OBJECTIVES: The aim of this study was to evaluate the role of amphiregulin protein, an epidermal growth factor receptor ligand, in cartilaginous tumors. METHODS: Amphiregulin expression was examined in 31 enchondromas and 67 chondrosarcomas using immunohistochemistry analysis. RESULTS: Overall, 15 enchondromas (48.40%) and 24 chondrosarcomas (35.82%) were positive for amphiregulin. According to the receiver operating characteristic curve test, no difference in amphiregulin expression was observed between enchondromas and low-grade chondrosarcomas (p=0.0880). Additionally, 39 lesions (16 in short bones, 13 in long bones, and 10 in flat bones) were positive for amphiregulin, exhibiting a higher percentage of positive cells (p=0.0030) and intensity of immunohistochemical expression (p=0.0055) in short bone lesions than in others. Among 25 enchondromas localized in short bones, 15 expressed amphiregulin; however, all 6 cases localized in long bones were negative for this marker (p=0.0177). CONCLUSIONS: Amphiregulin did not help in distinguishing enchondromas from low-grade chondrosarcomas. The present study is the first to document the expression of this immunohistochemical marker in enchondromas. Furthermore, amphiregulin expression in enchondromas was localized in short bones, indicating a phenotypic distinction from that in long bones. This distinction may contribute to an improved understanding of the pathogenesis of these lesions.

OBJECTIVE: This study aimed to develop a new histological scoring system for use in a partial-thickness cartilage repair animal model. Although previous papers have investigated the regeneration of articular cartilage, the good results achieved in small animals have not been replicated in large animal models or humans, possibly because of the frequent use of models with perforation of the subchondral bone plates. Partial-thickness lesions spare the subchondral bone, and this pattern is the most frequent in humans; therefore, new therapies should be tested using this model. However, no specific histological score exists to evaluate partial-thickness model results. METHODS: Histological sections from 30 ovine knees were reviewed to develop a new scoring system. The sections were subjected to H&E, Safranin O, and Masson’s trichrome staining. RESULTS: This paper describes a new scoring tool that is divided into sections in detail: repair of tissue inside the lesion, cartilage around the lesion and degenerative changes at the base of the lesion. Scores range from 0 to 21; a higher score indicates better cartilage repair. DISCUSSION: Unlike existing tools, this new scale does not assign points for the positioning of a tidemark; we propose evaluation of the degenerative changes to the subchondral bone and calcified cartilage layer. It is necessary to remove the whole joint to access and study the evolution of the lesion as well as the surrounding tissue. CONCLUSION: This article emphasizes the importance of a partial-thickness animal model of cartilage repair and presents a new histological scoring system.

Twelve adult male Wistar rats (220 g average weight) were divided in 3 experimental groups: GI -15. GII 30 and GIII 60 days, after mandibular molar extraction, with three experimental animals and one control per group. Qualitatively, ultrastructural changes of protein filaments from myofibrils of these muscles and ipsilateral to the extractions were observed. Ultrastructure asymmetry and disorganization of Z line and I band, in the experimental group GII, of Medial Pterigoid muscle (MPT) were observed. The temporomandibular dysfunction, stimulated by the unilateral extractions of mandibular molars in rats may lead to modifications in the Z line and I band, which showed to be sensitive to this dysfunction. Changes in the MPT muscle, probably related to its own functional characteristics and major participation in the dynamics of mastication, compared to Masseter were also observed. However, the muscular fibres seem to adapt to the new conditions along the experiment.

Doce ratas Wistar machos adultos (220 g de peso promedio) se dividieron en 3 grupos experimentales: GI - 15, GII - 30 y GIII - 60 días, después de una extracción molar mandibular. En cada grupo se dispusieron tres animales experimentales y un animal como control. Cualitativamente, se observaron cambios ultraestructurales de filamentos de proteínas de miofibrillas de estos músculos masticadores ipsilaterales a las extracciones. Se observó asimetría de la ultraestructura y desorganización de la línea Z y la banda I, en el músculo pterigoideo medial del grupo experimental GII, (MPT). La disfunción temporomandibular, estimulada por las extracciones unilaterales de los molares mandibulares en ratas, puede conducir a modificaciones en la línea Z y en la banda I, que mostraron ser sensibles a esta disfunción. Los cambios en el músculo pterigoideo medial, se debieron, probablemente, con sus propias características funcionales y una mayor participación en la dinámica de la masticación, en comparación con el músculo masetero. Sin embargo, las fibras musculares parecen adaptarse a las nuevas condiciones a lo largo del experimento.

