49 research outputs found

    Expression and glucocorticoid-dependent regulation of the stress-inducible protein DRR1 in the mouse adult brain

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    Identifying molecular targets that are able to buffer the consequences of stress and therefore restore brain homeostasis is essential to develop treatments for stress-related disorders. Down-regulated in renal cell carcinoma 1 (DRR1) is a unique stress-induced protein in the brain and has been recently proposed to modulate stress resilience. Interestingly, DRR1 shows a prominent expression in the limbic system of the adult mouse. Here, we analyzed the neuroanatomical and cellular expression patterns of DRR1 in the adult mouse brain using in situ hybridization, immunofluorescence and Western blot. Abundant expression of DRR1 mRNA and protein was confirmed in the adult mouse brain with pronounced differences between distinct brain regions. The strongest DRR1 signal was detected in the neocortex, the CA3 region of the hippocampus, the lateral septum and the cerebellum. DRR1 was also present in circumventricular organs and its connecting regions. Additionally, DRR1 was present in non-neuronal tissues like the choroid plexus and ependyma. Within cells, DRR1 protein was distributed in a punctate pattern in several subcellular compartments including cytosol, nucleus as well as some pre- and postsynaptic specializations. Glucocorticoid receptor activation (dexamethasone 10\ua0mg/kg s.c.) induced DRR1 expression throughout the brain, with particularly strong induction in white matter and fiber tracts and in membrane-rich structures. This specific expression pattern and stress modulation of DRR1 point to a role of DRR1 in regulating how cells sense and integrate signals from the environment and thus in restoring brain homeostasis after stressful challenges

    MR Volumetry of Lung Nodules: A Pilot Study.

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    Introduction: Computed tomography (CT) is currently the reference modality for the detection and follow-up of pulmonary nodules. While 2D measurements are commonly used in clinical practice to assess growth, increasingly 3D volume measurements are being recommended. The goal of this pilot study was to evaluate preliminarily the capabilities of 3D MRI using ultra-short echo time for lung nodule volumetry, as it would provide a radiation-free modality for this task. Material and Methods: Artificial nodules were manufactured out of Agar and measured using an ultra-short echo time MRI sequence. CT data were also acquired as a reference. Image segmentation was carried out using an algorithm based on signal intensity thresholding (SIT). For comparison purposes, we also performed manual slice by slice segmentation. Volumes obtained with MRI and CT were compared. Finally, the volumetry of a lung nodule was evaluated in one human subject in comparison with CT. Results: Using the SIT technique, minimal bias was observed between CT and MRI across the entire range of volumes (2%) with limits of agreement below 14%. Comparison of manually segmented MRI and CT resulted in a larger bias (8%) and wider limits of agreement (-23% to 40%). In vivo, nodule volume differed of <16% between modalities with the SIT technique. Conclusion: This pilot study showed very good concordance between CT and UTE-MRI to quantify lung nodule volumes, in both a phantom and human setting. Our results enhance the potential of MRI to quantify pulmonary nodule volume with similar performance to CT

    Clinical, physiologic, and radiographic factors contributing to development of hypoxemia in moderate to severe COPD:a cohort study

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    Background: Hypoxemia is a major complication of COPD and is a strong predictor of mortality. We previously identified independent risk factors for the presence of resting hypoxemia in the COPDGene cohort. However, little is known about characteristics that predict onset of resting hypoxemia in patients who are normoxic at baseline. We hypothesized that a combination of clinical, physiologic, and radiographic characteristics would predict development of resting hypoxemia after 5-years of follow-up in participants with moderate to severe COPD Methods: We analyzed 678 participants with moderate-to-severe COPD recruited into the COPDGene cohort who completed baseline and 5-year follow-up visits and who were normoxic by pulse oximetry at baseline. Development of resting hypoxemia was defined as an oxygen saturation ≀88% on ambient air at rest during follow-up. Demographic and clinical characteristics, lung function, and radiographic indices were analyzed with logistic regression models to identify predictors of the development of hypoxemia. Results: Forty-six participants (7%) developed resting hypoxemia at follow-up. Enrollment at Denver (OR 8.30, 95%CI 3.05–22.6), lower baseline oxygen saturation (OR 0.70, 95%CI 0.58–0.85), self-reported heart failure (OR 6.92, 95%CI 1.56–30.6), pulmonary artery (PA) enlargement on computed tomography (OR 2.81, 95%CI 1.17–6.74), and prior severe COPD exacerbation (OR 3.31, 95%CI 1.38–7.90) were independently associated with development of resting hypoxemia. Participants who developed hypoxemia had greater decline in 6-min walk distance and greater 5-year decline in quality of life compared to those who remained normoxic at follow-up. Conclusions: Development of clinically significant hypoxemia over a 5-year span is associated with comorbid heart failure, PA enlargement and severe COPD exacerbation. Further studies are needed to determine if treatments targeting these factors can prevent new onset hypoxemia. Trial registration COPDGene is registered at ClinicalTrials.gov: NCT00608764 (Registration Date: January 28, 2008) Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0331-0) contains supplementary material, which is available to authorized users

