Une craniosynostose est une pathologie caractérisée par la fusion prématurée d'une ou plusieurs sutures crâniennes. C'est un défaut de naissance assez fréquent (1/2500 naissances) qui résulte en une forme anormale du crâne et qui peut être accompagné d'une déficience mentale dans certains cas. Des mutations du gène TWIST1, qui encode un facteur de transcription basique Helix-Loop-Helix (bHLH) de classe II, causent le syndrome de Saethre-Chotzen qui est associé à une synostose de la suture coronale (El Ghouzzi et al. 1997; Howard et al. 1997). Un nouveau gène a récemment été découvert comme étant une nouvelle cause du syndrome Saethre-Chotzen ainsi que de synostose coronale asyndromique (Sharma, Fenwick, Brockop, et al., 2013): il s'agit du gène TCF12, qui encode un facteur de transcription bHLH de classe I.Nous démontrons qu'une reduction de l'expression génique de Twist1 et Tcf12 chez la souris cause une synostose coronale, et nous suggérons que les protéines bHLH Twist1 et Tcf12 forment des hétérodimères dont le dosage est critique pour le développement de la suture coronale.Nous nous concentrons aussi sur Twist1 et prouvons que son expression est requise dans les tissus dérivant du mésoderme ainsi que ceux dérivant des crêtes neurales pour le développement normal de la suture coronale.De plus, nous notons que dans la suture coronale, Twist1 exclut Notch2 afin de garder la suture ouverte, et beta-catenin joue un rôle dans la maintenance de l'ouverture de la suture en ciblant Jagged1 lors du développement de la suture coronale chez la souris.Enfin, nous mentionnons de nouveaux gènes qui pourraient avoir un impact sur le développement normal de la suture coronale: Aggrecan, Goosecoid, Gucy1a3 et Gucy1b3. / Craniosynostosis, the premature fusion of one or more cranial sutures, is a common birth defect (1/2500 live births) that results in abnormalities in skull shape and sometimes in neurological deficiencies (Wilkie, 1997; Wilkie and Morriss-Kay, 2001). Mutations in TWIST1, which encodes a class II basic helix-loop-helix (bHLH) transcription factor, cause Saethre-Chotzen syndrome, associated with coronal synostosis (El Ghouzzi et al. 1997; Howard et al. 1997). We recently discovered a new craniosynostosis gene, TCF12, which encodes a class I bHLH transcription factor. Tcf12 causes.Saethre-Chotzen syndrome and asyndromic coronal synostosis. (Sharma, Fenwick, Brockop, et al., 2013). We show that a reduction in the dosage of Twist1 and Tcf12 in mouse causes coronal synostosis, and we suggest that the Twist1 and Tcf12 form heterodimers whose dosage is critical for coronal suture development. We also demonstrate that Twist1 is required in both neural-crest and mesoderm-derived tissues for the normal coronal suture development. Moreover, we show that in the coronal suture, Twist1 excludes Notch2 thus maintaining suture patency. and we show that beta-catenin also plays a role in the maintenance of suture patency by regulating Jagged1. Finally, we identified Aggrecan, Goosecoid, Gucy1a3 and Gucy1b3 as Twist1-regulated genes that could have an impact on the normal development of the coronal suture.

La modélisation des structures magnétiques qUI définissent depuis le plateau continental sud-armoricain jusqu'à l'intérieur du Bassin Aquitain un "marqueur" linéaire d'une longueur d'environ six cents kilomètres, confirme l'existence d'un accid ent crustal majeur dont les diverses signatures géophysiques (magnétisme, gravimétrie, séismicité) sont compatibles avec une interprétation de suture interplaque. Une tentative de reconstitution spatiale des principales limites interplaques et intraplaques du domaine ibéro-armoricain a conduit à envisager l'existence de deux sutures dont la plus interne délimiterait une éventuelle microplaque "ébroaquitaine". La répartition des zones de magmatisme et de subsidence de la période cambro-ordovicienne ainsi que l'enregristrement à la même époque de mouvements "calédoniens" possiblement compressifs pou;raient s'expliquer en terme d'un processus de convergence de plaques initiés dès le Cambrien supérieur.

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.

