Thesis (M.D.)--Boston University

No description available.

Osteoarthritis is a chronic degenerative joint disease that affects the whole joint, including the articulating surfaces and capsular tissues in and around the joint (Hügle and Geurts 2016). Osteoarthritis currently impacts 27 million Americans (Racine 2015). Two prominent features in osteoarthritis that are correlated with greater pain and reduced function are MRI-identified bone marrow lesions and CT-identified subchondral bone cysts (Kumar et al. 2013). At this time, the relationship between bone marrow lesions and subchondral bone cysts has not been confirmed. Nor has the nature of the tissues associated with these clinical signs been fully characterized, pointing to the need for further research to identify the composition of subchondral bone cysts as these cysts could be a potential target for therapeutic intervention. This study focused on characterizing the tissue content of subchondral bone cysts in osteoarthritic femoral heads. Osteoarthritic femoral heads were collected from male and female patients, ranging in age from 43-72 years old, who underwent total hip replacement. After surgery, the femoral heads were fixed in 4% paraformaldehyde and scanned via micro-computed tomography (MicroCT). The MicroCT images were used to identify regions in each head containing large subchondral bone cysts, the primary compressive bone, and anterior cartilage. These regions were mapped to the actual femoral head and guided the dissection of the femoral head. Samples from each of the regions were decalcified, embedded in paraffin, and cut into 5-micron-thick histological sections which were then mounted onto slides. Each section was stained in Safranin-O/Fast green and hematoxylin and eosin to visualize the tissues present. Immunohistochemistry with anti-CD31 was carried out on selected slides to identify blood vessels. The samples within all three regions of the femoral head were graded histologically for the presence of subchondral bone cysts, whether cartilage was within the cyst region, if the histological section matched its corresponding MicroCT image, if the articular cartilage was fibrillated, the presence of sclerotic bone, the presence of osteophytes, and the presence of blood vessels. It was clear that many of these samples were in later stages of osteoarthritis considering most samples exhibited all of the above characteristics, contained fibrous tissue, and had little normal fatty marrow. Typically, subchondral bone cysts presented beneath fibrillated and degenerated articular cartilage, contained fibrous tissue that was much more intensely vascularized and innervated as compared to normal fatty marrow, and was surrounded by sclerotic trabecular bone. In some cases, osteophytes also formed at the articular surface beneath areas of degenerated cartilage. Some subchondral bone cysts contained cartilage and even smooth muscle cells in addition to fibrous connective tissue. The varied location of the subchondral bone cysts shows the need for further research as to how their etiologies develop. The content of the subchondral bone cysts suggests that areas with disrupted trabeculae become intensely vascularized to allow the influx of inflammatory materials and mesenchymal stem cells to lay down fibrous tissue and thicken the surrounding trabeculae to stabilize the weakened microstructure of the femoral head. By gaining a comprehensive understanding of the pathology of osteoarthritis and of subchondral bone cysts in particular, the progression of the disease can be more firmly established and potential new treatments can be developed.

