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Biomedical subjects

G Lesèche

Publications and source records attributed to G Lesèche.

At least 19 recordsLinked to original sources
PubMed2001

Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.

BACKGROUND: Interleukin (IL)-18 is a potent proinflammatory cytokine with potential atherogenic properties. Its expression and role in atherosclerosis, however, are unknown. METHODS AND RESULTS: In the present study, we examined stable and unstable human carotid atherosclerotic plaques retrieved by endarterectomy for the presence of IL-18 using reverse transcription-polymerase chain reaction (PCR), Western blot, and immunohistochemical techniques. IL-18 was highly expressed in the atherosclerotic plaques compared with control normal arteries and was localized mainly in plaque macrophages. IL-18 receptor was also upregulated in plaque macrophages and endothelial cells, suggesting potential biological effects. To examine the role of IL-18 in atherosclerosis, we determined the relation between IL-18 mRNA expression and signs of plaque instability using real-time quantitative PCR. Interestingly, significantly higher levels of IL-18 mRNA were found in symptomatic (unstable) plaques than asymptomatic (stable) plaques (P<0.01). CONCLUSIONS: These results suggest, for the first time, a major role for IL-18 in atherosclerotic plaque destabilization leading to acute ischemic syndromes.

Aged↗
PubMed2001

Influence of preservation solution on early graft failure in clinical lung transplantation.

The aim of this study was to assess the influence of preservation solution type and extra- or intracellular composition on the occurrence of early graft dysfunction after clinical lung transplantation. For 170 patients who underwent a single (n = 124) or bilateral (n = 46) lung transplantation in two centers in Paris between 1988 and 1999, the preservation technique applied to the donor lung was single-flush perfusion of the pulmonary artery with one of several solutions of intracellular (Euro-Collins, n = 61; University of Wisconsin, n = 24) or extracellular composition (Cambridge, n = 64; Celsior, n = 21). The early postoperative outcome of these patients was reviewed. Reimplantation edema occurred in 48% of all patients, and the overall 1-mo survival rate was 84%. No significant difference in the incidence of edema, duration of mechanical ventilation, and 1-mo survival rate was observed between the four groups or between intra- and extracellular groups. After adjustment for graft ischemic time by means of multivariate analysis, the use of extracellular preservation fluid was associated with a lower incidence of reimplantation edema without effect on 1-mo mortality. Graft ischemic time was associated with both edema occurrence and 1-mo survival rate (p = 0.02 and p = 0.01, respectively). We conclude that extracellular-type solutions are associated with better lung preservation than intracellular-type solutions in clinical transplantation.

Female↗
PubMed2001

Preventive effect of inhaled nitric oxide and pentoxifylline on ischemia/reperfusion injury after lung transplantation.

BACKGROUND: The preventive effect of inhaled nitric oxide (NO) and pentoxifylline (PTX) administered during reperfusion has been demonstrated on experimental models of lung ischemia/reperfusion (I/R) injury but this strategy is not validated in clinical lung transplantation. The aim of this study was to assess retrospectively the protective effect of inhaled NO and PTX after lung transplantation. METHODS: Twenty-three consecutive patients who received inhaled NO (10 ppm) and PTX (NO-PTX group) at the time of reperfusion were compared retrospectively with (1) 23 consecutive patients transplanted just before the use of NO-PTX (control group 23); (2) 95 patients representing all the patients of the series who did not receive NO-PTX (control group 95), with respect to I/R injury related complications. In particular, the incidence of pulmonary reimplantation edema and early hemodynamic failure, the PaO2/FIO2 ratio as well as the duration of mechanical ventilation and the 2-month mortality rates were compared. RESULTS: Reimplantation edema was observed in 6/23 patients (26%) in the NO-PTX group vs. 13/23 patients (56%) in the control group 23 (P=0.035) and 48/95 patients (50%) in the control group 95 (P=0.035). The worst PaO2/FIO2 ratio during the first three postoperative days was 240-102 mmHg in the NO-PTX group vs. 162+/-88 mmHg (P=0.01) and 176+/-107 mmHg (P=0.01) in the control group 23 and the control group 95, respectively. The duration of mechanical ventilation was 2.1+/-2.4 days in the NO-PTX group vs. 7+/-9 days in the control group 23 (P=0.02) and 6+/-7 days in the control group 95 (P=0.01). The 2-month mortality rate was 4.3% in the NO-PTX group vs. 26% (P=0.04) and 21% (P=0.07) in the control group 23 and the control group 95, respectively. CONCLUSIONS: The marked decrease in the incidence of allograft dysfunction compared with two historical control groups suggests that PTX and inhaled NO given before and throughout reperfusion are protective against I/R injury in the setting of clinical transplantation.