Objetivo: Avaliar a influência da mitomicina C a 0,02% (MMC), aplicada em dose única por 3 minutos, na proliferação e diferenciação das células epiteliais da córnea de coelhos. Métodos: A MMC tópica foi aplicada na episclera da área límbica temporal, mediante tecido epitelial corneano intacto (um olho) e após desepitelização epitelial parcial da córnea (outro olho). Durante o procedimento cirúrgico, MMC ou solução fisiológica 0,9% (SF) foi aplicada e a solução escolhida para cada animal foi determinada por sorteio. Os animais foram divididos em grupo A (20 olhos), grupo B (16 olhos) e grupo C (14 olhos). Foram sacrificados respectivamente em 4º, 15º e 45º dia de pós-operatório. Para estimular a proliferação celular, os animais do grupo C foram submetidos à desepitelização central da córnea 3 dias antes do dia do sacrifício. Marcadores de diferenciação celular (AE1, AE3 e AE5) e de proliferação (5Bromo-2-Deoxiuridina, BrdU) foram utilizados. Nas lâminas coradas com BrdU, as áreas nasal, temporal e central foram delimitadas. O número de células coradas pela BrdU foram contadas nos 3 diferentes campos e a média aritmética de cada área foi analisada estatisticamente. Resultados: Houve diferença estatística entre MMC e SF nas áreas central e temporal da córnea previamente desepitelizada em todos os grupos. Não houve diferença estatística durante a análise de diferenciação celular. Conclusão: A MMC na dose de 0,02%, aplicada por 3 minutos sobre a episclera, interfere na proliferação celular da área exposta à droga e previamente desepitelizada. Não interfere na diferenciação celular e sua ação possui efeito prolongado.

Objective: To evaluate the influence of a three-minute application of 0.02% mitomycin C (MMC) on proliferation and differentiation of rabbit corneal epithelial cells. Methods: Topical MMC or 0.9% saline solution was applied to the episclera of the temporal limbal area of both eyes, maintaining intact epithelial tissue in one eye, and after partial corneal deepithelialization in the contralateral eye. The animals were arranged in groups A (20 eyes), B (16 eyes) and C (14 eyes) and sacrificed respectively on the 4th, 15th and 45th postoperative days. In order to stimulate cell proliferation, group C was submitted to central corneal deepithelialization three days before sacrifice. Cell differentiation markers (AE1, AE3 and AE5) were used for differentiation analysis and 5-bromo-2-deoxyuridine (BrdU) for detection of corneal epithelial cells proliferation. Results: There was no statistical difference in differentiation cells when drugs or surgical techniques were analyzed. Cell proliferation when using MMC or SF was statis-tically significant at central and temporal areas when applied after partial corneal deepithelialization in all groups. Conclusion: These results suggest that the three-minute episcleral application of 0.02% MMC does not affect epithelial cell differentiation; however, when MMC application occurs after corneal deepithelialization, it may affect cell proliferation.

OBJECTIVE: The aim of this study was to investigate bone repair after the implantation of vancomycin-loaded poly-L-lactic acid/poly-ethylene oxide microspheres compared with vancomycin-unloaded poly-L-lactic acid/poly-ethylene oxide microspheres. METHODS: Poly-L-lactic acid/poly-ethylene oxide microspheres were implanted in rat tibiae and evaluated for periods of 2, 4, 8, and 12 days and 4, 8, 16, and 32 weeks. The groups implanted with vancomycin-loaded and vancomycin-unloaded microspheres were compared. Histopathologic (semi-quantitative) and histomorphometric analyses were performed to evaluate the bone formation process. RESULTS: During the first period (second day), fibrin and hemorrhaging areas were observed to be replaced by granulation tissue around the microspheres. Woven bone formation with progressive maturation was observed. All of the histopathological findings, evaluated by a semi-quantitative assay and a quantitative analysis (percentage of bone formation), were similar between the two groups. CONCLUSION: Vancomycin-loaded poly-L-lactic acid/poly-ethylene oxide microspheres are a good bone substitute candidate for bone repair. Local antibiotic therapy using vancomycin-loaded poly-L-lactic acid/poly-ethylene oxide microspheres should be considered after the microbiological evaluation of its efficacy.

OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1) higher-grade chondrosarcomas, 2) tumors that developed in flat bones, and 3) over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields). Moreover, CD34 expression (measured using the Chalkley method) revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS: These results provide evidence that CD34 microvessel density in chondrosarcomas can be helpful in predicting patient outcome and may add to our understanding of chondrosarcoma pathogenesis.

