Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 6 uppsatser.

Thesis--Aarhus. / Summary in Danish.

Thesis--Aarhus. / Summary in Danish.

INTRODUCTION: Osteochondritis dissecans (OCD) of the capitellum is a focal condition affecting the articular cartilage and subchondral bone, typically in adolescent athletes. Limited data exists regarding the indications and expected outcomes of the various treatment methods of capitellar OCD, and the optimal treatment strategy remains controversial. Risks of progressive capitellar OCD include osteoarthritic changes and permanent elbow disability. STUDY AIMS: The objective of this literature review is to assess the data and the conclusions to be drawn from the existing literature on the differential indications for the various treatment options for capitellar OCD, using low-level meta-analysis and qualitative observations, to suggest a course of future study with the purpose of clarifying the differential treatment indications and improving the care of capitellar OCD patients. The most recent 10 years (2004-2014) of data are the focus, in order to evaluate the most modern indications, surgical techniques, surgical skills, and clinical outcomes. DISCUSSION OF PUBLISHED DATA: Ultrasound reportedly offers a high predictive value for screening baseball players for capitellar OCD, although sensitivity, specificity, and cost-effectiveness are unknown. Plain radiographs and magnetic resonance imaging (MRI) are useful diagnostic resources for making the decision to operate, but their sensitivities and specificities are imperfect. Evidence suggest that early stage OCD in physically immature patients may recover with non-operative management, while advanced stage OCD in older patients will likely achieve a better recovery with operative management. Risk factors for poor outcomes following surgical management of capitellar OCD may reportedly include patient age, physical maturity, athletic competition level, large lesion diameter and thickness, and lateral lesion location. The advantages of removal, debridement, and marrow stimulation techniques include the minimal invasiveness associated with arthroscopy. Successful fragment fixation can preserve normal articular properties, but may risk implant complications and secondary surgeries. Mosaicplasty is frequently suggested when patient or lesion characteristics seem to preclude other surgical methods, or when prior surgical treatment attempts fail, but disadvantages of mosaicplasty include the technical complexity of the procedure and the risk of donor site morbidity. CONCLUSIONS: The capitellar OCD literature has accumulated a wealth of level IV case series reporting generally satisfactory short-term results of the various surgical options. There is little need for more descriptive literature on this topic at this time. Modern treatment strategies are incomplete and poorly defined, based upon the suggestions of small case series offering disorganized, low-quality data. A study of the cost-effectiveness of ultrasound screening in high-risk athletes would be useful. A large, comparative case-control study or prospective cohort study of higher methodological quality and better standardization is needed to advance the knowledge on this topic, and classification and regression tree analysis could be applied meaningfully. With more organized data and analysis, it will become easier to take a systematic approach to treating capitellar OCD, settle clinical controversy and improve patient outcomes.

