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Diana J.,Hopital Saint Vincent de Paul
Discovery medicine | Year: 2011

Type 1 diabetes (T1D) is a complex autoimmune disease that is untimely caused by the destruction of insulin-producing pancreatic β-cells by autoreactive T cells. The development of the pathology involved several cell types of both the innate and adaptive immune systems. This disease is under the control of several genetic loci of susceptibility but it is also influenced by environmental factors such as infectious agents. Studies in animal models, such as the non-obese diabetic (NOD) mouse, reveal that during the development of T1D multiple interactions occur between macrophages, dendritic cells (DC), natural killer (NK) cells, NKT cells, and lymphocytes. As a consequence, the various components of the immune system can be of peculiar interest as therapeutic targets for disease prevention or cure. This review focuses on the involvement of innate immune cells in the development and the prevention of T1D.


Mondoulet L.,DBV Technologies | Dioszeghy V.,DBV Technologies | Ligouis M.,DBV Technologies | Dhelft V.,DBV Technologies | And 2 more authors.
Clinical and Experimental Allergy | Year: 2010

Background: Allergen-specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods. Objective: Proof of concept of efficacy of EPIT on intact skin in mice sensitized to aeroallergens or food allergens. Methods: Mice were sensitized to pollen (n=18), house dust mite (HDM, n=24), ovalbumin (OVA, n=18) or peanut (n=18), and allocated to four groups: EPIT, SCIT, not treated (NT) and control. Specific Ig (sIg)E, sIgG1 and sIgG2a were monitored. After 8 weeks of treatment, plethysmography was performed after aerosol provocation with appropriate allergens. Results: At the highest doses of methacholine, pause enhancement (Penh) values were significantly decreased in the EPIT group vs. the sensitized NT groups (7.5 vs. 12.3 - pollen, 7.6 vs. 8.9 - HDM, 11.5 vs. 14.5 - OVA, 7.6 vs. 12.8 - peanut, respectively) (P<0.05). With all the allergens tested, Penh values were similar in SCIT, EPIT and control. IgG2a for pollen, HDM, OVA and peanuts were significantly increased in the EPIT group vs. NT: 0.97 vs. 0.42 μg/mL, 2.5 vs. 0.46 μg/mL, 0.39 vs. 0.05 μg/mL and 15.0 vs. 5.5 μg/mL, respectively (P<0.05). There were no significant differences between EPIT and SCIT groups. The IgE/IgG2a ratio decreased significantly in the EPIT group for the four allergens from 70 to 58 (pollen), 175 to 26 (HDM), 5433 to 120 (OVA) and 49 to 6 (peanut), respectively (P<0.05). Conclusion: In mice sensitized to the four allergens tested, EPIT was as efficacious as SCIT, considered as the reference immunotherapy. These first results have to be confirmed by clinical studies. © 2009 Blackwell Publishing Ltd.


Garabedian M.,Hopital Saint Vincent de Paul
OCL - Oleagineux Corps Gras Lipides | Year: 2011

Besides its well known anti-rachitic properties, vitamin D has numerous in vitro and in vivo actions on the proliferation-differentiation of epidermal and cancer cells, as well as on the recruitment, differentiation and activities of the immune cells. Even though numerous association studies have suggested a possible link between a low vitamin D status and the risk of developing tumoral, auto-immune, neurologic or cardiovascular diseases, further data have proven to be more discordant and at best modest. In addition, the range of vitamin D doses or status active on these extra-skeletal pathologies remains poorly defined, between insufficiency and overload. Looking forward to clearly needed randomized intervention studies, optimal vitamin D status and intakes remain best defined on the basis of the vitamin D indisputable effects on calcium homeostasis and skeletal mineralization.


Bonneau N.,CNRS Mechanical Adaptation and Evolution | Simonis C.,CNRS Mechanical Adaptation and Evolution | Seringe R.,Hopital Saint Vincent de Paul | Tardieu C.,CNRS Mechanical Adaptation and Evolution
American Journal of Physical Anthropology | Year: 2011

The developing fetus is protected from external environmental influences by maternal tissues. However, these structures have a limited elasticity, such that the fetus must grow in a confined space, constraining its size at the end of pregnancy. Can these constraints modify the morphology of the fetal skeleton? The intensity of these constraints increases between 5 months and birth, making it the most appropriate period to address this question. A sample of 89 fetal femora was analyzed, and results provide evidence that during this period, the torsion of the femoral shaft (quantified by means of a new three-dimensional method) increases gradually. Two explanations were considered: this increase could signal effects of constraints induced by the intrauterine cavity, developmental patterning, or some combination of these two. Different arguments tend to support the biomechanical explanation, rather than a programming pattern formation. Indeed, the identification of the femur as a first degree lever, created by the hyperflexion of the fetal lower limbs on the pelvis, could explain the increase in femoral shaft torsion during prenatal life. A comparison with femora of infants is in accordance with this mechanical interpretation, which is possible through bone modeling/remodeling. Although genetic and epigenetic mechanisms may regulate timing of fetal development, our data suggest that at birth, the fetal skeleton also has an intrauterine mechanical history through adaptive bone plasticity. Copyright © 2011 Wiley-Liss, Inc.