O Cisto Ósseo Simples (COS) ou Cisto Ósseo Traumático (COT), é uma cavidade óssea não epitelizada, de conteúdo fluido sero-sanguinolento ou vazia. Muito se discute sobre sua etiopatogenia que ainda continua incerta. O tratamento de escolha ainda é a exploração cirúrgica, embora haja vários casos de sucesso descritos na literatura nos quais escolheu-se a proservação após criteriosa avaliação clínica e radiográfica. A porposta deste trabalho foi: 1) Analisar o estado atual de remodelação óssea espontânea em casos diagnosticados clínica e radiograficamente, sem cirurgia, que estão sendo seguidos por diferentes períodos de tempo (proservados). 2) Analisar a contribuição da Tomografia Computadorizada de Feixe Cônico (TCFC) no diagnóstico imaginológico do COS. 3) Comparar características do COS na radiografia panorâmica com as características encontradas no exame tomográfico. Foram selecionados 22 pacientes diagnosticados com COS e em acompanhamento clinico e radiográfico, segundo protocolo proposto por Damante et al. (2002). Dos 22 pacientes, 13 foram avaliados clinica e radiograficamente e nove pacientes foram avaliados apenas radiograficamente, através do banco de imagens do Departamento de Estomatologia. Foram avaliados 7 exames tomográficos, sendo que 6 deles também estavam disponíveis no banco de imagens. Três examinadores avaliaram as radiografias panorâmicas dos 22 pacientes e apenas 1 examinador avaliou as tomografias computadorizadas. Foi realizado o teste Kappa para calibração intra e interexaminador e aplicada uma estatística indutiva e descritiva aos resultados. Apenas um paciente apresentou resposta positiva à palpação e percussão dos dentes na região afetada. A concordância intra e interexaminador foi calculada pelo teste Kappa e valores satisfatórios foram encontrados. A maioria dos cistos avaliados foram classificados nas categorias 3, 4 ou 5 (em involução, quase completamente resolvido ou completamente resolvido, respectivamente). Das 7 TCFCs analisadas 6 demonstraram presença de adelgaçamento e perfuração de pelo menos uma das corticais. A amostra estudada evidenciou um processo de resolução espontânea do COS, uma vez que a maioria das lesões encontrou-se em processo de regressão ou já resolvidos, após diferentes períodos de acompanhamento. Isso reafirma as hipóteses presentes na literatura, sobre a possível resolução espontânea do COS, diante da qual a cirurgia torna-se desnecessária, uma vez que em sua maioria, são assintomáticos e não apresentam sinais clínicos. O exame tomográfico forneceu maiores detalhes imaginológicos do COS em relação à radiografia panorâmica, uma vez que foi possível detectar a presença de adelgaçamento e perfuração das corticais ósseas em 86% dos casos. / Simple Bone Cyst (SBC) or Traumatic Bone Cyst (TBC) is a non- epithelialized bone cavity, with sero-bloody fluid or empty content. There is debate regarding its pathogenesis that still remains unclear. The treatment of choice is still the surgical exploration, although there are successful cases described in the literature in which just the follow-up with clinical and radiographic evaluation were done. 1)To analyze the current state of spontaneous bone remodeling (self-healing) in cases diagnosed clinically and radiographically without surgery, being followed by different periods of time. 2) Analyze the contribution of Cone Beam Computed Tomography (CBCT) imaging in the diagnosis of SBC. 3) To compare the characteristics of SBC panoramic radiograph with features found on CT scan. Twenty-two patients diagnosed with SBC without surgery and submitted to Damante et al. protocol of follow-up (2002), were selected. Thirteen patients (13/22) were evaluated clinically and radiographically and nine patients (9/22) were evaluated only radiographically. Of these 22 patients, 7 patients had CT scans in the images database and these exams were evaluated too. Three observers evaluated the panoramic radiographs of 22 patients and only one examiner evaluated the CT scans. Kappa test was performed for intra and inter-calibration and inductive an descriptive statistics was applied to the results. Only one patient had a positive response to palpation and percussion of the teeth in the cyst area. The intra and inter agreement was calculated by Kappa test and values were found satisfactory. Most of the cysts evaluated were rated as 3, 4 or 5 (\"remodeling,\" \"almost completely resolved\" or \"completely resolved,\" respectively). Six of the 7 TCFCs analyzed showed the presence of thinning and perforation of at least one bone cortical. The study showed a process of spontaneous resolution (self-healing) of the SBC, since most cysts found in the regression process and resolved after different follow-up periods. This reaffirms the assumptions in the literature about the spontaneous resolution of the SBC, since the majority are asymptomatic and do not exhibit clinical signs. A CT scan can give new information about the imaging aspects of SBC, since it was possible to detect the presence of thinning and perforation of cortical bone in 86% of cases.

Thesis--København Tandlægehøjskole. / Summary in Danish. Bibliography: p. 179-194.

Thesis--København Tandlægehøjskole. / Summary in Danish. Bibliography: p. 179-194.

