Estudou-se prospectivamente o comportamento das calcificações, da atrofia, das alterações da substância branca e alterações vasculares nas imagens de tomografia computadorizada de crânio de 162 crianças e adolescentes infectados pelo vírus da imunodeficiência humana (HIV) por transmissão vertical e que estavam ou estiveram em acompanhamento clínico no Ambulatório de Infectologia Pediátrica do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, entre 1992 e 2002. Analisaram-se as possíveis correlações entre estas alterações e seu aspecto evolutivo. Para tal finalidade, foram avaliadas 606 tomografias computadorizadas de crânio (média de 3,74 exames por paciente), as quais constituíram o grupo de estudo. Após a caracterização quanto à presença ou não das alterações supracitadas, e suas possíveis inter-relações, realizou-se a análise estatística dos resultados obtidos através do teste exato de Fisher com nível de significância de 5%. Posteriormente, os mesmo aspectos foram avaliados em função do seu comportamento evolutivo em um subgrupo de 61 pacientes (média, 4,18 exames por paciente, totalizando 321 exames tomográficos). Estes pacientes tinham, pelo menos, quatro estudos tomográficos seriados (com intervalo mínimo de noventa dias entre os exames subseqüentes e pelo menos dois anos de intervalo total entre o primeiro e o último exame). As alterações tomográficas foram abordadas individual e qualitativamente segundo o critério de presença e intensidade. Inicialmente, o conjunto dos resultados foi tratado de forma individual (para cada paciente) e, depois, em relação à totalidade do grupo em questão. As calcificações foram encontradas em 46,30% dos pacientes; a atrofia, em 37,65%; as alterações da substância branca, em 25,93%; as anomalias vasculares, em 25,19%. Constatou-se uma correlação significativa entre as alterações de substância branca e a atrofia, bem como entre as calcificações e as alterações vasculares. A análise evolutiva destas características demonstrou haver um acréscimo significativo das alterações entre o momento inicial e o quarto momento no conjunto das alterações, sobretudo para as calcificações e para as alterações vasculares. Concluiu-se que as calcificações e a atrofia foram as alterações mais freqüentes nesta série de crianças e adolescentes com HIV adquirido por transmissão vertical. A atrofia e as alterações da substância branca apresentaram uma inter-relação importante na amostra descritiva, assim como as alterações vasculares e as calcificações mostraram uma associação evolutiva significativa em relação à sua progressão / We prospectively studied the behavior of calcifications, atrophy, white matter and vascular abnormalities on the images of computed tomography (CT) of 162 children and adolescents infected with the human immunodeficiency virus (HIV) acquired by vertical transmission, who are or were clinically followed in the Ambulatory of Pediatric Infectology of the Children Institute at the Clinics Hospital of University of São Paulo Medical School, from 1992 to 2002. We analyzed the possible correlation between these abnormalities, as well as, their evolutive aspects. For this purpose, we evaluated 606 CT scans (mean 3.74 exams per patient), which composed the group of study. After the characterization according to the presence or not of the anomalies mentioned above, and their possible inter-relations, we performed a statistical analysis of the obtained results with the Fisher test with a level of significance below 5%. Later, these aspects were evaluated regarding its evolutive behavior in a subgroup of 61 patients (mean, 4.18 exams per patient, summing 321 exams). These patients had, at least, four serial cranial CT (with minimum interval of ninety days between the subsequent exams and, at least, two years of total interval between the first and the fourth exam). The cranial CT abnormalities presented were assessed individually as absent or present. Initially, the set results were assessed individually (for each patient) and, later in relation to the totality of the group. Calcifications were found in 46.30% of all patients, atrophy in 37.65%, white matter abnormalities in 25.93% and vascular anomalies in 25.19%. We found a significant correlation between white matter abnormalities and atrophy, as well as, between calcifications and vascular anomalies. Evolutive analysis of these characteristics demonstrated a significant increase of the abnormalities between the first and the fourth moment, with emphasis to the calcifications and vascular anomalies. We concluded that, calcifications and atrophy were the most frequent abnormalities in this series of children and adolescents with HIV acquired by vertical transmission. Atrophy and white matter abnormalities presented a significant correlation in the descriptive sample, as well as, vascular anomalies and calcifications that also demonstrated a significant evolutive association regarding its progression

