The morphologic variability seen in the domestic dog, Canis lupus familiaris, is unique among mammals. Selective pressures imposed by humans have divided dogs into almost 400 separate breeds. Selection has also led to the development of approximately 450 hereditary diseases, many of which are limited to specific breeds. Over half of these diseases present with similar clinical characteristics to those of many human hereditary diseases, making the dog an ideal model for study of the genetic bases of such diseases. Many diseases do not have candidate genes or have too many candidates to characterize. This is exacerbated in complex diseases that are caused by several genes. Whole-genome scans can provide insight into diseases by identifying marker(s) that co-segregate with a disease phenotype. The Minimal Screening Set - 2 (MSS-2) is the most recent set of microsatellites suitable for whole-genome screens. The first objective of this work was to streamline genomic screens in order to efficiently analyze large numbers of animals. To this end, chromosome-specific microsatellite panels were developed for the MSS-2. Canine hip dysplasia (CHD) is the most common orthopedic disease of the dog. CHD primarily affects medium and large breed dogs, but is found in almost every breed. The major objective of this work was to use linkage analysis to identify chromosomal regions that contain genes that are involved in CHD. Two populations were screened using the MSS-2. The first was a small family of Boykin Spaniels, though no markers were statistically significant in a whole-genome screen. An outcrossed pedigree of Greyhound/Labrador Retrievers was created for quantitative trait loci (QTL) mapping of CHD. The informativeness of markers in the F2 and backcrossed generations were calculated to show the utility of using such a population. Other factors that affect the power of this pedigree to identify QTL were also highlighted. Chromosomes that were identified in a previous screen as harboring putative QTLs were examined using the chromosome-specific panels to further define and confirm the regions of interest. Although no markers reached statistical significance, several areas of interest were identified.

Twelve normal mixed-breed dogs were selected and assigned to acetabular rotation or sham-operated groups. Rotation group dogs had pelvic osteotomies followed by application of an ilial bone plate, causing rotation of the acetabulum to reduce dorsal coverage of the femoral head. Sham group dogs received identical osteotomies but were plated in normal orientation. All dogs had force plate and subjective lameness evaluations pre-operatively and post-operatively. Pelvic radiographs were evaluated pre-operatively and at four-week intervals post-operatively. The dogs were killed at the conclusion of the study, and samples were taken for evaluation. Analysis of vertical ground reaction forces indicated a significant difference between treatment groups, however no difference was noted based on subjective scores. No difference was observed between groups based on radiographic estimations of degenerative changes or Norberg angle, however the coverage of the femoral head was less in rotated dogs. Mild inflammatory changes were discernible in the joint capsule of some dogs in both groups. A trend toward more severe change was present in the left hip of the treatment group, but statistically significant difference was noted only when comparing the right and left legs of the acetabular rotation group. Although evidence of osteoarthritis was noted histologically, only minor differences were detected in the dogs by other means. Because of the minimal changes noted over the duration of the study, we conclude that the model does result in histopathologic change consistent with osteoarthritis, but that force plate analysis, radiographic evaluation, and clinical lameness evaluation are insensitive measures of this change. / Master of Science

ABSTRACT A group of 133 hips with developmental dysplasia of the hip (DDH) are reviewed in the form of a clinical audit. The aim of the study is to determine the relevance of measuring the ossific nucleus centre edge angle (ONCEA) to determine if this measurement can be used to predict the final outcome and the need for a secondary procedure at an earlier age than currently determined. The ONCEA is defined as an approximation of the lowest centre edge angle within six months of removal of the Batchelor POP, following reduction (mean age 24.1 months). It is measured earlier than the centre edge angle (CEA), which is generally used from the age of five years. The ONCEA was divided into three groups: - Reduced (>=10°) – Group A - Mild subluxation (-9° to 9°) – Group B - Severe subluxation (<=-10°) – Group C The significance of the ONCEA was confirmed using the ONCEA/AI ratio, which was also divided into three groups: - Reduced (>0.5) – Group A - Mild subluxation (0 to 0.5) – Group B - Severe subluxation (<0) – Group C Outcome was assessed radiologically by way of the Severin score: In group C there were only 1/13 hips (8%) with an excellent result, in group B there were 20/44 hips (45%) with an excellent result and in group A there were 39/76 hips (51%) with an excellent result. Using Fisher’s exact test, a statistically significant association was shown between each group and subsequent outcome (p=0.001). A significant result was also shown in a comparison of the three ONCEA groups using the McKay classification (a clinical outcome measurement). The ONCEA/AI ratio was also used to include the degree of acetabular coverage. It had similar statistically significant results as described for the above ONCEA results, thus confirming the findings. In conclusion, the ONCEA or ONCEA/AI ratio can be used at an early age (within six months following removal of POP after reduction, at a mean of 18 months of age) for two purposes: 1. To prognosticate the medium and long-term outcome of the patient. 2. To enable the clinician to determine whether a secondary procedure should be performed at an earlier age than usual. A prospective study will be necessary to confirm this.

