Éditeur(s) : HAL CCSD Publisher : Paris : Baillière [1980-. Latest Publisher : Paris : Elsevier
Résumé : National audience
Introduction L’atteinte œsophagienne est fréquente chez les patients présentant une sclérodermie systémique. Le diagnostic est confirmé par la manométrie œsophagienne. La sensibilité et la spécificité de la manométrie œsophagienne ont été améliorées par l’avènement de la manométrie de haute résolution. L’objectif principal de cette étude observationnelle est de caractériser les troubles moteurs œsophagiens par manométrie de haute résolution, à la lumière de la troisième version de la classification de Chicago, chez des patients présentant une sclérodermie systémique selon les critères de l’EULAR/ACR 2013. Patients et méthodes Trente-six patients répondant au diagnostic de sclérodermie systémique selon les critères EULAR/ACR 2013 et ayant bénéficié d’une manométrie de haute résolution dans un centre de compétence français ont été inclus de manière consécutive. Les résultats de la manométrie de haute résolution ont été interprétés selon la troisième version de la classification de Chicago. Les caractéristiques cliniques, biologiques et les atteintes viscérales des patients ont également été relevées et confrontées aux données manométriques. L’atteinte pulmonaire était évaluée selon la méthode de Goh et al. en aveugle des données manométriques. Résultats L’âge moyen à l’inclusion était de 58,4 ans (SD = 14,2 ans) ; 83,3 % des patients étaient de sexe féminin. 22,2 % des patients avaient une sclérodermie systémique avec atteinte cutanée diffuse selon la classification de LeRoy ; 67 % des patients avaient un pyrosis, 30,6 % une dysphagie, 33,3 % une dyspepsie. 11 % des patients avaient des épisodes de fausses routes. D’après les résultats de la manométrie de haute résolution, 55,6 % des patients avaient un apéristaltisme, 33,3 % une hypotonie du sphincter inférieur de l’œsophage et 19,4 % une hypotonie du sphincter supérieur de l’œsophage. En analyse univariée, il n’était pas retrouvé d’association significative entre la présence d’une hypotonie du sphincter inférieur de l’œsophage et les caractéristiques cliniques ou biologiques quelles qu’elles soient. La présence d’un apéristaltisme était associée avec une symptomatologie de pyrosis (p = 0,004). L’apéristaltisme était associé de manière significative avec la présence de télangiectasies (p = 0,007) et d’anticorps anti-centromères (p = 0,038). La présence de calcinose ou d’une sclérodactylie n’était pas spécifiquement associée à une atteinte sphinctérienne ou motrice œsophagienne. Vingt-neuf patients (80,6 %) avaient bénéficié d’une TDM thoracique dans l’année de la réalisation de la manométrie de haute résolution. Parmi eux, 7 patients étaient atteints d’une pneumopathie interstitielle diffuse sévère (atteinte interstitielle de plus de 20 % du parenchyme pulmonaire évaluée sur 5 coupes standardisées). Il existait une association significative entre la présence d’un apéristaltisme et la présence d’une dilatation œsophagienne en TDM (p = 0,002) et la présence d’une atteinte pulmonaire sévère (p = 0,005, OR = 6,85 IC95 % (1,12–41,82)). Discussion L’association retrouvée entre apéristaltisme en manométrie de haute résolution et sévérité de la PID est confirmée par ce travail. Néanmoins un lien de causalité n’est pas certain. Une étude prospective évaluant la mise en évidence d’une atteinte œsophagienne par manométrie de haute résolution au moment du diagnostic de sclérodermie systémique et l’atteinte pulmonaire par TDM à distance serait nécessaire. L’entité nosologique représentée par le syndrome CREST n’est pas retrouvée dans cette cohorte de patients atteints de sclérodermie systémique selon les critères EULAR/ACR 2013, où 2 des critères diagnostiques (présence de calcinose et sclérodactylie) ne sont pas associés de manière significative à l’atteinte œsophagienne d’après les résultats de la manométrie de haute résolution. Conclusions Dans cette série, chez plus de la moitié des patients atteints de sclérodermie systémique la manométrie de haute résolution permet de détecter un apéristaltisme. La présence de troubles moteurs œsophagiens est associée à une atteinte pulmonaire plus sévère en TDM
ISSN: 0248-8663

hal-01321854
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01321854
DOI : 10.1016/j.revmed.2016.04.267