L’impact de la correction chirurgicale de la rupture du ligament croisé crânial (LCC) sur la cinématique 3D du grasset a peu été étudiée chez le chien. Plusieurs techniques tentent de restaurer la fonction normale du grasset suite à la rupture du LCC, mais les succès demeurent mitigés comme en témoignent le retour à une fonction suboptimale et la progression de l’arthrose. L’incapacité de ces techniques à restaurer la cinématique 3D pourrait être un élément clé expliquant ces succès suboptimaux. L’objectif de ce projet de recherche était d’évaluer l’impact d’une des techniques fréquemment utilisées, la stabilisation par suture latérale (SSL), sur la cinématique 3D du grasset. Dix membres pelviens provenant de grands chiens (25-40kg) ont été utilisés avec un montage préalablement validé simulant le trot. Trois situations ont été comparées : i) grasset sain, ii) grasset instable par transsection du LCC, et iii) grasset stabilisé par SSL. Pour chaque situation, la cinématique 3D était enregistrée durant 5 cycles dans le montage. Les courbes ont été analysées en utilisant un test statistique Wilcoxon signed rank test. La SSL a restauré la cinématique du grasset intact sain sur l’entièreté de la phase d’appui pour la translation crânio-caudale, médio-latérale, la flexion et l’abduction. Elle a restauré la translation proximo-distale sur 90% de la phase d’appui. La rotation interne a été limitée par la SSL, mais n’a pas été restaurée. Ces résultats montrent que cette technique chirurgicale reproduit une cinématique 3D globalement semblable à celle du grasset sain. La progression de l’arthrose rapportée suite à la stabilisation du grasset par SSL pourrait donc ne pas résulter d’une cinématique 3D anormale. / The impact of surgical correction of cranial cruciate ligament rupture (CCLR) on 3D kinematics has not been thoroughly evaluated in dogs. The success of current techniques remains limited, as illustrated by suboptimal weightbearing and progression of osteoarthritis. The inability to restore the stifle’s 3D kinematics might be a key element in understanding these suboptimal outcomes. The objective of this study was to evaluate the impact of lateral suture stabilization (LSS) on the 3D kinematics of the canine stifle joint. We hypothesized that LSS would not restore 3D kinematics in our model. Ten pelvic limbs collected from euthanized large dogs (25-40 kg) were tested with a previously validated apparatus that simulates trot. Three experimental conditions were compared: (a) intact stifle; (b) unstable stifle following cranial cruciate ligament transection (CCLt) and (c) CCLt stabilized by LSS. Three-dimensional kinematics were collected through 5 gait cycles and curves were analyzed using a Wilcoxon signed-rank test. LSS restored baseline kinematics for the entire stance phase for cranial and lateromedial translation, sagittal flexion, and abduction. It restored distraction over 90% of the stance phase. Internal rotation was limited, but not restored. This in vitro study had limitations, as it used a simplified model of stifle motion and weight-bearing. The results of this study demonstrate that LSS can restore physiologic 3D kinematics largely comparable to those of healthy stifles. Suboptimal outcome in patients following CCLR stabilization by LSS may therefore result from causes other than immediate postoperative abnormal 3D kinematics.