Thesis (M.Tech.: Chiropractic)- Dept. of Chiropractic, Durban Institute of Technology, 2005. xvii, 109 leaves : ill. ; 30 cm / The paucity of clinical research into the cause of canine hip dysplasia, efficacy and effects of the different treatment protocols available for the management of symptoms, as well as the differing presentations, has led to a continued variation in standardized care for this condition. The aim of this study was to contribute further information on the use of instrument manipulation as an alternative or adjunctive means of managing the symptoms of canine hip dysplasia. Both manual and instrument manipulation have effectively been used in the short-term management of human musculoskeletal pconditions, it was hypothesized that the use of instrument manipulation would benefit the canine patient. The use of human based studies was a guideline, as no previous chiropractic studies have been conducted on the canine subject.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-05-03T19:44:16Z No. of bitstreams: 1 LEANDRO ZIEMER CARNEIRO.pdf: 5141284 bytes, checksum: 967ea86595423b1d3aa3442bdec2b570 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-05-03T19:45:34Z (GMT) No. of bitstreams: 1 LEANDRO ZIEMER CARNEIRO.pdf: 5141284 bytes, checksum: 967ea86595423b1d3aa3442bdec2b570 (MD5) / Made available in DSpace on 2016-05-03T19:45:34Z (GMT). No. of bitstreams: 1 LEANDRO ZIEMER CARNEIRO.pdf: 5141284 bytes, checksum: 967ea86595423b1d3aa3442bdec2b570 (MD5) Previous issue date: 2015-03-31 / Osteotomia intertrocantérica varizante (OIV) objetiva diminuir o ângulo de inclinação de cabeça e colo femoral, comumente aumentado em animais displásicos. Pode ser estabilizada por diferentes métodos, sendo a placa de compressão e parafusos o método mais tradicional. Embora a haste intramedular bloqueada (HIB) ainda não tenha sido relatada em estabilizações pós OIV, sabe-se que em fraturas femorais este método é considerado mais eficiente que as placas compressivas, além de permitir tempo cirúrgico menor. Deste modo, objetivou-se avaliar a aplicabilidade da HIB como método de fixação pós OIV em comparação com a placa compressiva. Foram utilizados dez cadáveres caninos com peso superior a 15 kg, com ambos os fêmures intactos. Nos fêmures esquerdos foram realizadas as OIVs, com remoção de cunha óssea de 20o na face medial e fixação por meio de HIB. Os fêmures contralaterais foram utilizados como controle e, após a realização da mesma técnica cirúrgica, fixou-se os segmentos ósseos por meio de placas de compressão e parafusos. As articulações coxofemorais foram radiografadas em projeção ventrodorsal e os ângulos de Norberg e de inclinação de cabeça e colo femoral comparados antes e após o procedimento cirúrgico entre os métodos de fixação. Também foi comparado o tempo dispendido para a colocação dos implantes. Os resultados demonstraram aumento do ângulo de Norberg em relação ao ângulo pré-operatório (passando de 106,84±5.55o para 111.22o ± 3.89) apenas no grupo HIB; ambos os grupos apresentaram redução do ângulo de ICF, mas sem diferença entre eles; e o tempo de colocação de cada implante também não diferiu entre os dois grupos. Assim, o uso da HIB na estabilização pós OIV foi factível em cadáveres, produzindo resultados similares à placa em relação ao tempo de execução e redução do ângulo ICF, além de permitir aumento o ângulo de Norberg. / Intertrochanteric varus osteotomy (IVO) aims to decrease the angle of head and femoral neck, commonly increased in dysplastic animals. It can be stabilized by different methods, and the compression plate and screws is the most commonly applied. The application of locked intramedullary nail (IN) in femoral fractures has been more efficient and faster than the compressive plates. However, is not known if the IN would be effective in stabilization post IVO. Thus, this study aimed to compare the application of the IN post IVO with compression plate. For this, were used ten canine cadavers weighing more than 15 kg, with both intact femurs. In the left femur were performed IVO, with bone wedge removal of 20o on the medial side and fixation with IN. The contralateral femurs were used as control and, after performing the same surgical technique, the bone segments were fixed with compression plates and screws. The hip joints were radiographed in Ventrodorsal projection, and compared the angles of Norberg and inclination of the head and femoral neck (IHF), obtained before and after surgery. The time spent for the placement of implants as compared too. IHF between the fixing methods before and after surgery. Finally, there was an increase of Norberg angle (from 106.84 ± 5.55o to 111.22o ± 3.89) only in the IN group; Similar results between the two groups were obtained with regard to reducing the IHF angle and the implant placement time compared to the compression plate. Thus, the use of IN post IVO stabilization was feasible in cadavers, producing similar results to the plate in relation to the execution time and reducing the angle IHF, and increasing the Norberg angle.

