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

O manejo clínico dos pacientes com pólipos colorretais é principalmente baseado na histologia das lesões removidas. Em conseqüência, o diagnóstico histológico tem um papel muito importante na decisão terapêutica e a uniformidade de interpretação dos diferentes laudos de patologia é essencial. Apesar destas relevantes implicações, poucos estudos existem avaliando a variabilidade interobservador na elucidação dessa doença e a concordância não é considerada satisfatória. Objetivo: avaliar a variabilidade interobservador no diagnóstico histológico dos pólipos colorretais. Metodologia: foram avaliados 230 pólipos colorretais no Serviço de Patologia do Hospital de Clínicas de Porto Alegre (HCPA). Quatro patologistas examinaram todas as lâminas de forma independente e “cega”, ou seja, sem conhecimento do diagnóstico elaborado pelo seu colega. As lesões colorretais foram classificadas em relação ao diagnóstico: pólipo e carcinoma invasivo e quanto ao tipo de pólipo: adenomatoso versus hiperplásico. Nos adenomas foi avaliado o tipo histológico (tubular, túbulo-viloso e viloso) e o grau de displasia (baixo e alto grau). Resultados: o Kappa médio, em relação ao tipo de lesão, foi de 0,794, considerado moderado. Quanto ao tipo de pólipo, o Kappa médio foi 0,852, ou seja, uma ótima concordância. Em relação aos adenomas, no que se refere ao tipo histológico, obteve-se um Kappa médio, fraco de 0,291, e na avaliação do grau de displasia o Kappa médio foi regular com valor de 0,420. Conclusão: o índice de concordância, entre os quatro observadores foi considerado de moderado a ótimo no tipo de lesão e de pólipo, porém a variabilidade foi grande na avaliação dos adenomas, tanto no que concerne ao tipo histológico quanto ao grau de displasia com um kappa de fraco a regular. / The clinical management of patients with colorectal polyps is mainly based on the histology of the removed lesions. Therefore, the histological diagnosis has a very important role in deciding the treatment and the uniform interpretation of the different pathology reports is essential. In spite of these relevant implications, there are only very few studies assessing the interobserver variability in such diagnosis and the concordance of reports among different examiners is not considered satisfactory. Objective: to assess interobserver variability in the pathology reports in the diagnosis of colorectal polyps. Method: at the Department of Pathology of HCPA [Hospital de Clínicas de Porto Alegre] 230 slides of colorectal polyps were examined by four independent pathologists “blindly”, that is, the diagnosis given by their colleagues was not known. Colorectal lesions were classified according to the diagnosis as polyp or invasive cancer and to the polyp type (adenomatous or hyperplasic). The histological type of the adenomas (tubular, tubulovillous and villous) and the grade of dysplasia (high or low) were also assessed. Results: mean kappa of the type of lesion was 0.794, which is considered moderate. The mean kappa of 0.852 for the type of polyp is considered excellent concordance. Regarding the histology of adenomas, the mean kappa was 0.291, considered weak. The assessment of the degree of dysplasia showed a regular Kappa of 0.420. Conclusion: the concordance rate among the four pathologists was considered to be moderate to excellent for the type of lesion and of polyp but there was great variability in the assessment of adenomas both for the histological type and for dysplasia, showing a weak to regular kappa.

