PubMed Health⌕ Search

Biomedical subjects

E Legrand

Publications and source records attributed to E Legrand.

At least 19 recordsLinked to original sources
PubMed2006

Bone microarchitecture in males with corticosteroid-induced osteoporosis.

SUMMARY: Microarchitectural changes in trabecular bone were analyzed by microcomputed tomography (microCT) and histomorphometry in 24 patients with corticosteroid-induced osteoporosis. The microCT images revealed a reduction in trabecular thickness only on frequency distribution curves, with no increase in trabecular separation. Trabecular plate thinning and perforations were easily identified. INTRODUCTION: Corticosteroid-induced osteoporosis (CSIOP) is mediated by direct actions of the drug on bone cells. The result is a decrease in trabecular bone mass and a reduction in trabecular thickness, but connectivity is believed to remain rather well preserved. METHODS: Twenty-four transiliac bone biopsies from patients with CSIOP were studied conjointly by histomorphometry [with two-dimensional (2D) architectural descriptors] and microCT (with 3D analysis of trabecular characteristics, including trabecular thickness and separation). The frequency distribution of thickness and separation were compared with data obtained in nine control subjects. RESULTS: 2D histomorphometry revealed a decrease in bone volume and trabecular thickness in the bone biopsies of the CSIOP patients when compared to those of the controls. MicroCT appeared to be able to identify the reduction in thickness only when the frequency distribution of trabecular thickness was computed. No difference for the curves of the frequency distribution of trabecular separation was evidenced between patients and controls. MicroCT and 2D histomorphometric results were correlated, but 2D analysis appeared to be more sensitive. However, microCT identified a very specific thinning of the trabecular plates in their center that corresponds to the earlier stages of perforations. CONCLUSION: Trabecular plate thinning can be observed and perforations occur on very thin plates in CSIOP patients.

Adrenal Cortex Hormones↗
PubMed2006

Endostatin variations in childhood acute lymphoblastic leukaemia--comparison with basic fibroblast growth factor and vascular endothelial growth factor.

Angiogenic factors such as basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) were previously studied in childhood acute lymphoblastic leukaemia (ALL) but little is known concerning the anti-angiogenic response in ALL. At diagnosis, the plasma levels of the anti-angiogenic factor endostatin were significantly higher in 33 children with ALL than in controls (median values 17.7 and 7.6 ng/ml, respectively, p=0.0192) but no relationship was observed with plasma bFGF or VEGF levels. The highest levels were observed in patients with an hyperdiploïd karyotype. Expression of mRNA for collagen XVIII/endostatin in lymphoblasts was detected in 19/24 cases but protein secretion was found only in 14/28 supernatants of cultured lymphoblasts. No direct relationship appeared between secretion of endostatin by lymphoblasts and plasma levels. In addition, endostatin levels remained elevated in remission, suggesting that endostatin could have a stromal origin as well. No prognostic value of plasma endostatin could be assessed. In conclusion, the present data indicate that an anti-angiogenic response is observed in some ALL children, but its physiopathological importance remains to be established.

Adolescent↗
PubMed2006

[SERMs for treatment of osteoporosis: state-of-the-art and perspectives].

Every year in France, we observe 60,000 vertebral fractures, 50,000 hip fractures and 35,000 wrist fractures. However, only 20% of these patients receive adequate pharmacologic therapy to prevent new fractures and their complications. At the present time, clinicians have not a perfect knowledge of the therapeutic class of SERMs (Selective Estrogen Receptor Modulators). In this paper, the authors show the strong capacity of these drugs to produce, in osteoporotic postmenopausal women, major therapeutic effects on bone (reduction of fracture risk), on breast (reduction of cancer risk), and without any side effects on arterial diseases except an increased risk of venous thromboembolism.

Breast Neoplasms↗
PubMed2005

[A mixed acid-base disorder revealing a cystic dystrophy of aberrant pancreatic tissue].