Kan, Wai Chi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (p. 111-116). / Abstract --- p.i / Acknowledgement --- p.iii / List of Publications --- p.vi / List of Figures --- p.xi / List of Tables --- p.xii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Terahertz Radiation --- p.1 / Chapter 1.2 --- Biomedical Applications of Terahertz Imaging --- p.3 / Chapter 1.3 --- THz Spectroscopy --- p.4 / Chapter 1.4 --- Osteoarthritis --- p.4 / Chapter 1.5 --- Aim and motivation --- p.5 / Chapter 1.6 --- Overview of thesis --- p.5 / Chapter 2 --- Theory --- p.7 / Chapter 2.1 --- Propagation of electromagnetic field through dielectric media --- p.7 / Chapter 2.2 --- Deconvolution --- p.10 / Chapter 2.3 --- Baseline offset --- p.12 / Chapter 2.4 --- Frequency-dependent Refractive Index and Absorption Coefficient --- p.15 / Chapter 2.4.1 --- Reflection Geometry --- p.15 / Chapter 2.4.2 --- Transmission Geometry --- p.17 / Chapter 2.5 --- Conversion of Optical Delay into Depth --- p.22 / Chapter 2.6 --- Finite Difference Time Domain Method --- p.23 / Chapter 2.7 --- Summary --- p.25 / Chapter 3 --- Terahertz Systems --- p.26 / Chapter 3.1 --- Terahertz Pulsed Generation --- p.26 / Chapter 3.2 --- Terahertz Pulsed Detection --- p.28 / Chapter 3.3 --- Terahertz Pulsed Imaging (TPI) System --- p.29 / Chapter 3.4 --- Reflection System --- p.29 / Chapter 3.4.1 --- Flatbed System --- p.29 / Chapter 3.4.2 --- Probe --- p.32 / Chapter 3.5 --- Transmission System --- p.36 / Chapter 3.5.1 --- Antenna --- p.39 / Chapter 3.6 --- Data Acquisition --- p.40 / Chapter 3.6.1 --- Flatbed System --- p.40 / Chapter 3.6.2 --- Probe --- p.42 / Chapter 3.7 --- Baseline Validation --- p.46 / Chapter 4 --- Osteoarthritis --- p.48 / Chapter 4.1 --- Introduction --- p.48 / Chapter 4.2 --- Cartilage Composition and Structure --- p.49 / Chapter 4.3 --- 〇A symptoms --- p.51 / Chapter 4.4 --- Other Imaging Techniques --- p.52 / Chapter 4.5 --- Sample Preparation and Histology --- p.54 / Chapter 5 --- THz Pulsed Imaging of OA --- p.58 / Chapter 5.1 --- Results --- p.58 / Chapter 5.1.1 --- Optical Delays --- p.59 / Chapter 5.1.2 --- Estimation of surface refractive index --- p.69 / Chapter 5.1.3 --- Conversion of Optical Delay into Cartilage Thickness --- p.72 / Chapter 5.1.4 --- Correlation with Histology --- p.74 / Chapter 5.1.5 --- Errors and Problems --- p.80 / Chapter 5.2 --- FDTD of cartilage layers --- p.85 / Chapter 5.3 --- Conclusion --- p.87 / Chapter 6 --- Sliced Cartilage Sample and Bone Measurement --- p.88 / Chapter 6.1 --- Sliced Cartilage Samples --- p.88 / Chapter 6.1.1 --- Multi-reflections of sliced cartilage samples --- p.89 / Chapter 6.1.2 --- The influence of pressure on cartilage thickness --- p.91 / Chapter 6.1.3 --- Estimation of surface refractive index of sliced cartilage samples --- p.93 / Chapter 6.1.4 --- Comparison between sliced cartilage and knee joint measurements --- p.95 / Chapter 6.2 --- Bone --- p.97 / Chapter 7 --- Transmission System Result --- p.99 / Chapter 7.1 --- Data Validation --- p.99 / Chapter 7.1.1 --- Water spectrum --- p.99 / Chapter 7.1.2 --- Quartz measurement --- p.100 / Chapter 7.2 --- Liquid cell --- p.100 / Chapter 7.3 --- Cartilage Transmission Result --- p.103 / Chapter 7.4 --- Difficulties and problems --- p.105 / Chapter 7.5 --- Conclusions --- p.106 / Chapter 8 --- Conclusions and future work --- p.107 / Chapter 8.1 --- Summary --- p.107 / Chapter 8.2 --- Discussion --- p.107 / Chapter 8.3 --- Suggestions for further study --- p.109 / Bibliography --- p.111

