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Biomedical subjects

Eric Allaire

Publications and source records attributed to Eric Allaire.

15 recordsLinked to original sources
PubMed2006

Heterogeneity in the remodeling of aneurysms of the ascending aorta with tricuspid aortic valves.

OBJECTIVES: The study addresses mechanisms driving the formation of ascending aortic aneurysms by comparing the maximal dilatation area with the transition area immediately adjacent to the normal aortic tissue left in place during surgical repair. METHODS: Aortic wall specimens were taken from the maximal dilatation area and transition area in 10 patients undergoing surgery for ascending aortic aneurysms and fixed for histology and immunohistochemistry for vascular smooth muscle cells (alpha-actin), endothelial cells (CD31), and macrophages (CD68). Tissue concentrations of vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 were determined by enzyme-linked immunosorbent assay. The results are expressed as medians with their 25th and 75th centiles. RESULTS: Vascular smooth muscle cells were significantly more abundant in the maximal dilatation area than in the transition area (20.3 [14.8-24.4]/10(-2) mm2 vs 8.0 [6.4-9.3]/10(-2) mm2, respectively, P = .002). In the maximal dilatation area, vascular smooth muscle cells had lost their typical lamellar organization, whereas it was preserved in the transition area. Microvessels were significantly more abundant in the media of transition area than in the maximal dilatation area (7.5 [2.9-10.1]/mm2 vs 1.75 [1.5-2.0]/mm2, respectively, P = .008) and were associated with an inflammatory cell infiltration that predominated in their immediate vicinity. There were no significant differences in vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 between both areas. CONCLUSIONS: The transition area appears as a disease progression front characterized by microvessel formation and inflammatory cell infiltration. In contrast, increased vascular smooth muscle cell density in the maximal dilatation area suggests a healing process, although inefficient to prevent aortic dilatation.

Actins↗
PubMed2006

Pathobiology of idiopathic ascending aortic aneurysms.

The majority of ascending aortic aneurysms cannot be related to any specific etiology and should be qualified as idiopathic. The pathobiology of ascending aortic aneurysms remains incompletely understood. Data from direct study are still scarce and often limited because of patient heterogenicity. Currently available information suggests that destructive remodeling of the aortic wall, inflammation and angiogenesis, biomechanical wall stress, and molecular genetics are relevant mechanisms of idiopathic ascending aortic aneurysm formation and progression. Further understanding of these mechanisms will likely provide novel diagnostic, prognostic, and therapeutical tools for the clinician.

Aorta↗
PubMed2006

[Differentiated thyroid carcinoma--how to improve the long-term results? Twenty-five-year outcomes of 850 patients].

About 4000 people are diagnosed with thyroid carcinoma each year in France and as many as one in three adult patients have thyroid nodules on sonography. Nine in ten cases are differentiated (DTC). DTC may recur in the neck or metastasize very late, and final outcomes should therefore only be assessed after at least 20 years of follow-up. The goals of this study were to provide a reference for the evaluation of other protocols, to evaluate the benefits and risks of radioiodine, and to identify the most effective management option. We examined 25-year outcomes in a series of 850 DTC patients who were operated on and monitored with the same protocols. We used an original classification (Ext-Tg) that includes both the initial extension and the thyroglobulin (Tg) level at the end of initial treatment. The low-risk group, composed of patients with Tg <10 microg/l after ablation of thyroid remnants, included patients at stage 1 (microcarcinoma, n=268), stage 2 (intra-thyroidal carcinoma, n=310), and stage 3 (DTC with node invasion, n=142). Stage 4 disease consisted of DTC with some non excisable tumor in the neck, and/or metastasis, and/or stimulated Tg >10 microg/l after remnant ablation. Most patients had total thyroidectomy followed by radioiodine ablation, periodic monitoring adapted to the stage, and suppressive therapy. At 25 years the actuarial rates of cancer-related death among patients with initial stage 1, 2, 3 and 4 disease were respectively 0%, 1,4%, 0% and 46,9%. The overall recurrence rates were respectively 3,6%, 3,8%, 5,3% and 44,5%. The rates of cervical recurrence necessitating surgery were 3,8%, 2,4%, 3,4% and 23,7%. Serious complications of treatment, including radioiodine, were rare. We conclude that:--good long-term results are more likely to be obtained when total thyroidectomy and radioiodine are combined with an early detection of recurrences (before they are visible by traditional imaging methods);--patients must be strictly staged in order to guide the modalities and duration of follow-up, and the Ext-TG classification seems more appropriate than all those which do not consider the Tg level at the end of initial treatment;--in experienced hands the benefits of total surgical ablation of the tumor greatly outweigh the potential risks;--radioiodine is effective and safe when appropriate measures are taken to prevent complications, and the long-term eficacy of surveillance without total body scanning should be verified before being universally adopted;--cost-reduction should focus on diagnosis, screening, and the selection of nodules eligible for surgery, rather than on monitoring of patients with DTC. DTC is thus a paradigm of a disease in which it is possible to optimize the long-term results and to lower costs by monitoring small and non-suspect nodules.

