Several hundred inherited disorders of the skeleton have been delineated. Individually these conditions are rare, but as a group they cause much crippling and hardship. Several factors, including the rarity and complexity of the manifestations of these conditions, as well as semantic overlap, impede the accurate diagnosis which is essential for effective treatment. In this regard, the adoption of microcomputers warrants evaluation as a high technology aid. Microcomputers have developed tremendous capabilities during recent years. The state of the art has become such that a diagnostic aid facility on such a device has been demonstrated in various disciplines of medicine and may also be feasible in the area of inherited skeletal disorders. The study which forms the basis of this thesis, concerns the investigation of this feasibility and has led to the development of an effective working model which sets the basis for microcomputer-aided diagnosis. The design features followed in this project are similar to those conventionally employed for "Expert systems" on mainframe computers. A comprehensive knowledge base consisting of over 200 skeletal disorders and 700 radiographic and clinical manifestations, has resulted. Furthermore, the application is capable of "learning", although inference as employed by the inference engines of real expert systems, is not employed. In this context learning implies that the knowledge base, with the passage of time, improves considerably when used by experts. Serendipitous findings in this regard are: • 1) Considerable improvement of existing profile descriptions can occur without any increased demands on computer memory and storage space; • 2) Growth of the knowledge base in the form of additional disease profiles can be effected with very modest inroads on memory and storage resources. The computerized diagnostic aid which resulted from this thesis, has been demonstrated to be successful in both the Department of Human Genetics of the University of Cape Town and the Department of Paediatrics of the Johannes Gutenberg University in Mainz. Evaluated both in terms of efficiency and utility, the system provides an enhancement to the specialist genetic diagnostician. These achievements have been effected by means of a unique newly developed application of compressed bit-mapping, attained by writing the applicable programs in Turbo Pascal and 8086- assembler languages. Calculations indicate that much larger data bases may possibly be implemented on present-day microcomputers by means of the methods developed in this project.

Or Pui Ching. / Thesis submitted in: December 1999. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 174-201). / Abstracts in English and Chinese. / acknowledgement --- p.i / abstract (english version) --- p.ii / abstract (chinese version) --- p.vii / table of contents --- p.xi / abbreviations --- p.xvi / list of tables --- p.xviii / list of figures --- p.xxii / Chapter chapter 1. --- introduction --- p.1 / Chapter chapter 2. --- literature review --- p.3 / Chapter 2.1. --- Bone structure --- p.3 / Chapter 2.1.1. --- Composition --- p.3 / Chapter 2.1.2. --- Cortical and Trabecular bone --- p.3 / Chapter 2.2. --- Bone Remodeling --- p.4 / Chapter 2.3. --- Bone Mass --- p.5 / Chapter 2.3.1. --- Peak Bone Mass --- p.5 / Chapter 2.3.1.1. --- Racial and Genetic Factors --- p.5 / Chapter 2.3.1.2. --- Gonadal Factors --- p.6 / Chapter 2.3.1.3. --- Nutrition Factors --- p.6 / Chapter 2.3.1.4. --- Exercise and Physical Activity --- p.7 / Chapter 2.3.2. --- Bone Loss --- p.7 / Chapter 2.3.2.1. --- Determinants of Osteoporotic Bone Loss --- p.7 / Chapter 2.3.2.2. --- Estrogen Deficiency --- p.8 / Chapter 2.3.2.3. --- Dietary Calcium deficiency and Vitamin D deficiency --- p.8 / Chapter 2.3.2.4. --- Physical Activity --- p.9 / Chapter 2.3.2.5. --- Alcoholism and Smoking --- p.9 / Chapter 2.3.2.6. --- Disease-specific Osteoporosis --- p.9 / Chapter 2.3.2.7. --- Drug-induced Osteoporosis --- p.10 / Chapter 2.3.3. --- Bone Mass and Fracture Risk --- p.11 / Chapter 2.4. --- Clinical Presentation of Osteoporosis --- p.12 / Chapter 2.4.1. --- Vertebral Fractures --- p.12 / Chapter 2.4.1.1. --- Radiological Aspects of Vertebral Fracture --- p.13 / Chapter 2.4.1.1.1. --- Changes in Trabecular Pattern --- p.13 / Chapter 2.4.1.1.2. --- Changes in Shape of the Vertebral bodies --- p.13 / Chapter 2.4.1.1.3. --- Changes of Intervertebral Discs --- p.14 / Chapter 2.4.1.2. --- Back Pain --- p.15 / Chapter 2.4.2. --- Hip Fractures --- p.15 / Chapter 2.4.3. --- Quality of Life --- p.16 / Chapter 2.5. --- Treatment of Established Osteoporosis --- p.18 / Chapter 2.5.1. --- Pain Relief --- p.18 / Chapter 2.5.2. --- Drug Therapy --- p.19 / Chapter 2.5.2.1. --- Calcium Supplement --- p.19 / Chapter 2.5.2.2. --- Vitamin D --- p.20 / Chapter 2.5.2.3. --- Estrogen --- p.21 / Chapter 2.5.2.4. --- Fluorides --- p.22 / Chapter 2.5.2.5. --- Calcitonin --- p.23 / Chapter 2.5.2.6. --- Bisphosphonates --- p.24 / Chapter 2.5.2.6.1. --- Physicochemical effects --- p.27 / Chapter 2.5.2.6.2. --- Mechanisms --- p.27 / Chapter 2.5.2.6.3. --- Therapeutic Use --- p.27 / Chapter 2.5.2.6.4. --- Side effects --- p.29 / Chapter 2.5.2.6.5. --- Alendronate --- p.30 / Chapter 2.5.2.7. --- Summary of drug treatment --- p.33 / Chapter 2.6. --- Diagnostic Methods of Osteoporosis --- p.40 / Chapter 2.6.1. --- Biochemical Markers of Bone Metabolism in Osteoporosis --- p.40 / Chapter 2.6.1.1. --- Bone Formation Markers --- p.41 / Chapter 2.6.1.1.1. --- Bone-specific Alkaline Phosphatase (bALP) --- p.41 / Chapter 2.6.1.2. --- Bone Resorption Markers --- p.42 / Chapter 2.6.1.2.1. --- Deoxypyridinoline (Dpd) --- p.43 / Chapter 2.6.2. --- Bone Densitometry --- p.45 / Chapter 2.6.2.1. --- Dual Energy X-ray Absorptiometry (DEXA) --- p.45 / Chapter 2.6.2.2. --- Peripheral Quatitative Computed Tomography (pQCT) --- p.47 / Chapter 2.6.2.3. --- Quantitative Ultrasound (QUS) --- p.48 / Chapter 2.6.3. --- Summary of Diagnostic Methods --- p.49 / Chapter chapter 3. --- methodology --- p.50 / Chapter 3.1. --- Study on Vertebral Structures --- p.51 / Chapter 3.1.1. --- Procedures --- p.51 / Chapter 3.1.2. --- Data analysis --- p.53 / Chapter 3.2. --- Alendronate Treatment --- p.54 / Chapter 3.2.1. --- Subject Selection --- p.54 / Chapter 3.2.2. --- Study design and drug administration --- p.55 / Chapter 3.2.3. --- Bone Densitometry --- p.56 / Chapter 3.2.3.1. --- Dual Energy X-ray absorptiometry --- p.56 / Chapter 3.2.3.2. --- Peripheral Quantitative Computed Tomography (pQCT) --- p.58 / Chapter 3.2.4. --- Biochemical Markers --- p.63 / Chapter 3.2.4.1. --- Bone formation marker --- p.63 / Chapter 3.2.4.2. --- Bone resorption marker --- p.64 / Chapter 3.2.5. --- Quality of Life --- p.65 / Chapter 3.2.6. --- New fracture assessment --- p.66 / Chapter 3.2.7. --- Statistical analysis --- p.67 / Chapter 3.3. --- Proximal femur fracture study --- p.68 / Chapter 3.3.1. --- Subject and study design --- p.69 / Chapter 3.3.2. --- Statistical analysis --- p.70 / Chapter chapter 4. --- results of study on vertebral structures --- p.71 / Chapter 4.1. --- Results of morphological change of vertebral bodes in osteoporotic patients --- p.71 / Chapter 4.2. --- Morphological changes of intervertebral discs --- p.71 / Chapter 4.3. --- Correlation between morphological changes of vertebrae and bulging ratio --- p.72 / Chapter chapter 5. --- results of alendronate study --- p.76 / Chapter 5.1. --- Baseline measurement --- p.76 / Chapter 5.1.1. --- Demographic characteristics --- p.76 / Chapter 5.1.2. --- Reasons for admission --- p.77 / Chapter 5.1.3. --- Social support --- p.77 / Chapter 5.1.4. --- Number of vertebral fracture(s) --- p.78 / Chapter 5.1.5. --- BMD measurement (Baseline) --- p.79 / Chapter 5.1.5.1. --- BMD of Lumbar spine and Hip (measured by DEXA) --- p.79 / Chapter 