INTRODUÇÃO: A Osteogênese Imperfeita (OI) é uma doença genética do tecido conjuntivo caracterizada por fragilidade óssea e grande suscetibilidade de fraturas aos mínimos traumas. OBJETIVO: Avaliar e descrever o tratamento com pamidronato de sódio cíclico nas formas moderada e grave de Osteogenesis Imperfecta (OI) em um Centro Referência de Tratamento para OI no Sul do Brasil. METODOLOGIA: Foi realizado um estudo de coorte retrospectivo com crianças e adolescentes, segundo os critérios da Organização Mundial de Saúde (OMS), de ambos os gêneros, com diagnóstico de OI nas formas moderada e grave que receberam tratamento cíclico de pamidronato de sódio no CROI – HCPA no período de 2002 a 2012. Os parâmetros clínicos foram obtidos durantes as consultas médicas para acompanhamento dos pacientes com OI e internações para tratamento com pamidronato de sódio. Os dados bioquímicos foram coletados durante a internação dos pacientes para infusão cíclica de pamidronato de sódio. Cálcio, Fósforo e Fosfatase Alcalina foram coletados sistematicamente. A densidade mineral óssea foi mensurada através do DXA (dual energy x-ray absoptometry) em coluna lombar (L1-L4) e corpo total. Para a análise dos dados foi utilizado Statistical Package for the Social Sciences (SPSS) Version 18. Foram considerados valores de significativos p < 0,05. RESULTADOS: Foram revisados dados de prontuário de 48 pacientes com OI, sendo 3 excluídos da amostra por apresentarem dados incompletos. A mediana da taxa de fraturas/mês reduziu significativamente após o primeiro ano de tratamento para todos os tipos de OI (p<0,01). Também para os tipos III e IV houve redução significativa da taxa de fraturas antes e após 1 ano de tratamento. Houve redução de 71,4% no número de fraturas após o tratamento na amostra geral. Esta redução foi maior na OI tipo III (86%) e tipo IV (78,6%) seguido do tipo I (60%). A mobilidade dos pacientes apresentou melhora significativa ao final do tratamento (p=0,004). Houve aumento significativo na DMO do corpo total do 1° ano para 6° em diante (p<0,001). Em relação à coluna lombar (L1-L4) o aumento foi observado a partir do 4° ano (p<0,001). Vinte e quatro pacientes (54,5%) tiveram alguma intercorrência durante o tratamento, sendo a maioria destas observadas no primeiro ciclo de tratamento. Quanto à adesão ao tratamento, a média do percentual foi de 92,3% (± 10,7). Houve associação positiva e significativa entre adesão ao tratamento e o número de fraturas por ano (rs=0,319; p=0,033), ou seja, maiores percentuais de adesão são obtidos em indivíduos com maior número de fraturas por ano. CONCLUSÃO: Nossos dados mostraram a variabilidade clínica da OI e a sua melhora ao longo do tratamento com pamidronato. Os resultados sugerem um incremento da DMO dos pacientes ao longo do tratamento e principalmente a redução das taxas de fratura ao longo do tratamento. O uso de pamidronato foi bem tolerado, com eventos adversos leves. / BACKGROUND: Osteogenesis Imperfecta (OI) is a genetic connective tissue disorder characterized by bone fragility and susceptibility to fractures to minimal trauma. OBJECTIVE: To evaluate and describe the treatment of cyclic sodium pamidronate in moderate and severe forms of Osteogenesis imperfecta (OI) at a Reference Center for OI Treatment in Southern Brazil. METHODS: A retrospective cohort study was conducted with children and adolescents diagnosed with OI in moderate and severe forms receiving cyclical sodium pamidronate from 2002 to 2012. The clinical data were obtained at hospitalization for treatment with sodium pamidronate and at follow-up visits. Biochemical data as calcium, phosphorus and alkaline phosphatase were systematically collected. Bone mineral density was measured using DXA (Dual Energy X-ray Absoptometry).For data analysis SPSS V. 18 was used. We considered significant p < 0.05. RESULTS: Medical charts were reviewed from 48 patients with OI and three were excluded due to incomplete data. The median fracture per month rate decreased significantly after the first year of treatment for all types of OI (p <0.01). Also for the types III and IV there was a significant reduction in the rate of fractures before and after 1 year of treatment. We observed a reduction of 71.4% in the number of fractures after treatment in the general sample. This reduction was higher in Type III (86%) and type IV (78.6%) followed by type I (60%). The median fracture/month rate decreased significantly after the first year of treatment for all types of OI (p <0.01). Also for the types III and IV there was a significant reduction in the rate of fractures before and after 1 year of treatment. In relation to the mobility of patients improved significantly after the end of treatment (p = 0.004). Was it is observed that regardless of the OI, a significant increase in BMD of the total body of 1 year to 6 onwards (p <0.001). In relation the spine (L1-L4) is increased from the 4 th year (P <0.001). Twenty-four patients (54.5%) had some problems during treatment, most of these observed in the first treatment cycle. As for adherence to treatment, the mean percentage was 92.3% (± 10.7). Of the total sample, 26 patients (57.8%) fully completed the full treatment. There were significant positive association between adherence to treatment and the number of fractures per year (rs = 0.319, p = 0.033), that is, higher adhesion percentages are obtained in individuals with more fractures per year. CONCLUSION: Our data showed improvement of BMD and mobility and decreasing of fracture rate with cyclic pamidronate treatment. The treatment was well tolerated with mild adverse events.