Orientador: João Guilherme Padilha Filho / Banca: André Luiz Selmi / Banca: Gustavo Garkalns de Souza Oliveira / Banca: Júlio Carlos Canola / Banca: Márcia Rita Fernandes Machado / Resumo: O objetivo deste estudo foi aplicar cunhas de polímero de mamona poroso com adição de cálcio na junção sacroilíaca, avaliar clinicamente a interferência da técnica na deambulação dos cães e, radiograficamente, verificar o aumento da cobertura acetabular à cabeça femoral. Para tal, foram utilizados oito cães, adultos, com peso entre 16,5 a 32 kg, quatro normais e quatro displásicos, porém sem sintomatologia dolorosa. Na junção sacroilíaca esquerda foi aplicada cunha de 30°. Foram realizadas avaliações clínicas pós-operatórias, perimetria da coxa, avaliação do apoio do membro do lado operado, aferição dos ângulos de flexão e extensão. Para avaliação da ventroversão acetabular foram empregados os métodos radiográficos do ângulo de Norberg e a porcentagem de cobertura acetabular. Os animais foram avaliados no pré-operatório, pós-operatório imediato, 30, 60 e 90 dias. Para a avaliação clínica, perimetria da coxa, avaliação da claudicação e apoio do membro, flexão e extensão, também se incluiu os períodos de sete, 14 e 21 dias. Observou-se na avaliação radiográfica aumento da cobertura acetabular logo no pós-operatório imediato, tanto no método do ângulo de Norberg quanto na porcentagem de cobertura acetabular. Não houve interferência na deambulação dos animais, uma vez que todos retornam a deambulação normal ao término do período de avaliação. Do ponto de vista clínico, a cunha comportou-se como biopolímero, suportando a aplicação de parafuso em efeito compressivo. A técnica promove aumento da cobertura acetabular, comprovado radiograficamente, podendo ser empregada em cães displásicos / Abstract: The goal of this study was to apply castor oil porous polymer wedges with addition of calcium in the sacroiliac joint; to evaluate clinically the interference of the technique in the walking of dogs and, radiographically, to check the increasing of the acetabular covering to the femoral head. In order to accomplish it, eight adult dogs weighting 16.5 - 32 kg were used, four of them normal and four of them dysplastic, although without painful symptomatology. In the left sacroiliac joint was applied 30 wedge. Postoperative clinical evaluations, thigh perimetry, evaluation of the support of the operated side member, gauging of the flection and extension angles were carried out. To evaluate the acetabular ventroversion the Norberg angle radiographic methods and the percentage of acetabular covering were used. The animals were evaluated in the preoperative, immediate postoperative, 30, 60 and 90 days. To the clinical evaluation, thigh perimetry, claudication evaluation and member support, flection and extension, they were also included the periods of seven, fourteen and twenty-one days. It was observed in the radiographic evaluation an increasing of the acetabular covering soon in the immediate postoperative, in both the Norberg angle method and the percentage of acetabular covering. There wasn't interference in the walking of the animals, considering that all of them recover the regular walking at the end of the evaluation period. From the clinical point of view, the wedge behaved as biopolymer, bearing the screw application in compression effect. Such technique promotes the acetabular covering increase, radiographically proven, and it can be employed in displastic dogs / Doutor

Made available in DSpace on 2014-06-11T19:31:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-30Bitstream added on 2014-06-13T20:01:44Z : No. of bitstreams: 1 regonato_e_dr_jabo.pdf: 1916142 bytes, checksum: faed3958cca20f37dac1aefd2d35de03 (MD5) / O objetivo deste estudo foi aplicar cunhas de polímero de mamona poroso com adição de cálcio na junção sacroilíaca, avaliar clinicamente a interferência da técnica na deambulação dos cães e, radiograficamente, verificar o aumento da cobertura acetabular à cabeça femoral. Para tal, foram utilizados oito cães, adultos, com peso entre 16,5 a 32 kg, quatro normais e quatro displásicos, porém sem sintomatologia dolorosa. Na junção sacroilíaca esquerda foi aplicada cunha de 30°. Foram realizadas avaliações clínicas pós-operatórias, perimetria da coxa, avaliação do apoio do membro do lado operado, aferição dos ângulos de flexão e extensão. Para avaliação da ventroversão acetabular foram empregados os métodos radiográficos do ângulo de