published_or_final_version / Earth Sciences / Doctoral / Doctor of Philosophy

No parto normal, o trauma provocado por episiotomia ou roturas, é freqüente e a anestesia local é bastante utilizada no reparo das lesões da região vulvoperineal. Na literatura especializada, os estudos sobre as soluções anestésicas mais adequadas são escassos para essa anestesia. No entanto existem recomendações para a adoção de anestésicos com vasoconstritor pela permanência mais prolongada da solução anestésica no local, garantindo maior ação e redução da concentração plasmática da droga, mas na prática seu uso é restrito. O objetivo do estudo foi comparar a quantidade de anestésico necessária para inibir a dor durante a sutura do trauma perineal, em mulheres com episiotomia ou laceração espontânea de primeiro ou segundo graus, conforme o uso ou não de vasoconstritor na solução anestésica. Trata-se de uma pesquisa aleatorizada e controlada com mascaramento duplo, realizada no Centro de Parto Normal do Amparo Maternal na cidade de São Paulo. Foram incluídas 96 parturientes, alocadas em três blocos - laceração de primeiro grau, laceração de segundo grau e episiotomia. Em cada bloco, constituído por 32 mulheres, 16 receberam solução anestésica com vasoconstritor e 16 sem vasoconstritor. Os resultados mostraram que, na laceração de primeiro grau, a média de anestésico com vasoconstritor apresentou diferença estatisticamente significante (p=0,002), com 1,0 ml (I.C. -1,6; -0,4) menos que a média do anestésico sem vasoconstritor; em 95% dos casos, foram usados de 1 a 2 ml de solução com vasoconstritor, e em 87,5% dos casos para o anestésico sem vasoconstritor, o volume usado variou de 2 a 4 ml. Para a laceração de segundo grau, a média do anestésico com vasoconstritor foi 3,7 ml (I.C. -5,8; -1,6) menos que a média do anestésico sem vasoconstritor, sendo estatisticamente significante (p=0,001); em 87,5% dos casos, a quantidade máxima de anestésico com vasoconstritor administrada foi 6 ml, e 81,3% das mulheres que receberam anestésico sem vasoconstritor, a dose administrada foi de 7 ml ou mais. Considerando a extensão da laceração, adotou-se o tamanho da episiotomia praticada nas mulheres do estudo, como parâmetro para classificar a extensão da laceração. Foram agrupadas como pequenas as lacerações de menor extensão, como médias aquelas com tamanho semelhante à episiotomia e como grandes aquelas cuja extensão superou o tamanho da episiotomia. Para a episiotomia, a média de anestésico com vasoconstritor foi 0,3 ml (I.C. -2,1; 1,5) a menos que a média do anestésico sem vasoconstritor, considerada sem significância estatística (p=0,724). Os resultados permitiram confirmar a hipótese de que uso de anestésico com vasoconstritor na anestesia local para a sutura de lacerações perineais no parto normal aumenta a eficácia da anestesia local. Embora o volume de anestésico utilizado na sutura de laceração de primeiro e segundo graus seja significativamente reduzido pela associação com vasoconstritor, a relevância clínica desse resultado deve ser considerada. / The perineal trauma, caused by episiotomy or ruptures, is quite frequent during the spontaneous delivery, being the local anesthesia widely utilized when repairing lesions in the vulvo-perineal region. Throughout the specialized literature, scarce are the studies on the most suitable anesthetic solutions for this kind of anesthesia. Even though there are recommendations for the adoption of the anesthetic with vasoconstrictor, because of the prolonged permanence of the anesthetic solution in the region, thus ensuring a bigger time of action, and because of the reduction in the plasmatic concentration of the drug, its utilization in practice is restricted. The goal of the study was to compare the necessary quantity of anesthetic to inhibit pain during the suture of the perineal trauma in women with an episiotomy or with first or second degree spontaneous lacerations, according to the use or not of vasoconstrictor in the anesthetic solution. This is a randomized and controlled research, with double blind trial, performed in the Birth Centre at Amparo Maternal, in the city of Sao Paulo. There were 96 parturients included in the study and then divided into three blocks: first degree laceration, second degree laceration and episiotomy. In each block, constituted of 32 women, 16 women were administered the anesthetic solution with vasoconstrictor and 16 with no vasoconstrictor. Results show that in the first degree laceration block the average of anesthetic with vasoconstrictor presented a statistically significant difference (p=0,002), with 1,0 ml (C.I. -1,6; -0,4) less than the average of the anesthetic without vasoconstrictor; in 95% of the cases, 1 to 2 ml of the solution with vasoconstrictor was utilized, while in 87,5% of the cases, the anesthetic without vasoconstrictor varied from 2 to 4 ml. In the second degree laceration block, the average of anesthetic solution with vasoconstrictor was 3,7 ml (C.I. -5,8; -1,6) less than the average of the anesthetic without vasoconstrictor, being statistically significant (p=0,001); in 87,5% of the cases, the maximum quantity of anesthetic with vasoconstrictor administered was 6 ml, while in 81,3% of the cases, women who were given the anesthetic without vasoconstrictor, received 7 ml or more. Considering the extent of the laceration, the size of the episiotomy practiced on the women of the study was adopted as a parameter to classify the extent of the laceration. The lacerations of a smaller extent were grouped as small-sized, the ones in which the size was similar to the size of the episiotomy were grouped as medium-sized, and as large-sized the ones that oversized the episiotomy. For the episiotomy, the average of anesthetic with vasoconstrictor was 0,3 ml (C.I. -2,1; 1,5) less than the average of the anesthetic without vasoconstrictor, with no statistic significance (p=0,724). Results allow us to confirm the hypothesis that the utilization of the anesthetic with vasoconstrictor in the local anesthesia during the suture of the perineal lacerations in the spontaneous delivery increases the effectiveness of the local anesthesia. Although the volume of anesthetic utilized in the suture of the first and second degree lacerations is significantly reduced by the association with vasoconstrictor, the clinical relevance of this result must be taken into further consideration.