Administration, Inhalation↗
PubMed2001

Long-term results of cryopreserved arterial allograft reconstruction in infected prosthetic grafts and mycotic aneurysms of the abdominal aorta.

PURPOSE: This prospective, observational study determined the long-term outcome in patients with abdominal aortic infection (primary or prosthetic graft) who were treated with simultaneous aortic/graft excision and cryopreserved arterial allograft reconstruction. METHODS: From April 1992 to March 2000, patients with abdominal aortic infection underwent complete or partial excision of the infected aorta/prosthetic graft and cryopreserved arterial allograft reconstruction. Arterial allografts were harvested from multiple organ donors and cryopreserved at -80 degrees C without rate-controlled freezing. The patients were observed for survival, limb salvage, persistence and/or recurrence of infection, and allograft patency. The results were calculated with life-table methods. RESULTS: During the 8-year study period, 28 consecutive patients (27 men, 1 woman; mean age, 64 years) underwent treatment for abdominal aortic infection (23 graft infections, including 7 graft-enteric fistulas and 5 primary aortic infections). Allograft reconstruction was performed as an emergency procedure in 13 patients (46%). The mean follow-up period was 35.4 months (range, 6-101 months). The overall treatment-related mortality rate was 17.8% (17% for graft infection, 20% for primary aortic infection). The overall 3-year survival was 67%. There was no early or late amputation. There was no persistent or recurrent infection, and none of the patients received long-term (> 3 months) antibiotic therapy. Reoperation for allograft revision, excision, or replacement was necessary in four patients (17%) who were available for examination, with no reoperative perioperative death. The 3-year primary and secondary allograft patency rates were 81% and 96%, respectively. CONCLUSION: Our experience with cryopreserved arterial allograft in the management of abdominal aortic infection suggests that this technique seems to be a useful option for treating one of the most dreaded vascular complications.

Adult↗
PubMed2001

Human mesothelial cells express tissue factor when switched to proliferating state. Pharmacological modulation in vitro.

Covering the inner surface of small-diameter arterial prostheses with endothelial cells (ECs) has been proposed as a means of improving biocompatibility and thrombosis resistance. Because the availability of autologous ECs is limited, autologous human mesothelial cells (HMCs) have been suggested as a substitute for ECs. However, HMCs express tissue factor (TF) in vitro, a deleterious characteristic in vivo. We investigated the distribution of TF antigen and of its inhibitor, tissue factor pathway inhibitor, on HMCs and the effect of pharmacological agents on TF expression. TF antigen was measured by enzyme-linked immunosorbent assay and localized by confocal microscopy. Three distinct pools of TF antigen were demonstrated: within the cells, at the cell surface, and in the extracellular matrix. The effects of ilomedin (10 microg/ml) and heparin (500 U/ml), known to affect procoagulant activity, were evaluated by incubating HMCs for 24 h with or without these agents. Ilomedin, but not heparin, decreased TF antigen expression by 30% (P < 0.05). Despite the theoretical potential of HMCs as a vascular prosthesis lining, TF expression by HMCs remains a major drawback. A technique capable of blocking TF expression until the HMCs return to their resting state is needed. Genetic manipulation of HMCs may hold promise for such a technique.

Cell Culture Techniques↗
PubMed2001

Ectopic hepatocellular carcinoma arising in the left chest wall: a long-term follow-up.

