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The topic of this thesis in medicine is based on the management of choroidal hemangiomas treated with photodynamic therapy (PDT) and is supervised by Professor P. De Potter, Head of the Ophthalmological Department and the Ocular Oncology Unit at the St. Luc university hospital. The ocular lesion we study is a benign vascular tumor which arises within the choroidal layer, the eyeball vascular tunic. Choroidal hemangioma may present itself with two patterns : a circumscribed form and a diffuse form. However, our study is focused on the circumscribed form. The first section of our work will be articulated into three parts firstly, we will aim at analyzing various epidemiological, histological and physiological data. Secondly, we will address symptoms and clinical signs that lead ophthalmologists to establish this diagnosis. We will then provide a detailed assessment that will allow us to ascertain the CCH diagnosis, since the differential diagnosis can be complex if a direct or indirect ophthalmoscopy is made. We will eventually describe PDT, the therapeutic method used in our study. CCH are not necessarily symptomatic, but we currently estimate the prevalence rate of symptomatic choroidal hemangiomas at about 1/2500000 a year. But their precise incidence is unknown as many CCH are asymptomatic and never clinically diagnosed. CHH is regarded as a benign tumor. Since it can be asymptomatic, this benign uveal tumor can be discovered during a routine eye examination. The exudative activity of the hemangioma with accumulation of sub retinal fluid will trigger visual symptoms such as blurred vision, metamorphosis, and/ or visual scotomas generally appearing during the fourth decade of life. Although the CHH usually show' Le sujet de ce mémoire en médecine est basé sur les hémangiomes choroïdiens traités par la photothérapie dynamique (PTD) et ce travail est supervisé par le Professeur P. De Potter, chef du service d'ophtalmologie de l'hôpital universitaire Saint-Luc. La lésion ophtahnique que nous étudions est une tumeur vasculaire se développant au sein de la choroïde, la tunique vasculaire du globe oculaire. Cette atteinte oculaire peut se subdiviser en deux grandes catégories : les hémangiomes circonscrits et les diffus. I'étude concerne la forme circonscrite. Dans un premier temps, l'ouvrage présente des données épidémiologiques, les différentes présentations histologiques et des explications physiopathologiques. Ensuite, nous discutons des symptômes et des signes cliniques qui amènent l'ophtahnologue à envisager ce diagnostic. Après, nous décrivons le bilan nécessaire pour poser définitivement le diagnostic d'HCC car le diagnostic différentiel peut être complexe si on ne s'octroie qu'une ophtalmoscopie directe ou inclirecte. Finalement, nous parlons de la PTD, la méthode thérapeutique utilisée dans notre étude. Les HCC ne sont pas obligatoirement symptomatiques mais on évalue actuellement la prévalence des hémangiomes choroïdiens symptomatiques à =1/ 2 500 000 / an. L'HCC peut donner une sévère altération de l'acuité visuelle au long terme. Néanmoins, on considère la lésion choroïdienne circonscrite comme une tumeur bénigne. Cette tumeur uvéale bénigne peut être découverte fortuitement puisque celle-ci peut être asymptomatique. Elle est très souvent cliagnostiquée lorsqu'elle présente une activité exsudative tarclive, habituellement pendant la quatrième décade. Les HCC peuvent se présenter de deux manières distinctes. La première situation est la découverte fortuite. C'est à l'ophtalmoscopie que le praticien observe un fond d'œil anormal. Soit, a contrario, le parient est symptomatique ce qui l'amène à consulter. Dans cette dernière situation, nous sommes confrontés soit, à un patient jeune (p.ex. il se présente avec une hypermétropie franche de cliagnostic récent) soit, à un patient d'une quarantaine d'années avec clivers symptôtnes possibles. Un large diagnostic différentiel existe et afin d'être certain du diagnostic, des examens complémentaires seront nécessaires. A notre disposition, nous retrouvons : l'échographie, l'IVFA, l'ICG, l'OCT, le CT, l'IRM, le phosphore radioactif, l'autofluorescence au fundus et la biopsie. Pour la prise en charge de ces tumeurs vasculaires bénignes, la photothérapie dynamique est proposée. Dans la PTD, on utilise une lumière monochromatique et un agent qui absorbe cette lumière, c'est-à-clire, un photosensibilisant. La vertéporfine (Visudyne®) est un photosensibilisant injecté en intraveineux qui, combiné à un environnement riche en oxygène et soumis à la lumière, donne une réaction photochimique. La fibrose du tissu vasculaire, qui fait suite à cette photothrombose, conduit à la régression tumorale (démontrable par angiographie). Dans le cadre des HCC, le but n'est pas d'éliminer totalement la tumeur mais plutôt d'annihiler sa propension exsudative. La PTD peut s'administrer selon différents protocoles qui sont fonction du temps d'injection, du temps d'intervalle entre la perfusion du photosensibilisant et l'exposition à la lumière, la taille du spot et l'énergie induite. Une courte synthèse de la littérature est réalisée pour cette thérapie exclusive afin de montrer ses avantages, ses éventuelles cotnplications et sa supériorité par rapport aux autres thérapies actuellement disponibles. Dans un second temps, nous rentrons au cœur du sujet en expliquant précisément le matériel utilisé ainsi que le protocole entrepris durant cette étude interventionnelle et prospective. Les résultats de notre étude viendront par la suite appuyer notre hypothèse clinique de départ : la PTD est une thérapie d'avenir dans le management des HCC par sa relative innocuité et sa grande efficacité. Effectivement, parni les 29 patients présents dans notre étude, seul un individu a souffert d'une complication visuelle et l'AV s'est amoindrie dans un seul cas. Une majorité nette de patients a bénéficié d'une augmentation ou d'une stabilisation de son AV sans aucune complication associée. Le chapitre final tirera des conclusions quant à fiabilité de notre étude, aux résultats obtenus et à l'impact potentiel au sein de la littérature scientifique dans le domaine de l'oncologie oculaire. Depuis la première publication au sujet des HCC, les experts se plaignent d'un manque éloquent de patients dans leurs études qui sont souvent rétrospectives. Des études n'arrivent parfois pas à suivre leurs patients sur une longue période. Ceci rend complexe l'établissement de conclusions statistiquement significatives. Cette étude a l'avantage d'outrepasser toutes ces embuches. Effectivement, c'est une étude prospective avec un nombre important de patients en comparaison aux autres études associées à cette problématique et le suivi des patients atteint parfois 11 ans. Nous comprenons alors aisément que l'étude clinique associée à ce travail deviendra incontournable dans le domaine des hémangiomes choroïdiens circonscrits .