O presente estudo avaliou por meio de teleradiografias em norma lateral as alterações do perfil facial frente à cirurgia Le Fort I com avanço e impactação da maxila utilizando fixação rígida e sutura V-Y, em 18 pacientes, com de classe III, leucoderma, com média de idade de 23 anos e 7 meses. As radiografias foram obtidas com os dentes em máxima intercuspidação, lábios em repouso, na fase précirúrgica imediata (M1) e 1 ano após a cirurgia (M2). Para responder o objetivo do estudo os valores das estruturas ósseas e tegumentares foram comparadas antes e depois da cirurgia por meio do teste t de Student pareados e foi aplicado o teste de correlações de Pearson entre as medidas ósseas e tegumentares de interesse. As relações entre as variações foram avaliadas com uso de regressão linear. Concluí-se após a análise dos resultados que não houve alteração estatisticamente significativa no sentido vertical, para os valores dentoesqueléticos e tegumentares estudados, exceto para o valor do ângulo do plano mandibular. Entretanto, houve correlação direta das alterações entre eles, exceto para os valores do plano mandibular com a espinha nasal anterior e posterior e do ângulo nasolabial com o incisivo superior. No sentido horizontal, houve alteração estatisticamente significativa entre os valores dentoesqueléticos e tegumentares relacionadas à maxila e não houve entre os valores relacionados à mandíbula. A previsibilidade numérica das alterações tegumentares decorrentes do avanço e impactação da maxila está sujeita a alterações individuais. / The purpose of this study was to determine retrospectively, by means of lateral cephalograms, the postsurgical changes in the facial soft tissue profile in class III patients (n=18) submitted to Le Fort I osteotomy, for maxillary impaction and advancement within the ?V-Y? suture. Caucasian individuals constituted the sample, and average age was 23 years old and 7 months. The cephalograms were obtained in maximum intercuspation with the lips at rest. The patients were evaluated in two times, the first period was in the immediate pre-surgical (M1) and, one year after the surgical procedure (M2). In order to answer the purpose of this study, skeletal and facial soft tissue measurements were compared before and after the surgery, by means of paired Student t tests, and the Pearson?s correlation coefficient for skeletal and facial soft tissue relevant measurements, using the variations (after and before) between the values. The relationship between the significant variations was evaluated by means of linear regression analysis. The findings indicated that there was not statically significant difference in the vertical plane, for the studied dentalskeletal and facial soft tissue values, exception for the value of the mandibular plane angle. However, there was direct correlation between then, except for the values of the mandibular plane angle-ANS; mandibular plane angle-PNS, and nasolabial angleupper incisors. In the horizontal plane, there was statically significant difference between the dental-skeletal values and facial soft tissue, related to the maxilla and there was not in the values related to the mandible. The numerical prediction of the facial soft tissue changes occasioned by the impaction and maxillary advancement is subject to individual responses.