We report about a patient presenting with a mixed acid-base disorder. His blood gas analysis showed a metabolic acidosis caused by renal failure and lactic acidosis combined with a hypochloraemic alkalosis. The underlying pathology was a cystic dystrophy of aberrant pancreatic tissue leading to excessive vomiting, extracellular dehydration with a renal failure and hypochloraemia.

Acid-Base Imbalance↗
PubMed2004

Ex vivo bone mineral density of the wrist: influence of medullar fat.

The cone beam technology was recently proposed in a third generation of densitometers (dual photon X-ray absorptiometry, DXA such as the Lexxos densitometer). Because fat is a well-known problem with DXA, we have designed a cadaver study to compare the influence of medullary lipids on the measures performed with the Hologic QDR4500 and the Lexxos. Twenty-three human distal radii were obtained and analyzed in parallel on both densitometers; bone mineral density (BMD) was measured at the distal radius with standard softwares and on a standardized square regions of interest (ROI). Bones were then defatted and a new series of measurement was performed. Bones were then thoroughly dried and a cube was prepared at the distal radius with a banding saw. Trabecular and total bone volumes were measured by microcomputerized tomography. Ash eight was obtained after calcination of the blocks. BMD could be measured on the Lexxos before and after delipidation but this was not possible with the QDR4500. The X-ray image quality was better with the Lexxos. Delipidation had a very significant effect on measurements: after defatting, BMD values were considerably reduced (-49.8 +/- 19.4%). BMD before/after defatting were significantly correlated (r = 0.81, P < 0.0001) but bone mass appeared to reflect 66% of the variance. BMD was significantly correlated with BV/TV after defatting (r = 0.44, P < 0.03) but the correlation improved when cortices were taken into account (r = 0.70, P < 0.0001). Ash weight was significantly correlated with BMD and total bone volume (respectively, r = 0.84, P < 0.0001; r = 0.53, P < 0.03), but not with BV/TV. BMD at the distal radius is influenced by marrow fat and cortical density.

Bone Density↗
PubMed2004

[Protein Z: a new regulator of coagulation in arterial vessels?].

Protein Z (PZ) is a vitamin K dependent factor identified in human plasma in 1984 whose physiological function was poorly understood. It was recently shown that protein Z is implicated in the down-regulation of coagulation by forming a complex with a plasma proteinase inhibitor called protein Z-dependent protease inhibitor (ZPI) which inhibits activated factor Xa on phospholipid surfaces. In the absence of an additional challenge, the disruption of PZ gene in mice is asymptomatic, but the association with the factor VLeiden mutation leads to a near complete mortality during the neonatal period with microvascular thrombosis. Unexpectedly, in humans, a relationship between protein Z deficiency and ischemic strokes, was firstly evidenced, but not confirmed by all the epidemiological study. Additional studies suggest that protein Z deficiency could be also a risk factor for acute coronary syndromes, early fetal losses, and increased the arterial risk in antiphospholipid syndrome. This review analyzes the different studies so far published and discusses the different results obtained in order to understand whether or not protein Z deficiency could be considered as an arterial ischemic risk factor.

Animals↗
PubMed2004

Isolated antibodies against the core antigen of hepatitis B virus in HIV-infected patients.

The aim of this study was to describe the frequency and significance of isolated antibodies against the hepatitis B virus (HBV) core antigen (HBc) in 2185 HIV-infected patients of the Aquitaine Cohort. Antibodies against HBc were found in 372 subjects (17%). Patients with isolated anti-HBc antibodies were more frequently coinfected with hepatitis C virus (HCV) (58.2%) than those who were anti-HB surface (HBs) antibody positive (22.9%, P<0.001) and those who were dually reactive anti-HBs/anti-HBc antibody positive (27.3%, P<0.001). These results suggest interactions between HBV and HCV. As observed in patients not infected with HIV, the "anti-HBc-alone" serological profile could reflect essentially late immunity with undetectable anti-HBs antibodies. However, an occult HBV infection cannot be ruled out.

Adult↗
PubMed2003

Fenofibrate inhibits angiogenesis in vitro and in vivo.

Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, used as a normolipidemic agent, is thought to offer additional beneficial effects in atherosclerosis. Since angiogenesis is involved in plaque progression, hemorrhage, and instability, the main causes of ischemic events, this study was designed to evaluate the action of fenofibrate on angiogenesis. Our results show that fenofibrate (i) inhibits endothelial cell proliferation induced by angiogenic factors, followed at high concentrations by an increase in apoptosis, (ii) inhibits endothelial cell migration in a healing wound model, (iii) inhibits capillary tube formation in vitro, and (iv) inhibits angiogenesis in vivo. Concerning the mechanism of action, the inhibition of endothelial cell migration by fenofibrate can be explained by a disorganization of the actin cytoskeleton. At the molecular level, fenofibrate markedly decreased basic fibroblast growth factor-induced Akt activation and cyclooxygenase 2 gene expression. This inhibition of angiogenesis could participate in the beneficial effect of fenofibrate in atherosclerosis.

Actins↗
PubMed2003

Image analysis measurements of roughness by texture and fractal analysis correlate with contact profilometry.

Surface properties of a biomaterial are important factors that govern in part its biocompatibility. Among them, surface roughness is now recognized as a very important factor for cell interactions. Surface roughness (Ra) is routinely measured by contact profilometry but other methods are presently usable. We compared two methods (contact profilometry and image analysis of scanning electron microscopic images SEM) on a series of 12 titanium test pieces. The texture analysis of SEM pictures was done by the heterogeneity and run-length methods. Fractal geometry was also used with the "skyscraper" and "blanket" methods providing respectively the D(SKY) and D(BLANK) fractal dimensions. The fractal dimension of the profilometric curve was also computed (D(MINK)). Computer-simulated textures were used to evaluate the pertinence of the algorithms. A significant correlation was found between Ra and all the texture descriptors except heterogeneity. The correlation coefficient was dependent on the microscopic magnification. The fractal dimension of the curve was correlated with D(SKY) and D(BLANK). Run-length, D(SKY) and D(BLANK) were highly correlated, independent of the magnification used, a finding related to the self-similarity of the images. Image texture analysis can be a useful alternative to profilometry with brittle or soft materials or with objects having a complex shape.

Algorithms↗
PubMed2003

T-lymphocyte populations in hepatitis C and HIV co-infected patients treated with interferon-alfa-2a and ribavirin.

OBJECTIVE: The effects on T-lymphocyte populations of two interferon-alfa-2a (IFN) regimens associated with ribavirin were evaluated in 36 HCV-HIV co-infected patients with chronic hepatitis C, T-CD4 cell count > 250 cells/ micro L and a plasma viral load of < 10 000 HIV RNA copies/mL. METHODS: Patients were given IFN for 48 weeks. Group A (18 patients) received 6 mega units (MU) subcutaneously three times a week for 24 weeks, then 3 MU three times a week for the last 24 weeks. Group B (18 patients) received 9 MU daily for 2 weeks, 3 MU daily for 22 weeks, then 3 MU three times a week for the last 24 weeks. Serum HCV RNA was evaluated at weeks 12 and 72. Ribavirin was added at week 16 for virologic nonresponders at week 12. CD3, CD3 CD4, CD3 CD8, CD3 CD4 human leucocyte antigen (HLA)-DR and CD3 CD8 HLA-DR lymphocyte subsets were evaluated before, during and after treatment by cytofluorometry. Controls were healthy and HCV mono-infected patients. RESULTS: CD3 CD4 and CD3 CD8 T-cells counts were both impaired during anti-HCV therapy, but returned to baseline value after treatment completion. Lymphopenia concerned mainly CD8 T-cells, the percentage of which decreased, whereas that of CD4 increased. Three patients displayed reversible CD4 lymphopenia < 200 cells/ micro L. HIV infection at inclusion was responsible for higher CD3 CD8 HLA-DR T-cell percentages in co-infected patients than in healthy and HCV mono-infected subjects. T-cell sequestration in lymphoid tissues and enhanced apoptosis may account for lymphopenia. CONCLUSION: High-dosed IFN anti-HCV therapy induced only moderate and transient CD4 lymphopenia in HIV co-infected patients.