Das vom endonasalen Neuroepithel der Rima olfactoria entstandenen Aesthesioneuroblastom gehört zu den seltenen malignen Tumoren der Rhinobasis. Eine generelle Therapieempfehlung für die Behandlung dieses Tumors gibt es nicht, da bis heute etablierte, durch umfassende onkologische Studien untermauerte diagnostische und therapeutische Standards fehlen und der klinische Verlauf oft unberechenbar ist. Die Aufgabe der vorliegenden Arbeit bestand in der Überprüfung des chirurgischen Konzeptes bei der Therapie von Aesthesioneuroblastomen und in der erstmaligen molekularzytogenetischen Charakterisierung von Aesthesioneuroblastomen. Dazu wurden 18 Patienten mit Aesthesioneuroblastomen, die im Zeitraum zwischen 1988 und 2001 in der HNO-Klinik (17 Patienten) sowie in der Neurochirurgischen Klinik des Klinikums Fulda operiert wurden, untersucht. Die daraus resultierenden 22 Aesthesioneuroblastome wurden alle mit Hilfe der Vergleichenden Genomischen Hybridisierung (CGH) analysiert. Nach derzeitigem Kenntnisstand besteht die optimale Therapie der Aesthesioneuroblastome in der chirurgischen Resektion des Tumors mit nachfolgender stereotaktischer Bestrahlung. Für die operative Sanierung der Aesthesioneuroblastome und auch anderer Malignome der vorderen Schädelbasis ist das nachfolgende neue Fuldaer Konzept empfehlenswert: 1) Endonasale Resektion, wenn keine intrakranielle bzw. orbitale Tumorinfiltration vorliegt; 2) Subfrontaler Zugang, bei Infiltration des Gehirns; 3) Midfacial degloving, bei weit lateraler Tumorausbreitung; 4) Laterale Rhinotomie nur bei der Notwendigkeit der simultanen Exenteratio orbitae (bei orbitaler Tumorinfiltration). Aesthesioneuroblastomen sind durch ein typisches genetisches Muster charakterisiert, das Deletionen im Bereich der chromosomalen Arme 1p, 2q, 3p/q, 4p/q, 5p/q, 6q, 8p/q, 9p, 10p/q, 11p, 12q, 13q, 18q und 21q sowie Amplifikationen der Chromosomen 1p, 7q, 9q, 11q, 14q, 16p/q, 17p/q, 19p/q, 20p/q und 22p/q umfasst. Die beim Aesthesioneuroblastom häufigen DNA-Verluste im Bereich der chromosomalen Banden 1p21-p31 scheinen mit der Prognose dieser Tumoren assoziiert zu sein. Die Tumoren aller in der vorliegenden Studie am Malignom verstorbenen Patienten zeigten eine Kombination aus 1p21-p31-Deletion, dem Vorliegen des klinischen Stadiums C oder D sowie gleichzeitig einer schlechten Differenzierung (Grad III oder IV). Vermittels der CGH ist es möglich, eine klonale Zuordnung von Metastasen bzw. auch Rezidiven zu ihren primären Aesthesioneuroblastomen vorzunehmen. Die vorliegende Arbeit zeigt nicht nur neue Ansätze in der chirurgischen Therapie von Aesthesioneuroblastomen sondern auch die erste umfassende molekularzytogenetische Analyse dieser Tumorentität, auf dem Weg, das biologische Verhalten dieser Malignome genauer charakterisieren zu können. / Esthesioneuroblastoma (ENB) is a very rare malignant neoplasm arising from the olfactory epithelium which is recognized for its propensity for local recurrence and distant dissemination. Therapeutic management approaches for this neoplasm lack uniformity. The present study describes therapeutic management in ENB: Complete surgical resection combined with adjuvant stereotactic radiation therapy. Thereby, a new surgical concept is recommended: 1) Endonasal approach in cases without tumor infiltration of the orbit and/or the brain; 2) Subfrontal approach in cases with extended tumor infiltration of the intradural space or of the brain; 3) Midfacial degloving in cases with far lateral tumor spread, particularly fossa pterygoidea or pterygopalatina; 3) Lateral rhinotomy in all cases where an exenteratio orbitae is needed. Secondarily, the study characterizes the specific chromosomal alterations of ENB analyzed using Comparative Genomic Hybridization (CGH). ENB show frequently deletions of chromosoms 1p, 2q, 3p/q, 4p/q, 5p/q, 6q, 8p/q, 9p, 10p/q, 11p, 12q, 13q, 18q and 21q as well as DNA gains of chromosoms 1p, 7q, 9q, 11q, 14q, 16p/q, 17p/q, 19p/q, 20p/q and 22p/q. Deletions of the chromosomal region 1p21-p31 could be associated with bad prognosis since the tumors of all patients who died were of stage C or D and grade III or IV, and showed 1p21-p31 deletions. The analysis of primary ENB and their corresponding metastases shows clonality by a high concordance of alterations between the tumor pairs. For the first time, this study presents the specific chromosomal alterations of ENB pathogenesis and progression.