Thibaut M.,University of Lille Nord de France | Tran T.H.C.,Hopital Saint Vincent de Paul | Delerue C.,University of Lille Nord de France | Boucart M.,University of Lille Nord de France
Ophthalmic and Physiological Optics | Year: 2015

Previous studies showed that people with age-related macular degeneration (AMD) can categorise a pre-defined target object or scene with high accuracy (above 80%). In these studies participants were asked to detect the target (e.g. an animal) in serial visual presentation. People with AMD must rely on peripheral vision which is more adapted to the low resolution required for detection than for the higher resolution required to identify a specific exemplar. We investigated the ability of people with central vision loss to identify photographs of objects and scenes. Methods: Photographs of isolated objects, natural scenes and objects in scenes were centrally displayed for 2 s each. Participants were asked to name the stimuli. We measured accuracy and naming times in 20 patients with AMD, 15 age-matched and 12 young controls. Results: Accuracy was lower (by about 30%) and naming times were longer (by about 300 ms) in people with AMD than in age-matched controls in the three categories of images. Correct identification occurred in 62-66% of the stimuli for patients. More than 20% of the misidentifications resulted from a structural and/or semantic similarity between the object and the name (e.g. spectacles for dog plates or dolphin for shark). Accuracy and naming times did not differ significantly between young and older normally sighted participants indicating that the deficits resulted from pathology rather than to normal ageing. Conclusions: These results show that, in contrast to performance for categorisation of a single pre-defined target, people with central vision loss are impaired at identifying various objects and scenes. The decrease in accuracy and the increase in response times in patients with AMD indicate that peripheral vision might be sufficient for object and scene categorisation but not for precise scene or object identification. © 2015 The College of Optometrists.


Sabourin M.,Arts et Metiers ParisTech | Jolivet E.,Arts et Metiers ParisTech | Miladi L.,Hopital Saint Vincent de Paul | Wicart P.,Hopital Saint Vincent de Paul | And 2 more authors.
Clinical Biomechanics | Year: 2010

Background: Early-onset scoliosis frequently leads to major thoracic deformity and pulmonary restrictive disease. Growing rods surgical techniques were developed to achieve a satisfactory correction of the spinal curves during growth. The effect on the rib cage deformity has not yet been documented. The purpose of this study was to analyze the changes of the thoracic geometry after implantation of a growing rod, and to evaluate a stereoradiographic reconstruction method among young scoliotic patients. Methods: Four patients were enrolled in the study, and four additional patients in the reproducibility study. Three-dimensional spine and rib cage models were generated after low-dose stereoradiographic imaging (EOS). Three-dimensional parameters were computed before and after surgery. Intra and inter-observer reproducibility was calculated, and the accuracy was assessed in comparison to volumetric CT-scan. Findings: The average Cobb angle was reduced from 50.8° to 26°. The surgery resulted in a complex 3D effect on the rib cage, combining frontal, lateral, and axial rotation. This effect was dependent of the side (concave or convex), and the position relative to the apical vertebra. Mean errors in comparison to CT-scan were 3.5 mm. Interpretation: The results on the spinal deformity are comparable to other series. The effect on the rib cage is of a smaller magnitude than in the case of a spinal arthrodesis. A longer follow-up is necessary to confirm the positive effect on the rib cage deformity. Further research should be performed to improve the reproducibility of 3D parameters. © 2010 Elsevier Ltd. All rights reserved.


Gattermann N.,Heinrich Heine University Düsseldorf | Finelli C.,Policlinico S. Orsola Malpighi | Porta M.D.,IRCCS Policlinico S. Matteo | Fenaux P.,University Paris - Sud | And 9 more authors.
Haematologica | Year: 2012

Background Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies. Design and Methods To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade® (EPIC) study using International Working Group 2006 criteria. Results Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders. Conclusions This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes. ©2012 Ferrata Storti Foundation.