5.1.5.2. --- BMD of distal tibia and radius measured by pQCT --- p.80 / Chapter 5.1.6. --- Biochemical Markers (Bone formation and resorption) --- p.86 / Chapter 5.2. --- After treatment --- p.88 / Chapter 5.2.1. --- Bone mineral density measurement (measured by DEXA) --- p.90 / Chapter 5.2.1.1. --- Lumbar spine --- p.90 / Chapter 5.2.1.2. --- Femoral Neck --- p.93 / Chapter 5.2.1.3. --- Trochanter --- p.95 / Chapter 5.2.1.4. --- Ward's Triangle --- p.98 / Chapter 5.2.1.5. --- Summary --- p.101 / Chapter 5.2.2. --- Bone Mineral Density measured by pQCT --- p.103 / Chapter 5.2.2.1. --- Distal Radius (Program 1) --- p.103 / Chapter 5.2.2.1.1. --- BMD change of D50 --- p.103 / Chapter 5.2.2.1.2. --- BMD changes of D100 --- p.106 / Chapter 5.2.2.1.3. --- BMD change of P100 --- p.108 / Chapter 5.2.2.2. --- Distal Radius (Program 2) --- p.111 / Chapter 5.2.2.2.1. --- BMD change of pure trabecular bone --- p.112 / Chapter 5.2.2.2.2. --- BMD changes of pure cortical bone --- p.114 / Chapter 5.2.2.3. --- Distal Tibia (Program 1) --- p.118 / Chapter 5.2.2.3.1. --- BMD changes of D50 --- p.118 / Chapter 5.2.2.3.2. --- BMD changes of D100 --- p.121 / Chapter 5.2.2.3.3. --- BMD changes of P100 --- p.124 / Chapter 5.2.2.4. --- Distal Tibia (Program 2) --- p.128 / Chapter 5.2.2.4.1. --- BMD changes of pure trabecular bone --- p.128 / Chapter 5.2.2.4.2. --- BMD changes of pure cortical bone --- p.131 / Chapter 5.2.3. --- Bone turnover --- p.135 / Chapter 5.2.3.1. --- Bone Resorption Marker (urinary Deoxypyridinoline) --- p.135 / Chapter 5.2.3.2. --- Bone Formation Marker (Bone Specific Alkaline Phosphatase) --- p.137 / Chapter 5.2.4. --- Quality of Life (QOL) --- p.139 / Chapter 5.2.5. --- Oswestry Disability Index (ODI) --- p.139 / Chapter 5.2.6. --- Pain --- p.141 / Chapter 5.2.6.1. --- Pain frequency --- p.141 / Chapter 5.2.6.2. --- Night Pain --- p.142 / Chapter 5.2.6.3. --- Administration of pain relief drugs --- p.143 / Chapter 5.2.7. --- Activity of daily living --- p.144 / Chapter 5.2.8. --- Prevention of new vertebral fracture(s) --- p.146 / Chapter 5.2.9. --- Safety and Tolerability --- p.147 / Chapter chapter 6. --- results on proximal femoral fractures study --- p.149 / Chapter 6.1. --- Epidemiological study on proximal femoral fractures --- p.149 / Chapter 6.2. --- The role of ultrasound equipment in the assessment osteoporosis in patients with proximal femoral fractures --- p.154 / Chapter 6.3. --- Summary --- p.155 / Chapter chapter 7. --- discussion --- p.156 / Chapter 7.1. --- The study on vertebral structures --- p.156 / Chapter 7.1.1. --- Changes in Shape of Vertebral Bodies --- p.156 / Chapter 7.1.2. --- Changes of Interevertbral Discs --- p.157 / Chapter 7.2. --- Alendronate treatment on Chinese elderly women with Osteoporotic vertebral fracture --- p.158 / Chapter 7.2.1. --- The Effect of Alendronate on BMD of Lumbar Spine --- p.159 / Chapter 7.2.2. --- The Effects of Alendronate on BMD of Proximal Femur --- p.159 / Chapter 7.2.3. --- The Effects of Alendronate on the BMD of Trabecular and Cortical Bone in the Distal Radius and Distal Tibia --- p.160 / Chapter 7.2.4. --- The Effects of Calcium Supplementation in the study --- p.162 / Chapter 7.2.5. --- The Effect of alendronate on Biochemical Turnover --- p.162 / Chapter 7.2.6. --- The Efficacy of Alendronate on Prevention of New Fractures --- p.163 / Chapter 7.2.7. --- The Effect of Alendronate on Quality of Life --- p.164 / Chapter 7.2.8. --- Adverse Effects of Alendronate --- p.165 / Chapter 7.3. --- Proximal Femur Fracture Study --- p.165 / Chapter chapter 8. --- conclusion --- p.168 / bibliography --- p.174 / epilogue --- p.202 / appendix --- p.xxv