Hemangioma --- Papilloma, Choroid Plexus --- Phototherapy

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Reptiles --- Choroid plexus. --- Plexus choroïdes. --- Plexus choroïde --- Anatomy. --- Anatomie. --- Thèses et écrits académiques. --- Morphologie

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The brain functions within an internal environment that is determined and controlled by morphological structures and cellular mechanisms present at interfaces between the brain and the rest of the body. In vertebrates these interfaces are across cerebral blood vessels (blood-brain barrier) choroid plexuses (blood-cerebrospinal fluid barrier) and pia-arachnoid. There is a CSF-brain barrier in the neuroepithelium lining the ventricular system that is only present in embryos. There is now substantial evidence that many brain barrier mechanisms develop early and that in some cases they are functionally more active and even more specialized compared to adult barriers. Therefore barriers in developing brain should be viewed as adapted appropriately for the growing brain and not, as is still widely believed, immature. Considerable advances in our understanding of these barrier mechanisms have come from studies of the developing brain and invertebrates. A striking aspect, to be highlighted in this special edition, is that many of the molecular mechanisms in these very diverse species are similar despite differences in the cellular composition of the interfaces. This Frontiers Topic comprises articles in three sections: Original studies, Reviews and Myths & Misconceptions. Original articles provide new information on molecular and cellular barrier mechanisms in developing brains of primates, including human embryos (Brøchner et al., Ek et al., Errede et al.), rodents (Bauer et al., Liddelow, Strazielle & Ghersi-Egea, Saunders et al., Whish et al.), chick (Bueno et al.) and zebrafish (Henson et al.) as well as studies in drosophila (Hindle & Bainton, De Salvo et al., Limmer et al.). The Reviews section includes evolutionary perspectives of the blood-brain and blood-CSF barriers (Bueno et al., Bill & Korzh). There are also detailed reviews of the current state of understanding of different interfaces and their functional mechanisms in developing brain (Bauer et al., Strazielle & Gjersi-Egea, Liddelow, Richardson et al., Errede et al., Henson et al., Brøchner et al.) and in invertebrates (Hindle & Bainton, De Salvo et al., Limmer et al). Different aspects of the relationship between properties of the internal environment of the brain and its development are discussed. (Stolp & Molnar, Johansson, Prasongchean et al.). A neglected area, namely barriers over the surface of the brain during development is also covered (Brøchner et al.). Clinically related perspectives on barrier disruption in neonatal stroke are provided by Kratzer et al. and other aspects of dysfunction by Morretti et al. and by Palmeta et al. on the continuing problem of bilirubin toxicity. Progress in this field is hampered by many prevailing myths about barrier function, combined with methodologies that are not always appropriately selected or interpreted. These are covered in the Misconceptions, Myths and Methods section, including historical aspects and discussion of the paracellular pathway, a central dogma of epithelial and endothelial biology (Saunders et al.) and a review of markers used to define brain barrier integrity in development and in pathological conditions (Saunders et al.). Use of inappropriate markers has caused considerable confusion and unreliable interpretation in many published studies. Torbett et al. deal with the complexities of the new field of applying proteomics to understanding blood-brain barrier properties as do Huntley at al. with respect to applying modern high throughput gene expression methods (Huntley et al.). The Editorial summarizes the contributions from all authors. This includes mention of some the main unanswered but answerable questions in the field and what the impediments to progress may be.