Éditeur(s) : HAL CCSD American Physiological Society
Résumé : Full text: http://jn.physiology.org/content/88/3/1475
International audience
The contribution of voltage-gated calcium channels (VGCC) to the development of cultured embryonic cockroach brain neurons was assessed using pharmacological agents. VGCC currents were recorded using the patch-clamp technique and were found to be blocked dose-dependently by micromolar concentrations of mibefradil. The activation and inactivation properties of the calcium channels enable a sizeable calcium current to flow at rest (about -30 and -20 mV in high-potassium culture media). As expected, the cytoplasmic-free calcium concentration was found to rise when the extracellular potassium concentration was raised from 3 to 15 and 30 mM. The effects of VGCC blockers and calcium chelators were different in fresh and in mature cultures in which the neurons were connected to each other to form a defined network. In fresh cultures, the two non-selective VGCC blockers (verapamil and mibefradil) induced a dose-dependent cell death that was proportional to their blocking effect on I(Ba). This effect could not be prevented by addition of fetal calf serum to the culture medium. A similar effect was obtained using intra- or extracellular calcium chelating agents (10 microM BAPTA-AM or 10 mM EGTA). Quite unexpectedly, blockade of the P/Q-like (omega-Aga WA-sensitive) component of the calcium current by 500 nM of omega-AgaTx IVA had no lethal effect, suggesting that the corresponding channels are not involved in the survival mechanism. As expected from their lack of effect on I(Ba), isradipine, nifedipine, and omega-CgTx GVIA did not induce cell death. When the neurons started growing neurites, their sensitivity to calcium channel blockade by mibefradil decreased, indicating a correlation between neurite outgrowth and resistance to calcium depletion. In mature cultures, the neurons became resistant to mibefradil, verapamil, and BAPTA-AM. However, these agents, as well as omega-AgaTx IVA, had a significant inhibitory effect on the increase in diameter of the connectives that linked adjacent clusters of neurons. This effect has been shown to result, in the case of mibefradil, from an inhibition of neurite outgrowth characterized by a significant reduction of the number of primary neurites and secondary branchings but not to a significant modification of the diameter of individual neurites. These results support the view that, as in vertebrates, calcium influx through VGCC plays an important role in survival and neurite outgrowth of cultured embryonic insect neurons. The differential contribution of the P/Q-like and R-like (omega-Aga WA-sensitive) calcium channels in these processes is discussed.
ISSN: 0022-3077

hal-00982287
https://hal.archives-ouvertes.fr/hal-00982287
DOI : 10.1152/jn.00749.2001
PUBMED : 12205168

Éditeur(s) : HAL CCSD Optical Society of America
Résumé : International audience
We present a theoretical simulation of the sarcomeric SHG intensity pattern (SHG-IP) that takes into account myofibrillar misalignment that is experimentally observed in SHG images of proteolysed muscles. The model predicts that myofibrillar displacement results in the conversion from one peak (1P) to two peaks (2P) sarcomeric SHG-IP in agreement with experimental results. This study suggests that sarcomeric SHG-IP is a powerful tool for mapping spatial myofibrillar displacement and its related excitation-contraction disruption that could occur during muscle physiological adaptation and disease.
ISSN: 1094-4087

hal-00820260
https://hal.archives-ouvertes.fr/hal-00820260
https://hal.archives-ouvertes.fr/hal-00820260/document
https://hal.archives-ouvertes.fr/hal-00820260/file/Studysur the_effect-accepted.pdf
DOI : 10.1364/OE.21.011404