Orientador: Anderson Marliere Navarro / Banca: Rebeca Antunes Beraldo / Banca: Vivian Marques Miguel Suen / Banca: Elen Almeida Romão / Banca: Rodrigo de Carvalho Santana / Resumo: A hepatite B é um importante problema de saúde pública mundial e se associa a consideráveis taxas de mortalidade. As medicações de uso oral para o tratamento da hepatite B, denominados em conjunto de análogos de nucleosídeo/nucleotídeo, são de uso prolongado e apresentam potenciais efeitos colaterais, como a redução na densidade mineral óssea que está associada ao uso do tenofovir. Objetivo: avaliar os efeitos do tenofovir, em comparação com outros análogos de nucleosídeo/nucleotídeo (entecavir e lamivudina), sobre a densidade mineral óssea de um grupo de pacientes com hepatite B crônica. Materiais e Métodos: foi realizado um estudo observacional do tipo transversal com 81 pacientes adultos, com Hepatite B crônica atendidos no Hospital das Clínicas de Ribeirão Preto - USP nos quais realizou-se os exames de densitometria óssea (dual energy x-ray absorptiometry-DXA), análises bioquímicas de osteocalcina, deoxipiridinolina, vitamina D, paratormônio, IGF-1, TSH, testosterona, estradiol, FSH, transaminases, ureia, creatinina, cálcio total, fósforo sérico e urinário, magnésio, FGF-23 e medidas antropométricas (peso, altura e índice massa corporal). Os participantes, de ambos os sexos, foram subdivididos segundo o uso ou não de antirretrovirais sendo: Grupo 1: 27 pacientes portadores inativos do vírus sem uso de medicamentos; Grupo 2: 27 pacientes em uso de Tenofovir; Grupo 3: 27 pacientes em uso de Lamivudina ou Entecavir. Resultados: não houve diferença entre a idade média e índic... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hepatitis B is one the most important public health problem worldwide and is associated with considerably high mortality rates. Oral medications, generally nucleoside/nucleotide analogs such as tenofovir, have been used as long-term therapy and have possible side effects such as the reduction in bone mineral density associated with their use. Objective: to evaluate the effects of tenofovir, compared with those of other nucleoside/nucleotide analogs (entecavir and lamivudine), on the bone mineral density of hepatitis B patients. Materials and Methods: a cross-sectional study was conducted with 81 adult patients with chronic hepatitis B treated. The average age of the participants was 42 years. Dual-energy x-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analyses were performed for osteocalcin, deoxypyridinoline, parathyroid hormone, vitamin D, IGF-1, TSH, testosterone, estradiol, FSH, transaminases, urea, creatinine, calcium, serum and urinary phosphorus, magnesium, FGF-23 and anthropometric measures of weight, height, and body mass index were performed. Participants, both gender, were divided according to the use of antiretrovirals: Group 1: 27 inactive virus carriers without medication; Group 2: 27 patients using tenofovir; Group 3: 27 patients using lamivudine or entecavir. Results: We did not find differences in mean age, body mass index, lean and fat mass between patients in both groups (p>0.05). DXA readings diagnosed osteopenia in the... (Complete abstract click electronic access below) / Doutor

A articulação temporomandibular (ATM) apresenta diversas limitações quando se obtém imagens pela radiologia convencional. A tomografia computadorizada é o exame mais indicado, pela alta especificidade e sensibilidade, para o diagnóstico, planejamento cirúrgico e tratamento das suas lesões ósseas. O objetivo deste trabalho consiste na comparação entre a tomografia computadorizada (TC) multislice e a tomografia computadorizada por feixe cônico (TCFC) para avaliação de lesões ósseas simuladas na cabeça da mandíbula. Foram utilizadas 30 cabeças de mandíbulas maceradas onde foram criadas lesões esféricas, com o auxílio de brocas cirúrgicas esféricas de uso odontológico com tamanhos variados (nº 1, 3, 6), em suas cinco porções (anterior, lateral, posterior, medial, superior). As lesões foram submetidas a TC multislice (64 canais) e a TCFC, sendo avaliadas em dois programas de pós-processamento por dois observadores independentemente, sendo