Adult↗
PubMed2002

Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection.

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.

Adult↗
PubMed2002

Comparison of histomorphometric descriptors of bone architecture with dual-energy X-ray absorptiometry for assessing bone loss in the orchidectomized rat.

We have compared different methods for measuring bone loss in the orchidectomized (ORX) rat model of male osteoporosis: densitometry (DXA), ash weight, anatomic bone indices, histomorphometry and two-dimensional trabecular architecture analysis. Forty-eight male Wistar rats were studied at 2, 4, 8 and 16 weeks (four groups). In each group, 6 rats were ORX and 6 sham-operated were used as control. DXA was performed on the whole body, tibia and femur. Histomorphometry was performed on the secondary spongiosa of the tibia: trabecular bone volume (BV/TV) and trabecular characteristics (number, separation and thickness) were measured. Architecture analysis comprised strut identification, star volume of the marrow spaces and trabeculae, Euler-Poincaré number (E) and Kolmogorov fractal dimension (Dk). Bone mineral densities of the whole body, tibia and femur were reduced at 16 weeks in the ORX group. BV/TV was significantly decreased in the ORX group from the fourth week. Differences in the sensitivity of the architectural methods were found. There were no differences in trabecular thickness nor in trabecular star volume between ORX and controls even after 16 weeks. E became different at 8 weeks. Trabecular number, node count, star volume of the marrow spaces and trabecular separation became significantly different at 4 weeks Dk was modified after 2 weeks (p < 0.05 at 2 weeks, p < 0.001 from 4 weeks). In the ORX model, Dk appeared the most potent descriptor of trabecular bone disorganization by revealing the earliest changes at the network level.

Absorptiometry, Photon↗
PubMed2002

Oncostatin M induces procoagulant activity in human vascular smooth muscle cells by modulating the balance between tissue factor and tissue factor pathway inhibitor.

Oncostatin M (OSM) is a cytokine of the interleukin-6 (IL-6) family secreted by activated monocytes, and is expressed in atherosclerotic plaque. Smooth muscle cells (SMC), by expressing tissue factor (TF) and tissue factor pathway inhibitor (TFPI) can contribute to the thrombogenicity of atherosclerotic plaque. Consequently, the aim of this study was to evaluate the effects of OSM on the procoagulant activity of SMC. We observed that OSM induced in a concentration-dependent manner a potent procoagulant activity (PCA) that was related in part to an increased synthesis of TF, both at the cell membrane and in SMC lysates. The increased expression of TF on SMC membrane induced by OSM was sustained and was still observed 24 h after stimulation by OSM. IL-6 and leukaemia inhibitory factor (LIF), two OSM-related cytokines, did not significantly modify TF expression at the surface of SMC. In addition to its effects on TF, OSM decreased the secretion of TFPI in the supernatants of SMC, as well as in the lysates, but was devoid of effect on TFPI bound at the membrane of SMC. IL-6 and LIF reduced also TFPI secretion, which could explain why the PCA of SMC lysates treated by IL-6 or LIF was increased, despite an absence of effect on TF expression. In conclusion, these data support the hypothesis that by increasing the PCA of SMC, OSM might be involved in the thrombotic complications associated with plaque rupture.

Aorta↗
PubMed2001

Impact of protease inhibitors on intrahepatic hepatitis C virus viral load.

During chronic hepatitis C, hepatitis C virus (HCV) load in plasma was shown to be higher in HIV-co-infected than in immunocompetent patients [1]. The reason for this increased HCV replication is not known. It may be as a result of HIV-induced immune deficiency [2], although some authors did not find any correlation with the CD4 cell count [3]. A direct interaction between HCV and HIV was also hypothesized [4]. Protease inhibitors (PI) used in highly active antiretroviral therapy (HAART) have no HCV reduction effect during the first months of treatment [5-8]. However, a decrease in HCV plasma load was recently described in patients treated with HAART for a year [9,10]. We therefore investigated the potential impact of HAART on intrahepatic HCV load.