Facial Artery Musculomucosal Flap in Skull Base Reconstruction Xie L. MD, Lavigne F. MD, Rahal A. MD, Moubayed SP MD, Ayad T. MD Introduction: Failure in skull base defects reconstruction can have serious consequences such as meningitis and pneumocephalus. The nasoseptal flap is usually the first choice but alternatives are necessary when this flap is not available. The facial artery musculomucosal (FAMM) flap has proven to be successful in head and neck reconstruction but it has never been reported in skull base reconstruction. Objective: To show that the FAMM flap can reach some key areas of the skull base and be considered as a new alternative in skull base defects reconstruction. Methods: We conducted a cadaveric study with harvest of modified FAMM flaps, endoscopic skull base dissection and maxillectomies in 13 specimens. Measures were taken for each harvested FAMM flap. Results: The approximate mean area for reconstruction from the combination of the distal FAMM and the extension flaps is 15.90 cm2. The flaps successfully covered the simulated defects of the frontal sinus, the ethmoid areas, the planum sphenoidale, and the sella turcica. Conclusion: The FAMM flap can be considered as a new alternative in the reconstruction of skull base defects. Modifications add extra length to the traditional FAMM flap and can contribute to a tighter seal of the defect as opposed to the FAMM flap alone. / Le lambeau musculomuqueux de la joue dans la reconstruction de la base du crâne Xie L. MD, Lavigne F. MD, Rahal A. MD, Moubayed SP MD, Ayad T. MD Introduction: Un échec dans la reconstruction de la base du crâne peut avoir des conséquences graves telles que la méningite ou la pneumocéphalie. Le premier choix de la reconstruction est le lambeau nasoseptal. Lorsque ce dernier n’est pas disponible, d’autres alternatives sont nécessaires. Le lambeau musculomuqueux de la joue (FAMM) a une place établie dans la reconstruction des déficits de la tête et du cou, mais il n’a pas jamais été décrit dans la reconstruction de la base du crâne. Objectif: Démontrer que le lambeau de FAMM peut atteindre des zones clés de la base du crâne et être considéré comme une nouvelle option de reconstruction de cette région. Méthode: Nous avons entrepris une étude cadavérique avec prélèvement de lambeaux de FAMM modifiés et une dissection endoscopique de la base du crâne sur 13 spécimens. Des mesures ont été prises pour chaque lambeau prélevé. Résultats: L’aire de reconstruction moyenne du lambeau de FAMM et des extensions est de 15.90 cm2. Les lambeaux couvrent totalement les déficits simulés du sinus frontal, des ethmoïdes, le toit du sphénoïde et la selle turcique. Conclusion: Le lambeau de FAMM peut être considéré comme une nouvelle alternative dans la reconstruction des déficits de la base du crâne. Les modifications apportent une longueur additionnelle et contribuent à une couverture plus étanche du déficit que le lambeau de FAMM seul.