um deles em duas ocasiões distintas. Foram utilizados também dois protocolos de análise para exame das imagens quanto à presença ou não de perfuração: reconstrução multiplanar (axial, coronal, sagital) e cortes sagitais e coronais ao longo eixo da cabeça mandibular. Posteriormente, os resultados brutos foram comparados com as lesões presentes na mandíbula macerada (Padrão-Ouro) avaliando a proporção de acertos de cada observador, o grau de especificidade e sensibilidade dos diferentes métodos da TC e da TCFC, e a comparação intra-observador e inter-observadores. O teste z foi utilizado como método estatístico. Os resultados demonstraram não haver diferenças estatisticamente significantes entre os métodos em relação às porcentagens de concordância e que todos estes são validados. Os protocolos para visibilização da região de cabeça da mandíbula foram estabelecidos no intuito de melhorar a identificação da presença de alterações de cada porção da cabeça da mandíbula. Houve maior dificuldade na avaliação de lesões simuladas de pequena dimensão (broca 1) / There are many limitations for image acquisition using conventional radiography of the temporomandibular joint (TMJ) region. Computerized tomography (CT) scan is a better option due to its higher specificity and sensitivity for diagnosis, surgical planning and treatment of bone injuries. The purpose of this study is to compare multislice CT and cone beam computed tomography for evaluation of simulated mandibular condyle lesions. Spherical lesions were created in 30 dry mandibular condiyle with dentist drills (sizes 1, 3, and 6). Condyles were submitted by multislice (64 bits) CT and cone beam computed tomography (CBCT) using two independent software by 2 observants alone, one of them in 2 different occasions, using 2 protocols: axial, coronal and sagittal, and sagittal plus coronal slices for the mandibular condyle visualization. The raw data were compared with the dry mandible (gold standard) regarding the presence of injuries, evaluating the proportion of agreement, degree of specificity and sensitivity of the CT and CBCT and observant analysis. The z test were used as statistical methods. The results showed there are no statistically significant differences between the methods, and the whole methods are validity. It was observed the advantage of the association of axial, coronal and sagittal slices and sagittal plus coronal slices for detection of lesions in mandibular condyles. For some lesions localized in regions, protocols did not show statistically significant differences regarding the proportion of agreement. Protocols were created to improve the visualization of lesions in each region of the mandibular condyle. There was more difficult for assessment small size simulated lesions (# 1).

INTRODUÇÃO: A obesidade é uma doença crônica com crescimento alarmante no mundo todo. Atualmente, o tratamento cirúrgico, especialmente o Bypass Gástrico em Y de Roux (BGYR), tem se mostrado como a forma mais eficiente para perda de peso e sua manutenção a longo prazo. Contudo, com a formação do neo-estômago e a mudança na conformidade intestinal, há alterações significantes das muitas propriedades físicas e funcionais desses órgãos que levam à deficiência de nutrientes, inclusive de cálcio. Com isso, podem ocorrer modificações no metabolismo ósseo e, conseqüentemente, na estrutura óssea. OBJETIVOS: Avaliar a ingestão de cálcio, as alterações no metabolismo ósseo e mineral; e a ocorrência de osteopenia e osteoporose em mulheres que se submeteram ao BGYR há oito anos. MÉTODO: Neste estudo transversal, foram estudadas 30 mulheres que se submeteram ao BGYR no período de outubro de 1995 a janeiro de 1999, no Hospital das Clínicas da Faculdade de Medicina da USP. Para avaliação da ingestão de cálcio, utilizamos o recordatório de 3 dias (R3D) e o questionário de freqüência alimentar (QFA). Também foram realizados exames laboratoriais