Cheuk, Yau Chuk. / Thesis submitted in: Dec 2008. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 132-144). / Abstracts in English and Chinese. / ABSTRACT --- p.i / 論文摘要 --- p.iii / PUBLICATIONS --- p.v / ACKNOWLEDGEMENT --- p.vi / LIST OF ABBREBIVIATIONS --- p.vii / INDEX FOR FIGURES --- p.x / INDEX FOR TABLES --- p.xiv / TABLE OF CONTENTS --- p.xv / Chapter CHAPTER ONE - --- INTRODUCTION / Chapter 1.1 --- "Joint function, structure and biochemistry" / Chapter 1.1.1 --- Function of joint --- p.1 / Chapter 1.1.2 --- Types of cartilage --- p.1 / Chapter 1.1.3 --- Composition and structure of articular cartilage --- p.2 / Chapter 1.1.4 --- The subchondral bone --- p.3 / Chapter 1.1.5 --- Maturation of articular cartilage and subchondral bone --- p.3 / Chapter 1.2 --- Osteochondral defect / Chapter 1.2.1 --- Clinical problem --- p.6 / Chapter 1.2.2 --- Spontaneous repair --- p.7 / Chapter 1.2.3 --- Current treatment strategies --- p.7 / Chapter 1.2.4 --- Limitations of current treatment strategies --- p.8 / Chapter 1.2.5 --- Treatments under development --- p.11 / Chapter 1.2.6 --- Potential and limitations in cell therapies --- p.14 / Chapter 1.3 --- The 3-D scaffold-free cartilage / Chapter 1.3.1 --- Fabrication of scaffold-free cartilage --- p.16 / Chapter 1.3.2 --- Scaffold-free cartilage for chondral / osteochondral defect repair --- p.18 / Chapter 1.3.3 --- Scaffold-free bioengineered chondrocyte pellet from our group --- p.20 / Chapter 1.3.4 --- BCP as a possible treatment for OCD --- p.21 / Chapter 1.4 --- The objectives of the study --- p.22 / Chapter 1.5 --- The study plan / Chapter 1.5.1 --- Design of the study --- p.23 / Chapter 1.5.2 --- Choice of animal model --- p.23 / Chapter 1.5.3 --- Selection of evaluation time points --- p.24 / Chapter 1.5.4 --- Choice and modification of histological scoring system --- p.24 / Chapter CHAPTER TWO - --- METHODOLOGY / Chapter 2.1 --- Preparation of reagents and materials for tissue culture and histology --- p.26 / Chapter 2.2 --- Creation of osteochondral defect model --- p.28 / Chapter 2.3 --- Synthesis of scaffold-free cartilage using 3-D chondrocyte pellet culture / Chapter 2.3.1 --- Isolation of rabbit costal chondrocytes --- p.31 / Chapter 2.3.2 --- Three-dimensional chondrocyte pellet culture --- p.31 / Chapter 2.3.3 --- BrdU labeling for cell fate tracing --- p.32 / Chapter 2.4 --- Further characterization of the 3-D scaffold-free chondrocyte pellet / Chapter 2.4.1 --- Gross appearance --- p.35 / Chapter 2.4.2 --- Cell viability / Chapter 2.4.2.1 --- Alamar blue reduction assay --- p.35 / Chapter 2.4.3 --- Preparation of samples for histology --- p.36 / Chapter 2.4.4 --- General morphology and histomorphology / Chapter 2.4.4.1 --- H&E staining --- p.36 / Chapter 2.4.5 --- Cartilage properties / Chapter 2.4.5.1 --- Safranin O /Fast Green staining --- p.37 / Chapter 2.4.5.2 --- Immunohistochemistry of type II collagen --- p.37 / Chapter 2.4.5.3 --- Immunohistochemistry of type I collagen --- p.38 / Chapter 2.4.6 --- Angiogenic properties / Chapter 2.4.6.1 --- Immunohistochemistry of VEGF --- p.40 / Chapter 2.4.7 --- Osteogenic properties / Chapter 2.4.7.1 --- ALP staining --- p.40 / Chapter 2.5 --- Implantation of scaffold-free cartilage into osteochondral defect model / Chapter 2.5.1 --- Surgical procedures --- p.41 / Chapter 2.5.2 --- Experimental groups --- p.42 / Chapter 2.6 --- Assessment of osteochondral defect healing / Chapter 2.6.1 --- Macroscopic evaluation --- p.43 / Chapter 2.6.2 --- Preparation of samples for histology --- p.43 / Chapter 2.6.3 --- Histology for general morphology / Chapter 2.6.3.1 --- H&E staining --- p.45 / Chapter 2.6.4 --- Histological scoring / Chapter 2.6.4.1 --- Modification of the scoring system --- p.45 / Chapter 2.6.4.2 --- Procedures of scoring and validation --- p.45 / Chapter 2.6.5 --- Cell proliferation / Chapter 2.6.5.1 --- Immunohistochemistry of PCNA --- p.49 / Chapter 2.6.6 --- Cartilage regeneration / Chapter 2.6.6.1 --- Safranin O /Fast Green staining --- p.49 / Chapter 2.6.6.2 --- Immunohistochemistry of type II collagen --- p.49 / Chapter 2.6.6.3 --- Immunohistochemistry of type I collagen --- p.50 / Chapter 2.6.6.4 --- Polarized light microscopy --- p.50 / Chapter 2.6.7 --- Expression of angiogenic factor / Chapter 2.6.7.1 --- Immunohistochemistry of VEGF --- p.50 / Chapter 2.6.8 --- Bone regeneration / Chapter 2.6.8.1 --- μCT analysis --- p.50 / Chapter 2.6.9 --- Histomorphometric analysis of cartilage and bone regeneration --- p.53 / Chapter 2.6.10 --- BrdU detection for cell fate tracing --- p.55 / Chapter 2.6.11 --- Statistical analysis --- p.55 / Chapter CHAPTER THREE - --- RESULTS / Chapter 3.1 --- Further characterization of the 3-D chondrocyte pellet culture / Chapter 3.1.1 --- Gross examination --- p.57 / Chapter 3.1.2 --- Cell viability --- p.57 / Chapter 3.1.3 --- Cartilage properties --- p.61 / Chapter 3.1.4 --- Angiogenic properties --- p.63 / Chapter 3.1.5 --- Osteogenic properties --- p.64 / Chapter 3.2 --- Implantation of scaffold-free cartilage and assessment / Chapter 3.2.1 --- Gross examination --- p.65 / Chapter 3.2.2 --- General morphology --- p.67 / Chapter 3.2.3 --- Histological scores --- p.71 / Chapter 3.2.4 --- Cell proliferation --- p.75 / Chapter 3.2.5 --- Cartilage regeneration --- p.78 / Chapter 3.2.6 --- Expression of angiogenic factor --- p.90 / Chapter 3.2.7 --- Bone regeneration --- p.93 / Chapter 3.2.8 --- Histomorphometric analysis on cartilage and bone regeneration --- p.96 / Chapter 3.2.9 --- Cell fate tracing --- p.100 / Chapter CHAPTER FOUR - --- DISCUSSION / Chapter 4.1 --- Summary of key findings / Chapter 4.1.1 --- Further characterization of BCP and determination of implantation time --- p.102 / Chapter 4.1.2 --- Implantation of BCP in OCD --- p.102 / Chapter 4.2 --- Spontaneous healing in osteochondral defect / Chapter 4.2.1 --- Findings from the current study --- p.104 / Chapter 4.2.2 --- Comparison with other studies --- p.104 / Chapter 4.2.3 --- Factors affecting spontaneous healing --- p.105 / Chapter 4.3 --- Fabrication and further characterization of the 3-D chondrocyte pellet / Chapter 4.3.1 --- Comparison of different methods of producing scaffold-free cartilage construct --- p.106 / Chapter 4.3.2 --- Cartilage phenotype of the BCP --- p.107 / Chapter 4.3.3 --- Angiogenic and osteogenic potential of the BCP --- p.108 / Chapter 4.3.4 --- Role of mechanical stimulation on tissue-engineered cartilage --- p.109 / Chapter 4.4 --- Repair of osteochondral defect with allogeneic scaffold-free cartilage / Chapter 4.4.1 --- Advantages of the current scaffold-free chondrocyte pellet --- p.111 / Chapter 4.4.2 --- Remodeling of BCP after implantation --- p.111 / Chapter 4.4.3 --- Effect of BCP on cartilage repair --- p.112 / Chapter 4.4.4 --- Effect of BCP on bone regeneration / Chapter 4.4.4.1 --- Findings in the present study --- p.113 / Chapter 4.4.4.2 --- Possible reasons of slow bone repair --- p.114 / Chapter 4.4.4.3 --- Effect of BCP on bone region peripheral to defect --- p.115 / Chapter 4.4.5 --- Immunorejection-free properties of the BCP --- p.116 / Chapter 4.4.6 --- Comparison with other animal studies using scaffold-free cartilage --- p.117 / Chapter 4.4.7 --- Possibility of implanting a BCP cultured for shorter or longer period --- p.118 / Chapter 4.4.8 --- Scaffold-free cartilage construct and construct with scaffold for OCD repair --- p.119 / Chapter 4.4.9 --- Chondrocytes and stem cells for OCD repair --- p.120 / Chapter 4.5 --- Limitations of the study / Chapter 4.5.1 --- Animal model --- p.122 / Chapter 4.5.2 --- Histomorphometric analysis --- p.122 / Chapter 4.5.3 --- Lack of quantitative data analysis --- p.122 / Chapter 4.5.4 --- BrdU labeling of cells --- p.123 / Chapter 4.5.5 --- Lack of biomechanical test --- p.123 / Chapter 4.5.6 --- Small sample size --- p.123 / Chapter CHAPTER FIVE - --- CONCLUSION --- p.124 / Chapter CHAPTER SIX - --- FUTURE STUDIES / Chapter 6.1 --- Identification of factors affecting bone repair after OCD treatment --- p.125 / Chapter 6.2 --- Modifications of BCP treatment --- p.125 / Chapter 6.3 --- Alternative cell source --- p.126 / Chapter 6.4 --- Alternative cell tracking methods --- p.126 / Chapter 6.5 --- Inclusion of biomechanical test --- p.126 / APPENDICES / Appendix 1. Conference paper 1 --- p.129 / Appendix 2: Conference paper 2 --- p.130 / Appendix 3: Animal experimentation ethics approval --- p.131 / BIBLIOGRAPHY --- p.132