This body of work is concerned with the genetics of craniofacial morphology and specifically with that of the cranial sutures which form fibrous articulations between the calvarial bones. The premature fusion of these sutures, known as craniosynostosis, is a common developmental abnormality and has been extensively utilised here as a tool through which to study the genetics of suture morphogenesis and craniofacial diversity. Investigations began with a search for polymorphisms associated with normal variation in human craniofacial characteristics. Denaturing High-Performance Liquid chromatography was used to identify polymorphisms in two genes causative for craniosynostosis by analysing DNA from a large cohort of individuals from four ethnogeographic populations. A single nucleotide polymorphism in fibroblast growth factor receptor 1 was identified as being associated with variation in the cephalic index, a common measure of cranial shape. To further, and specifically, investigate the molecular processes of suture morphogenesis gene expression was compared between unfused and prematurely fusing/fused suture tissues isolated from patients with craniosynostosis. Two approaches, both utilising Affymetrix gene expression microarrays, were used to identify genes differentially expressed during premature suture fusion. The first was a novel method which utilised the observation that explant cells from both fused and unfused suture tissue, cultured in minimal medium, produce a gene expression profile characteristic of minimally differentiated osteoblastic cells. Consequently, gene expression was compared between prematurely fused suture tissues and their corresponding in vitro de-differentiated cells. In addition to those genes known to be involved in suture morphogenesis, a large number of novel genes were identified which were up-regulated in the differentiated in vivo state and are thus implicated in premature suture fusion and in vivo osteoblast differentiation. The second microarray study involved an extensive analysis of 16 suture tissues and compared gene expression between unfused (n=9) and fusing/fused sutures (n=7). Again, both known genes and a substantially large number of novel genes were identified as being differentially expressed. Some of these novel genes included retinol binding protein 4 (RBP4), glypican 3 (GPC3), C1q tumour necrosis factor 3 (C1QTNF3), and WNT inhibitory factor 1 (WIF1). The known functions of these genes are suggestive of potential roles in suture morphogenesis. Realtime quantitative RT PCR (QRT-PCR) was used to verify the differential expression patterns observed for 11 genes and Western blot analysis and confocal microscopy was used to investigate the protein expression for 3 genes of interest. RBP4 was found to be localised on the ectocranial surface of unfused sutures and in cells lining the osteogenic fronts while GPC3 was localised to suture mesenchyme of unfused sutures. A comparison between each unfused suture (coronal, sagittal, metopic, and lambdoid) demonstrated that gene expression profiles are suture-specific which, based on the identification of differentially expressed genes, suggests possible molecular bases for the differential timing of normal fusion and the response of each suture to different craniosynostosis mutations. One observation of particular interest was the presence of cartilage in unfused lambdoid sutures, suggesting a role for chondrogenesis in posterior skull sutures which have generally been thought to develop by intramembranous ossification without a cartilage precursor. Finally, the effects of common media supplements used in in vitro experiments to stimulate differentiation of calvarial suture-derived cells were investigated with respect to their ability to induce in vivo-like gene expression. The response to standard differentiation medium (ascorbic acid + β-glycerophosphate) with and without dexamethasone was measured by both mineralisation and matrix formation assays and QRT-PCR of genes identified in the above described microarray studies. Both media induced collagen matrix and bone nodule formation indicative of differentiating osteoblasts. However, the genes expression profiles induced by both media differed and neither recapitulated the levels and profiles of gene expression observed in vivo for cells isolated from both fused and unfused suture tissues. This study has implications for translating results from in vitro work to the in vivo situation. Significantly, the dedifferentiation microarray study identified differentially expressed genes whose products may be considered candidates as more appropriate osteogenic supplements that may be used during in vitro experiments to better induce in vivo-like osteoblast differentiation. This study has made a substantial contribution to the identification of novel genes and pathways involved in controlling human suture morphogenesis and craniofacial diversity. The results from this research will stimulate new areas of inquiry which will one day aid in the development of better diagnostics and therapeutics for craniosynostosis, and other craniofacial and more general skeletal abnormalities.

Thesis (MA)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Socially responsible writing has been a feature of South African literature for many years. Under apartheid, many novels dealt with apartheid, as it was one of the main features of our social landscape. The end of apartheid did not however bring about the end of a need for socially responsible writing. South Africa is still faced with many problems, one of which is reconciliation. This thesis investigates whether reconciliation may have become a new theme in South African novels, and whether these novels could playa role in assisting the process of reconciliation in the country. For this purpose, three South African works are analysed, namely Country of My Skull by Antjie Krog, Smell of Apples by Mark Behr and Disgrace by J .M. Coetzee. The introduction attempts to explain the psychological discourse surrounding reconciliation, especially Post-Traumatic Stress Disorder (PTSD), and parallels that may exists. The main body presents detailed readings of the three works, with the focus being on the presentation of reconciliation in the works, and the role that the individual works could play in assisting the reader in coming to terms with his or her feelings of guilt. / AFRIKAANSE OPSOMMING: Vir baie jare was apartheid die onderwerp van baie Suid Afrikaanse skrywers aangesien dit die mees problematiese element van Suid Afrikaanse samelewing was. Die einde van apartheid het egter nie die einde van alle probleme beteken nie. Een van die belangrike probleme is versoening. Hierdie tesis ondersoek die moontlikheid dat versoening die nuwe tema in Suid Afrikaanse letterkunde geword het en ofhierdie werke 'n bydrae kan lewer tot werklike versoening. Vir hierdie doel word drie werke behandel, naamlik Country of My Skull deur Antjie Krog, Smell of Apples deur Mark Behr en Disgrace deur J .M. Coetzee. Die inleiding poog om die sielkundige diskoers om versoening te verduidelik, veral rondom posttraumatiese stres, en die ooreenkomste wat mag voorkom. Die hoofdeel van die tesis bestaan uit 'n diepgaande bespreking van die drie werke, met die fokus op versoening in die werk, maar ook die rol wat die werke kan speel om die leser deur sy ofhaar skuld gevoelens te help.