Norberg e a porcentagem de cobertura acetabular. Os animais foram avaliados no pré-operatório, pós-operatório imediato, 30, 60 e 90 dias. Para a avaliação clínica, perimetria da coxa, avaliação da claudicação e apoio do membro, flexão e extensão, também se incluiu os períodos de sete, 14 e 21 dias. Observou-se na avaliação radiográfica aumento da cobertura acetabular logo no pós-operatório imediato, tanto no método do ângulo de Norberg quanto na porcentagem de cobertura acetabular. Não houve interferência na deambulação dos animais, uma vez que todos retornam a deambulação normal ao término do período de avaliação. Do ponto de vista clínico, a cunha comportou-se como biopolímero, suportando a aplicação de parafuso em efeito compressivo. A técnica promove aumento da cobertura acetabular, comprovado radiograficamente, podendo ser empregada em cães displásicos / The goal of this study was to apply castor oil porous polymer wedges with addition of calcium in the sacroiliac joint; to evaluate clinically the interference of the technique in the walking of dogs and, radiographically, to check the increasing of the acetabular covering to the femoral head. In order to accomplish it, eight adult dogs weighting 16.5 - 32 kg were used, four of them normal and four of them dysplastic, although without painful symptomatology. In the left sacroiliac joint was applied 30 wedge. Postoperative clinical evaluations, thigh perimetry, evaluation of the support of the operated side member, gauging of the flection and extension angles were carried out. To evaluate the acetabular ventroversion the Norberg angle radiographic methods and the percentage of acetabular covering were used. The animals were evaluated in the preoperative, immediate postoperative, 30, 60 and 90 days. To the clinical evaluation, thigh perimetry, claudication evaluation and member support, flection and extension, they were also included the periods of seven, fourteen and twenty-one days. It was observed in the radiographic evaluation an increasing of the acetabular covering soon in the immediate postoperative, in both the Norberg angle method and the percentage of acetabular covering. There wasn´t interference in the walking of the animals, considering that all of them recover the regular walking at the end of the evaluation period. From the clinical point of view, the wedge behaved as biopolymer, bearing the screw application in compression effect. Such technique promotes the acetabular covering increase, radiographically proven, and it can be employed in displastic dogs

Beukes Hip Dysplasia (BHD) is an autosomal dominant disorder where the abnormal shape of the hip joint leads to secondary osteoarthritis. The locus of BHD has been previously mapped to 4q35 and screening of candidate genes within this region revealed a mutation in the gene encoding the Ubiquitin-fold modifier 1 specific protease 2 (Ufsp2). The mutation prevents Ufsp2 from cleaving its target, Ufm1. Ufsp2 and Ufm1 are both components of a novel ubiquitin-like protein modification system which involves Ufm1 being processed via the E1, E2 and E3 enzymes (Uba5, Ufc1 and Ufl1, respectively) and attachment to target protein(s) one of which has been identified (Ddrgk1). The aim of this study was to investigate the link between the UFSP2 mutation and the BHD phenotype by: (i) examining the expression of components of the Ufm1 system in vivo and in vitro; (ii) development of an in vitro Ufm1 conjugation system; and (iii) generation and analysis of transgenic mice overexpressing the Ufsp2 gene with the BHD mutation. The expression of Ufsp2 was determined by radioactive RNA in situ hybridisation of mouse tissue sections. The analysis revealed Ufsp2 expression predominantly in the bone of the hip joint and in the bone and secondary ossification centres of the knee of 10 day old mice. Real-Time PCR analysis showed increased expression of components of the Ufm1 system during in vitro osteogenic and chondrogenic differentiation which coincided with induction of ER stress evidenced by upregulation of Bip. These components were also upregulated in response to chemically induced ER stress in vitro. Analysis of the promoter regions of Ufm1 system genes identified unfolded protein response elements in the upstream sequences of Uba5, Ufl1, Ufm1 and Lzap genes and the elements in Uba5 and Lzap were found to be required and responsive to ER stress using luciferase promoter assays. A Tandem Affinity Purification method was