CONTEXTO: Os tumores desmóides representam uma das manifestações extraintestinais mais importantes na síndrome da polipose adenomatosa familiar. O aparecimento desta neoplasia está relacionada ao aumento da morbimortalidade nos doentes com polipose adenomatosa familiar. OBJETIVOS: Avaliar a ocorrência dos tumores desmóides nos casos de polipose adenomatosa familiar submetidos a colectomia profilática e avaliar o seguimento em ambulatório. MÉTODOS: Entre 1984 e 2008, 68 pacientes foram submetidos a colectomia por polipose adenomatosa familiar no Hospital das Clínicas da Faculdade de Ciências Médicas da Universidade de Campinas, SP. Os tumores desmóides ocorreram em nove pacientes (13.2%), que foram estudados retrospectivamente, por meio da análise de prontuários, buscando dados clínicos e cirúrgicos. RESULTADOS: Dos nove pacientes, sete (77,8%) foram submetidos a laparotomia para ressecção do tumor. A média de idade no momento da cirurgia foi de 33,9 anos (variando 22-51 anos). Os tumores desmóides da parede abdominal ocorreram em 3/9 casos (33.3%) e os intra-abdominais em seis casos (66,7%). O tempo médio entre a cirurgia do reservatório ileal e o diagnóstico do tumor desmóide foi de 37,5 meses (variando 14-60 meses), enquanto o tempo médio entre a cirurgia de colectomia com anastomose íleorretal e o diagnóstico foi de 63,7 meses (variando 25-116 meses). Em 6/9 (66,7%) pacientes com tumor desmóide, a doença estava controlada ou não havia evidência de recidiva do tumor em 63,1 meses (variando de 12 a 240 meses) de tempo médio de seguimento. CONCLUSÃO: Os tumores desmóides ocorreram em 13,2% dos casos de polipose adenomatosa familiar após a cirurgia do cólon; desta maneira, os pacientes com polipose adenomatosa familiar devem manter seguimento em ambulatório e o rastreamento deve incluir o exame abdominal minucioso a fim de identificar sinais e sintomas que possam conduzir ao diagnóstico de tumor desmóide. As opções de tratamento incluem cirurgia e manejo clínico com antiestrogênios, anti-inflamatórios ou quimioterapia.

CONTEXT: Desmoid tumors constitute one of the most important extraintestinal manifestations of familial adenomatous polyposis. The development of desmoids is responsible for increasing morbidity and mortality rates in cases of familial adenomatous polyposis. OBJECTIVES: To evaluate the occurrence of desmoid tumors in familial adenomatous polyposis cases following prophylactic colectomy and to present patient outcome. METHODS: Between 1984 and 2008, 68 patients underwent colectomy for familial adenomatous polyposis at the School of Medical Sciences Teaching Hospital, University of Campinas, SP, Brazil. Desmoid tumors were found in nine (13.2%) of these patients, who were studied retrospectively by consulting their medical charts with respect to clinical and surgical data. RESULTS: Of nine patients, seven (77.8%) were submitted to laparotomy for tumor resection. Median age at the time of surgery was 33.9 years (range 22-51 years). Desmoid tumors were found in the abdominal wall in 3/9 cases (33.3%) and in an intra-abdominal site in the remaining six cases (66.7%). Median time elapsed between ileal pouch-anal anastomosis and diagnosis of desmoid tumor was 37.5 months (range 14-60 months), while the median time between colectomy with ileorectal anastomosis and diagnosis was 63.7 months (range 25-116 months). In 6/9 (66.7%) patients with desmoid tumors, the disease was either under control or there was no evidence of tumor recurrence at a follow-up visit made a mean of 63.1 months later (range 12-240 months). CONCLUSIONS: Desmoid tumors were found in 13.2% of cases of familial adenomatous polyposis following colectomy; therefore, familial adenomatous polyposis patients should be followed-up and surveillance should include abdominal examination to detect signs and symptoms. Treatment options include surgery and clinical management with antiestrogens, antiinflammatory drugs or chemotherapy.