La Dysplasie Ectodermique Hypohidrotique liée à l'X (DEX) est une maladie génétique liée à une mutation du gène EDA. Le phénotype exprimé par le modèle murin Tabby est l'équivalent de celui observé dans l'espèce humaine et présente des anomalies dentaires, cranio-faciales, vertébrales et des défauts de trabéculation osseuse. Dans ce contexte, une cartographie de ces anomalies chez le mutant Tabby était nécessaire et l'analyse de l’impact de la mutation Eda/Ta sur la croissance du squelette crânien et post-crânien a été étudiée. Un suivi longitudinal d'une cohorte d'individus murin Tabby (5 mâles hémizygotes EdaTa/Y, 6 femelles hétérozygotes EdaTa/+) et sauvages (n=12) a été réalisé à partir d’une succession d’acquisitions TDM pendant plus de 2 ans. L'observation des profils de croissance et de leurs paramètres a montré des anomalies de croissance du complexe crânio-facial, de la base du crâne (hypo-développement crânien) et un déficit de croissance relatif des os longs (fémur et humérus) chez les souris hémizygotes EdaTa/Y. Ces résultats mettent pour la première fois en évidence des anomalies de développement des os longs et confirment le rôle d’EDA-A dans la formation normale du squelette. Ces données constituent un pré-requis essentiel pour tester l’efficacité de tentatives de réversion phénotypique à partir de protéines recombinantes. / X-linked Hypohidrotic Ectodermal Dysplasia (XLHED) is a genetic disorder due to a mutation of the EDA gene. The phenotype expressed by Tabby mice, murine model of XLHED, is equivalent to that observed in humans including dental anomalies, craniofacial and vertebral trabecular bone defects. In this context, a mapping of these anomalies in Tabby mice was necessary and the impact of the EdaTa mutation on cranial and post -cranial skeletal growth was studied. A 2 years (112 weeks) μCT follow-up of Tabby mice (5 hemizygous males EdaTa/Y, 6 heterozygous females EdaTa/+) and Wild Type group (n = 12) hasbeen performed. The observation of growth patterns and parameters showed a relative cranial hypodevelopment, abnormal growth of the craniofacial complex and a relative hypo-development of appendicular skeleton (femur and humerus) in Tabby mice. These results allowed for the first time to highlight appendicular developmental abnormalities, confirming the role of EDA-A in the normal formation of the skeleton. While enriching the phenotypic picture of this syndrome, in a therapeuticperspective, all of these data are an essential prerequisite to test the effectiveness of attempts to phenotypic reversion from recombinant proteins.