zebra fish --- development --- Influx mechanisms --- Tight Junctions --- Drosophila --- Efflux mechanisms --- blood-CSF barrier --- Choroid Plexus --- Blood-Brain Barrier

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The brain functions within an internal environment that is determined and controlled by morphological structures and cellular mechanisms present at interfaces between the brain and the rest of the body. In vertebrates these interfaces are across cerebral blood vessels (blood-brain barrier) choroid plexuses (blood-cerebrospinal fluid barrier) and pia-arachnoid. There is a CSF-brain barrier in the neuroepithelium lining the ventricular system that is only present in embryos. There is now substantial evidence that many brain barrier mechanisms develop early and that in some cases they are functionally more active and even more specialized compared to adult barriers. Therefore barriers in developing brain should be viewed as adapted appropriately for the growing brain and not, as is still widely believed, immature. Considerable advances in our understanding of these barrier mechanisms have come from studies of the developing brain and invertebrates. A striking aspect, to be highlighted in this special edition, is that many of the molecular mechanisms in these very diverse species are similar despite differences in the cellular composition of the interfaces. This Frontiers Topic comprises articles in three sections: Original studies, Reviews and Myths & Misconceptions. Original articles provide new information on molecular and cellular barrier mechanisms in developing brains of primates, including human embryos (Brøchner et al., Ek et al., Errede et al.), rodents (Bauer et al., Liddelow, Strazielle & Ghersi-Egea, Saunders et al., Whish et al.), chick (Bueno et al.) and zebrafish (Henson et al.) as well as studies in drosophila (Hindle & Bainton, De Salvo et al., Limmer et al.). The Reviews section includes evolutionary perspectives of the blood-brain and blood-CSF barriers (Bueno et al., Bill & Korzh). There are also detailed reviews of the current state of understanding of different interfaces and their functional mechanisms in developing brain (Bauer et al., Strazielle & Gjersi-Egea, Liddelow, Richardson et al., Errede et al., Henson et al., Brøchner et al.) and in invertebrates (Hindle & Bainton, De Salvo et al., Limmer et al). Different aspects of the relationship between properties of the internal environment of the brain and its development are discussed. (Stolp & Molnar, Johansson, Prasongchean et al.). A neglected area, namely barriers over the surface of the brain during development is also covered (Brøchner et al.). Clinically related perspectives on barrier disruption in neonatal stroke are provided by Kratzer et al. and other aspects of dysfunction by Morretti et al. and by Palmeta et al. on the continuing problem of bilirubin toxicity. Progress in this field is hampered by many prevailing myths about barrier function, combined with methodologies that are not always appropriately selected or interpreted. These are covered in the Misconceptions, Myths and Methods section, including historical aspects and discussion of the paracellular pathway, a central dogma of epithelial and endothelial biology (Saunders et al.) and a review of markers used to define brain barrier integrity in development and in pathological conditions (Saunders et al.). Use of inappropriate markers has caused considerable confusion and unreliable interpretation in many published studies. Torbett et al. deal with the complexities of the new field of applying proteomics to understanding blood-brain barrier properties as do Huntley at al. with respect to applying modern high throughput gene expression methods (Huntley et al.). The Editorial summarizes the contributions from all authors. This includes mention of some the main unanswered but answerable questions in the field and what the impediments to progress may be.

zebra fish --- development --- Influx mechanisms --- Tight Junctions --- Drosophila --- Efflux mechanisms --- blood-CSF barrier --- Choroid Plexus --- Blood-Brain Barrier

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Blood-brain barrier. --- Blood-cerebral barrier --- Blood-cerebrospinal fluid barrier --- Brain-blood barrier --- Hemato-encephalic barrier --- Hematoencephalic barrier --- Brain --- Cerebrospinal fluid --- Choroid plexus --- Blood-vessels