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
Childhood absence epilepsy is a prototypic form of generalized nonconvulsive epilepsy characterized by short impairments of consciousness concomitant with synchronous and bilateral spike-and-wave discharges in the electroencephalogram. For scientists in this field, the BS/Orl and BR/Orl mouse lines, derived from a genetic selection, constitute an original mouse model "in mirror" of absence epilepsy. The potential of MALDI imaging mass spectrometry (IMS) for the discovery of potential biomarkers is increasingly recognized. Interestingly, statistical analysis tools specifically adapted to IMS data sets and methods for the identification of detected proteins play an essential role. In this study, a new cross-classification comparative design using a combined discrete wavelet transformation-support vector machine classification was developed to discriminate spectra of brain sections of BS/Orl and BR/Orl mice. Nineteen m/z ratios were thus highlighted as potential markers with very high recognition rates (87-99%). Seven of these potential markers were identified using a top-down approach, in particular a fragment of Synapsin-I. This protein is yet suspected to be involved in epilepsy. Immunohistochemistry and Western Blot experiments confirmed the differential expression of Synapsin-I observed by IMS, thus tending to validate our approach. Functional assays are being performed to confirm the involvement of Synapsin-I in the mechanisms underlying childhood absence epilepsy.
ISSN: 1535-3893

hal-00877728
https://hal.archives-ouvertes.fr/hal-00877728
DOI : 10.1021/pr3006974
PUBMED : 22994238

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers Inc.
Résumé : International audience
An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the 'latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury. © 2016 IEEE.
38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2016
Unknown, Unknown or Invalid Region

hal-01467552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467552
DOI : 10.1109/EMBC.2016.7591605

Éditeur(s) : HAL CCSD
Résumé : International audience
Over the past few years, genetics has significantly improved the understanding of interstitial lung diseases (ILD)...
European Respiratory Journal

hal-01534151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01534151
DOI : 10.1183/13993003.00407-2017
PUBMED : 28495697

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
o abstract
ISSN: 0735-1097

hal-01446568
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01446568
DOI : 10.1016/j.jacc.2016.09.036
PUBMED : 27970295

Éditeur(s) : HAL CCSD Optical Society Optical Society - SOA Publishing
Résumé : International audience
We show that the canonical single frequency sarcomeric SHG intensity pattern (SHG-IP) of control muscles is converted to double frequency sarcomeric SHG-IP in preserved mdx mouse gastrocnemius muscles in the vicinity of necrotic fibers. These double frequency sarcomeric SHG-IPs are often spatially correlated to double frequency sarcomeric two-photon excitation fluorescence (TPEF) emitted from Z-line and I-bands and to one centered spot SHG angular intensity pattern (SHG-AIP) suggesting that these patterns are signature of myofibrillar misalignement. This latter is confirmed with transmission electron microscopy (TEM). Moreover, a good spatial correlation between SHG signature of myofibrillar misalignment and triad reduction is established. Theoretical simulation of sarcomeric SHG-IP is used to demonstrate the correlation between change of SHG-IP and -AIP and myofibrillar misalignment. The extreme sensitivity of SHG microscopy to reveal the submicrometric organization of A-band thick filaments is highlighted. This report is a first step toward future studies aimed at establishing live SHG signature of myofibrillar misalignment involving excitation contraction defects due to muscle damage and disease.
ISSN: 2156-7085

hal-00952823
https://hal.archives-ouvertes.fr/hal-00952823
https://hal.archives-ouvertes.fr/hal-00952823/document
https://hal.archives-ouvertes.fr/hal-00952823/file/boe-5-3-858_002.pdf
DOI : 10.1364/BOE.5.000858

Éditeur(s) : HAL CCSD Massachusetts Medical Society
Résumé : International audience
o abstract
ISSN: 0028-4793

hal-01390975
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390975
DOI : 10.1056/NEJMoa1515319
PUBMED : 27626530

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers (IEEE)
Résumé : International audience
Non-alcoholic fatty liver disease (NAFLD) is defined as an excessive accumulation of fat in the liver in the absence of excessive drinking of alcohol. Initially considered as benign and self-limited, NAFLD may progress to the malignant stage of non-alcoholic steatohepatitis (NASH) characterized by degenerate hepatocellular ballooning and lobular inflammation. NASH can lead to hepatic fibrosis and ultimately to cirrhosis and hepatocellular carcinoma. Unfortunately, the transition from NAFLD to NASH is difficult to detect so far. In this paper, we propose to evaluate the characterization of NASH using mid infrared fiber evanescent wave spectroscopy on blood serum. We used an heuristic variable selection method and a generalized linear model to classify NAFLD and NASH spectra. The obtained results proved that this technique is a promising non-invasive and simple diagnosis tool for NASH.
ISSN: 1557-170X

inserm-01476033
http://www.hal.inserm.fr/inserm-01476033
http://www.hal.inserm.fr/inserm-01476033/document
http://www.hal.inserm.fr/inserm-01476033/file/EMBC_2016_CameraReady.pdf
DOI : 10.1109/EMBC.2016.7591507