Este estudo analisou experimentalmente as propriedades de tração no local da neurorrafia em nervos ciáticos seccionados dos porcos. Trata-se de um estudo comparativo entre quatro técnicas de suturas. Foram utilizados 25 nervos ciáticos distribuídos em cinco grupos com cinco nervos cada, de acordo com o tipo de técnica de sutura. Grupo 1: grupo controle composto por nervos, sem lesão; Grupo 2: com nervos lesionados submetidos à sutura epineural; Grupo 3: com nervos lesionados submetidos à sutura epineural e reforço com duas suturas extra lesionais; Grupo 4: composto por nervos lesionados submetidos à sutura epineural e reforço com Ultrapro® (Tela Cirúrgica Sintética não Absorvível) e Grupo 5: com nervos lesionados submetidos à sutura epineural reforçada com duas veias com suturas extra lesionais. A força máxima (N), deformação de ruptura (mm) e energia na força máxima (N.mm) foram medidos em ensaios mecânicos de tração em máquina universal de teste. Os resultados mostraram que não houve diferença estatística entre os Grupos 3 e 4 e Grupos 2 e 5. A sutura do Grupo 3 apresentou maior resistência a tração, maior capacidade de absorver energia. Conclui-se que a técnica de sutura utilizada no Grupo 3 alcançou melhor desempenho. / This study aimed to analyze experimentally, in the laboratory, the tensile properties at the neurorrhaphy site on sectioned sciatic nerves of pigs. A comparative study of four suture techniques. Twenty-five sciatic nerves were used. They were randomly distributed into 5 groups with 5 nerves each, according to the type of suturing technique. Group 1, Control group, consisting of nerves, without injury. Group 2, with injured nerves submitted to epineural suture. Group 3, with injured nerves submitted to epineural suture and reinforcement using 2 extralesional sutures. Group 4, composed of injured nerves submitted to epineural suture and reinforcement with Ultrapro® (Synthetic Non-Absorbable Surgical Patch). And Group 5, with injured nerves submitted to reinforced epineural suture with two veins using extralesional sutures. Maximum force (N), rupture deformation (mm), and energy at maximum force (N.mm) were measured in mechanical trials using a universal test machine. The results showed that there was no statistical difference between Groups 3 and 4 and between Groups 2 and 5. The Group 3 suture presented greater tensile strength, greater capacity to absorb energy. It was concluded that the suture technique used in group 3 achieved better performance.

Este estudo analisou experimentalmente as propriedades de tração no local da neurorrafia em nervos ciáticos seccionados dos porcos. Trata-se de um estudo comparativo entre quatro técnicas de suturas. Foram utilizados 25 nervos ciáticos distribuídos em cinco grupos com cinco nervos cada, de acordo com o tipo de técnica de sutura. Grupo 1: grupo controle composto por nervos, sem lesão; Grupo 2: com nervos lesionados submetidos à sutura epineural; Grupo 3: com nervos lesionados submetidos à sutura epineural e reforço com duas suturas extra lesionais; Grupo 4: composto por nervos lesionados submetidos à sutura epineural e reforço com Ultrapro® (Tela Cirúrgica Sintética não Absorvível) e Grupo 5: com nervos lesionados submetidos à sutura epineural reforçada com duas veias com suturas extra lesionais. A força máxima (N), deformação de ruptura (mm) e energia na força máxima (N.mm) foram medidos em ensaios mecânicos de tração em máquina universal de teste. Os resultados mostraram que não houve diferença estatística entre os Grupos 3 e 4 e Grupos 2 e 5. A sutura do Grupo 3 apresentou maior resistência a tração, maior capacidade de absorver energia. Conclui-se que a técnica de sutura utilizada no Grupo 3 alcançou melhor desempenho. / This study aimed to analyze experimentally, in the laboratory, the tensile properties at the neurorrhaphy site on sectioned sciatic nerves of pigs. A comparative study of four suture techniques. Twenty-five sciatic nerves were used. They were randomly distributed into 5 groups with 5 nerves each, according to the type of suturing technique. Group 1, Control group, consisting of nerves, without injury. Group 2, with injured nerves submitted to epineural suture. Group 3, with injured nerves submitted to epineural suture and reinforcement using 2 extralesional sutures. Group 4, composed of injured nerves submitted to epineural suture and reinforcement with Ultrapro® (Synthetic Non-Absorbable Surgical Patch). And Group 5, with injured nerves submitted to reinforced epineural suture with two veins using extralesional sutures. Maximum force (N), rupture deformation (mm), and energy at maximum force (N.mm) were measured in mechanical trials using a universal test machine. The results showed that there was no statistical difference between Groups 3 and 4 and between Groups 2 and 5. The Group 3 suture presented greater tensile strength, greater capacity to absorb energy. It was concluded that the suture technique used in group 3 achieved better performance.