INTRODUCTION: Women’s gymnastics has the highest injury incidence rates for NCAA female college athletes. Gymnastics maneuvers may require support and transfer of the entire body weight from the feet to the hands. Such motions cause excessive loading and stress across joint surfaces which on occasion can exceed the mechanical strength of upper limb joints and supportive musculoskeletal structures, resulting in injuries ranging from acute fractures to chronic overuse injuries like osteochondritis dissecans. Recent technological advances have only now made it possible to analyze the complex and simultaneous motions in multiple planes required for evaluation of even the most basic gymnastic maneuvers like the round-off back handspring (ROBHS). OBJECTIVES: There is a paucity of data characterizing upper extremity injury causation and biomechanical risk factors in the small number of gymnastics studies conducted. The first hand contact for any gymnastics skill has never been quantitatively assessed. Therefore, the primary objective of this study is to perform a detailed 3D biomechanical characterization of the round-off back handspring (ROBHS) first hand contact and evaluate any potential correlations to upper extremity injury determinants. METHODS: A 3D motion capture camera and force plate system captured the relative positon of reflective markers affixed to 62 anatomical positions on subjects during performance of an ROBHS. A virtual model of each subject was constructed using Nexus C-motion software. Programming with Visual3D and MATLAB software was used to calculate desired force, kinematic and kinetic variables such as joint torques and angles. Past medical history questionnaires were administered, and clinical range of motion and strength measures were assessed. RESULTS: Compared with other factors analyzed, hand contact order appeared to have the highest degree of influence on upper extremity biomechanics at both the time of initial contact and throughout the entire movement sequence. The second contact limb was correlated with a larger average ground contact force, whereas while the first contact limb was related to a shorter time to peak force development and larger magnitude rotational kinematic variables, especially at the elbow—the primary site of upper extremity injury. For the first hand contact, torque development at the elbow and shoulder appeared to be related, and wrist and shoulder variables were presumably related to ground reaction force (GRF) development. The proposed literature elbow injury mechanism may need some adjustment to reflect the impact of elbow flexion angle on GRF and elbow valgus torque, key variables tied to chronic elbow joint capsule overload injuries. CONCLUSIONS: The novel information provided by this study can be used to guide future recommendations for the prevention of upper extremity injury in gymnastics training and competition. Improved understanding of associated force, kinetic, and kinematic biomechanical variables like joint torque could have implications for movement specific body positioning with the potential for extrapolation to gymnastics moves with similar loading patterns. Possible protective technique interventions based on study findings include increasing second hand elbow flexion during the round-off phase of motion or minimizing the time between hand contacts.