Adolescent↗
PubMed2005

Overexpression of transforming growth factor-beta1 stabilizes already-formed aortic aneurysms: a first approach to induction of functional healing by endovascular gene therapy.

BACKGROUND: The cell response to transforming growth factor-beta1 (TGF-beta1), a multipotent cytokine with healing potential, varies according to tissue context. We have evaluated the ability of TGF-beta1 overexpression by endovascular gene therapy to stabilize abdominal aortic aneurysms (AAAs) already injured by inflammation and proteolysis. METHODS AND RESULTS: Active TGF-beta1 overexpression was obtained in already-developed experimental AAAs in rats after endovascular delivery of an adenoviral construct encoding for a mutated form of active simian TGF-beta1 and in an explant model using human atherosclerotic AAA fragments incubated with recombinant active TGF-beta1. Transient exogenous TGF-beta1 overexpression by endovascular gene delivery was followed by induction of endogenous rat TGF-beta1. Overexpression of active TGF-beta1 in experimental AAAs was associated with diameter stabilization, preservation of medial elastin, decreased infiltration of monocyte-macrophages and T lymphocytes, and a decrease in matrix metalloproteinase-2 and -9, which was also observed in the explant model, in both thrombus and wall. In parallel with downregulation of the destructive process, active TGF-beta1 overexpression triggered endoluminal reconstruction, replacing the thrombus by a vascular smooth muscle cell-, collagen-, and elastin-rich intima. CONCLUSIONS: Local TGF-beta1 self-induction after transient exogenous overexpression reprograms dilated aortas altered by inflammation and proteolysis and restores their ability to withstand arterial pressure without further dilation. This first demonstration of stabilization of expanding AAAs by delivery of a single multipotent self-promoting gene supports the view that endovascular gene therapy should be considered for treatment of aneurysms.

Animals↗
PubMed2005

Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation.

PURPOSE: To perform a quantitative analysis of anionic maghemite nanoparticle-labeled cells in vitro and determine the effect of labeling on signal intensity at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the institutional animal care and use committee at Hôpital Bichat. In vitro cell proliferation, iron content per cell, and MR signal intensity of cells were measured in agarose phantoms for 0-14 days of culture after labeling of rat smooth muscle cells with anionic maghemite nanoparticles. Next, iron oxide-labeled smooth muscle cells were injected into healthy hearts and hearts with ischemic injury in seven live Fisher rats. Ex vivo MR imaging experiments in excised hearts 2 and 48 hours after injection were performed with a 1.5-T medical imaging system by using T2-weighted gradient-echo and spin-echo sequences. Histologic sections were obtained after MR imaging. Correlation analyses between division factor of iron load and cell amplification factor and between 1/T2 and number of labeled cells or number of days in culture were performed by using linear regression. RESULTS: Viability of smooth muscle cells was not affected by magnetic labeling. Transmission electron micrographs of cells revealed the presence of iron oxide nanoparticles in vesicles up to day 14 of culture. Intracellular iron concentration decreased in parallel with cell division (r2 = 0.99) and was correlated with MR signal intensity (r2 = 0.95). T2*-weighted MR images of excised rat hearts showed hypointense signal in myocardium at 2 and 48 hours after local injection of labeled cells. Subsequent histologic staining evidenced iron oxide nanoparticles within cells and confirmed the presence of the original cells at 2 and 48 hours after implantation. CONCLUSION: Magnetic labeling of smooth muscle cells with anionic maghemite nanoparticles allows detection of cells with MR imaging after local transplantation in the heart.

Animals↗
PubMed2005

Delayed complications following EVAR.

