Laboratory of Clinical Epidemiology

Marseille, France

Laboratory of Clinical Epidemiology

Marseille, France
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McDermott M.M.,50 North Lake Shore Dr | Liu K.,50 North Lake Shore Dr | Criqui M.H.,University of California at San Diego | Tian L.,Stanford University | And 10 more authors.
Circulation: Cardiovascular Imaging | Year: 2011

Background-The clinical significance of magnetic resonance-imaged plaque characteristics in the superficial femoral artery (SFA) is not well established. We studied associations of the ankle-brachial index (ABI) and leg symptoms with MRI-measured plaque area and percent lumen area in the SFA in participants with and without lower-extremity peripheral arterial disease (PAD). Methods and Results-Four hundred twenty-seven participants (393 with PAD) underwent plaque imaging of the first 30 mm of the SFA. Twelve 2.5-mm cross-sectional images of the SFA were obtained. Outcomes were normalized plaque area, adjusted for artery size (0 to 1 scale, 1=greatest plaque), and lumen area, expressed as a percent of the total artery area. Adjusting for age, sex, race, smoking, statins, cholesterol, and other covariates, lower ABI values were associated with higher normalized mean plaque area (ABI <0.50:0.79; ABI 0.50 to 0.69:0.73; ABI 0.70 to 0.89:0.65; ABI 0.90 to 0.99:0.62; ABI 1.00 to 1.09:0.48; ABI 1.10 to 1.30:0.47 (P trend <0.001)) and smaller mean percent lumen area (P trend <0.001). Compared with PAD participants with intermittent claudication, asymptomatic PAD participants had lower normalized mean plaque area (0.72 versus 0.65, P=0.005) and larger mean percent lumen area (0.30 versus 0.36, P=0.01), adjusting for the ABI and other confounders. Conclusions-Lower ABI values are associated with greater MRI-measured plaque burden and smaller lumen area in the first 30 mm of the SFA. Compared with PAD participants with claudication, asymptomatic PAD participants have smaller plaque area and larger lumen area in the SFA. © 2011 American Heart Association, Inc.


Ferrario M.,Fondazione IRCCS Policlinico S. Matteo | Arbustini E.,Center for Inherited Cardiovascular Diseases | Massa M.,Biotechnology Laboratory | Rosti V.,Organ Transplantation Laboratory | And 17 more authors.
International Journal of Cardiology | Year: 2011

Background: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. Methods: The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10 3 IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. Results: CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/μl [36-217] vs 22 cells/μl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling. Conclusions: Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials. © 2009 Elsevier Ireland Ltd. All rights reserved.


Campanelli R.,Laboratory of Clinical Epidemiology | Rosti V.,Laboratory of Clinical Epidemiology | Villani L.,Laboratory of Clinical Epidemiology | Castagno M.,University of Pavia | And 6 more authors.
Cytokine | Year: 2011

TGFβ1 is secreted as latent protein that requires activation to become biologically active. It negatively regulates the progenitor cell growth, and favours the deposition of extra-cellular matrix in different tissues. We have studied TGFβ1 levels in Philadelphia-negative (Ph-) myeloproliferative diseases, evaluating patients with primary myelofibrosis (PMF) that is characterized by increased numbers of circulating progenitor cells and bone marrow (BM) fibrosis, and patients with polycythemia vera (PV) or essential thrombocythemia (ET) that do not present BM fibrosis.We found that patients with PMF, PV or ET have higher peripheral blood (PB) plasma levels of both bioactive and total TGFβ1 than healthy controls, with a balance bioactive/total TGFβ1 in favour of the latter. The balance between bioactive/total TGFβ1 in the BM plasma of patients mirrored that of PB, with most of TGFβ1 in the latent form; on the contrary, in the BM plasma of healthy controls most of the TGFβ1 was in the bioactive form.In conclusion, increased plasma levels of TGFβ1 and an altered ratio bioactive/total TGFβ1 in BM are not peculiar of patients with PMF suggesting that, whether altered levels of TGFβ1 have a role in myelofibrosis, this may not be related to the induction of BM fibrosis. © 2010 Elsevier Ltd.


Miranda L.H.M.,Oswaldo Cruz Foundation | Santiago M.A.,Laboratory of Diagnostic Technology | Schubach T.M.P.,Oswaldo Cruz Foundation | Morgado F.N.,Oswaldo Cruz Institute IOC | And 4 more authors.
Medical Mycology | Year: 2016