referentes ao metabolismo ósseo e mineral e densitometria óssea do seguimento L1-L4, colo femoral (CF) e fêmur proximal (FP). RESULTADOS: Em média, o consumo de cálcio foi de 525,5 ± 250,7 mg/dia pelo R3D e de 542,2 ± 195,6 mg/dia pelo QFA. Houve uma relação estatisticamente significativa entre a ingestão de cálcio por esses dois métodos (p<0,001). Não houve alteração nas determinações de cálcio total e ionizado, magnésio, fósforo e CTX. Os níveis de PTH, Fosfatase alcalina fração óssea (BSAP) e osteocalcina estavam elevados em 53%, 57% e 20% das mulheres, respectivamente; 90% apresentavam deficiência de 25 (OH) vitamina D (40% leve e 50% moderada), e em 70% a calciúria estava abaixo dos valores normais. Observou-se uma correlação positiva entre 25 (OH) vitamina D e a calciúria (p<0,04) e negativa entre 25 (OH) vitamina D e PTH (p<0,017). Com relação à densidade mineral óssea, 13% das mulheres foram diagnosticadas com osteoporose com relação ao CF e FP; 67%, 40% e 27% apresentavam osteopenia em L1-L4, CF e FP, respectivamente. CONCLUSÃO: Na maioria das mulheres estudadas verificou-se um consumo de cálcio cerca de 50% abaixo da recomendação diária para esta faixa etária. Observou-se também, uma deficiência de 25 (OH) vitamina D e elevação de PTH e BSAP. Além disso, houve uma ocorrência de osteopenia superior à esperada indicando que alterações no metabolismo ósseo são provavelmente uma complicação do BGYR. Mais estudos são necessários para definir uma rotina de suplementação de cálcio e vitamina D, e também para a prevenção das alterações ósseas. / INTRODUTION: Obesity is a chronic disease that rises rapidly around the world. Nowadays bariatric surgical procedures, especially Roux-en-Y Gastric Bypass (RYGB) has been shown the most efficient way to lose weight and maintain the weight loss for a long time. However, with the neo-stomach and the modification of intestinal anatomy by the surgery there are significant changes on physiological properties of these organs that lead to a nutrient deficiency, including calcium. Thus, bone metabolism changes may occur leading to a metabolic bone disease. OBJECTIVES: To evaluate calcium intake, bone and mineral metabolism changes and the prevalence of metabolic bone disease in women who were submitted to RYGB after eight years. METHOD: we studied 30 women who were submitted to RYGB during the period between October of 1995 and January of 1999 at Clinical Hospital of Medicine School of São Paulo University. To access calcium intake we used a 3 day dietary recall (3DR) and food frequency questionnaire (FFQ). Laboratory tests of bone metabolism and bone mass density of L1-L4, femoral neck (FN) and proximal femur (PF) were also accessed. RESULTS: calcium intake was 525,5 ± 250,7 mg/day according 3RD and 542,2 ± 195,6 mg/day according FFQ. There was a significantly relation between both methods (p<0,001). Total and ionic calcium, magnesium, phosphorus and CTX were not altered. PTH, bone specific alkaline phosphatase (BSAP) and osteocalcin levels were elevated respectively in 53%, 57% and 20% of women. 90% presented 25 (OH) vitamin D deficiency (40% mild and 50% moderate) and 70% had low urinary calcium. Was observed a positive correlation between 25 (OH) vitamin D and urinary calcium (p<0,04); and a negative correlation between 25 (OH) vitamin D and PTH (p<0,017). 13% of women had osteoporosis in FN and PF; 67%, 40% and 27% had metabolic bone disease in L1-L4, FN and PF respectively. CONCLUSION: Most studied women had a low calcium intake, about 50% of daily recommendation. We also noticed a 25 (OH) vitamin D deficiency and elevated levels of PTH and BSAP. Besides, there was a high prevalence of metabolic bone disease than expected, suggesting that this could be a complication of this surgery. Further studies are needed to define a supplementation routine of calcium and vitamin D to prevent bone metabolic diseases in these patients.