Estudou-se prospectivamente o comportamento das calcificações, da atrofia, das alterações da substância branca e alterações vasculares nas imagens de tomografia computadorizada de crânio de 162 crianças e adolescentes infectados pelo vírus da imunodeficiência humana (HIV) por transmissão vertical e que estavam ou estiveram em acompanhamento clínico no Ambulatório de Infectologia Pediátrica do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, entre 1992 e 2002. Analisaram-se as possíveis correlações entre estas alterações e seu aspecto evolutivo. Para tal finalidade, foram avaliadas 606 tomografias computadorizadas de crânio (média de 3,74 exames por paciente), as quais constituíram o grupo de estudo. Após a caracterização quanto à presença ou não das alterações supracitadas, e suas possíveis inter-relações, realizou-se a análise estatística dos resultados obtidos através do teste exato de Fisher com nível de significância de 5%. Posteriormente, os mesmo aspectos foram avaliados em função do seu comportamento evolutivo em um subgrupo de 61 pacientes (média, 4,18 exames por paciente, totalizando 321 exames tomográficos). Estes pacientes tinham, pelo menos, quatro estudos tomográficos seriados (com intervalo mínimo de noventa dias entre os exames subseqüentes e pelo menos dois anos de intervalo total entre o primeiro e o último exame). As alterações tomográficas foram abordadas individual e qualitativamente segundo o critério de presença e intensidade. Inicialmente, o conjunto dos resultados foi tratado de forma individual (para cada paciente) e, depois, em relação à totalidade do grupo em questão. As calcificações foram encontradas em 46,30% dos pacientes; a atrofia, em 37,65%; as alterações da substância branca, em 25,93%; as anomalias vasculares, em 25,19%. Constatou-se uma correlação significativa entre as alterações de substância branca e a atrofia, bem como entre as calcificações e as alterações vasculares. A análise evolutiva destas características demonstrou haver um acréscimo significativo das alterações entre o momento inicial e o quarto momento no conjunto das alterações, sobretudo para as calcificações e para as alterações vasculares. Concluiu-se que as calcificações e a atrofia foram as alterações mais freqüentes nesta série de crianças e adolescentes com HIV adquirido por transmissão vertical. A atrofia e as alterações da substância branca apresentaram uma inter-relação importante na amostra descritiva, assim como as alterações vasculares e as calcificações mostraram uma associação evolutiva significativa em relação à sua progressão / We prospectively studied the behavior of calcifications, atrophy, white matter and vascular abnormalities on the images of computed tomography (CT) of 162 children and adolescents infected with the human immunodeficiency virus (HIV) acquired by vertical transmission, who are or were clinically followed in the Ambulatory of Pediatric Infectology of the Children Institute at the Clinics Hospital of University of São Paulo Medical School, from 1992 to 2002. We analyzed the possible correlation between these abnormalities, as well as, their evolutive aspects. For this purpose, we evaluated 606 CT scans (mean 3.74 exams per patient), which composed the group of study. After the characterization according to the presence or not of the anomalies mentioned above, and their possible inter-relations, we performed a statistical analysis of the obtained results with the Fisher test with a level of significance below 5%. Later, these aspects were evaluated regarding its evolutive behavior in a subgroup of 61 patients (mean, 4.18 exams per patient, summing 321 exams). These patients had, at least, four serial cranial CT (with minimum interval of ninety days between the subsequent exams and, at least, two years of total interval between the first and the fourth exam). The cranial CT abnormalities presented were assessed individually as absent or present. Initially, the set results were assessed individually (for each patient) and, later in relation to the totality of the group. Calcifications were found in 46.30% of all patients, atrophy in 37.65%, white matter abnormalities in 25.93% and vascular anomalies in 25.19%. We found a significant correlation between white matter abnormalities and atrophy, as well as, between calcifications and vascular anomalies. Evolutive analysis of these characteristics demonstrated a significant increase of the abnormalities between the first and the fourth moment, with emphasis to the calcifications and vascular anomalies. We concluded that, calcifications and atrophy were the most frequent abnormalities in this series of children and adolescents with HIV acquired by vertical transmission. Atrophy and white matter abnormalities presented a significant correlation in the descriptive sample, as well as, vascular anomalies and calcifications that also demonstrated a significant evolutive association regarding its progression