Sporotrichosis is a subcutaneous mycosis with worldwide distribution, especially in tropical and subtropical areas. Zoonotic transmission is described with cats being the main animal species involved. The occurrence of severe feline sporotrichosis with high fungal levels demonstrates the susceptibility of cats to this disease and the importance of studying its pathogenesis. This study describes the leukocytes profile in blood of cats with sporotrichosis by flow cytometry and its correlation with histopathology and fungal load. The cats with sporotrichosis were separated into groups L1, L2, and L3 (lesions at one, two, and three or more noncontiguous skin locations, respectively) and were classified as good, fair, or poor general conditions. The highest percentage of CD4+ cells was associated to L1 (P = .04) and to good general condition (P = .03). The percentage of CD8+ cells was greater in L2 and L3 (P = .01). CD8low expression occurred in 20 animals with sporotrichosis, mainly in L3 (P = .01) and was not observed in healthy controls. This expression was related to macrophage granulomas (P = .01) and predominated in cases with high fungal load. Altogether, the results indicated that control over feline sporotrichosis, with maintenance of a good general condition, fixed lesions, well-organized response and lower fungal load, is associated with increased CD4+ cells percentages. In contrast, a poor general condition, disseminated lesions and high fungal load were related to increased CD8+ cell percentages and increased expression of CD8low. As conclusion these results point to an important role of the CD4:CD8 balance in determining the clinical outcome in feline sporotrichosis. © The Author 2015.


PubMed | Oswaldo Cruz Foundation, Laboratory of Diagnostic Technology, Oswaldo Cruz Institute IOC and Laboratory of Clinical Epidemiology
Type: Journal Article | Journal: Medical mycology | Year: 2015

Sporotrichosis is a subcutaneous mycosis with worldwide distribution, especially in tropical and subtropical areas. Zoonotic transmission is described with cats being the main animal species involved. The occurrence of severe feline sporotrichosis with high fungal levels demonstrates the susceptibility of cats to this disease and the importance of studying its pathogenesis. This study describes the leukocytes profile in blood of cats with sporotrichosis by flow cytometry and its correlation with histopathology and fungal load. The cats with sporotrichosis were separated into groups L1, L2, and L3 (lesions at one, two, and three or more noncontiguous skin locations, respectively) and were classified as good, fair, or poor general conditions. The highest percentage of CD4+ cells was associated to L1 (P = .04) and to good general condition (P = .03). The percentage of CD8+ cells was greater in L2 and L3 (P = .01). CD8(low) expression occurred in 20 animals with sporotrichosis, mainly in L3 (P = .01) and was not observed in healthy controls. This expression was related to macrophage granulomas (P = .01) and predominated in cases with high fungal load. Altogether, the results indicated that control over feline sporotrichosis, with maintenance of a good general condition, fixed lesions, well-organized response and lower fungal load, is associated with increased CD4+ cells percentages. In contrast, a poor general condition, disseminated lesions and high fungal load were related to increased CD8+ cell percentages and increased expression of CD8(low). As conclusion these results point to an important role of the CD4:CD8 balance in determining the clinical outcome in feline sporotrichosis.


Sebag F.,Aix - Marseille University | Vaillant-Lombard J.,Aix - Marseille University | Berbis J.,Laboratory of Clinical Epidemiology | Griset V.,Clinical Investigation Center | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Elastography uses ultrasound (US) to assess elasticity. Shear wave elastography (SWE) is anew technique that estimates tissue stiffness in real time and is quantitative and user independent. Objectives: The aim of the study was to assess the efficiency of SWE in predicting malignancy and to compare SWE with US. Design: Ninety-three patients and 39 control subjects were included in the study. Predictive value of SWE was assessed by correlation between elasticity, US parameters, and histology. Elasticity index (EI) was first analyzed alone. Scores have been constructed with echographic parameters, i.e. vascularity, hypoechogenicity, and microcalcifications (Score 1 = US Score), and with the same parameters plus EI (Score 2 = US+SWE Score). For statistical analysis, univariate and multivariate analysis and receiver operating characteristic curves were used. Results: A total of 146 nodules from 93 patients were analyzed. Twenty-nine nodules (19.9%) were malignant. Mean (±SD) EI was 150 ± 95 kPa (range, 30-356) in malignant nodules vs. 36 ± 30 (range, 0-200) kPa in benign nodules (P < 0.001, Student's t test). For a positive predictive value of at least 80%, characteristics of tissue elasticity (cutoff, 65 kPa) were: sensitivity = 85.2%, and specificity = 93.9%. Characteristics of the US Score were: sensitivity = 51.9% [95% confidence interval (CI), 33.1; 70.7], and specificity = 97% (95% CI, 93.6; 1). Characteristics of the US+SWE Score were: sensitivity = 81.5% (95% CI, 66.9; 96.1), and specificity = 97.0% (95% CI, 93.6; 1). Conclusion: Promising results have been obtained with SWE. This technique may be applied to multinodular goiters. Larger prospective studies are needed to confirm these results and to define the respective places of SWE, US, and FNA. Copyright © 2010 by The Endocrine Society.