INTRODUÇÃO: A Osteogênese Imperfeita (OI) é uma doença genética do tecido conjuntivo caracterizada por fragilidade óssea e grande suscetibilidade de fraturas aos mínimos traumas. OBJETIVO: Avaliar e descrever o tratamento com pamidronato de sódio cíclico nas formas moderada e grave de Osteogenesis Imperfecta (OI) em um Centro Referência de Tratamento para OI no Sul do Brasil. METODOLOGIA: Foi realizado um estudo de coorte retrospectivo com crianças e adolescentes, segundo os critérios da Organização Mundial de Saúde (OMS), de ambos os gêneros, com diagnóstico de OI nas formas moderada e grave que receberam tratamento cíclico de pamidronato de sódio no CROI – HCPA no período de 2002 a 2012. Os parâmetros clínicos foram obtidos durantes as consultas médicas para acompanhamento dos pacientes com OI e internações para tratamento com pamidronato de sódio. Os dados bioquímicos foram coletados durante a internação dos pacientes para infusão cíclica de pamidronato de sódio. Cálcio, Fósforo e Fosfatase Alcalina foram coletados sistematicamente. A densidade mineral óssea foi mensurada através do DXA (dual energy x-ray absoptometry) em coluna lombar (L1-L4) e corpo total. Para a análise dos dados foi utilizado Statistical Package for the Social Sciences (SPSS) Version 18. Foram considerados valores de significativos p < 0,05. RESULTADOS: Foram revisados dados de prontuário de 48 pacientes com OI, sendo 3 excluídos da amostra por apresentarem dados incompletos. A mediana da taxa de fraturas/mês reduziu significativamente após o primeiro ano de tratamento para todos os tipos de OI (p<0,01). Também para os tipos III e IV houve redução significativa da taxa de fraturas antes e após 1 ano de tratamento. Houve redução de 71,4% no número de fraturas após o tratamento na amostra geral. Esta redução foi maior na OI tipo III (86%) e tipo IV (78,6%) seguido do tipo I (60%). A mobilidade dos pacientes apresentou melhora significativa ao final do tratamento (p=0,004). Houve aumento significativo na DMO do corpo total do 1° ano para 6° em diante (p<0,001). Em relação à coluna lombar (L1-L4) o aumento foi observado a partir do 4° ano (p<0,001). Vinte e quatro pacientes (54,5%) tiveram alguma intercorrência durante o tratamento, sendo a maioria destas observadas no primeiro ciclo de tratamento. Quanto à adesão ao tratamento, a média do percentual foi de 92,3% (± 10,7). Houve associação positiva e significativa entre adesão ao tratamento e o número de fraturas por ano (rs=0,319; p=0,033), ou seja, maiores percentuais de adesão são obtidos em indivíduos com maior número de fraturas por ano. CONCLUSÃO: Nossos dados mostraram a variabilidade clínica da OI e a sua melhora ao longo do tratamento com pamidronato. Os resultados sugerem um incremento da DMO dos pacientes ao longo do tratamento e principalmente a redução das taxas de fratura ao longo do tratamento. O uso de pamidronato foi bem tolerado, com eventos adversos leves. / BACKGROUND: Osteogenesis Imperfecta (OI) is a genetic connective tissue disorder characterized by bone fragility and susceptibility to fractures to minimal trauma. OBJECTIVE: To evaluate and describe the treatment of cyclic sodium pamidronate in moderate and severe forms of Osteogenesis imperfecta (OI) at a Reference Center for OI Treatment in Southern Brazil. METHODS: A retrospective cohort study was conducted with children and adolescents diagnosed with OI in moderate and severe forms receiving cyclical sodium pamidronate from 2002 to 2012. The clinical data were obtained at hospitalization for treatment with sodium pamidronate and at follow-up visits. Biochemical data as calcium, phosphorus and alkaline phosphatase were systematically collected. Bone mineral density was measured using DXA (Dual Energy