Este projeto teve como finalidade fornecer informações sobre o contingente brasileiro de garanhões afetados pela osteocondrose dissecante (OCD), particularmente no estado de São Paulo. A OCD é uma doença ortopédica do desenvolvimento que acomete os humanos e os animais. É o distúrbio de desenvolvimento esquelético mais importante nos potros em crescimento. É uma falha no processo de ossificação endocondral, que compromete as cartilagens articular e de crescimento, principalmente a articulação tíbio-társica. É uma afecção importante pela incapacitação de atletas e é questão de caráter mundial para o bem-estar animal e para a eqüinocultura, implicando o seu tratamento e estratégias de controle. Há várias modalidades diagnósticas utilizadas na triagem da população acometida pela OCD, que se distinguem de acordo com a acurácia de cada uma. Entretanto, a radiologia, com imagens digitais, ainda se mantém como a ferramenta mais utilizada no campo. Os garanhões foram escolhidos considerando-se a idade, a sanidade, a maturidade, a docilidade e estavam obrigatoriamente registrados no stud-book da ABCCH. Os eqüinos foram submetidos a duas incidências radiográficas bilaterais das articulações tíbio-társicas. Os arquivos foram armazenados em sistema digital e os achados classificaram os animais em positivos e negativos para OCD. Os resultados demonstraram uma ocorrência de 7,7% (2/26) de OCD na população brasileira de garanhões, produtos de inseminação artificial com sêmen importado com a garantia OCD-Free de centrais européias de reprodução. Esta porcentagem se apresentou menor do que as relatadas por pesquisadores de outros países, indicando que o plantel brasileiro de garanhões se apresenta controlado para a OCD e abaixo da expectativa. A baixa ocorrência de OCD nos eqüinos no Brasil, em relação aos outros países, pode ser atribuída ao método de seleção dos reprodutores e também a fatores climáticos. / This project provides information about osteochondrosis dissecans (OCD) affection in Brazilian Warmblood stallions, particularly in the state of Sao Paulo. Osteochondrosis dissecans is a developmental orthopaedic disease, which can involve both humans and animals. It is the most important skeletal disorder in growing foals. It is a failure of the endochondral ossification, which affects both articular and growth-plate cartilages. The tibiotarsal joint is the primary region involved. It is a remarkably disabling condition for competing animals and a serious worldwide issue for animal welfare and the horse industry and involves various treatments and control strategies. There are several modalities of diagnosis used to investigate the OCD, which differ from each other according to their rate of accuracy. However, radiology utilizing digitized images remains the most appropriate tool in the field. The stallions were chosen by the criteria of age, official registration in the ABCCH (Brazilian Sport Horses Breeders\' Association), soundness, maturity and behaviour. The horses were submitted bilaterally to two radiographic views of their hocks. The images were stored in digital files for further individual classification into positive or negative diagnosis. The results yielded an incidence of 7.7% (2/26) of OCD within the Brazilian population of stallions, all of whom were artificial insemination drives offspring, sired from imported European stallions using \"OCD-free\" semen. These results show a lower incidence of OCD than obtained by other countries\' researchers, indicating that the Brazilian stallions are under control for OCD and below the expected mean. The low incidence of OCD in Brazil, in comparison with other countries may be due to the methods of selection established for choosing quality of the semen or to climate differences.