INTRODUÇÃO. Durante a última década, os avanços tecnológicos, o maior domínio da anatomia e das técnicas operatórias e de reconstrução da base do crânio por via endonasal propiciaram a expansão da cirurgia endoscópica para além dos limites da sela túrcica. O acesso transpterigóideo é uma etapa comum ao acesso as fossas cranianas média e posterior, e o conhecimento da anatomia endoscópica da artéria carótida interna (ACI) é um ponto fundamental e comum a estes acessos. OBJETIVO. Descrever a anatomia endoscópica relacionada ao acesso transpterigóideo e da ACI utilizando um modelo anatômico em cabeças cadavéricas frescas procurando definir os parâmetros seguintes: reparos anatômicos do acesso endoscópico a região supra e infrapetrosa, os limites para exposição endoscópica da ACI, os reparos anatômicos para localização dos seus segmentos lacerum, petroso e parafaríngeo. MÉTODOS. Foi realizado estudo anatômico em 20 espécimes (10 cabeças) de cadáveres frescos. As cabeças foram previamente preparadas com a injeção intravascular de silicone corado para enaltecer as estruturas vasculares (ACI, artéria maxilar e seus ramos e seio cavernoso). Em todos os casos foi realizado o acesso transpterigóideo às regiões supra e infrapetrosa, assim como a fossa infratemporal, e a dissecção endoscópica da ACI. RESULTADOS. A injeção de silicone corado no sistema arterial e venoso proporcionou modelo anatômico adequado para dissecção e documentação do acesso transpterigóideo assim como dos diferentes segmentos da ACI. A dissecção por etapas proporcionou exposição adequada da ACI do seu segmento cavernoso ao parafaríngeo distal. O acesso transpterigóideo forneceu exposição adequada do segmento lacerum da ACI e região suprapetrosa e seus principais reparos anatômicos foram o nervo vidiano, nervos maxilar e mandibular (V2, V3) e gânglio de Gasser. A exposição caudal da ACI (segmentos petroso e parafaríngeo) e região infrapetrosa requer maxilectomia medial para exposição e remoção de todo o processo pterigóideo, seguida pela ressecção da tuba auditiva e do tecido fibrocartilaginoso do forame lacerum. Os principais reparos anatômicos desta etapa foram a tuba auditiva e V3. CONCLUSÃO. Durante o acesso endoscópico à região suprapetrosa, o nervo vidiano, os ramos maxilar e mandibular do nervo trigêmeo (V2 e V3) e o gânglio de Gasser são reparos anatômicos para localização da artéria carótida interna e fossa craniana média. Durante o acesso endoscópico à região infrapetrosa, o tecido fibrocartilaginoso do forame lacerum, a tuba auditiva e o nervo mandibular (V3) são reparos anatômicos para identificação da artéria carótida interna. O acesso endoscópico endonasal por etapas permite acesso à artéria carótida interna extracraniana desde o segmento cavernoso até seu segmento parafaríngeo inferiormente ao nível do assoalho da cavidade nasal. O reparo anatômico para localização do segmento lacerum e porção horizontal do segmento petroso da ACI é o nervo vidiano; para as porções petrosa horizontal junto ao joelho posterior e canal carotídeo os reparos anatômicos são o nervo mandibular (V3), forame oval, tecido fibrocartilaginoso do forame lacerum e a tuba auditiva; para o segmento parafaríngeo os reparos anatômicos são o tronco posterior do nervo mandibular (V3) e a tuba auditiva / INTRODUCTION. During the last decade, the technological advances, the mastery of the anatomy and operative techniques and skull base reconstruction using endonasal approaches have propelled endoscopic surgery for beyond the limits of sella turcica. The transpterygoid approach is a common step of the endoscopic approach to the middle and posterior cranial fossa and knowledge of the endoscopic anatomy of the internal carotid artery (ICA) is a common and paramount point to these approaches. OBJECTIVE. Describe the endoscopic anatomy related to the transpterygoid approach and ICA using an anatomical model with fresh human cadaveric heads to define: anatomical landmarks related to the endoscopic supra and infrapetrous areas approach, limits for endoscopic exposure of the ICA, anatomical endoscopic landmarks to lacerum, petrous and parapharyngeal ICA segments. METHODS. An anatomical study was performed using 20 specimens (10 heads) of fresh cadaveric heads. The heads were previously prepared with the injection of colored silicone to enhance the vascular structures (ICA, maxillary artery and its branches and cavernous sinus). In all cases we performed the transpterygoid approach to the supra and infrapetrous areas, as well as the infratemporal fossa, and the endoscopic dissection of the ICA. RESULTS. The injection of colored silicone in the arterial and venous system provided an adequate anatomical model for dissection and documentation of the transpterygoid approach as well as the different segments of the ICA. A stepwise dissection provided adequate exposure of the ICA from its