We report the case of a 66-year-old man with chronic hepatitis C and a slowly growing left chest wall mass. Two years after the patient first noticed the mass, it was resected. A diagnosis of hepatocellular carcinoma (HCC) was established. The liver was studied by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, but no mass was found. Blind liver biopsy showed mild chronic hepatitis without cirrhosis or HCC. Three years after the discovery of the chest wall HCC, no liver mass had appeared at CT and MRI. We conclude that solitary extrahepatic HCC (i) may arise in ectopic liver tissue; (ii) should not be considered as a metastasis of an occult HCC; and (iii) can be amenable to cure through resection.

Carcinoma, Hepatocellular↗
PubMed2000

Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques.

BACKGROUND: Blood flow characteristics influence endothelial cell apoptosis. However, little is known about the occurrence of endothelial cell apoptosis in human atherosclerosis and its relation to blood flow. METHODS AND RESULTS: A total of 42 human carotid atherosclerotic plaques were retrieved by endarterectomy; they were examined in the longitudinal axial direction. Plaques were included in this study when upstream and downstream parts were clearly visible, occlusion was absent, and immunostaining for luminal endothelium was present all along the plaque. Using these criteria, 13 plaques were processed for further immunohistochemical studies (using anti-CD31, anti-Ki-67, and anti-splicing factor antibodies) and in situ detection of apoptosis (terminal dUTP nick end-labeling and ligase assay). Eight plaques showed > or =1 apoptotic endothelial cell at the luminal surface. Quantitative analysis of endothelial cell apoptosis in these plaques showed a systematic preferential occurrence of apoptosis in the downstream parts of plaques, where low flow and low shear stress prevail, in comparison with the upstream parts (18.8+/-3.3% versus 2.7+/-1.2%, respectively, P<0.001). Endothelial cell apoptosis was barely detectable in plaque microvessels. CONCLUSIONS: Our results suggest that in vivo local shear stress influences luminal endothelial cell apoptosis and may be a major determinant of plaque erosion and thrombosis.

Apoptosis↗
PubMed2000

[Penetrating atheromatous ulcers of the aorta].

UNLABELLED: THORACIC PAINFUL SYNDROME: Penetrating atherosclerotic aortic ulcers represent a condition in which an atherosclerotic plaque ulcerates and disrupts the internal elastic lamina, allowing intramural hematoma formation into the aortic media. Recently individualized as an entity from all vascular thoracic painful syndromes, they affect preponderantly the elderly patients with a medical hypertensive and atherosclerotic history and with multiple cardiovascular risk factors. The descending thoracic aorta is most frequently involved. IMAGING: Computed tomography scanning and magnetic resonance imaging tend to replace aortography in providing an accurate diagnosis of the ulceration and of its parietal extent. Moreover, they allow the discrimination with aortic dissection or with intramural hematoma without intimal rupture which outcome and treatment should differ. RISKS: In the absence of complication, progressive aneurysmal dilatation at the level of the ulcer is a rule. Pseudoaneurysms formation, embolization, and acute transmural aortic rupture can however occur and may justify, in selected cases, a preventive or curative surgical treatment. STENT-GRAFTING: Endovascular stent-grafting techniques may appear as a safe and effective less invasive choice in high-risk patients with suitable anatomical conditions.

Age Factors↗
PubMed2000

Morbidity and mortality related to the native lung in single lung transplantation for emphysema.

It has been advocated that a major drawback of single lung transplantation (SLT) is the risk of serious complications arising from the native lung. The morbidity and mortality related to the native lung in 46 patients who underwent SLT for pulmonary emphysema in Clichy from 1988 to 1997 were reviewed retrospectively. In particular, infectious complications and native lung hyperinflation were searched. Complications arising from the native lung are not unusual after SLT for subjects with emphysema, and it was concluded they are not responsible for a substantial mortality.

Humans↗
PubMed2000

Guidelines for perioperative cardiac evaluation from the American College of Cardiology/American Heart Association task force are effective for stratifying cardiac risk before aortic surgery.