Mutations in genes of importance for cartilage development may lead to skeletal malformations, chondroskeletal dysfunction and increased susceptibility to degenerative joint disease. Characterization of these mutations and identification of molecular pathways for the corresponding gene products have contributed to our understanding of mechanisms regulating skeletal patterning, endochondral ossification and joint formation. A five generation family segregating autosomal dominant osteochondritis dissecans (OCD) was identified. Affected family members presented with OCD in knees, hips and elbows, short stature, and early osteoarthritis. A genome wide scan and a multipoint linkage analysis identified aggrecan (ACAN) as a prime candidate gene. DNA sequence analysis of the ACAN-gene revealed heterozygosity for a missense mutation (c.6907G>A) in affected subjects, resulting in a p.V2303M substitution in the aggrecan G3 domain C-type lectin. This domain is important for the interaction with other proteins in the cartilage extracellular matrix. To determine the effect of the V2303M substitution on secretion and interaction, we performed binding studies with recombinant mutated and wild type G3 proteins. We found decreased affinity or complete loss of interaction between V2303M aggrecan and fibulin1, fibulin2 and tenascin-R. Analysis of articular cartilage from an affected family member confirmed that V2303M aggrecan is produced and present. In search for gene mutations associated with multiple epiphyseal dysplasia (MED) we considered the ACAN-gene a likely candidate. The ACAN-gene was analysed in 39 individuals with MED and screened negative for mutations in six previously known MED genes. Sequence analysis revealed a heterozygous missense mutation (c.1448G>T) in one adult male and compound heterozygous missense mutations (c.1366T>C and c.836G>A) in a five year old boy with healthy parents, each of them carrier for one of the mutations. A large family segregating autosomal dominant brachymesophalangia and OCD in finger joints was characterised. The clinical presentation in six affected family members was consistent with the diagnosis Brachydactyly type A1, in this family characterized by shortening of the middle phalanges, short ulnar styloid process, flattening of the metacarpal heads and mild osteoarthritis. The condition may be caused by mutations in the Indian hedgehog gene (IHH) or a yet unidentified gene on chromosome 5p13. Sequence analysis of the IHH-gene in affected individuals revealed a novel C to T transition (c.472C>T) leading to a p.158Arg>Cys substitution. Residue 158 in IHH is highly conserved throughout evolution and molecular structure modelling of IHH suggests that the R158C substitution leads to a conformational change at the site of interaction with the IHH-receptor. This supports that the substitution causes Brachydactyly type A1 in this family. In summary, we report on the clinical, radiological and molecular genetic characteristics of the three skeletal disorders OCD, MED and BDA1. Our results provide a novel molecular mechanism in the pathophysiology of familial osteochondritis dissecans confirming the importance of aggrecan C-type lectin for cartilage function. We also show that ACAN-gene mutations may be associated with MED extending the spectrum of skeletal dysplasias associated with the aggrecan gene. Finally, we report on a novel missense mutation in a conserved region of the IHH-gene associated with BDA1.