    CT features of pulmonary interstitial emphysema

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    Aspergillose bronchopulmonaire allergique (ABPA) et mucoviscidose : mécanismes, diagnostic et alternatives thérapeutiques

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    INTRODUCTION: Les colonisations fungiques aspergillaires et l’aspergillose bronchopulmonaire allergique (ABPA) peuvent impacter fortement le pronostic dans la mucoviscidose. Nous avons rĂ©alisĂ© des tables rondes d’experts français de centres pĂ©diatriques et adultes prenant en charge des patients atteints de mucoviscidose, des microbiologistes, radiologues et pharmaciens. Le but Ă©tait d’explorer l’état des connaissances actuelles sur les mĂ©canismes physiopathologiques d’Aspergillus et autres micromycĂštes dans la mucoviscidose (tel que Scedosporium sp.), et sur le diagnostic clinicobiologique d’ABPA actualisĂ©. En perspectives, les experts ont explorĂ© l’intĂ©rĂȘt de l’imagerie dans le diagnostic d’APBA et des signaux spĂ©cifiques au scanner et en IRM, ainsi que l’intĂ©rĂȘt de la fibroscopie dans la prise en charge. Enfin, la prise en charge thĂ©rapeutique revoit les diffĂ©rents schĂ©mas de corticothĂ©rapie, les antifungiques et la place des anti-IgE. CONCLUSION: Le diagnostic d’ABPA dans la mucoviscidose peut s’appuyer sur des dosages biologiques plus standardisĂ©s et sur l’imagerie pour optimiser une prise en charge et le suivi.INTRODUCTION: Fungal aspergillosis colonization and allergic bronchopulmonary aspergillosis (ABPA) can have a strong impact on the prognosis in cystic fibrosis (CF). We conducted round table discussions involving French experts from pediatric and adult centers caring for patients with CF, microbiologists, radiologists and pharmacists. The aim was to explore the current state of knowledge on: the pathophysiological mechanisms of Aspergillus and other micromycetes infections in CF (such as Scedosporium sp.), and on the clinico-biological diagnosis of ABPA. In perspective, the experts explored the role of imaging in the diagnosis of APBA, specifically CT and MRI; as well as the role of bronchoscopy in the management. We also reviewed the therapeutic management, including different corticosteroid regimens, antifungals and anti-IgE antibodies. CONCLUSION: The diagnosis of ABPA in CF should be based on more standardized biological assays and imaging to optimize treatment and follow-up

    Ultrashort echo time imaging of the lungs under high-frequency noninvasive ventilation: A new approach to lung imaging.

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    Although ultrashort echo time (UTE) sequences allow excellent assessment of lung parenchyma, image quality remains lower than that of computed tomography (CT). To investigate a high-frequency noninvasive ventilation (HF-NIV) technique allowing a stabilized inspiration and to compare image quality with current dedicated MR sequences. Prospective. Ten healthy volunteers. 3D radial UTE sequence at 1.5T. UTE-HF-NIV sequence was compared with UTE-free-breathing (UTE-FB), reconstructed at end expiration (UTE-Exp) and average (UTE-Avg), and breath-hold VIBE sequences. The distance from lung apex to the dome of the right hemidiaphragm was measured. Visual assessment of the visibility and sharpness of normal anatomical structures was carried out. Dedicated software also quantitatively evaluated vessel-lung and right lung-liver interface sharpness. Apparent signal ratio (Sr) and contrast ratios (Cr) were quantitatively evaluated. Wilcoxon signed rank test for visual scores, paired t-test for continuous variables, significance at P < 0.05. The distance between apex and the right hemidiaphragmatic dome was significantly larger (P < 0.001) with UTE-HF-NIV compared with UTE-FB and VIBE acquisitions. Vessel and airway visibility had identical median visual scores with all UTE methods. Median visual scores for sharpness of vessels and airways were significantly higher (P < 0.001) with HF-NIV (vessels = 3; airways = 2) than in UTE-FB (vessels = 2; airways = 1) and VIBE (vessels = 1; airways = 1). Software-based vessel sharpness evaluation resulted in larger values in 8/10 volunteers with UTE-HF-NIV (67.3 ± 9.8) compared with UTE-Avg (62.3 ± 12.6) but the average difference was not significant (P = 0.28). The sharpness of the lung-liver interface was significantly higher (P < 0.001) with HF-NIV (17.3 ± 5.3) compared with UTE-Avg (14.1 ± 3.9). Significantly higher values (P < 0.01) of Sr and Cr were observed with UTE-HF-NIV compared with UTE-FB and VIBE. HF-NIV allowing acquisition at full inspiration significantly improves image quality for lung imaging. This could offer the option to alternate some follow-up CT studies by using this technique. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1789-1797
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