More than a decade after the first clinical attempts, two large randomized studies have proven that endovascular aortic aneurysm repair (EVAR) provides immediate advantages over open repair. In the long run, however, a relatively high number of reinterventions is necessary to improve the long-term efficacy of EVAR, which may outweigh the early benefits. Since EVAR is gaining popularity in the medical community and in patients with abdominal aortic aneurysm (AAA), it is expected that a growing number of patients will present with delayed complications requiring some kind of reinterventions. For the patient's safety, vascular surgeons and interventional radiologists involved in EVAR must be well aware of these complications and the ways to overcome them. We began our endovascular program for AAA in 1994 and currently follow 485 patients with a variety of manufactured grafts. In this article we describe the delayed complications observed with EVAR, their mechanisms, favoring factors, and ways to treat them.

Aortic Aneurysm, Abdominal↗
PubMed2004

Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis.

OBJECTIVE: To investigate the efficiency of endovascular smooth muscle cell (VSMC) seeding in promoting healing and stability in already-developed aneurysms obtained by matrix metalloproteases (MMPs)-driven injury. SUMMARY BACKGROUND DATA: VSMCs are instrumental in arterial healing after injury and are in decreased number in arterial aneurysms. This cellular deficiency may account for poor healing capabilities and ongoing expansion of aneurysms. METHODS: Aneurysmal aortic xenografts in rats displaying extracellular matrix injury by inflammation and proteolysis were seeded endoluminally with syngeneic VSMCs, with controls receiving culture medium only. Diameter, structure, and the destruction/reconstruction balance were assessed. RESULTS: Eight weeks after endovascular infusion, aneurysmal diameter had increased further, from 3.0 +/- 0.3 mm to 10.9 +/- 6.5 mm (P = 0.009), and medial elastin content had decreased from 36.5 +/- 8.5 to 5.2 +/- 5.5 surface-percent (S%; P = 0.009) in controls, whereas these parameters remained stable in the seeded group (3.0 +/- 0.3 to 2.7 +/- 0.2 mm, P = 0.08; 36.5 +/- 8.4 to 31.6 +/- 9.7 S%, P = 0.22). VSMC seeding was followed by a decrease in mononuclear infiltration. MMP-1, -3, -7, -9, and -12 mRNA contents were sharply decreased in the diseased wall in response to seeding. Tissue inhibitor of metalloproteinase-1, -2, and -3 mRNAs in the intima were increased in a 2 to 10 magnitude in comparison with controls. Gelatin zymography showed the disappearance of MMP-9 activity and reverse zymography a strong increase in tissue inhibitor of metalloproteinase-3 activity in the seeded group. VSMC-seeded aneurysms were rich in collagen and lined with an endothelium instead of a thrombus in controls. CONCLUSIONS: VSMCs endovascular seeding restores the healing capabilities of proteolytically injured extracellular matrix in aneurysmal aortas, and stops expansion.

Animals↗
PubMed2003

Iliac artery rupture during balloon dilatation: what treatment?

Intraoperative and postoperative arterial ruptures associated with 657 iliac artery balloon dilatation procedures in our department from 1981 to 2000 were prospectively collected and retrospectively analyzed. Our results showed that failure to exercise basic safety principles and the presence of heavily calcified plaque are the major predictors of iliac artery rupture during balloon dilatation. If rupture is contained, surveillance alone is unreliable. Optimal treatment requires temporary hemostasis by balloon tamponade followed by placement of a covered stent to occlude the opening.

Aged↗
PubMed2003

Paracrine secretion of transforming growth factor-beta1 in aneurysm healing and stabilization with endovascular smooth muscle cell therapy.