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Polarization dependence second harmonic generation (P-SHG) microscopy is gaining increase popularity for in situ quantification of fibrillar protein architectures. In this report, we combine P-SHG microscopy, new linear least square (LLS) fitting and modeling to determine and convert the complex second-order non-linear optical anisotropy parameter ρ of several collagen rich tissues into a simple geometric organization of collagen fibrils. Modeling integrates a priori knowledge of polyhelical organization of collagen molecule polymers forming fibrils and bundles of fibrils as well as Poisson photonic shot noise of the detection system. The results, which accurately predict the known sub-microscopic hierarchical organization of collagen fibrils in several tissues, suggest that they can be subdivided into three classes according to their microscopic and macroscopic hierarchical organization of collagen fibrils. They also show, for the first time to our knowledge, intrahepatic spatial discrimination between genuine fibrotic and non-fibrotic vessels. CCl 4-treated livers are characterized by an increase in the percentage of fibrotic vessels and their remodeling involves peri-portal compaction and alignment of collagen fibrils that should contribute to portal hypertension. This integrated P-SHG image analysis method is a powerful tool that should open new avenue for the determination of pathophysiological and chemo-mechanical cues impacting collagen fibrils organization.
ISSN: 2045-2322

hal-01592192
https://hal.archives-ouvertes.fr/hal-01592192
https://hal.archives-ouvertes.fr/hal-01592192/document
https://hal.archives-ouvertes.fr/hal-01592192/file/s41598-017-12398-0.pdf
DOI : 10.1038/s41598-017-12398-0

Éditeur(s) : HAL CCSD Optical Society of America
Résumé : International audience
A linear least square (LLS) method is proposed to process polarization dependent SHG intensity analysis at pixel-resolution level in order to provide an analytic solution of nonlinear susceptibility χ(2) coefficients and of fibril orientation. This model is applicable to fibrils with identical orientation in the excitation volume. It has been validated on type I collagen fibrils from cell-free gel, tendon and extracellular matrix of F1 biliary epithelial cells. LLS is fast (a few hundred milliseconds for a 512 × 512 pixel image) and very easy to perform for non-expert in numerical signal processing. Theoretical simulation highlights the importance of signal to noise ratio for accurate determination of nonlinear susceptibility χ(2) coefficients. The results also suggest that, in addition to the peptide group, a second molecular nonlinear optical hyperpolarizability β contributes to the SHG signal. Finally from fibril orientation analysis, results show that F1 cells remodel extracellular matrix collagen fibrils by changing fibril orientation, which might have important physiological function in cell migration and communication.
ISSN: 1094-4087

hal-01139871
https://hal.archives-ouvertes.fr/hal-01139871
DOI : 10.1364/OE.23.013309
PUBMED : 26074581

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction Le cancer du pancréas est une néoplasie souvent diagnostiquée au stade métastatique et au pronostic sombre. Les lésions secondaires pulmonaires, pléiomorphes, sont souvent présentes au diagnostic et peuvent faire découvrir une maladie par ailleurs asymptomatique. Observations Nous rapportons une série rétrospective de trois patientes, âgées de 32 à 74 ans, qui présentaient des images de pneumopathie interstitielle diffuse (PID) ayant conduit au diagnostic de métastases pulmonaires de cancer du pancréas. Pour la première patiente, une sarcoïdose avait été évoquée devant son jeune âge et la négativité des prélèvements écho-endoscopiques digestifs répétés. La deuxième présentait de multiples nodules pulmonaires excavés et un tableau de compression médullaire a conduit à l’obtention rapide du diagnostic anatomopathologique sur les lésions osseuses. Pour la troisième, le terrain de polyarthrite rhumatoïde et l’absence de symptomatologie abdominale faisait rechercher une atteinte en rapport avec son rhumatisme inflammatoire. L’anatomopathologie, sur biopsies pulmonaires pour deux patientes a permis de redresser le diagnostic. Conclusion Devant une PID atypique le recours à des prélèvements invasifs doit être rapide afin de ne pas retarder un diagnostic de cancer, notamment pancréatique
ISSN: 0761-8425

hal-01334066
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334066
DOI : 10.1016/j.rmr.2016.04.019