O Cisto Ósseo Simples (COS) ou Cisto Ósseo Traumático (COT), é uma cavidade óssea não epitelizada, de conteúdo fluido sero-sanguinolento ou vazia. Muito se discute sobre sua etiopatogenia que ainda continua incerta. O tratamento de escolha ainda é a exploração cirúrgica, embora haja vários casos de sucesso descritos na literatura nos quais escolheu-se a proservação após criteriosa avaliação clínica e radiográfica. A porposta deste trabalho foi: 1) Analisar o estado atual de remodelação óssea espontânea em casos diagnosticados clínica e radiograficamente, sem cirurgia, que estão sendo seguidos por diferentes períodos de tempo (proservados). 2) Analisar a contribuição da Tomografia Computadorizada de Feixe Cônico (TCFC) no diagnóstico imaginológico do COS. 3) Comparar características do COS na radiografia panorâmica com as características encontradas no exame tomográfico. Foram selecionados 22 pacientes diagnosticados com COS e em acompanhamento clinico e radiográfico, segundo protocolo proposto por Damante et al. (2002). Dos 22 pacientes, 13 foram avaliados clinica e radiograficamente e nove pacientes foram avaliados apenas radiograficamente, através do banco de imagens do Departamento de Estomatologia. Foram avaliados 7 exames tomográficos, sendo que 6 deles também estavam disponíveis no banco de imagens. Três examinadores avaliaram as radiografias panorâmicas dos 22 pacientes e apenas 1 examinador avaliou as tomografias computadorizadas. Foi realizado o teste Kappa para calibração intra e interexaminador e aplicada uma estatística indutiva e descritiva aos resultados. Apenas um paciente apresentou resposta positiva à palpação e percussão dos dentes na região afetada. A concordância intra e interexaminador foi calculada pelo teste Kappa e valores satisfatórios foram encontrados. A maioria dos cistos avaliados foram classificados nas categorias 3, 4 ou 5 (em involução, quase completamente resolvido ou completamente resolvido, respectivamente). Das 7 TCFCs analisadas 6 demonstraram presença de adelgaçamento e perfuração de pelo menos uma das corticais. A amostra estudada evidenciou um processo de resolução espontânea do COS, uma vez que a maioria das lesões encontrou-se em processo de regressão ou já resolvidos, após diferentes períodos de acompanhamento. Isso reafirma as hipóteses presentes na literatura, sobre a possível resolução espontânea do COS, diante da qual a cirurgia torna-se desnecessária, uma vez que em sua maioria, são assintomáticos e não apresentam sinais clínicos. O exame tomográfico forneceu maiores detalhes imaginológicos do COS em relação à radiografia panorâmica, uma vez que foi possível detectar a presença de adelgaçamento e perfuração das corticais ósseas em 86% dos casos. / Simple Bone Cyst (SBC) or Traumatic Bone Cyst (TBC) is a non- epithelialized bone cavity, with sero-bloody fluid or empty content. There is debate regarding its pathogenesis that still remains unclear. The treatment of choice is still the surgical exploration, although there are successful cases described in the literature in which just the follow-up with clinical and radiographic evaluation were done. 1)To analyze the current state of spontaneous bone remodeling (self-healing) in cases diagnosed clinically and radiographically without surgery, being followed by different periods of time. 2) Analyze the contribution of Cone Beam Computed Tomography (CBCT) imaging in the diagnosis of SBC. 3) To compare the characteristics of SBC panoramic radiograph with features found on CT scan. Twenty-two patients diagnosed with SBC without surgery and submitted to Damante et al. protocol of follow-up (2002), were selected. Thirteen patients (13/22) were evaluated clinically and radiographically and nine patients (9/22) were evaluated only radiographically. Of these 22 patients, 7 patients had CT scans in the images database and these exams were evaluated too. Three observers evaluated the panoramic radiographs of 22 patients and only one examiner evaluated the CT scans. Kappa test was performed for intra and inter-calibration and inductive an descriptive statistics was applied to the results. Only one patient had a positive response to palpation and percussion of the teeth in the cyst area. The intra and inter agreement was calculated by Kappa test and values were found satisfactory. Most of the cysts evaluated were rated as 3, 4 or 5 (\"remodeling,\" \"almost completely resolved\" or \"completely resolved,\" respectively). Six of the 7 TCFCs analyzed showed the presence of thinning and perforation of at least one bone cortical. The study showed a process of spontaneous resolution (self-healing) of the SBC, since most cysts found in the regression process and resolved after different follow-up periods. This reaffirms the assumptions in the literature about the spontaneous resolution of the SBC, since the majority are asymptomatic and do not exhibit clinical signs. A CT scan can give new information about the imaging aspects of SBC, since it was possible to detect the presence of thinning and perforation of cortical bone in 86% of cases.