O manejo clínico dos pacientes com pólipos colorretais é principalmente baseado na histologia das lesões removidas. Em conseqüência, o diagnóstico histológico tem um papel muito importante na decisão terapêutica e a uniformidade de interpretação dos diferentes laudos de patologia é essencial. Apesar destas relevantes implicações, poucos estudos existem avaliando a variabilidade interobservador na elucidação dessa doença e a concordância não é considerada satisfatória. Objetivo: avaliar a variabilidade interobservador no diagnóstico histológico dos pólipos colorretais. Metodologia: foram avaliados 230 pólipos colorretais no Serviço de Patologia do Hospital de Clínicas de Porto Alegre (HCPA). Quatro patologistas examinaram todas as lâminas de forma independente e “cega”, ou seja, sem conhecimento do diagnóstico elaborado pelo seu colega. As lesões colorretais foram classificadas em relação ao diagnóstico: pólipo e carcinoma invasivo e quanto ao tipo de pólipo: adenomatoso versus hiperplásico. Nos adenomas foi avaliado o tipo histológico (tubular, túbulo-viloso e viloso) e o grau de displasia (baixo e alto grau). Resultados: o Kappa médio, em relação ao tipo de lesão, foi de 0,794, considerado moderado. Quanto ao tipo de pólipo, o Kappa médio foi 0,852, ou seja, uma ótima concordância. Em relação aos adenomas, no que se refere ao tipo histológico, obteve-se um Kappa médio, fraco de 0,291, e na avaliação do grau de displasia o Kappa médio foi regular com valor de 0,420. Conclusão: o índice de concordância, entre os quatro observadores foi considerado de moderado a ótimo no tipo de lesão e de pólipo, porém a variabilidade foi grande na avaliação dos adenomas, tanto no que concerne ao tipo histológico quanto ao grau de displasia com um kappa de fraco a regular. / The clinical management of patients with colorectal polyps is mainly based on the histology of the removed lesions. Therefore, the histological diagnosis has a very important role in deciding the treatment and the uniform interpretation of the different pathology reports is essential. In spite of these relevant implications, there are only very few studies assessing the interobserver variability in such diagnosis and the concordance of reports among different examiners is not considered satisfactory. Objective: to assess interobserver variability in the pathology reports in the diagnosis of colorectal polyps. Method: at the Department of Pathology of HCPA [Hospital de Clínicas de Porto Alegre] 230 slides of colorectal polyps were examined by four independent pathologists “blindly”, that is, the diagnosis given by their colleagues was not known. Colorectal lesions were classified according to the diagnosis as polyp or invasive cancer and to the polyp type (adenomatous or hyperplasic). The histological type of the adenomas (tubular, tubulovillous and villous) and the grade of dysplasia (high or low) were also assessed. Results: mean kappa of the type of lesion was 0.794, which is considered moderate. The mean kappa of 0.852 for the type of polyp is considered excellent concordance. Regarding the histology of adenomas, the mean kappa was 0.291, considered weak. The assessment of the degree of dysplasia showed a regular Kappa of 0.420. Conclusion: the concordance rate among the four pathologists was considered to be moderate to excellent for the type of lesion and of polyp but there was great variability in the assessment of adenomas both for the histological type and for dysplasia, showing a weak to regular kappa.