骺軟骨板是位於長骨骨骺的一個軟骨結構，其主要功用為使骨骼延伸生長。 若人類骺軟骨板基因出現障礙，骨骼生長往往會受到嚴重的影響，使骨骼變得短小、畸形，造成殘障。此外，一些後天的系統性失調也會損害骺軟骨板的正常運作，導致矮小症。現今常用來醫治骨骼生長障礙的包括重組的人類生長荷爾蒙。然而，它的功效並非顯著，亦帶來很多的副作用；因此，我們希望能尋求更好的醫治方法。 / 近有的研究結果顯示，很多的內分泌及分泌因子能夠刺激骺軟骨板進行軟骨增生。但是，研究者卻往往未能將這些因子轉化及運用作醫療用途，原因是它們通常都是局部性地於骺軟骨板產出及發生效用。倘若以上提及的生長因子能給骺軟骨板的靶子蛋白鏈準確地被帶往骺軟骨板，那麼這些因子便能有效地被利用作治療用途，而其效能亦會給大大提高，副作用也會被減低。因此，我們現在進行研究的首要目標為於採用噬菌體展示和酵母展示方法， 尋找那些能認辨出骺軟骨板的靶子蛋白鏈及單鏈抗體。 / 於噬菌體展示庫裡，我們找出了兩條能認辨出小鼠骨骼軟骨細胞的靶子蛋白鏈 － C1 (RLDPTSYLRTFW) 和 C19 (HDSQLEALIKFM)。然而於體外測試實驗中， 它們對軟骨細胞及細胞外基質只擁有中度的親近性和特異性。此後，於酵母展示庫裡，我們亦發現三條可認辨某骺軟骨板蛋白的單鏈抗體 － 它們的親近性甚高 (達至1 nM)，而其對軟骨組織的特異性也為良好 (它們只認辨軟骨組織，但卻沒能認辨出其他的軟組織，包括腦、心臟、肝臟、肺臟、腎臟、脾臟、小腸及肌肉)。 其後，於小鼠胚胎免疫染色測試實驗中，這些單鏈抗體只亦選擇地認辨軟骨組織。再者，當這些單鏈抗體被注射入小鼠的靜脈中，它們也會準確地停留在軟骨組織裡，顯示出其特異性於體內測試實驗中亦存在。 / 總括而言，利用噬菌體展示和酵母展示方法，我們發現了一些能認辨出骺軟骨板的靶子蛋白鏈及單鏈抗體。這些單鏈抗體擁有對軟骨組織非常高的親近性和特異性。我們預計，若然將這些單鏈抗體和內分泌及分泌因子連結在一起，它們或能成為醫治骨骼生長障礙的新方法。 / The growth plate is a specialized cartilage structure at the ends of long bones that is responsible for bone elongation. Many human genetic disorders of the growth plate impair skeletal growth, often resulting in bones that are severely short and malformed, causing serious disability. Many acquired systemic disorders also impair growth plate function, causing short stature. Currently, recombinant human growth hormone is used to treat growth disorders, but it has limited efficacy for severe diseases and causes significant adverse effects. / Recent studies have identified many endocrine and paracrine factors that are capable of promoting chondrogenesis at the growth plate. However, the development of these molecules into effective therapies has been hampered by their action mechanism; they are produced locally and act locally in the growth plate and thus fail to lend themselves to systemic therapeutic approaches. We envisioned that, if these growth factors could be linked to growth plate-targeting peptides or polypeptides and then administered systemically, these molecules might provide a better treatment strategy for growth disorders because targeting might augment the therapeutic effect on the growth plate but diminish undesirable effects on non-target tissues. Toward this goal, we sought to identify peptides and antibody fragments that bind to cartilage tissue using phage display and yeast display technologies. / We used a phage display library that expressed linear peptides of 12 random amino acids on the phage surface and then selected for binding to murine primary cultured chondrocytes. This approach successfully identified two peptides, namely C1 (RLDPTSYLRTFW) and C19 (HDSQLEALIKFM), which exhibited moderate binding affinity and specificity to chondrocytes and extracellular matrix in vitro. We also used a yeast display library to identify three single-chain variable(scFv) antibody fragments that bound strongly to a growth plate-specific protein(EC50 values less than 1 nM). These antibody fragments demonstrated specific binding in vitro to homogenates of cartilage tissues, but not homogenates of brain, heart, liver, lung, kidney, spleen, small intestine, or muscle. Moreover, they also exhibited tissue-specific binding to cartilage structures in sections of mouse embryos. When these purified antibody fragments were injected intravenously in mice, they localized to cartilage and were not detectable in other tissues, including brain, heart, liver, lung, kidney, spleen, small intestine, or muscle, indicating that the antibody fragments were capable of specifically targeting cartilage tissue in vivo. / In conclusion, we employed phage display and yeast display methods to identify peptides and antibody fragments that bind to cartilage tissues. The selected antibody fragments showed particularly high binding affinity and specificity to cartilage. Conjugating these antibody fragments to endocrine and paracrine signaling molecules has the potential to provide targeted therapy for growth plate disorders. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Cheung, Sao Fong. / Thesis (Ph.D.) Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 89-102). / Abstracts also in Chinese.