Made available in DSpace on 2014-12-17T14:13:36Z (GMT). No. of bitstreams: 1 GildasioLL_TESE.pdf: 952665 bytes, checksum: 96197adbbfc671543c2756fd03d62d1e (MD5) Previous issue date: 2010-11-17 / Osgood-Schlatter (O-S) syndrome, a pathology of the musculoskeletal system, exhibits high incidence in adolescence, a phase of accelerated bone growth. Detection of physiopathological mechanisms that may cause disorders and dysfunctions in bone growth must be taken into account when planning physical activities, in order to promote normal physiological growth patterns. The aim of this epidemiological investigation was to identify and analyze the relationships between sociodemographic, anthropometric and clinical aspects and O-S. A cross-sectional design was used, with a representative sample of 956 subjects: 474 (49.6%) males and 482 (50.4%) females. Age range varied between 12 and 15 years (mean = 13.7?1.04). We used a battery of tests, previously applied in a pilot study, which met the aims of the investigation. Descriptive statistics (frequency, mean and standard deviation) were used and the odds ratio was calculated from bivariate and multivariate logistic regression (p<0.05). A prevalence of 9.8% was found (n = 94 cases): 11% males and 8.3% females. Hierarchized multivariate analysis showed a significant association between regular physical activities (OR= 1.94; CI 95%, 1.22-3.10) and shortening of the rectus femoris muscle (OR= 7.15; CI 95%, 2.86-17.86). The results may serve as a basis for therapeutic and prophylactic measures, in addition to increasing our knowledge of this syndrome in Brazilian adolescents. This investigation used a multidisciplinary approach, involving elements of anatomy, nutrition, physical education and physical therapy to elucidate the object under study related to Osgood-Schlatter syndrome / A S?ndrome de Osgood-Schlatter (O-S) representa uma enfermidade do sistema m?sculo-esquel?tico com uma incid?ncia elevada na adolesc?ncia, fase onde se evidencia uma acelera??o do crescimento ?sseo. A detec??o de mecanismos fisiopatol?gicos que possam gerar dist?rbios e disfun??es do crescimento ?sseo, representam fatores de prote??o e devem ser considerados nas a??es de planejamento de atividades f?sicas, visando propiciar um crescimento dentro de padr?es fisiol?gicos. O objetivo dessa investiga??o epidemiol?gica foi identificar e analisar as rela??es dos aspectos s?cio-demogr?ficos, antropom?tricos e cl?nicos com a O-S. Este estudo teve um delineamento transversal, com uma amostra representativa 956 sujeitos, sendo 474 (49,6%) do sexo masculino e 482 (50,4%)do sexo feminino. A faixa et?ria variou de 12 a 15 anos (m?dia = 13,7?1,04). Para o exame cl?nico, foi utilizada uma bateria de testes que atendesse aos objetivos da investiga??o; testes estes previamente aplicados em um estudo piloto. Para an?lise foram utilizados procedimentos da estat?stica descritiva (frequ?ncia, m?dia e desvio padr?o) e o c?lculo da raz?o de chance (Odds Ratio) mediante regress?o log?stica bivariada e multivariada; p<0,05. Encontrou-se uma preval?ncia de 9,8% (n=94 casos), sendo 11% para o sexo masculino e 8,3% para o feminino, nos quais, a partir de an?lise multivariada hierarquizada, verificou-se associa??o significativa na pr?tica regular de atividades (OR= 1,94; IC 95%, 1,22-3,10) com o encurtamento do m?sculo reto femoral (OR= 7,15; IC 95%, 2,86-17,86). Os resultados do estudo poder?o servir como base terap?utica e na tomada de medidas profil?ticas, al?m de possibilitar um aprofundamento no que se sabe sobre acerca desta s?ndrome entre os adolescentes brasileiros. Esta investiga??o teve a xv abordagem multidisciplinar, momento em que envolveu elementos da anatomia, nutri??o, educa??o f?sica e fisioterapia na elucida??o do objeto de estudo relacionado ? s?ndrome de Osgood-Schlatter