X-ray Absoptometry).For data analysis SPSS V. 18 was used. We considered significant p < 0.05. RESULTS: Medical charts were reviewed from 48 patients with OI and three were excluded due to incomplete data. The median fracture per month rate decreased significantly after the first year of treatment for all types of OI (p <0.01). Also for the types III and IV there was a significant reduction in the rate of fractures before and after 1 year of treatment. We observed a reduction of 71.4% in the number of fractures after treatment in the general sample. This reduction was higher in Type III (86%) and type IV (78.6%) followed by type I (60%). The median fracture/month rate decreased significantly after the first year of treatment for all types of OI (p <0.01). Also for the types III and IV there was a significant reduction in the rate of fractures before and after 1 year of treatment. In relation to the mobility of patients improved significantly after the end of treatment (p = 0.004). Was it is observed that regardless of the OI, a significant increase in BMD of the total body of 1 year to 6 onwards (p <0.001). In relation the spine (L1-L4) is increased from the 4 th year (P <0.001). Twenty-four patients (54.5%) had some problems during treatment, most of these observed in the first treatment cycle. As for adherence to treatment, the mean percentage was 92.3% (± 10.7). Of the total sample, 26 patients (57.8%) fully completed the full treatment. There were significant positive association between adherence to treatment and the number of fractures per year (rs = 0.319, p = 0.033), that is, higher adhesion percentages are obtained in individuals with more fractures per year. CONCLUSION: Our data showed improvement of BMD and mobility and decreasing of fracture rate with cyclic pamidronate treatment. The treatment was well tolerated with mild adverse events.

INTRODUÇÃO: A Osteogênese Imperfeita (OI) é uma doença genética do tecido conjuntivo caracterizada por fragilidade óssea e grande suscetibilidade de fraturas aos mínimos traumas. OBJETIVO: Avaliar e descrever o tratamento com pamidronato de sódio cíclico nas formas moderada e grave de Osteogenesis Imperfecta (OI) em um Centro Referência de Tratamento para OI no Sul do Brasil. METODOLOGIA: Foi realizado um estudo de coorte retrospectivo com crianças e adolescentes, segundo os critérios da Organização Mundial de Saúde (OMS), de ambos os gêneros, com diagnóstico de OI nas formas moderada e grave que receberam tratamento cíclico de pamidronato de sódio no CROI – HCPA no período de 2002 a 2012. Os parâmetros clínicos foram obtidos durantes as consultas médicas para acompanhamento dos pacientes com OI e internações para tratamento com pamidronato de sódio. Os dados bioquímicos foram coletados durante a internação dos pacientes para infusão cíclica de pamidronato de sódio. Cálcio, Fósforo e Fosfatase Alcalina foram coletados sistematicamente. A densidade mineral óssea foi mensurada através do DXA (dual energy x-ray absoptometry) em coluna lombar (L1-L4) e corpo total. Para a análise dos dados foi utilizado Statistical Package for the Social Sciences (SPSS) Version 18. Foram considerados valores de significativos p < 0,05. RESULTADOS: Foram revisados dados de prontuário de 48 pacientes com OI, sendo 3 excluídos da amostra por apresentarem dados incompletos. A mediana da taxa de fraturas/mês reduziu significativamente após o primeiro ano de tratamento para todos os tipos de OI (p<0,01). Também para os tipos III e IV houve redução significativa da taxa de fraturas antes e após 1 ano de tratamento. Houve redução de 71,4% no número de fraturas após o tratamento na amostra geral. Esta redução foi maior na OI tipo III (86%) e tipo IV (78,6%) seguido do tipo I (60%). A mobilidade dos pacientes apresentou melhora significativa ao final do tratamento (p=0,004). Houve aumento significativo na DMO do corpo total do 1° ano para 6° em diante (p<0,001). Em relação à coluna lombar (L1-L4) o aumento foi observado a partir do 4° ano (p<0,001). Vinte e quatro pacientes (54,5%) tiveram alguma intercorrência durante o tratamento, sendo a maioria destas observadas no primeiro ciclo de tratamento. Quanto à adesão ao tratamento, a média do percentual foi de 92,3% (± 10,7). Houve associação positiva e significativa entre adesão ao tratamento e o número de fraturas por ano (rs=0,319; p=0,033), ou seja, maiores percentuais de adesão são obtidos em indivíduos com maior número de fraturas por ano. CONCLUSÃO: Nossos dados mostraram a variabilidade clínica da OI e a sua melhora ao longo do tratamento com pamidronato. Os resultados sugerem um incremento da DMO dos pacientes ao longo do tratamento e principalmente a redução das taxas de fratura ao longo do tratamento. O uso de pamidronato foi bem tolerado, com eventos adversos leves. / BACKGROUND: Osteogenesis Imperfecta (OI) is a genetic connective tissue disorder characterized by bone fragility and susceptibility to fractures to minimal trauma. OBJECTIVE: To evaluate and describe the treatment of cyclic sodium pamidronate in moderate and severe forms of Osteogenesis imperfecta (OI) at a Reference Center for OI Treatment in Southern Brazil. METHODS: A retrospective cohort study was conducted with children and adolescents diagnosed with OI in moderate and severe forms receiving cyclical sodium pamidronate from 2002 to 2012. The clinical data were obtained at hospitalization for treatment with sodium pamidronate and at follow-up visits. Biochemical data as calcium, phosphorus and alkaline phosphatase were systematically collected. Bone mineral density was measured using DXA (Dual Energy X-ray Absoptometry).For data analysis SPSS V. 18 was used. We considered significant p < 0.05. RESULTS: Medical charts were reviewed from 48 patients with OI and three were excluded due to incomplete data. The median fracture per month rate decreased significantly after the first year of treatment for all types of OI (p <0.01). Also for the types III and IV there was a significant reduction in the rate of fractures before and after 1 year of treatment. We observed a reduction of 71.4% in the number of fractures after treatment in the general sample. This reduction was higher in Type III (86%) and type IV (78.6%) followed by type I (60%). The median fracture/month rate decreased significantly after the first year of treatment for all types of OI (p <0.01). Also for the types III and IV there was a significant reduction in the rate of fractures before and after 1 year of treatment. In relation to the mobility of patients improved significantly after the end of treatment (p = 0.004). Was it is observed that regardless of the OI, a significant increase in BMD of the total body of 1 year to 6 onwards (p <0.001). In relation the spine (L1-L4) is increased from the 4 th year (P <0.001). Twenty-four patients (54.5%) had some problems during treatment, most of these observed in the first treatment cycle. As for adherence to treatment, the mean percentage was 92.3% (± 10.7). Of the total sample, 26 patients (57.8%) fully completed the full treatment. There were significant positive association between adherence to treatment and the number of fractures per year (rs = 0.319, p = 0.033), that is, higher adhesion percentages are obtained in individuals with more fractures per year. CONCLUSION: Our data showed improvement of BMD and mobility and decreasing of fracture rate with cyclic pamidronate treatment. The treatment was well tolerated with mild adverse events.