Introdução: A displasia do desenvolvimento do quadril (DDQ) acomete de 1,5 a 2,5, em cada 1000 nascidos vivos. O tratamento pode variar desde o uso do suspensório até a redução cruenta, associada ou não a osteotomias da bacia e do fêmur. A avalição da redução, após as reduções incruentas ou cruentas, é feita por meio de radiografias uniplanares e complementada com imagens de tomografia ou de ressonância magnética. Uma incidência radiográfica, geralmente não usada para essa finalidade, pode ajudar nessa avaliação: a radiografia Inlet. Este estudo tem como objetivo avaliar a eficácia da radiografia Inlet, em comparação com a tomografia, método utilizado atualmente em nosso serviço para essa avaliação. Secundariamente, busca avaliar a reprodutibilidade da avaliação, através de correlações intra e inter observadores. Métodos: Foram avaliados pacientes com diagnóstico de DDQ, operados entre 2013 e 2015. Todos os pacientes foram submetidos à incidência radiográfica Inlet pós-operatória e a tomografia. Foram realizadas avaliações cegas, em imagens distribuídas randomicamente intra e entre avaliadores, correlacionadas pelo índice Kappa (IC 95%). Foi também realizado um consenso entre os avaliadores que foi comparado com os resultados da tomografia. Essa correlação foi avaliada pelo índice Kappa ponderado (IC 95%) e assim foram obtidas as medidas diagnósticas: sensibilidade, especificidade, valor preditivo positivo (VPP), valor preditivo negativo (VPN), likelihood positivo (LR+) e likelihood negativo (LR). Resultados: Foram obtidas 25 radiografias de um total de 22 pacientes, que foram incluídas neste estudo. A idade média de tratamento foi de 2,95 anos e variou entre um e cinco anos, com maior prevalência no sexo feminino e maior incidência no lado esquerdo. As avaliações intra e inter-observadores tiveram valores semelhantes e com índice Kappa alto, 0,834 (IC 95%). A correlação entre o consenso e a tomografia mostrou alta concordância Kappa = 0,834 (IC95%), com 100% de sensibilidade, especificidade de 95,5% e valor preditivo negativo de 100 (83,9-100). Conclusão: A incidência radiográfica Inlet se mostrou um método viável e confiável, em comparação com a tomografia computadorizada para a avaliação pós-operatória da redução, na displasia do desenvolvimento do quadril / Introduction: Development dysplasia of the Hip (DDH) affects 1.5 to 2.5 per 1000 live births. The treatment varies according to the age and can range from the use of the suspensory to open reduction associated with pelvic osteotomies and, or femur osteotomies. The evaluation of the reduction after the surgeries is done by means of uniplanar radiographs and complemented with tomography or magnetic resonance images. A complementary radiograph not used for this purpose may help in this evaluation: Inlet radiography. This study aims to evaluate the effectiveness of the Inlet radiography in comparison to the Tomography method currently used in our service for this evaluation. Secondarily, it seeks to evaluate the reproducibility of the evaluation through intra and inter-observer correlations. Methods: Patients with a diagnosis of DDQ operated between 2013 and 2015 were evaluated. All patients underwent postoperative inlet radiography and tomography. Blind evaluations were performed on images randomly distributed intra and between evaluators correlated by Kappa index (95% CI). A consensus was also reached among the evaluators and this was compared with the results of tomography as a gold method. This correlation was evaluated by the weighted Kappa index (95% CI) and the diagnostic measures, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood (LR +) and negative likelihood (LR) were obtained. Results: A total of 25 radiographs obtained from 22 patients were included in the study. The mean age of treatment was 2.95 years and ranged from one to five years, with a higher prevalence in females and a higher incidence on the left side. Intra and interobserver evaluations obtained similar values and high Kappa = 0.834 (95% CI). The correlation between consensus and tomography showed high Kappa agreement = 0.834 (95% CI), with 100% sensitivity, 95.5% specificity and negative predictive value of 100 (83.9-100). Conclusion: Inlet radiography proved to be a viable and reliable method compared with CT for postoperative evaluation of hip reduction in Developmental Hip Dysplasia

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.