Made available in DSpace on 2017-07-10T14:57:30Z (GMT). No. of bitstreams: 1 Dissertacao_Renata Zoraida_ Rizental Delgado.pdf: 2641394 bytes, checksum: c9a23494ed97bde58dcc144b147a740f (MD5) Previous issue date: 2015-02-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Introduction: Gorlin syndrome (GS) also known as Nevoid Basal Cell Carcinoma Syndrome, is a rare disease resulting from mutations in Patched-1 gene and characterized by triad of disorders comprising multiple basal cell carcinomas, numerous keratocystic odontogenic tumors (KOT) and skeletal abnormalities. About 90% of patients develop KOTs in gnathic bones, preferably in the posterior mandible, presenting radiographically as radiolucent lesions uni- or multilocular. Studies suggests that KOTs associated with GS (KOTGSs) have distinct and more aggressive behavior compared to those who developing sporadically (KOTSPs). Objectives: This study aimed at comparing clinical, histopathological and immunohistochemical features of KOTSPs and KOTGSs from different institutions in Brazil and abroad, and understand the role of proteins associated with proliferation/cell cycle (p53, p63 and Ki-67), the alpha-smooth muscle actin (α-SMA) and syndecan-1 (CD138) in an attempt to associate the expression with biological behavior of KOTs. Methodology: Were previously reviewed and selected 30 KOTGSs and 8 KOTSPs, in which were performed qualitative and semi-quantitative analysis histopathological and immunohistochemical to p53, p63, Ki-67, SMA and CD138. Results: 30 cases of KOTGSs were obtained from 12 patients with GS, 5 females (41.66%) and 7 men (58.33%); whereas in group of KOTSPs, 5 cases (62.50%) was in females and 3 males (37.50%). About 58.33% of patients with GS had more than one lesion throughout life. The average age of individuals with GS was 14.66 ± 16.81 years, while in patients with KOTSPs was 41 ± 39.59. The predominant radiographic pattern was radiolucent unilocular, preferably affecting the posterior mandible. Histopathological features in both groups was analyzed, and the most frequent was pleomorphism in KOTGSs. In addition, there was increased expression of p53 and p63 in KOTGSs and similar expression of SMA and Ki-67 between groups. It was also observed that there was a lower reactivity for CD138 in the basal epithelial layer of KOTGSs and stromal expression of CD138 was similar between the groups. Conclusions: Agressiveness of KOTGSs can be explained by increased cellular pleomorphism rate and expression of p53 and p63 and tendency to loss of syndecan-1 expression compared to KOTSPs. / Introdução: A Síndrome de Gorlin (SG) também conhecida como Síndrome do Carcinoma Nevóide Basocelular, é uma doença rara resultante de mutações no gene Patched-1 e caracterizada por uma tríade de alterações que inclui múltiplos carcinomas basocelulares, numerosos tumores odontogênicos queratocísticos (TOQs) e anormalidades esqueléticas. Cerca de 90% dos portadores desenvolvem TOQs no interior dos ossos gnáticos, preferencialmente na região posterior da mandíbula, apresentando-se radiograficamente como lesões radiolúcidas uni ou multiloculares. Estudos têm sugerido que os TOQs associados à SG (TOQSG) apresentam comportamento distinto e mais agressivo em comparação àqueles que desenvolvem-se de modo esporádico (TOQEs). Objetivos: O presente estudo teve como objetivo analisar comparativamente os aspectos clínicos, histopatológicos e imuno-histoquímicos de TOQEs e TOQSGs oriundos de diferentes instituições do Brasil e do exterior, além de entender o papel de proteínas associadas com proliferação/ciclo celular (p53, p63 e Ki-67), da actina de músculo liso-alfa (α-SMA) e da proteína sindecano-1 (CD138), na tentativa de associar a expressão das mesmas com o comportamento biológico dos TOQs. Metodologia: Foram previamente revisados e selecionados 30 TOQSGs e 8 TOQEs, nos quais foram realizadas análises qualitativas e semi-quantitativas histopatológicas e imuno-histoquímicas para p53, p63, Ki-67, AML e CD138. Resultados: Trinta casos de TOQSGs foram obtidos de 12 pacientes com SG, 5 do gênero feminino (41,66%) e 7 do gênero masculino (58,33%); ao passo que no grupo dos TOQEs, 5 casos (62,50%) acometeram o gênero feminino e 3 o masculino (37,50%). Cerca de 58,33% dos pacientes com SG apresentaram mais de uma lesão ao longo da vida. A média de idade dos indivíduos com SG foi de 16,81 anos ± 14,66 enquanto dos portadores de TOEs foi de 41 anos ± 39,59. O padrão radiográfico predominante foi o radiolúcido unilocular, afetando preferencialmente a região posterior de mandíbula. Foram avaliadas as características histopatológicas de ambos os grupos de lesões, sendo o pleomorismo celular mais frequente nos TOQSGs. Além disso, observou-se maior expressão de p53 e p63 nos TOQSG e expressão similar de AML e Ki-67 entre os grupos. Observou-se ainda que houve menor reatividade para CD138 no estrato epitelial basal dos TOQSGs e a expressão estromal de CD138 foi similar entre os grupos analisados. Conclusões: A maior agressividade dos TOQSGs pode ser explicada pela maior taxa de pleomorfismo celular, maior expressão de p53 e p63 e tendência à perda de expressão de sindecano-1 quando comparados aos TOQEs.