BACKGROUND: Identification of molecular factors involved in artery wall stabilization after extracellular matrix injury elicited by inflammation and proteolysis has a major role in the development of new therapies for atherosclerosis. A study from our group demonstrated that endovascular seeding of vascular smooth muscle cells (VSMCs) promotes healing and stabilizes experimental aneurysms by downregulating matrix metalloproteinase and upregulating tissue inhibitor of metalloproteinase and collagen gene expression. We analyzed expression of transforming growth factor-beta (TGF-beta) and its receptors in experimental aneurysms treated with endovascular VSMC therapy. METHODS AND RESULTS: Aneurysms were generated in Fischer 344 rats by 14-day orthotopic implantation of a segment of guinea pig abdominal aorta (xenograft). During an endovascular repeat operation, syngeneic VSMCs were seeded in the aneurysm, always resulting in aneurysm diameter stabilization after 8 weeks, whereas diameter of control aneurysms infused with culture medium further increased. Seven days after repeat operation the intima or thrombus was separated from the aneurysmal wall in the two groups. Reverse transcriptase polymerase chain reaction with the domestic gene 18s as a standard demonstrated that aneurysm stabilization was associated with a statistically significant increase in TGF-beta(1), but not TGF-beta(2) or TGF-beta(3), messenger RNA levels in the intima. Enzyme-linked immunosorbent assay demonstrated increased TGF-beta(1) protein in the aneurysmal wall. mRNA levels of the two serine and threonine kinase TGF-beta receptors remained unchanged. CONCLUSIONS: Healing and stabilization of aneurysms with endovascular cell therapy is associated with a specific pattern of gene expression, resulting in paracrine secretion of TGF-beta(1). Our study provides insight into the molecular mechanisms of arterial aneurysm healing and stabilization.

Animals↗
PubMed2003

Gadolinium-enhanced MR angiography as first-line preoperative imaging in high-risk patients with lower limb ischemia.

PURPOSE: To assess the clinical relevance of gadolinium-enhanced MR angiography (Gd-MRA) as the first-line angiographic examination for planning lower limb revascularization in patients at high risk of complications after contrast arteriography (CA). METHOD: Forty-five consecutive patients at high risk of post-CA complications because of chronic renal insufficiency, diabetes mellitus, advanced age, or the need for brachial artery catheterization or graft puncture had Gd-MRA as first-line angiography before a surgical or endovascular procedure for lower limb ischemia. RESULTS: After Gd-MRA, 59 procedures were performed, including 38 surgical reconstructions, 17 endovascular procedures, and four amputations. Complementary CA was only required in seven patients for whom a below-knee bypass was planned. Cumulative patency rates at 1 and 24 months were, respectively, 91% and 91% for suprainguinal bypasses, 100% and 92% for infrainguinal above-knee bypasses, 80% and 57% for below-knee bypasses, and 92% and 76% for iliofemoral angioplasties. After 24 months of follow-up, limb salvage, amputation, and mortality rates were, respectively, 86%, 3.5%, and 7% for stage II ischemia and 48%, 11%, and 30% for stages III and IV. CONCLUSION: Gd-MRA can be proposed for first-line preoperative imaging in the management of lower limb ischemia for patients at high risk and permits the selective use of CA as a second-line examination if a below-knee bypass is required.

Adult↗
PubMed2002

Paracrine effect of vascular smooth muscle cells in the prevention of aortic aneurysm formation.

OBJECTIVE: Inflammation and elastinolysis are observed in the media of abdominal aortic aneurysms (AAAs) where vascular smooth muscle cell (VSMC) density is decreased. In contrast, elastin and VSMCs are preserved in the noninflammatory media of stenotic atherosclerotic lesions. We have tested the hypothesis that VSMCs exert a protective effect against inflammation and proteolysis in a model of AAA in rats, in which medial elastin degradation is driven by inflammation and matrix metalloproteinases. METHOD: Decellularized guinea pig aortas (xenografts) were implanted orthotopically into Fischer-344 rats and seeded with a suspension of rat VSMCs syngeneic to the rat recipient, or were infused with culture medium as a control. Diameter and elastin in the media were quantified 8 weeks after implantation. Inflammation, matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) expression were analyzed 1 and 2 weeks after implantation. RESULTS: VSMC addition prevented AAA formation (mean +/- standard deviation diameter increase: 198.2% +/- 106.6% vs 35.3% +/- 17.8%, P =.009), elastin degradation, and decreased infiltration by monocyte-macrophages. Reverse-transcriptase polymerase chain reaction, zymography and reverse zymography for MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 demonstrated a shift of the proteolytic-antiproteolytic balance upon addition of VSMCs. Transcriptional changes were observed in the adventitia, although seeded VSMCs remained located in the intima. CONCLUSIONS: VSMCs exert a paracrine effect on the adventitia that participate in artery wall homeostasis against inflammation and proteolysis. Failure of this protective mechanism results in AAA formation. The understanding of the molecular mechanisms underlying VSMC protective effect may represent a new approach in the treatment of aneurysm and plaque rupture.

Animals↗
PubMed2002

Endograft fabric disintegration simulating a type II endoleak.