Éditeur(s) : HAL CCSD
Résumé : International audience
Objectives: Using in silico simulations from histopathological cancer prostate specimen, the objectives were to identify the total dose corresponding to various fractionations necessary to destroy the tumor cells (50% to 99.9%) and to assess the impact of the Gleason score on those doses. © 2017 IEEE.
14th IEEE International Symposium on Biomedical Imaging, ISBI 2017
Melbourne, Australia

hal-01618934
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01618934
DOI : 10.1109/ISBI.2017.7950643

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction Les cas d’asthmes induits par les anti-TNF-α sont rares, et il n’a jamais été décrit de tentative de réintroduction d’une molécule de même classe. Il n’existe pas de recommandations concernant la conduite à tenir dans ces situations. Observation Nous rapportons le cas d’une femme de 45 ans, non-fumeuse, sans antécédent personnel d’asthme, qui était atteinte d’une maladie de Crohn depuis l’adolescence. En 2009, elle a été traitée par infliximab. La réponse digestive a été rapidement efficace, cependant après 4 semaines de traitement, elle commençait à présenter une toux sèche associée à une dyspnée inhabituelle. Ces symptômes évocateurs d’hyperréactivité bronchique s’aggravèrent progressivement, et les explorations fonctionnelles respiratoires confirmèrent le diagnostic d’asthme. Malgré des traitements adaptés, la sévérité de la situation imposa l’arrêt de l’infliximab. L’asthme s’est alors amélioré, mais en raison de l’atteinte digestive un nouveau traitement dut être débuté : l’adalimumab, sans rechute d’asthme à ce jour. Conclusion Ce cas clinique met en évidence la possibilité de réintroduire un nouvel anti-TNF-α après un premier épisode d’asthme induit par cette classe médicamenteuse. Cette option pourrait être extrêmement utile chez les patients présentant des atteintes sévères (polyarthrite rhumatoïde, maladies inflammatoires chroniques de l’intestin) en l’absence d’alternative thérapeutique
ISSN: 0761-8425

hal-01334071
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334071
DOI : 10.1016/j.rmr.2016.04.012

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Voltage-gated calcium currents are important for the survival and growth of embryonic cockroach brain neurons in primary culture. In the present experiments, we have studied, using the patch-clamp technique, the evolution with time in culture of the voltage-dependency and of the pharmacological properties of the calcium conductance of these neurons during the formation of a network. We have observed a progressive increase of the high-voltage-activated calcium conductance and a 10mV shift of the voltage-dependency of activation towards more negative potentials. The proportion of the R-like calcium current component increased during network formation. At the same time, the highly omega-AgaTxIVA-sensitive P-like component of the current is progressively replaced by a component which is less sensitive to the toxin. The origin and functional implications of these modifications are discussed.
ISSN: 0304-3940

hal-00982273
https://hal.archives-ouvertes.fr/hal-00982273
DOI : 10.1016/j.neulet.2004.05.002
PUBMED : 15246554

Éditeur(s) : HAL CCSD Biophysical Society
Résumé : International audience
SHG angular intensity pattern (SHG-AIP) of healthy and proteolysed muscle tissues are simulated and imaged here for the first time to our knowledge. The role of the spatial distribution of second-order nonlinear emitters on SHG-AIP is highlighted. SHG-AIP with two symmetrical spots is found to be a signature of healthy muscle whereas SHG-AIP with one centered spot in pathological mdx muscle is found to be a signature of myofibrillar disorder. We also show that SHG-AIP provides information on the three-dimensional structural organization of myofibrils in physiological and proteolysed muscle. Our results open an avenue for future studies aimed at unraveling more complex physiological and pathological fibrillar tissues organization.
ISSN: 0006-3495

hal-00825645
https://hal.archives-ouvertes.fr/hal-00825645
https://hal.archives-ouvertes.fr/hal-00825645/document
https://hal.archives-ouvertes.fr/hal-00825645/file/Theoretical-SHG-accepted.pdf
DOI : 10.1016/j.bpj.2013.02.047