Em quadros de monoartrite crônica devem ser investigadas doenças inflamatórias como a artrite reumatoide (AR), doenças infecciosas como a tuberculose e outras doenças que causem espessamento sinovial e derrame articular como sinovite vilonodular pigmentada (SVNP), hemangioma sinovial, osteocondromatose sinovial e lipoma arborescente sinovial. Relatamos o caso de uma jovem paciente com quadro de monoartrite em ombro, cujo exame por imagem mostrou sinovite e cujo exame histopatológico obtido através de artroscopia com biópsia revelou tratar-se de SVNP. RELATO DO CASO: J C M, 15 anos, sexo feminino, branca, estudante, foi encaminhada ao reumatologista com hipótese diagnóstica de artrite idiopática juvenil (AIJ) pauciarticular. Apresentava, há um ano, dor no ombro D, que melhorava com o uso de anti-inflamatório não-esteroidal (AINE) em dois dias. Teve nesse período de cinco a seis destes episódios que duravam poucos dias. Negava outras queixas articulares ou sistêmicas. Trazia exames normais ou negativos: hemograma, VHS, proteína C reativa, fator reumatoide, sedimento de urina. O FAN era positivo 1/80, pontilhado fino. Trazia Ressonância Magnética do ombro indicativa de sinovite glenoumeral com derrame articular com conteúdo expansivo de tecidos moles na bursa subescapular, segundo o laudo, podendo corresponder a pannus. Como história e exame físico não eram compatíveis com AIJ, foi realizada outra RM que mostrou aumento da lesão já descrita. Foi então encaminhada à artroscopia para biópsia, que revelou SVNP. Durante o procedimento, foi realizada sinovectomia, e uma nova RM feita após nove meses mostrou ausência de sinovite. A SVNP do ombro é incomum e a sinovectomia foi curativa nesse caso.

Chronic monoarthritis demand an investigation of inflammatory diseases, such as rheumatoid arthritis (RA), infectious diseases like tuberculosis; and other diseases that cause synovitis and joint effusion, such as pigmented villonodular synovitis (PVNS), synovial hemangioma, synovial osteochondromatosis and arborescence lipoma. We report the case of a young patient with chronic right shoulder monoarthritis, who's magnetic resonance imaging (MRI) showed synovitis. Arthroscopy was performed and the biopsy revealed PVNS. CASE REPORT: J C M, 15 years-old, female, Caucasian, student. She was sent to a Rheumatologist along with a diagnosis of juvenile idiopathic arthritis (JIA). The patient presented, for one year, a mild pain of insidious onset in her right shoulder, with relief of the symptoms in two days under nonsteroidal anti-inflammatory therapy (NSAIDs). During this year, the patient presented five or six episodes of pain with the same characteristics. No other signs and symptoms were related. The following tests showed normal or negative results:complete blood count, ESR, C-reactive protein, rheumatoid factor and urinalysis. The antinuclear antibody (ANA) was 1/80 speckled pattern. The MRI of the shoulder showed glenohumeral synovitis with joint effusion and soft tissue swelling in the subscapular bursa, which could correspond to pannus. As the medical history and physical examination were not compatible to JIA, a second MRI was performed, which showed an increase of the synovitis. The patient was submitted to an arthroscopy with biopsy and the histopathological examination showed PVNS. A complete synovectomy was performed and a new MRI, nine months later, showed no synovitis. PVNS of the shoulder is uncommon, and synovectomy was curative in this case.

O osteossarcoma é definido como um tumor maligno mesenquimatoso produtor de matriz óssea. É relativamente raro entre os animais domésticos, contudo em cães, corresponde a aproximadamente 85% das neoplasias ósseas malignas. A finalidade deste trabalho foi estudar o osteossarcoma canino, em nosso meio, correlacionando os achados clínico-morfológicos com o prognóstico. Retrospectivamente foram levantados 52 cases de cães com osteossarcoma. Foram avaliados quanto a idade, sexo, raça, peso, porte físico, distribuição topográfica e presença de metástases ao diagnóstico. Os tumores foram classificados histologicamente segundo POOL14. A idade variou de 6 meses a 14 anos (média = 8 anos); sexo: 31 F/ 19 M; cães de raça pura (67.5%) e sem raça definida (SRD) (32.5%); cães de grande porte foram os mais afetados (71,9%). Esqueleto apendicular (75,6%), axial (17.1%) e extraesquelético (7.3%); Metástase ao diagnóstico em 17.1%. Histopatologia: padrão puro (52%); osteoblastic (38.6%); condroblastic (9.4%) e telangiectásico (4%) e padrão combinado 48%. Conclusão: Afeta, em geral, fêmeas adultas e o esqueleto apendicular é o mais comprometido. A raça é fator predisponente e histologicamente predomina o padrão puro osteoblastic. Os pulmões são sede comum de metástases, sendo os cães machos e de raça pura os mais predispostos, independente do padrão morfológico do osteossarcoma.