Adult↗
PubMed2001

Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules.

Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1.

Antineoplastic Agents↗
PubMed2001

Fractal dimension of trabecular bone: comparison of three histomorphometric computed techniques for measuring the architectural two-dimensional complexity.

Trabecular bone has been reported as having two-dimensional (2-D) fractal characteristics at the histological level, a finding correlated with biomechanical properties. However, several fractal dimensions (D) are known and computational ways to obtain them vary considerably. This study compared three algorithms on the same series of bone biopsies, to obtain the Kolmogorov, Minkowski-Bouligand, and mass-radius fractal dimensions. The relationships with histomorphometric descriptors of the 2-D trabecular architecture were investigated. Bone biopsies were obtained from 148 osteoporotic male patients. Bone volume (BV/TV), trabecular characteristics (Tb.N, Tb.Sp, Tb.Th), strut analysis, star volumes (marrow spaces and trabeculae), inter-connectivity index, and Euler-Poincaré number were computed. The box-counting method was used to obtain the Kolmogorov dimension (D(k)), the dilatation method for the Minkowski-Bouligand dimension (D(MB)), and the sandbox for the mass-radius dimension (D(MR)) and lacunarity (L). Logarithmic relationships were observed between BV/TV and the fractal dimensions. The best correlation was obtained with D(MR) and the lowest with D(MB). Lacunarity was correlated with descriptors of the marrow cavities (ICI, star volume, Tb.Sp). Linear relationships were observed among the three fractal techniques which appeared highly correlated. A cluster analysis of all histomorphometric parameters provided a tree with three groups of descriptors: for trabeculae (Tb.Th, strut); for marrow cavities (Euler, ICI, Tb.Sp, star volume, L); and for the complexity of the network (Tb.N and the three D's). A sole fractal dimension cannot be used instead of the classic 2-D descriptors of architecture; D rather reflects the complexity of branching trabeculae. Computation time is also an important determinant when choosing one of these methods.

Cluster Analysis↗
PubMed2001

Bone microarchitecture and bone fragility in men: DXA and histomorphometry in humans and in the orchidectomized rat model.

In men, the risk of fragility fractures increases as bone mineral declines but there is an overlap in the bone mineral density (BMD) measurements between patients with and those without fractures. Biomechanical competence of trabecular (Tb) bone depends on the amount of bone and on microarchitecture. We have developed new histomorphometric methods for evaluating microarchitecture on histological sections. These methods were used in the orchidectomized male rat (ORX--a model of hypogonadism-induced osteoporosis) and on transiliac bone biopsies performed in male osteoporotic patients. ORX rats were studied at 2, 4, 8, and 16 weeks post-ORX. Bone mineral content (BMC) was reduced at 16 weeks. Trabecular bone volume (BV/TV) was significantly decreased from the 4th week. Differences in the sensitivity of the methods were found. Fractal dimension was modified as early as 2 weeks and appeared the most potent descriptor of Tb disorganization. The architectural changes in this model mimic those observed in hypogonadic men. We examined the relationships among BMD, micro-architecture, and vertebral fracture in 108 men with lumbar osteopenia (T-score <-2.5). At least one vertebral fracture was observed in 62 patients and none in 46 patients. After adjusting for age, body mass index (BMI), and BMD, there was no significant difference between the two groups in BV/TV, Tb.Th, and Star volume. In contrast, the mean values of ICI and Tb.Sp were significantly higher whereas Tb.N and nodes were lower in patients with vertebral fracture. Logistic regression analysis showed that ICI, strut analysis, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of I SD ranged from 1.7 for nodes to 3.2 for ICI. These results strongly suggest that bone Tb microarchitecture is a major and independent determinant of vertebral fracture in men with osteoporosis.

Absorptiometry, Photon↗