PURPOSE: To report a case of endograft disintegration misinterpreted as a type II endoleak. CASE REPORT: An 86-year-old man underwent successful Vanguard stent-graft implantation for a 49-mm abdominal aortic aneurysm. At 1 month, a distal type I endoleak was repaired, but another endoleak thought to arise from the lumbar or inferior mesenteric arteries remained. Multiple interventions to embolize the feeding arteries were unsuccessful, and the endoleak persisted. At 1 year, the leak was still present, and the aneurysm had increased to 69 mm. After failing to demonstrate the source of the leak radiographically, surgery was performed. At operation, the endoleak was traced to small holes in the graft fabric. The endograft was removed without difficulty, and the flow was re-established with an aortobi-iliac woven graft. CONCLUSIONS: Chronically implanted stent-grafts can show signs of failure that are confusing or misleading. Correct diagnosis of endoleaks may be difficult, but every effort must be made to identify their source. It is vital that no enlarging aneurysm be left untreated.

Aged↗
PubMedDate not supplied

Foot gangrene in patients with end-stage renal disease: a case control study.

The prevalence of peripheral arterial disease (PAD) in patients with end-stage renal disease (ESRD) is high, with an annual risk of amputation estimated at 13%, and indications for limb revascularization in patients combining ESRD with stage IV PAD (foot gangrene) are still controversial. This case-controlled study compared survival, limb salvage, and quality of life in a group of patients hospitalized for foot gangrene according to their renal status (ESRD versus no renal insufficiency). All patients with ESRD hospitalized for foot gangrene (n = 16) from 1996 to 2002 were compared with a control group with normal creatininemia (n = 24) hospitalized for foot gangrene due to peripheral atherosclerotic arterial disease. The 2 groups were matched for age, sex ratio, and number with diabetes mellitus. After a mean follow-up of 467 +/-410 days, patients with ESRD had a more severe prognosis as regards mortality (68.7% vs 12.5%, p = 0.0005) and major amputation (31% versus 8%, p = 0.09). The ESRD group was characterized by more frequent extensive arterial calcifications (16/16 vs 13/24, p = 0.002), owing to a higher level of the calcium phosphorus product (3.54 +/-1.2 vs 2.4 +/-0.6, p = 0.0023), and by impaired microcirculatory perfusion, as indicated by a lower oxygen pressure (TcPO(2)) (15.6 +/-12 mm Hg vs 26 +/-16, p = 0.07). ESRD implies a poor prognosis in patients with stage IV peripheral arterial disease.

Aged↗
PubMedDate not supplied

Extensive unilateral iliofemoral occlusions: durability of four techniques of arterial reconstructions.

In patients with long unilateral iliofemoral occlusive disease unfit for percutaneous transluminal angioplasty (PTA), most surgeons would choose some type of prosthetic bypass (aortounifemoral, iliofemoral or cross over). All these bypasses would provide excellent early results, but some may not be sufficient in patients with a good life expectancy who also need durable patency. The purpose of the study was to compare the long-term results of four types of arterial reconstructions. Over 20 years, 468 unilateral iliofemoral occlusions were treated primarily by one of the following techniques: aortounifemoral bypass (group 1, n = 108), iliofemoral bypass (group 2, n = 144), crossover bypass (group 3, n = 108), and iliofemoral endarterectomy (group 4, n = 108). Patients in group 3 presented with more severe comorbidities, and patients in group 4 had more superficial femoral artery occlusions. All data were prospectively registered after discharge and during the survey. Patency was assessed with duplex ultrasonography on a yearly basis. Perioperative complications and death rates were similar in all groups. The standard error was less than 10% for a period of over 10 years in all groups, except for group 3, in which it was more than 10% after 8 years. At 8 years, primary patency rates in groups 1, 2, 3, and 4 were 79%, 66%, 74%, and 89%, respectively. The difference was significant between group 4 and group 2 (p < .02) and group 3 (p < .01). Secondary patency and limb salvage rates were not significantly different. In this study, for an equal perioperative risk, the primary patency rates of iliac endarterectomies were superior to those of the other techniques, suggesting that these procedures should be the first choice in patients in good physical condition. Iliofemoral bypasses and crossover bypasses needed much more redo surgery. A crossover bypass should be reserved for patients who are unfit for an abdominal approach or who have a short life expectancy.

Arterial Occlusive Diseases↗