Osteosarcoma is defined as a bone matrix-producing malignant mesenchymal tumor. It is relatively rare among domestic animals, but corresponds to 85% of all malignant bone tumors in dogs. To study canine osteosarcoma in animals living in Brazil and correlate the clinical-morphological findings with prognosis, forty-six cases of dogs with osteosarcoma were studied retrospectively out of a total of 56 malignant primary bone tumors on file. The animals were assessed in terms of age, sex, breed, topographic tumor distribution, and presence of metastases at diagnosis. The tumors were classified histologically by the method of Pool¹. Osteosarcomas corresponded to 82% of primary malignant bone dysplasias in the sample studied. Age ranged from 6 months to 14 years (C = 8 y), sex: 32 F/18 M; breed: large dogs (86%), topographic location: appendicular skeleton (64%), axial skeleton (28.5%) and extraskeletal (7.5%); presence of metastases in 17.4%. Histopathology: osteoblastic (32.6%), chondroblastic (9.6%) and telangiectatic (5.8%) patterns; combined: 52%. Osteosarcoma mainly affects adult females. Breed is a predisposing factor, the appendicular skeleton is most often involved, and an osteoblastic histological pattern predominates. The lungs are a common site of metastasis, with pure-bred male dogs being most predisposed regardless of the morphological pattern of osteosarcoma.

O objetivo deste trabalho é avaliar as características demográficas, clínicas, laboratoriais e histopatológica de pacientes com diagnóstico de síndrome de Churg Strauss (SCS) acompanhados no ambulatório de vasculites do Hospital das Clínicas da Universidade Estadual de Campinas (HC/Unicamp). Foi realizado estudo retrospectivo dos prontuários dos pacientes com vasculite primária, classificados como SCS pelos critérios do American College of Rheumathology (ACR). Foram observados cinco pacientes com diagnóstico de SCS (M/F:3/2, caucasóides). A média de idade do início da doença foi 46 anos (40-55). A média de tempo de seguimento foi de 2,37 anos (0,25-6). Sintomas sistêmicos, asma, neuropatia periférica e lesão cutânea foram observados em todos os pacientes. Envolvimento cardiovascular, renal e de trato gastrintestinal estiveram presentes cada qual em um paciente. Todos os pacientes apresentaram eosinofilia (>10%),e o p-ANCA foi positivo nos três casos investigados. A radiografia de tórax revelou infiltrado pulmonar intersticial em dois casos; em um, associado à derrame pleural. Na histopatologia, evidências de eosinófilos extravascular foram encontradas nas biópsias cutâneas de 3/4 pacientes. Todos os pacientes foram tratados com prednisona. Em 3, houve a necessidade de associar-se imunossupressor. Nenhum paciente evoluiu a óbito. A SCS é uma patologia rara, com acometimento sistêmico, sendo a asma uma das principais e mais precoce manifestação. Todos os pacientes apresentaram sintomas sistêmicos, acometimento de pele e sistema nervoso periférico. Envolvimento renal, cardíaco e gastrointestinal foi observado, cada qual em um único paciente, diferindo de outras séries nas quais esses acometimentos são mais freqüentes. Embora seja uma patologia grave e de prognóstico reservado, observamos evolução favorável com tratamento.

The aim of this report is to verify the demographic, clinical, laboratorial and histopathological findings of patients with CSS followed in a University Clinical Hospital. We reviewed the medical records of all patients with the diagnosis of CSS. Only patients who fulfilled ACR criteria were included. Five Caucasian patients were found, with a sex ratio M/F: 3/2. The mean age at disease onset was 46 years old (40 to 55) and the mean time of follow-up was 2.37 years (0.25 to 6). General symptoms, asthma, peripheral neuropathy and skin lesions were the most common clinical findings in all patients. Cardiovascular, gastrointestinal and renal involvement was found in one patient each. All patients presented hypereosinophilia (> 10%) and p-ANCA was present in 3 patients. The chest x-ray showed pulmonary parenchymal infiltrate in 2 cases and in 1 of them an unilateral pleural effusion. Skin biopsies showed extravascular eosinophylia in 3 out of 4. All patients were treated with prednisone and in 3 it was added immunosuppressive drug. No patient died during the follow-up. CSS is a rare disease with a multivisceral involvement and asthma is the main and the earliest symptom. General symptoms and involvement of skin and peripheral nerves were found in all patients. Renal, cardiovascular and gastrointestinal involvement was rare, differently from the literature series where these findings are more frequent. In spite of the CSS being a serious and life-threatening disease, these patients presented adequate response to the treatment and a favorable outcome.