Foram estudados prospectivamente 33 pacientes cujos cistos tinham volume médio de 298,4 + 346,9 (30 - 1700) ml. A punção foi realizada sob anestesia local com agulha 18 gauge, de 20 cm. Após seu esvaziamento, injetou-se etanol absoluto no volume equivalente a um terço do volume aspirado, até o máximo de 100 ml. Os volume médios observados após um, três e seis meses foram 47,9 + 59,4 (0 - 286) ml, 25,2 + 42,8 (0 - 208) ml e 12,7 + 30 (0 - 120) ml, respectivamente. Após esse período, 30 (91%) apresentaram remissão total dos sintomas, 2 (6%) mantiveram os sintomas, sendo um com cisto residual e outro sem cisto e um (3%) apresentou melhora parcial dos sintomas / A prospective series of 33 patients with symptomatic simple renal cysts varying from 30 to 1700 ml, were considered eligible for the study. The cysts were punctured under local anesthesia with an 18 gauge, 20 centimeters needle. A volume of ethanol equivalent to one third of the aspirated volume, up to a maximum of 100 ml, was injected into the cyst and left there. After one, three and six months, the average volume of the cyst was 47.9 + 59.4 (0 - 286)ml, 25.2 + 42.8 (0 - 208)ml and 12.7 + 30 (0 - 120)ml, respectively. After this period, 30 patients (91%) showed total remission of the symptoms, two patients (6%) maintained them and one patient (3%) had partial remission of the symptoms

Foram estudados prospectivamente 33 pacientes cujos cistos tinham volume médio de 298,4 + 346,9 (30 - 1700) ml. A punção foi realizada sob anestesia local com agulha 18 gauge, de 20 cm. Após seu esvaziamento, injetou-se etanol absoluto no volume equivalente a um terço do volume aspirado, até o máximo de 100 ml. Os volume médios observados após um, três e seis meses foram 47,9 + 59,4 (0 - 286) ml, 25,2 + 42,8 (0 - 208) ml e 12,7 + 30 (0 - 120) ml, respectivamente. Após esse período, 30 (91%) apresentaram remissão total dos sintomas, 2 (6%) mantiveram os sintomas, sendo um com cisto residual e outro sem cisto e um (3%) apresentou melhora parcial dos sintomas / A prospective series of 33 patients with symptomatic simple renal cysts varying from 30 to 1700 ml, were considered eligible for the study. The cysts were punctured under local anesthesia with an 18 gauge, 20 centimeters needle. A volume of ethanol equivalent to one third of the aspirated volume, up to a maximum of 100 ml, was injected into the cyst and left there. After one, three and six months, the average volume of the cyst was 47.9 + 59.4 (0 - 286)ml, 25.2 + 42.8 (0 - 208)ml and 12.7 + 30 (0 - 120)ml, respectively. After this period, 30 patients (91%) showed total remission of the symptoms, two patients (6%) maintained them and one patient (3%) had partial remission of the symptoms