PURPOSE: We assessed whether the American College of Cardiology/American Heart Association (ACC/AHA) task force guidelines for perioperative cardiac evaluation could reliably stratify cardiac risk before aortic surgery. METHODS: We retrospectively applied the guidelines to a closed database, set up prospectively. The setting was a referral center in an institutional practice with hospitalized patients. The closed database included 133 patients who had a routine cardiac examination, which comprised an estimation of functional capacity and noninvasive testing, before aortic surgery. This cardiac evaluation led to the proposal of coronarography in 23 patients and to treating an underlying coronary artery disease in 21 patients (including three myocardial revascularizations). One patient died after myocardial revascularization, and two patients died of cardiac causes after aortic surgery. The algorithm of the ACC/AHA guidelines was applied independently by two investigators to each patient's file that was included in the existing database. The main outcome measure was a comparison between cardiac risk stratification with the ACC/AHA guidelines and the results of the routine cardiac evaluation. RESULTS: The ACC/AHA guidelines were successfully applied to all 133 files by the two investigators. After applying the algorithm, 73 patients were stratified as low cardiac risk, and 60 patients were stratified as high risk. The 21 patients who had undergone a preoperative coronary artery disease optimization were stratified as high risk by means of the ACC/AHA guidelines. The patients who died from cardiac causes were stratified as high risk by means of the ACC/AHA guidelines, whereas none of the patients stratified as low risk died during hospitalization. CONCLUSION: The ACC/AHA guidelines were effective in stratifying cardiac risk by using clinical predictors and an estimate of the physical capacity of the patient. Their use may allow a reduction in unnecessary noninvasive testing in patients stratified as being at low risk, while permitting the selection of all patients likely to benefit from preoperative coronary artery disease optimization.

Algorithms↗
PubMed1999

Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity.

BACKGROUND: The specific role of apoptosis in human atherosclerosis remains unknown. During apoptotic cell death, phosphatidylserine exposure on the cell surface confers a high tissue-factor (TF)-dependent procoagulant activity. METHODS AND RESULTS: In this study, we examined the role of apoptotic cell death in the promotion of plaque thrombogenicity. TF expression and its relation to apoptosis was analyzed in 16 human atherosclerotic plaques by the use of immunohistochemical techniques. The presence of shed membrane apoptotic microparticles was analyzed in extracts from 6 human atherosclerotic plaques and 3 underlying arterial walls. The microparticles were captured by annexin V and their amounts estimated with respect to their phospholipid content by use of a prothrombinase assay. The prothrombogenic potential of the microparticles was further assessed by the measurement of total and microparticle-dependent TF activity in the extracts. The cell origin of the microparticles was determined after capture by specific antibodies. We were able to detect marked TF expression in the plaques in close proximity to apoptotic cells and debris, suggesting a potential interaction between TF and the apoptotic cell surfaces. High levels of shed membrane apoptotic microparticles were detected in extracts from atherosclerotic plaques but not in the underlying arterial walls (29.5+/-3.7 nmol/L phosphatidylserine equivalent versus 1.3+/-0.4 nmol/L, respectively, P<0.02). The microparticles were mainly of monocytic and lymphocytic origin and retained 97+/-2% of total TF activity, indicating a direct causal relationship between shed membrane microparticles and procoagulant activity of plaque extracts. CONCLUSIONS: These results indicate that shed membrane microparticles with procoagulant potential are produced in human atherosclerotic plaques. Apoptosis could be a critical determinant of plaque thrombogenicity after plaque rupture.

Acute Disease↗
PubMed1999

In vitro endothelialization of PTFE vascular grafts: A comparison of various substrates, cell densities, and incubation times.

