atherosclerosis does not worsen heart failure development in mice and, although the beneficial cardiovascular effects of AT1 receptor blockade are greater in ApoE(-/-) than in C57, reduction in mortality is similar in both strains.
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.
BACKGROUND: In the pediatric population, glutaraldehyde-preserved bovine pericardium conduit containing a stentless porcine valve has been proposed as an alternative to homografts for right ventricular outflow tract reconstruction. METHODS: Between June 1996 and March 2000, a total of 55 patients, 20 with truncus arteriosus, 21 with pulmonary atresia with ventricular septal defect, and 14 with miscellaneous defects, received this conduit. Median age at implantation was 3.4 months (range, 3 days to 19 years), and 27 patients (50%) were less than 3 months old. Clinical outcome, echocardiographic data, and pathologic analysis were recorded. End points for conduit failure were conduit replacement or dilation. A mean follow-up of 27 months (range, 2 to 46 months) was available for 47 survivors. RESULTS: Procedure for conduit obstruction was required in 13 patients. The most common procedure was operation, and all but 3 patients had an unsuccessful balloon angioplasty before reoperation. Actuarial freedom from conduit dilation or reoperation was 93.6% (95% confidence limits, 82% to 99%), 81.9% (95% confidence limits, 64% to 91%), 77.8% (95% confidence limits, 39% to 78%), and 64.3% (95% confidence limits, 26% to 73%) at 1, 2, 3, and 4 postoperative years, respectively. Univariate analysis identified small conduit size as a risk factor for conduit obstruction. CONCLUSIONS: Although this new conduit was not free from progressive obstruction, our clinical results (easy to work and good valvular function) and the availability in small sizes encouraged us to use it as an alternative to small-size homografts when those were not available.
OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
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.
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The relationship between aging and apoptosis remains unclear. We wondered whether apoptosis could be enhanced in arterial aging in the absence of overt or advanced arterial disease. Apoptosis-related proteins were investigated using three methods: TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique, active cysteine-dependant aspartate specific proteases (caspase)-3 and poly ADP-ribose polymerase (PARP) in coronary arteries of human subjects ranging from 25 to 92 years. We found no significant correlation between age and the apoptotic index using the three methods. The percentage of active caspase-3 positive cells was found to be significantly higher in men than in women (9.11 +/- 12.3 cells/mm(2) versus 2.01 +/- 4.55 cells/mm(2), respectively, p = 0.017). These sex-related differences did not reach statistical significance using TUNEL (9.93 +/- 17 and 2.61 +/- 4.58 cells/mm(2), p = 0.32) and PARP methods (3.42 +/- 7.74 and 0.86 +/- 0.95 cells/mm(2), p < 0.49). This is the first report of detection of apoptotic cells in the human arterial wall in adult subjects free from arterial diseases. Apoptosis is an attractive hypothesis to account for organ aging, but our study suggests that apoptosis is not a key factor in aging of the arterial wall.
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Diagnosis of incidental adrenal masses is a real challenge to radiologists. The most common incidental tumors of the adrenal gland are adenomas and metastases. This article presents our experience with uncommon adrenal incidentalomas. Most of the magnetic resonance imaging characteristic features are demonstrated. When possible, they are correlated with the findings at gross and microscopic analysis, to help in understanding the mechanisms by which magnetic resonance imaging may aid in the characterization of the incidental adrenal mass.