developed for isolation and identification of Ufm1 conjugation targets from cell lines expressing modified forms of Ufm1. Mass spectrometry analysis of Ufm1 conjugates purified from HEK293T cell line identified Uba5 and Ufc1 but no new Ufm1 targets. Western blot comparison of Ufm1 conjugated proteins purified from the HEK293T and 2T3 osteoblast cell lines identified putatative Ufm1 conjugation targets and increased conjugation in osteoblasts in response to ER stress. One of these targets was identified as Ddrgk1 but the remaining putative targets remain to be identified by mass spectrometry. Transgenic mice overexpressing the mutated Ufsp2 gene were generated and subjected to phenotypic analysis. No significant differences were found between transgenic and wild type mice following X-ray, histological and weight analysis. Higher expression of Ufsp2 in bone and secondary ossification centres as well as upregulation of components of the Ufm1 system in response to ER stress suggests that the molecular pathway between the UFSP2 mutation and the BHD phenotype may relate to abnormal ER stress responses during osteoblast differentiation. Further studies are however required to determine how the Ufm1 system modulates ER stress responses and how disruption of these processes caused by the UFSP2 mutation causes BHD.

Hip dysplasia, also known as congenital dysplasia of the hip (CDH) or Developmental Dysplasia of the Hip (DDH), is a mal-alignment of the hip joint. Left untreated within the first nine months, DDH could lead to permanent disability. Luckily however, this condition is diagnosed at an early age and is usually treated without surgery through the use of the Pavlik harness. In this thesis, a 3D computational model and dynamic finite element analysis of the muscles and tissues involved in hip dysplasia and the mechanics of the Pavlik harness, as rendered by Dr. Alain J. Kassab’s research group in the College of Mechanical and Aerospace Engineering in the University of Central Florida over the past 3 years, were reviewed and discussed to evaluate the accuracy of the hip reduction mechanism. I examine the group’s usage of CT-based images to create accurate models of the bony structures, muscle tensions and roles that were generated using biomechanical analyses of maximal and passive strain, and the usage of adult and infant hips. Results, as produced by the group indicated that the effects and force contribution of the muscles studied are functions of severity of hip dislocation. Therefore, I discussed complications with real world-to-computational modeling with regards to structural systems and data interpretations. Although this design could be applied to more anatomical models and mechanistic analyses, more research would have to be completed to create more accurate models and results.

Newborns diagnosed with hip dysplasia face severe consequences when treatments fail. The Pavlik harness presents the most common worldwide treatment for correcting this medical hip abnormality in newborns, but becomes increasingly ineffective as subluxation increases. A dynamic finite element analysis on the hip joint would yield results that could provide insight to physicians as to how the Pavlik harness could be optimized to increase its success rate and develop patient-specific treatment plans. The study completes the first step in such an analysis by generating a three-dimensional model of an infant hip joint directly derived from computed tomography imaging in order to accurately represent the anatomical locations of muscle origins and insertions points as well as the unique cartilaginous characteristics of a neonate hip and femur. Such models will further enhance findings on the biomechanics of hip dysplasia that resulted from a preliminary study using computer-aided design to recreate the hip joint. In addition to the models, the orientation of the psoas tendon in a dysplastic hip through full range abduction and flexion was analyzed using a cadaveric dissection. It was determined that the psoas tendon was not an obstruction to reduction when the hip was in flexion so long as the tendon was not adherent to the hip capsule, and therefore can be disregarded in a finite element analysis or dynamic simulation that introduces flexion. The work of this thesis will lay the foundation for complex finite element analyses regarding the biomechanics of hip dysplasia in neonates as well as other hip abnormalities relevant to early child development.