Rothenbuhler A.,Hopital Saint Vincent de Paul | Piquard C.,Hopital Saint Vincent de Paul | Gueorguieva I.,Hopital Saint Vincent de Paul | Lahlou N.,Hopital Saint Vincent de Paul | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Mutations in the cathepsin K gene (CTSK) cause a very rare form of short-limb dwarfism called pyknodysostosis (online inheritance in man 265800) that reduces adult height to 130-150 cm. Objective: To study the effects of GH in children with pyknodysostosis. Design and Methods: This was a pilot open study of three children with pyknodysostosis (P1, P2, P3) and 16 age-matched children with idiopathic short stature (ISS) treated with a similar IGF-Ibased dosing of GH therapy. P1, P2, and P3 received a mean GH dose of 29, 67, and 120 μg/kg · d, respectively, during 12, 6.5, and 5 yr, whereas the ISS group received a mean dose of 62 ± 21 μg/kg · d during 5.4 ± 2 yr. Results: P1, P2, and P3 had the typical clinical and radiological features of pyknodysostosis. They wereshownto carry three different homozygous missense mutations of the CTSK gene. After onset of GH at 4.5, 5.4, and 10.9 yr of age, respectively, height increased from -2, -4.2, and -3 SD score to -1, -0.5, and -1 SD score after a 12, 6.5, and 5 yr GH treatment. Remarkably, body disproportion was largely corrected by GH treatment. IGF-I levels in P1, P2, and P3 were within the range of the ISS group. Conclusions: Pyknodysostotic patients can reach near-normal stature and skeletal proportions with a personalized GH treatment targeted at appropriate IGF-I levels. Given the severity of this rare dwarfism, we propose that GH should be offered to affected children. Copyright © 2010 by The Endocrine Society.


Lafon Y.,Arts et Metiers ParisTech | Lafage V.,Arts et Metiers ParisTech | Steib J.-P.,Hopitaux Universitaires Of Strasbourg | Dubousset J.,Hopital Saint Vincent de Paul | Skalli W.,Arts et Metiers ParisTech
Spine | Year: 2010

Study Design: A numerical study was conducted to identify the intervertebral stiffness of scoliotic spines from spinal flexibility tests. Objective: To study the intervertebral 3-dimensional (3D) stiffness distribution along scoliotic spine. Summary of Background Data: Few methods have been reported in literature to quantify the in vivo 3D intervertebral stiffness of the scoliotic spine. Based on the simulation of flexibility tests, these methods were operator-dependent and could yield to clinically irrelevant stiffnesses. Methods: This study included 30 patients surgically treated for severe idiopathic scoliosis. A previously validated trunk model, with patient-specific geometry, was used to simulate bending tests according to the in vivo displacements of T1 and L5 measured from bending test radiographs. Differences between in vivo and virtual spinal behaviors during bending tests (left and right) were computed in terms of vertebral rotations and translation. An automated method, driven by a priori knowledge, identified intervertebral stiffnesses in order to reproduce the in vivo spinal behavior. Results: Because of the identification of intervertebral stiffnesses, differences between in vivo and virtual spinal displacements were drastically reduced (95% of the differences less than ±3 mm for vertebral translation). Intervertebral stiffness distribution after identification was analyzed. On convex side test, the intervertebral stiffness of the compensatory curves increased in most cases, whereas the major curve became more flexible. Stiffness singularities were found in junctional zones: these specific levels were predominantly flexible, both in torsion and in lateral bending. Conclusion: The identification of in vivo intervertebral stiffness may improve our understanding of scoliotic spine and the relevance of patient-specific methods for surgical planning. © 2010, Lippincott Williams & Wilkins.


Querques G.,University Paris Est Creteil | Querques G.,Vita-Salute San Raffaele University | Tran T.H.C.,Hopital Saint Vincent de Paul | Forte R.,University Paris Est Creteil | And 3 more authors.
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2012

Background To investigate changes in indocyanine green angiography (ICGA) features of occult choroidal neovascularization (CNV) after intravitreal ranibizumab injections. Methods We reviewed the charts of all consecutive patients with newly diagnosed occult CNV secondary to age-related macular degeneration (AMD) treated by intravitreal ranibizumab. In all patients, optical coherence tomography (OCT) and ICGA were performed at baseline, after 3 months and 12 months. Results Fifty-one eyes of 44 patients (ten males, 34 females, mean age 77.8±7.3 years) were included. Mean follow-up was 20.3±6.2 months. During the first 12 months, patients received 5.5±2.7 intravitreal ranibizumab injections. When compared with baseline, best-corrected visual acuity (BCVA) significantly improved at the 3-month follow-up visit (60.5 ±22.0 vs 50.9 ±20.7 letters, p=0.04), and stabilized at 12-month visit (55.7 ±18.2 letters; p=0.05). Central macular thickness (CMT) significantly improved during follow-up (229.0 ±54.7 ?m vs 281.0 ±61.3 ?m at baseline, p=0.003). An overall stabilization was observed on ICGA in both the lesion area (5.27±3.9 mm 2 at baseline vs 4.60±3.5 mm 2 at month 12, p=0.4), and greatest linear dimension (GLD 2.66± 1.2 mm at baseline vs 2.55±1.0 mm at month 12, p=0.3). Eight eyes (15.7%) showed CNV growth on ICGA (lesion area 3.98±3.2 mm2 at baseline vs 4.3±2.7 mm2 at month-12, p=0.6; GLD 2.11±1.0 mm at baseline vs 2.70±0.8 mm at month-12, p=0.05). Conclusion ICGA suggests that functional outcomes after intravitreal ranibizumab is related to CMT reduction rather than CNV regression. © 2011 Springer-Verlag.

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