Sanchez-Hernandez Y.,University of Pavia | Laforenza U.,University of Pavia | Bonetti E.,Laboratory of Clinical Epidemiology | Fontana J.,University of Pavia | And 9 more authors.
Stem Cells and Development | Year: 2010

Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to sites of tissue regeneration to sustain neovascularization and reendothelialization after acute vascular injury. This feature makes them particularly suitable for cell-based therapy. In mature endothelium, store-operated Ca2+ entry (SOCE) is activated following emptying of inositol-1,4,5-trisphosphate-sensitive stores, and controls a wide number of functions, including proliferation, nitric oxide synthesis, and vascular permeability. The present work aimed at investigating SOCE expression in EPCs harvested from both peripheral blood (PB-EPCs) and umbilical cord blood (UCB-EPCs) by employing both Ca2+ imaging and molecular biology techniques. SOCE was induced upon either pharmacological (ie, cyclopiazonic acid) or physiological (ie, ATP) depletion of the intracellular Ca2+ pool. Further, store-dependent Ca2+ entry was inhibited by the SOCE inhibitor, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2, 3-thiadiazole-5-carboxamide (BTP-2). Real-time reverse transcription-polymerase chain reaction and western blot analyses showed that both PB-EPCs and UCB-EPCs express all the molecular candidates to mediate SOCE in differentiated cells, including TRPC1, TRPC4, Orai1, and Stim1. Moreover, pharmacological maneuvers demonstrated that, as well as in differentiated endothelial cells, the signal transduction pathway leading to depletion of the intracellular Ca2+ pool impinged on the phospholipase C/inositol-1,4,5-trisphosphate pathway. Finally, blockage of SOCE with BTP-2 impaired PB-EPC proliferation. These findings provide the first evidence that EPCs express SOCE, which might thus be regarded as a novel target to enhance the regenerative outcome of cell-based therapy. © 2010, Mary Ann Liebert, Inc.


Bergamaschi G.,University of Pavia | Di Sabatino A.,University of Pavia | Albertini R.,Clinical Chemistry Laboratory | Ardizzone S.,University of Milan | And 9 more authors.
Haematologica | Year: 2010

Background: Anemia is a common complication of inflammatory bowel disease, but its epidemiology may be changing due to earlier diagnosis and improved treatments. We investigated the prevalence and pathogenesis of anemia in patients with inflammatory bowel disease. Design and Methods: In a cross-sectional study 263 out-patients with inflammatory bowel disease (165 with Crohn's disease, 98 with ulcerative colitis) were investigated. The influence of time from diagnosis, disease activity, inflammation and the status of iron and hematinic vitamins on the level of hemoglobin and prevalence of anemia were evaluated. In a second group of 27 patients with Crohn's disease, undergoing anti-tumor necrosis factor-α treatment with infliximab because of refractory or fistulizing disease, we determined the effects of infliximab on disease activity, hemoglobin, serum erythropoietin levels, iron status and inflammation. Results: In all, 104 of the 263 patients with inflammatory bowel disease were anemic. Age, gender and azathioprine treatment had no influence on anemia. The prevalence of anemia was highest at diagnosis (65%), decreased during the first 4 years after disease onset, and was stable thereafter. Active disease was associated with higher rates of anemia. At diagnosis most anemic patients had anemia of chronic disease; during follow-up iron deficiency and multifactorial forms of anemia became more prevalent. Eighteen of 27 patients undergoing treatment with infliximab were anemic; most of them had anemia of chronic disease. Infliximab reduced disease activity and improved anemia in 12 patients. This was mediated by an increased production of erythropoietin for the degree of anemia. In vitro infliximab increased the growth of erythroid progenitors from the peripheral blood of patients with active disease. Conclusions: Anemia is a common problem in out-patients with inflammatory bowel disease; the prevalence and severity of anemia are related to the activity of the bowel disorder. The pathogenesis of anemia changes during the course of the disease, with anemia of chronic disease having a major role at diagnosis and iron deficiency and multifactorial forms of anemia during follow-up. In patients requiring anti-tumor necrosis factor-α treatment, response to therapy improves erythropoiesis. ©2010 Ferrata Storti Foundation.


Coni A.,University of Bologna | Mellone S.,University of Bologna | Colpo M.,Laboratory of Clinical Epidemiology | Bandinelli S.,Laboratory of Clinical Epidemiology | Chiari L.,University of Bologna
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2015

The purpose of this study was to investigate the functional decline associated with aging and gender-related differences by means of a set of sensor-based measures. A actor analysis has been performed in order to classify domains of an instrumented Timed Up and Go (TUG) test in a group of community-dwelling elderly people. 239 elderly people were recruited and underwent an instrumented TUG test. Features extracted from TUG trials, were grouped by the factor analysis in six factors with a clear clinical value. Significant correlations and gender-related differences were found between age and factors associated with the global fitness, the turning ability, and the dynamics of the trunk during postural transitions. Results provide evidence that a sensor-based assessment is a feasible and effective tool for assessing functional decline in the general population. © 2015 IEEE.

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