To establish the optimal conditions for achieving endothelial cell coverage of the luminal surfaces of small-caliber vascular grafts in vitro, the attachment of endothelial cells (ECs) cultured from human umbilical veins to polytetrafluoroethylene (PTFE) grafts was studied. Cell attachment and spreading were compared after PTFE grafts were (a) precoated with fibronectin (HFN), type I collagen, type IV collagen, plasma and fibrin with or without thrombin, singly or in combination; (b) seeded with cell densities varying from 0.5 x 10(5) to 6 x 10(5) cells/cm2; and (c) incubated at 30, 60, or 90 min. Cell coverage and spreading were assessed by means of scanning electron microscopy. Quantification of graft surface coverage was performed with computer-assisted image analysis. To determine optimal conditions of endothelialization among the 189 treatment combinations, analysis of variance was used. We conclude that a virtually confluent cell monolayer can be established on small-caliber PTFE grafts when precoated with fibrin glue or plasma, seeded with cell densities >/=4 x 10(5) cells/cm2, and incubated for 60 min. These parameters are compatible with an operating room vascular procedure.

Blood Vessel Prosthesis↗
PubMed1999

Early experience with cryopreserved arterial allografts in below-knee revascularization for limb salvage.

BACKGROUND: Below-knee revascularization for limb salvage in the absence of a suitable autogenous saphenous vein is a frequent challenge associated with a high amputation rate. The aim of this prospective study was to evaluate the usefulness of cryopreserved arterial allografts in such cases. METHODS: Arterial allografts were harvested from multiple organ donors and cryopreserved at -80 degrees C. From March 1993 to December 1997, 35 cryopreserved arterial allografts were used as below-knee bypasses for repeated limb salvage in 32 patients. There were 15 men and 17 women with a mean age of 75 years (+/-10.7). Seven patients had rest pain and 25 patients (78%) had gangrene or nonhealing ulceration. Runoff was through a single tibial vessel in 25 cases (71%) and two vessels in 10 cases. Previous ipsilateral bypasses had been done in 26 of 35 limbs (74%). Patients were followed up prospectively for an average period of 18 months (range 2 to 56). RESULTS: Aneurysmal dilatation occurred in two patent grafts, requiring segmental replacement at 13 and 18 months, respectively. The overall primary patency rate was 75% at 6 months, 57% at 12 months, and 39% at 18 months. The overall secondary patency rate was 75% at 6 months, 75% at 12 months, and 59% at 18 months. Overall limb salvage rate was 80% at 12 months, 73% at 18 months. CONCLUSIONS: These early data indicate that below-knee bypass with arterial allografts results in acceptable patency and limb salvage. Arterial allografts may be a useful alternative to other arterial substitutes in a difficult group of patients with critical ischemia and no suitable saphenous vein.

Aged↗
PubMed1999

Expression of interleukin-10 in advanced human atherosclerotic plaques: relation to inducible nitric oxide synthase expression and cell death.

Inflammation is a major feature of human atherosclerosis and is central to development and progression of the disease. A variety of proinflammatory cytokines are expressed in the atherosclerotic plaque and may modulate extracellular matrix remodeling, cell proliferation, and cell death. Little is known, however, about the expression and potential role of anti-inflammatory cytokines in human atherosclerosis. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine whose expression and potential effects in advanced human atherosclerotic plaques have not been evaluated. We studied 21 advanced human atherosclerotic plaques. IL-10 expression was analyzed by use of reverse transcription-polymerase chain reaction and immunohistochemical techniques. Inducible nitric oxide synthase expression was assessed by using immunohistochemistry, and cell death was determined by use of the TUNEL method. Reverse transcription-polymerase chain reaction identified IL-10 mRNA in 12 of 17 atherosclerotic plaques. Immunohistochemical staining of serial sections and double staining identified immunoreactive IL-10 mainly in macrophages, as well as in smooth muscle cells. Consistent with its anti-inflammatory properties, high levels of IL-10 expression were associated with significant decrease in inducible nitric oxide synthase expression (P<0.0001) and cell death (P<0. 0001). Hence, IL-10, a potent anti-inflammatory cytokine, is expressed in a substantial number of advanced human atherosclerotic plaques and might contribute to the modulation of the local inflammatory response and protect from excessive cell death in the plaque.

Aorta, Abdominal↗
PubMed1999

The relationship of hydroxyeicosatetraenoic acids and F2-isoprostanes to plaque instability in human carotid atherosclerosis.