The Method of Difference Potentials (DPM) has proven an efficient tool for the solution of boundary value problems (BVPs) in various fields of research including acoustics and fluid mechanics. The method converts the solution of problems of complex geometry to the multiple solutions of a simple, well defined auxiliary problem, on which efficient solvers can be used, and which also avoids the numerical computation of stiffness matrices. So far, most problems solved by the method have been considered for regular domains. Here the method is considered for the solution of Linear Elastic Fracture Mechanics (LEFM) problems. These problems contain a crack which introduces irregularities into the solution space in the form of a discontinuity across the crack boundary and a strain singularity at the crack tip. The relative ease with which the DPM can solve problems of complex geometry makes it particularly attractive for LEFM problems due to the often complex geometries of cracks and the possibility of multiple cracks. The DPM is developed here for the solution of crack problems with the aim of demonstrating the method's potential within this field. As part of this development, for the first time the DPM is combined with the Finite Element Method (FEM). In particular the Extended Finite Element Method (XFEM) is used in order to deal with the irregularities at the crack. Using a geometrical enrichment scheme for the XFEM, near-optimal convergence rates are achieved. The computation time is then significantly reduced by introducing a system of basis functions along the physical boundary of the problem. Applying the DPM with the XFEM, the discontinuity and singularity are dealt with entirely within the XFEM space, therefore avoiding the need to approximate the singularity along the physical crack boundary. With the intention of further reducing the computation time, a Fast Fourier Transform (FFT) algorithm is provided for the solution of the enriched auxiliary problem. The algorithm utilises the regular grid of the auxiliary problem to provide a potentially fast solution method. The above research was applied using Matlab. A Matlab script was written formulating the DPM and XFEM along with various interpolation functions required for the utilisation of the system of boundary basis functions. These included local spline functions and Lagrange polynomials. The FFT algorithm was also applied within Matlab. A Python script was also written for the application of a simple DPM algorithm within Code_Aster, EDF's open source finite element code for thermo-mechanical analyses. These developments are documented in two academic journal papers submitted during the course of the PhD and included in the appendix of this thesis. The Python script for the application of the method within Code_Aster is also included in the appendix.

Introduction: The aim of this in vitro study was to determine the influence of two glide path preparation methods on the fracture rate of the Primary 25/08 WaveOne reciprocating instrument. The number of simulator Endo-Training-Blocks in each group were calculated at the time of instrument fracture and compared to determine the influence of glide path preparation on the failure rate of the Primary 25/08 WaveOne reciprocating instrument. Preparation times for different glide path methods and total time for root canal preparation, with or without glide path, was also calculated. Materials and Methods: Simulator Endo-Training-Blocks (n = 300) were selected and randomly divided into 3 groups (n = 100). The 3 groups were then sub-divided into 5 smaller groups (n = 20). Root canal preparation was done with new primary 25/08 WaveOne instruments allocated to each group (5 in total for each group, 1 for each sub-group) following different methods for glide path preparation. Group 1: no glide path (control); Group 2: glide path preparation with stainless-steel hand files (size 10 K-File followed by size 15 K-File and finally size 20 K-File until loose fitting); and Group 3: glide path preparation with rotary PathFiles (size 10 K-File until loose fitting followed by PathFile no.1 (ISO 13 tip), PathFile no.2 (ISO 16 tip) and finally PathFile no. 3 (ISO 19 tip)). The Primary 25/08 WaveOne reciprocating instrument was used with the WaveOne endodontic motor in “WaveOne All “mode with a brushing motion on the outstroke. Simulated root canals were irrigated with sterile water and Glyde was used as lubricating agent. The outcome was measured by recording how many simulators could be prepared with one instrument before instrument breakage occurred. The preparation protocol was repeated 5 times. The time it took to prepare the glide path and the total preparation time was also calculated. The data of the different parts of the project were collected and statistically analysed using the ANOVA / Bonferroni test. Results: Glide path preparation with PathFiles was significantly faster (13.3 s ± 2.60 s) than with hand files (25.1 s ± 1.70 s) (P < 0.001). The highest number of simulators could be prepared after glide path preparation was performed with PathFiles (19.2 ± 0.84) (P < 0.001). Pairwise comparisons at the Bonferroni adjusted significance level of 0.017 demonstrated that there were statistical significant differences (P < 0.001) when PathFiles (19.2 ± 0.84) and hand files (17.6 ±1.14) were compared to the no glide path group (7.4 ± 0.89). There was no statistical significant difference between PathFiles and hand files groups. Total Preparation time was significantly shorter (P < 0.001) when an initial glide path was prepared with PathFiles (12.7 ± 0.22 s). The longest preparation time (P < 0.001) was calculated in group 1 where no glide path (21.2 ± 0.20 s) was present and the Endo-Training-Blocks were left undisturbed. Conclusion: Initial glide path preparation with PathFiles resulted in shorter preparation time (glide path and total preparation) and allowed a higher number of simulators prepared before failure of the WaveOne instrument. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Odontology / unrestricted