Éditeur(s) : HAL CCSD Oxford Scholarship Online
Résumé : Brain aromatase in fish is an exciting research topic because of several unconventional features that challenge the established view based on studies in other vertebrates. First, the brain of teleost fish exhibits a high degree of aromatase activity, especially in sexually mature animals. Given the emerging roles of estrogens in neurogenesis, the unique features of the adult fish brain suggest that, in addition to classical functions on brain sexual differentiation and sexual behavior, aromatase expression in radial glial cells could be involved in the modulation of the high proliferative activity in the brain of fish.
Brain Aromatase, Estrogens, and Behavior

ISBN : 9780199841196
hal-00905522
https://hal.archives-ouvertes.fr/hal-00905522
DOI : 10.1093/acprof:oso/9780199841196.003.0007

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The objective of the study was to evaluate the distribution of methotrexate (MTX) in cerebrospinal fluid (CSF) lateral ventricles and in cisterna magna after 3rd intraventricular CSF administration in a rabbit model.MTX or gadolinium chelate (Gd-DOTA) was administered in the 3rd ventricle with a local microdialysis to study the pharmacokinetics at the site of administration and with a simultaneous magnetic resonance imaging (MRI) acquisition in the 3rd ventricle, the lateral ventricles and in the cisterna magna. A specific CSF Physiologically Based Pharmacokinetic (PBPK) model was then extrapolated for MTX from Gd-DOTA data.The relative contribution of elimination and distribution processes to the overall disposition of MTX and Gd-DOTA in the 3rd ventricle was similar (i.e., around 60% for CLE and 40% for CLI) suggesting that Gd-DOTA was a suitable surrogate marker for MTX disposition in ventricular CSF. The PBPK predictions for MTX both in CSF of the 3rd ventricle and in plasma were in accordance with the in vivo results.The present study showed that the combination of local CSF microdialysis with MRI acquisition of the brain ventricles and a PBPK model could be a useful methodology to estimate the drug diffusion within CSF ventricles after direct brain CSF administration. Such a methodology would be of interest to clinicians for a rationale determination and optimization of drug dosing parameters in the treatment of leptomeningeal metastases.
ISSN: 0939-6411

hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562/document
https://hal.archives-ouvertes.fr/hal-01335562/file/PBPK%20model%20of%20methotrexate%20in%20cerebrospinal%20fluid.pdf
DOI : 10.1016/j.ejpb.2016.04.012

Éditeur(s) : HAL CCSD IEEE
Résumé : International audience
The main challenge in prostate cancer radiotherapy is to deliver the prescribed dose to the clinical target while minimizing the dose to the neighboring organs at risk and thus avoiding subsequent toxicity-related events. With the aim of improving toxicity prediction following prostate cancer radiotherapy, the goal of our work is to propose a new predictive variable computed with independent component analysis to predict late rectal toxicity, and to compare its performance to other models (logistic regression, normal tissue complication probability model and recent principal component analysis approach). Clinical data and dose-volume histograms were collected from 216 patients having received 3D conformal radiation for prostate cancer with at least two years of follow-up. Independent component analysis was trained to predict the risk of 3-year rectal bleeding Grade extgreater= 2. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve. Clinical parameters combined with the new variable were found to be predictors of rectal bleeding. The mean area under the receiving operating curve for our proposed approach was 0:75. The AUC values for the logistic regression, the Lyman-Kutcher-Burman model and the recent principal component analysis approach were 0:62, 0:53 and 0:62, respectively. Our proposed new variable may be an useful new tool in predicting late rectal toxicity. It appears as a strong predictive variable to improve classical models
2015 37th annual international conference of the IEEE Engineering in Medicine and Biology Society
Milan, Italy

hal-01304750
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01304750