Evidence for increased oxidant stress has been reported in human atherosclerosis. However, no information is available about the importance of in situ oxidant stress in relation to plaque stability. This information is relevant because the morbidity and mortality of atherosclerosis are essentially the consequences of acute ischemic syndromes due to unstable plaques. We studied 30 carotid atherosclerotic plaques retrieved by endarterectomy from 18 asymptomatic (stable plaques) and 12 symptomatic patients (unstable plaques). Four normal arteries served as controls. After lipid extraction and ester hydrolysis, quantitation of different indices of oxidant stress were analyzed, including hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatetraenoic acids (EETs), ketoeicosatetraenoic acids (oxo-ETEs), and F2-isoprostanes using online reverse-phase high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). All measurements were carried out in a strictly double-blind procedure. We found elevated levels of the different compounds in atherosclerotic plaques. Levels of HETEs were 24 times higher than EETs, oxo-ETEs, or F2-isoprostanes. Levels of HETEs, but not those of EETs, oxo-ETEs or F2-isoprostanes, were significantly elevated in plaques retrieved from symptomatic patients compared with those retrieved from asymptomatic patients (1, 738 +/- 274 vs. 1,002 +/- 107 pmol/ micromol lipid phosphorous, respectively; P < 0.01). One monooxygenated arachidonate species, 9-HETE, which cannot be derived from known enzymatic reactions, was the most abundant and significant compound observed in plaques, suggesting that nonenzymatic lipid peroxidation predominates in advanced atherosclerosis and may promote plaque instability.

Arteriosclerosis↗
PubMed1998

Limitations of radionuclide angiographic assessment of left ventricular systolic function before lung transplantation.

To evaluate the influence of increased right ventricular afterload on radionuclide assessment of the left ventricular ejection fraction (LVEF), we compared the preoperative and postoperative value of isotopic LVEF in 11 patients who underwent lung transplantation and had a preoperative LVEF value below 55% (normal value: 68 +/- 8%). The underlying disease conditions were obstructive lung disease (n = 7) and pulmonary fibrosis (n = 4). The transplantation procedure was unilateral in 10 patients and bilateral in one. The mean value of isotopic LVEF prior to transplantation was 51 +/- 3% (range: 49% to 55%). At 42 +/- 13 mo postoperatively, isotopic LVEF increased significantly, to 65 +/- 10% (p = 0.001), suggesting that intrinsic left ventricular systolic function was in fact normal in these patients. We hypothesize that the low preoperative isotopic LEVF was not related to intrinsic dysfunction of the left ventricle, but rather to right ventricular pressure overload, leading to bulging of the interventricular septum into the left ventricle and to subsequent geometric distortion of the left ventricle. We conclude that isotopic LVEF may underestimate intrinsic left-ventricular systolic function in patients with severe chronic lung disease. Candidates for lung transplantation should not be rejected on the basis of a low isotopic LVEF, provided echocardiographic examination does show apparently normal left ventricular contraction.

Adult↗
PubMed1998

Early release of proinflammatory cytokines after lung transplantation.

BACKGROUND: Systemic hypotension may complicate the early postoperative period after lung transplantation. A release of proinflammatory cytokines secondary to lung ischemia/reperfusion injury could be involved in the pathogenesis of this early hemodynamic failure (EHF). STUDY OBJECTIVE: To assess prospectively whether the occurrence of EHF is associated with a release of cytokines in the systemic circulation. DESIGN: Blood samples were taken daily during the first postoperative week in 26 patients who underwent a double or a single-lung transplantation. These patients were divided into three groups: 7 patients who experienced EHF and subsequently died (EHF group); 15 patients without EHF (control group); and 4 patients without EHF but with an identified sepsis (sepsis group). The serum levels of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 were compared among the three groups. RESULTS: In the EHF group, the levels of each cytokine peaked at day 1 postoperatively. Cytokine levels at day 1 were significantly higher in the EHF group than in the control group (p<0.0006) or in the sepsis group (p<0.003 except for TNF-alpha). CONCLUSION: We conclude that EHF is associated with a massive release of proinflammatory cytokines that could play a determinant role in the pathogenesis of this complication.

Adolescent↗