cavernous to the distal parapharyngeal segment. The transpterygoid approach provided adequate exposure of the lacerum segment of the ICA and suprapetrous area and the landmarks were the vidian nerve, maxillary and mandibular nerves (V2, V3) and the Gasserian ganglion. Exposure of the caudal ICA (petrous and parapharyngeal) and the infrapetrous area required a medial maxillectomy for exposure and resection of the entire pterygoid process, followed by the Eustachian tube and the fibrocartilaginous tissue of the foramen lacerum. The main anatomical landmarks to this step were V3 and the Eustachian tube. CONCLUSION. During the endoscopic approach to the suprapetrous area, the vidian nerve, the maxillary and mandibular divisions of the trigeminal nerve (V2, V3) and the Gasserian ganglion are the anatomical landmarks to the internal carotid artery and middle cranial fossa. During the endoscopic approach to the infrapetrous area, the fibrocartilaginous tissue of the foramen lacerum, the Eustachian tube and V3 are the landmarks to the internal carotid artery. A stepwise endoscopic endonasal approach provided access to the extracranial internal carotid artery from its cavernous to the parapharyngeal segment down to the level of the nasal fossa floor. The anatomical landmark to the lacerum and horizontal petrous segments of the internal carotid artery is the vidian nerve; to the horizontal petrous segment before the posterior bend and carotid canal, the anatomical landmarks are the mandibular nerve (V3), foramen ovale, fibrocartilaginous tissue of the foramen lacerum and the Eustachian tube; to the parapharyngeal segment, the anatomical landmarks are the posterior trunk of the mandibular nerve (V3) and the Eustachian tube

Le rat Dumbo présente un aspect malformatif évoquant certains syndromes crânio-faciaux humains. La compréhension du phénotype Dumbo pourrait expliquer les événements cellulaires et moléculaires à l’origine de ces syndromes. Le données recueillies chez le rat Dumbo et comparées à celles du rat Wistar sont susceptibles de constituer de précieuses informations éventuellement transposables à l’espèce humaine.<p><p>La première étape de cette étude a consisté en des analyses morphologiques et morphométriques afin de vérifier les perturbations morphologiques communes entre les rats Dumbo et les syndromes malformatifs humains :la brièveté des os zygomatique, maxillaire, mandibulaire et la position basse des oreilles. Ces analyses ont été réalisées sur les squelettes embryonnaires âgés de 16 jours à 21 jours de rats Dumbo et Wistar à l’aide d’une coloration in toto au Bleu Alcian – Alizarine. La deuxième étape de cette étude consistait en une analyse cytogénétique. Pour ce faire, nous avons établi le caryotype du rat Dumbo et nous l’avons comparé avec le caryotype du rat Wistar. L’étape suivante fut de procéder à l’analyse histologique des malformations crânio-faciales chez le rat Dumbo en observant la chondrogenèse pendant la morphogenèse crânio-faciale. Enfin, l’examen de l’expression des gènes Msx1 sens (S) ,Msx1 antisens (AS) et Dlx1 dans l’extrémité céphalique des rats Dumbo a été réalisé par les techniques de RT–PCR (Reverse Transcription Polymerase Chain Reaction method). Des estimations semi-quantitatives ont été validées en utilisant des dilutions ADNc du rat Wistar. Des densitométries de la densité d’amplicons fluorescence ont été réalisées à l’aide du logiciel VilberLourmat Bio1D software.<p><p>Les résultats obtenus ont permis de caractériser de manière précise les malformations crânio-faciales chez le rat Dumbo.<p> <p>1-\ / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Alors que les individus dans la société contemporaine sont unis non par une propriété mais par un devoir et par une dette, par un manque, par une limite prenant la forme d’une charge pour celui qui en est affecté, la postmodernité rend à la mort et à l’absence toute sa densité. À travers la répétition, entre jubilation et désespérance, les artistes figurent la temporalité de l’épreuve par une écriture qui travaille l’instant. Ils racontent ces évènements infimes qui sont les plus fragiles, les plus précaires, ayant pourtant une forte efficacité. Il s’agira ici d’étudier les nouvelles postures devant l’événement historique, quand l’artiste se tient au plus singulier. / While individuals in contemporary society are united not by property but by a duty and a debt, a lack, by a limit taking the shape of a responsibility for the one who is affected, postmodernism returns to death and absence all its density. Through repetition, between jubilation and despair, the artist represents the temporality of the event. His writing works the moment. He tells these tiny events that are the most fragile, the most precarious, having nevertheless a strong efficiency. This thesis will try to study the new postures in front of the historic event, when the artist stands in the most singular.