Orientadores: Maria Aparecida Marques dos Santos Mezzacappa, José Dirceu Ribeiro / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T05:32:42Z (GMT). No. of bitstreams: 1 Mendes_ThaisdeBarros_D.pdf: 2709718 bytes, checksum: 980600cf933c0edd1c628440ceb42c40 (MD5) Previous issue date: 2010 / Resumo: Recém-nascidos (RN) com displasia broncopulmonar (DBP) apresentam alta frequência de tratamento para doença do refluxo gastroesofágico (DRGE). O agravamento da evolução desta doença pulmonar é atribuído à associação entre as duas entidades. Em virtude das indefinições quanto à ocorrência da DRGE em RN com DBP e dadas as possíveis consequências sobre a sua morbidade, bem como as altas frequências de tratamento clínico, considerou-se ser de interesse estudar a presença de anormalidades da monitorização prolongada do pH esofágico em RN com e sem DBP. Objetivos- Determinar a prevalência de índice de refluxo (IR) ?10% na monitorização prolongada do pH esofágico em RNMBP com e sem o diagnóstico de DBP e estabelecer fatores associados. Métodos- Foi realizado um estudo prospectivo e de corte transversal com um componente longitudinal. Foram selecionados 35 casos com DBP e 15 sujeitos para o grupo de comparação que foram submetidos à monitorização prolongada do pH esofágico distal, no período de abril de 2004 a dezembro de 2008. Foram analisadas as variáveis demográficas, de evolução pós-natal, referentes a procedimentos e medicamentos no período neonatal, bem como os escores de gravidade clínica e radiológica da DBP e de gravidade da doença pulmonar na primeira semana de vida. Foram empregados os testes de Qui-quadrado e Exato de Fisher para as variáveis categóricas, e para as numéricas o teste U de Mann-Whitney. Em seguida foi realizada a análise por regressão logística univariada e múltipla para determinar o odds-ratio (OR) e o seu intervalo de confiança (IC) de 95%. Resultados- A prevalência de IR ?10% nos grupos com e sem DBP foi de 65,7% e 93,3%, respectivamente. O peso ao nascer foi o fator preditor independente de risco para o IR ?10% (OR 1,769 IC95% 1,172-2,669). Conclusão- Foi encontrada uma prevalência de IR ?10% em RN com DBP de 65,7% e no grupo de comparação de 93,3% sem sinais clínicos de DRGE. A chance de IR ?10% aumentou em 76,9% a cada aumento de 100 gramas no PN. Os resultados deste estudo permitem concluir que a prevalência de IR ?10% não é maior em RN com DBP do que no grupo de comparação. RN assintomáticos ou com apneia da prematuridade podem apresentar IR ?10%, sendo assim o diagnóstico de DRGE baseado nos resultados da monitorização do pH esofágico e a indicação de qualquer modalidade terapêutica precisa ser criteriosa até que se definam quais são os RN que necessitam de tratamento / Abstract: Neonates with bronchopulmonary dysplasia (BPD) present high frequency of treatment for gastroesophageal reflux disease (GERD). The relationship between these illnesses is controversy. Due to indefinations for ocorrency of GERD in newborns with BPD and considering the possible consequences about his morbidity so as the high frequency of clinical treatment, seems to us important to study the presence of abnormalities in the prolonged esophageal pH monitoring in neonates with and without BPD. Objectives- To determine the prevalence pH esophageal monitoring alterations in very low birth weight infants with and without BPD and establish associated factors for reflux index (RI) ?10%. Methods- A prospective, cross-sectional study, with a longitudinal component was realized, including 35 newborns with BPD and 15 subjects for the comparison group, that were submitted to 24 hours esophageal pH monitoring and studied from April 2004 to December 2008. Were evaluated variables demographics, postnatal evolution, procedures and medications used in the neonatal period, scores of clinical and radiologic severity and initial lung disease in the first week of life. For the statistic analysis were utilized the chi-square test and the Fisher's exact test for the category variables, and Mann-Whitney's test for numerical variables. Multiple logistic regression was used for to determine odds-ratio (OR) and confidence interval (CI) of 95%. Results- The prevalence of RI ?10% in the groups with e without BPD was 65.7% and 93.3%, respectively. The birth weight (BW) was the independent predictor factor for RI ?10% (OR 1.769 CI95% 1.172-2.669). Conclusions- High frequency of RI altered was demonstrated in newborns with BPD and the comparison group without clinics signs of GERD. The chance of RI ?10% increased in 76.9% in each increase of 100 grams in the BW. The results showed that the prevalence of RI ?10% not is major in neonates with BPD. Asymptomatic newborns or infants with apnea of prematurity may present IR ?10%, so the diagnosis of GERD based on the results of esophageal pH monitoring and indication of any therapeutic modality needs to be careful until a definition of which are infants who need treatment / Doutorado / Saude da Criança e do Adolescente / Doutor em Saude da Criança e do Adolescente