Zielstellung: Gegenwärtig wird nach Ruptur des vorderen Kreuzbandes (VKB) beim Hund häufig eine laterale Fadenzügelungen (LFZ) vorgenommen. In der vorliegenden Arbeit wurden folgende Ziele verfolgt: (1) Bestimmung der kranio-kaudalen Kniegelenkstabilität nach LFZ und passiver Kniegelenksbewegung. (2) Bestimmung der Schlaufenspannung nach Knotung mit der Hand. (3) Einfluss von vier häufig verwendeten Verankerungsformen auf die LFZ und von drei Kniegelenkwinkeln zum Zeitpunkt der Knotung des Fadenzügels auf den Spannungsverlauf innerhalb des Fadens. Material und Methode: Die kranio-kaudale Kniegelenkstabilität (KKStab) wurde anhand von latero-medialen Röntgenaufnahmen an 10 rechten Kniegelenken orthopädisch gesunder Hunde (>20 kg KM) ex-vivo bestimmt. Die Messung der KKStab erfolgte am intakten Gelenk, nach Durchtrennung des VKB und nach lateraler Ethibondfadenzügelung. Anschließend wurden die Gelenke 350 mal passiv gebeugt und gestreckt und die KKStab nach 50, 100, 250 und 350 Bewegungszyklen erneut bestimmt. Des Weiteren wurde die Spannung in 7 Ethibondfadenschlaufen an einer Materialprüfmaschine bestimmt. Die Spannung in der Schlaufe wurde nach dem ersten (FMax) und nach dem letzten Knoten (FEnd) gemessen. Mit Hilfe eines speziell konstruierten Kraftaufnehmers wurde die Spannung in der lateralen Fadenzügelung über den passiven Bewegungsradius des Kniegelenks in weiteren 9 Kniegelenken in-vitro gemessen. Dabei wurde nach Durchtrennung des VKB jedes Kniegelenk mit 4 Formen der LFZ bei 3 unterschiedlichen Kniegelenkswinkeln zur Zeit der Fixierung der Fadenschlaufe stabilisiert. Ergebnisse: KKStab nach Stabilisierung des Gelenkes betrug im Mittel 3,7 mm und war im Mittel um 2,7 mm größer als bei intaktem Kreuzband. Bereits 250 passive Bewegungszyklen bewirkten eine signifikante Destabilisierung um weitere 1,5 mm. FMax beim Knüpfen von sieben Fadenschlaufen betrug im Mittel 133 N und fiel auf 6 N (FEnd) im Mittel nach dem fünften Knoten ab. Alle 4 untersuchten LFZ-Formen zeigten eine Zunahme der Fadenspannung bei Beugung des Kniegelenkes. Die LFZ, bei der die Zügelung um die laterale Fabella geführt und in 2 parallelen Bohrungen in der proximalen Tibia fixiert wurde, zeigte die geringsten Spannungsänderungen über einen kompletten Bewegungsradius des Kniegelenks. Die Fixation der LFZ in einen Gelenkwinkel von 70° ergab einen signifikanten Abfall der Fadenspannung in Extension des Gelenkes. Schlussfolgerungen: Eine LFZ aus Ethibondfäden mit fünffacher Knotung erlaubt es nicht, die physiologische Gelenkstabilität nach Durchtrennung des VKB herzustellen. Bereits wenige passive Bewegungszyklen bewirken eine signifikante weitere Destabilisierung. Die in diesem Teil der Studie angewendete Knotentechnik erlaubte es nicht, die manuell in der Fadenzügelung aufgebaute Spannung dauerhaft zu konservieren und sollte deshalb keine Klinische Verwendung haben. Keine der getesteten LFZ-Formen zeigte einen gleichmäßigen Spannungsverlauf bei Bewegung des Kniegelenks. Aus diesem Grund sollten die aktuellen Empfehlungen hinsichtlich „isometrischer“ Verankerungspunkte kritisch betrachtet werden. Die Fixierung der LFZ bei gebeugtem Kniegelenk ist nicht zu empfehlen, da es in Extension zur Destabilisierung kommt.