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-06-09T15:51:35Z No. of bitstreams: 2 Tese - Fernanda Aparecida de Oliveira Peixoto - 2015.pdf: 1346302 bytes, checksum: 7ffcffc54a65cec4c0a8986361b2cfb2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-06-09T15:51:55Z (GMT) No. of bitstreams: 2 Tese - Fernanda Aparecida de Oliveira Peixoto - 2015.pdf: 1346302 bytes, checksum: 7ffcffc54a65cec4c0a8986361b2cfb2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-06-09T15:51:55Z (GMT). No. of bitstreams: 2 Tese - Fernanda Aparecida de Oliveira Peixoto - 2015.pdf: 1346302 bytes, checksum: 7ffcffc54a65cec4c0a8986361b2cfb2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2015-08-07 / Despite the improvement in survival of premature infants, there was no progress in the incidence of bronchopulmonary dysplasia, especially in the last 20 years. Systemic corticosteroids, which has always been a therapeutic option, fell into disuse because of its adverse effects on the neurological development of premature infants and other routes of admistration have been researched for use of corticosteroids. Budesonide, which is an inhaled steroid, has been studied in an attempt to prevent bronchopulmonary dysplasia. The objectives of this study were to determine if the intratracheal instillation of budesonide with surfactant, improved lung performance, prevents chronic lung disease and reduces mortality in premature infants with minimal adverse effects. This is a clinical trial, blind and randomized 90 preterm infants who required prophylaxis or early rescue therapy with surfactant: 45 were randomized in the treated group (0.25 mg/kg of budesonide and 100 mg/kg surfactant) and 45 in the control group (100 mg/kg of surfactant). The evaluated final outcomes were mortality and bronchopulmonary dysplasia. Although the treatment group has shown better results than the control group, in both cases, mortality (10x15) and bronchopulmonary dysplasia at 36 weeks corrected gestational age (8/35 x 10/32), there was no significant statistical difference (p = 0.501 and p = 0.571). No clinically significant adverse events were observed in the study. The study concludes that, despite not having been demonstrated statistically significant difference in your results, we can not rule out the benefits of budesonide instilled into the trachea through the surfactant. Other randomized and multicenter studies should be encouraged. / Apesar da melhora na sobrevida dos recém-nascidos prematuros, não houve progresso em relação à incidência da displasia broncopulmonar, sobretudo nos últimos 20 anos. O corticoide sistêmico, que sempre foi uma opção terapêutica, entrou em desuso devido aos seus efeitos adversos no desenvolvimento neurológico dos prematuros. Outras vias têm sido pesquisadas para a utilização do corticoide. A budesonida, que é um esteroide de uso inalatório, tem sido estudada na tentativa de prevenir a displasia broncopulmonar. Os objetivos deste estudo foram determinar se a instilação intratraqueal de budesonida, por meio do surfactante, melhora o desempenho pulmonar, previne a doença pulmonar crônica e reduz a mortalidade em prematuros, com o mínimo de efeitos adversos possíveis. Trata-se de um ensaio clínico, cego e randomizado com 90 recém-nascidos prematuros que necessitaram de profilaxia ou de terapia de resgate precoce com surfactante: 45 foram randomizados no grupo tratado (0,25 mg/kg de budesonida e 100 mg/kg de surfactante) e 45 no grupo controle (100 mg/kg de surfactante). Os desfechos finais avaliados foram mortalidade e displasia broncopulmonar. Embora o grupo de tratamento tenha mostrado resultados melhores do que o grupo de controle, tanto para a mortalidade (10x15) quanto para displasia broncopulmonar avaliada com 36 semanas de idade gestacional corrigida (8/35 x 10/32), não houve diferença estatística significativa (p = 0,501 e p = 0,571). Nenhum evento adverso clinicamente significativo foi observado no estudo. O estudo conclui que, apesar de não ter sido demonstrado nenhuma diferença estatística significativa em seus resultados, não se pode descartar os benefícios da budesonida instilada na traqueia por meio do surfactante. Outros estudos randomizados e multicêntricos devem ser encorajados.

Developmental dysplasia of the hip (DDH) refers to some hip disorders, from mildly dysplastic to hip joint dislocation. The main feature of DDH is the deficient acetabular coverage, which is related to a small contact area in the hip joint, and causes an increase in contact pressure. Ganz periacetabular osteotomy (PAO) is a surgical procedure to correct acetabular orientation in DDH. It changes the position of the acetabulum to increase the femoral head coverage and distribute the contact pressure over the cartilage surface. The procedure of Ganz PAO is technically demanding and its success depends significantly on the surgeon’s experience. The aim of this research is to investigate whether it is possible to optimize the position of the acetabular fragment in patients suffering DDH before a Ganz PAO by using finite element (FE) analysis. Using computed tomography (CT) data from patients with DDH, five three-dimensional (3D) hip models were developed. A virtual Ganz PAO was then performed on the hip models. FE analyses were carried out on the hip models before and after virtual Ganz PAO. Contact area, contact pressure and Von Mises stress in the hip cartilage were checked and analysed in order to find an optimal acetabular position. The first virtual surgery performed was only to rotate the acetabular fragment in the lateral direction to improve the acetabular coverage. Analyses were conducted under loading conditions associated with four commonly daily activities: one leg stance, normal walking, descending stairs and knee bend. Second virtual surgery performed was to rotate the fragment in both the lateral and anterior directions and FE analysis conducted for one leg stance loading condition. Contact area, contact pressure and Von Mises stress in the cartilage all varied according to the change of the acetabular fragment position through virtual Ganz PAO. The optimal lateral position of the acetabular fragment occurs close to the inferior border of its normal range. Large anterior position of the acetabular fragment results in large contact area, low contact pressure and Von Mises stress. However, an overcorrection of the acetabular fragment, especially in the anterior correction, leads to problems in performing normal hip movements. The optimal anterior position of the acetabular fragment is therefore close to the superior limit of the normal range. In conclusion, the present analysis shows that an optimal position of the acetabular fragment for patients suffering DDH which improves the acetabular femoral head coverage in the normal range, maximizes the contact area and minimizes the contact pressure and Von Mises stress can be established using 3D models and FE analysis. This information will be useful to the surgeons for the planning of PAO.

Sclerosteosis is a rare genetic bone dysplasia disorder characterised by generalised craniotubular bone modelling. Alongside many clinical appearances marked in sclerosteosis, the auditory system is considerably compromised on several levels during the disease progression. Extensive otolaryngological research on the history of sclerosteosis, the clinical presentation of sclerosteosis, radiographic studies and the gene causing the condition had been documented. No studies had been found describing the audiological profiles, auditory functioning and abnormalities for subjects with sclerosteosis. Thus the object of this study aimed to describe the auditory profile of subjects with sclerosteosis. A cross-sectional descriptive research design and quantitative research approach was followed to investigate the auditory characteristics of subjects with sclerosteosis. Subjects were selected from a database of patients with confirmed diagnoses of sclerosteosis. Ten subjects responded and provided written informed consent. Test procedures included otoscopy, tympanometry, acoustic reflexes, diagnostic pure-tone airand bone-conduction audiometry, speech audiometry, distortion product otoacoustic emissions (DPOAE), auditory brainstem responses (ABR) and computed tomographic (CT) scans. The subjects were assessed with a comprehensive audiological test-battery within a single test session lasting approximately two hours. A CT scan was conducted on a separate occasion shortly after the audiological data were obtained. Normal type A tympanograms were obtained in 50% (n=10/20) of ears. All subjects presented with mixed hearing losses varying from moderate (5%; n=1), severe (55%; n=11) and profound (40%; n=8) degrees across ears. Hearing loss configurations ranged from rising (15%), sloping (35%) and air-conduction thresholds peaking at 2000 Hz (50%). Air bone gaps (ABG) were larger in older subjects, although not statistically significant (p>.05). The CT scans indicated anatomical abnormalities of the external auditory canal, tympanic membrane, middle ear space, ossicles, oval window, round window and the internal auditory canal. The progressive abnormal bone formation in sclerosteosis involved the middle ear, the round and oval windows of the cochlea and internal auditory canal. The progressive abnormal bony overgrowth, which is the hallmark of sclerosteosis, led to functional impairment at various levels in the auditory system. The current findings provided a comprehensive auditory profile for sclerosteosis. Results might be utilised alongside future research findings to direct criteria and audiological indications for surgical and audiological intervention. / Dissertation (MCommunication Pathology)--University of Pretoria, 2013. / gm2014 / Speech-Language Pathology and Audiology / Unrestricted

Magister Scientiae Dentium - MSc(Dent) / Ossifying fibroma (OF) is the most frequent of the three fibro-osseous lesions of the jaws. It occurs mostly in patients between the age of 20 and 40 years. Females are more commonly affected than males. Clinically, OF usually presents as a painless expansive intra-bony mass. Swelling and pain may be present in some cases while some lesions are discovered incidentally. Radiographically, OF is usually well-defined and unilocular or multilocular. Early lesions present as well-defined radiolucency that are small in size. Over time, the lesions tend to enlarge in size and become mixed radiolucent-radiopaque and finally become completely radiopaque. The aim of this study was to determine the clinical and radiological features of ossifying fibroma presenting at the Departments of Maxillo-Facial and Oral Surgery and Diagnostics and Radiology, University of the Western Cape Oral Health Centre as well as to assess its management and recurrence patterns. A retrospective case series analysis was performed of all histopathologically diagnosed ossifying fibroma cases available at the Departments of Maxillo-Facial and Oral Surgery and Diagnostics and Radiology at the Faculty of Dentistry, University of the Western Cape from 1976-2014. Patient's age, gender and ethnicity were recorded. The clinical presentation of the lesion as well as the history was analyzed. Radiographic features including density, size, shape, location, locularity and its effect on adjacent structures was noted. Management of each case and follow-up was also documented. A total 61 cases were included in the study. The majority of patients were females (63.9%) and below 40 years of age (73.9%). Few cases were symptomatic (29.5%) with an average period 22 months from first symptoms to presentation. The mandibular posterior region was most affected (55.5%) while larger lesions occurred more frequently in younger patients. Majority of lesions were radiopaque (49.2%) and had well-defined margins (93.6%). Most cases were managed by surgical curettage (68.2%). Following an average follow-up period of 20 months only one case recurred (recurrence rate =6.7%). In conclusion, the majority of the clinical and radiographic findings of ossifying fibroma were similar in South African patients as those of other populations. Differences include that the lesions in this population were more radio-opaque and larger in size than in the reported literature. Surgical curettage is an acceptable management protocol with low rate of recurrence.

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.

No description available.