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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

The sagittal soft-tissue changes of the lower lip and chin associated with surgical maxillary impaction and consequent mandibular autorotation

Ksiezycki-Ostoya, Beata Katarzyna 17 November 2006 (has links)
Student Number : 9000040F - M Dentistry research report - Faculty of Health Sciences / This study assessed the sagittal soft-tissue changes of the lower lip and chin area in 22 patients subsequent to mandibular autorotation following surgical vertical impaction of the maxilla. A subgroup of six patients in addition had undergone advancement genioplasty procedures. Lateral cephalometric radiographs were taken immediately prior to surgery and on average 15 months following surgery. Sixteen cephalometric landmarks were identified on each radiograph and these were digitized using a Kontron Videoplan Image Analysis System to enable differences reflecting changes to be assessed. The comparison between those cases that had had maxillary elevation only and the six cases that had received additional advancement genioplasty procedures revealed statistically significant differences in relation to the proportional changes in the chin area. Therefore, when studying the soft-tissue chin changes following mandibular autorotation, these six patients were excluded from the sample. It was found that there was no significant difference in the lower lip response between the two groups and therefore when studying the lower lip changes, the two groups could be pooled. The soft-tissue changes in the chin area showed statistically and clinically significant correlations. In the horizontal plane, a ratio of 0.9:1 was found for the changes between sulcus inferior and point B, between soft-tissue pogonion and hard-tissue pogonion, and between soft-tissue gnathion and hard-tissue gnathion. In the vertical dimension, soft-tissue gnathion followed hard-tissue gnathion in a ratio of 0.9:1, whereas soft-tissue menton followed hardtissue menton in a ratio of 1:1. In the study of the lower lip response, a significant correlation with a ratio of 1:1 existed for the horizontal change in the lower lip as measured at labrale inferius relative to both lower incisor tip and lower incisor anterius. In the vertical dimension, stomion inferius followed lower incisor anterius in a ratio of 1.3:1, while labrale inferius followed lower incisor anterius in a ratio of 1.5:1. Multiple regression analyses revealed that presurgical tissue thickness exerted no influence upon the strength of the correlations between changes expressed at corresponding soft- and hard-tissue landmarks located in the lower lip and soft-tissue chin area. Based on the findings of this study, it is suggested that the soft-tissue to hard-tissue ratios may be applied to prediction tracings with enhanced confidence. As a result, the tracings will reflect a more accurate prediction of the lower lip and soft-tissue chin positions following autorotation of the mandible.
62

Deformação de tecidos moles para simuladores médicos: uma abordagem sem malha / Soft tissue deformation for medical simulators: a meshless approach

Moreira, Hipólito Douglas França 03 December 2015 (has links)
Esta dissertação de mestrado propõe o estudo e a implementação de um método de deformação usando modelos tridimensionais sem o uso de malhas baseado na técnica Smoothed Particles Hydrodynamics (SPH), que consiste num sistema de resolução de equações diferenciais para aplicação de conceitos físicos para simular deformação de tecidos moles. A opção pelo método sem malha para processo de deformação é apresentado nesta dissertação como alternativa a um dos métodos mais comuns em simulação de deformação de tecidos, o método massa-mola, explorando questões referentes ao uso de recursos computacionais. Para chegada a definição do método foram analisados os temas envolvendo métodos de deformação, modelos baseados em pontos e o SPH como plataformas para alcançar o desenvolvimento do método proposto pela dissertação. Como forma de comprovar as propriedades do método desenvolvido foi realizada a implementação e testes levando em consideração os modelos de deformação e a interação em tempo real num ambiente de simulação que contempla a deformação de uma mama, levando em conta a comparação com o método massa-mola, o uso de recursos do próprio método em função do aumento de detalhe e do uso de objeto com múltiplas propriedades / This master thesis proposes a study and implementation of deformation method using tridimensional models without edge composed meshes based on Smoothed Particles Hydrodynamics (SPH) technique, that consists on diferential equation solving system to reproduce physical concepts to simulate soft tissue deformation. The option for a meshless method to deformation process is shown in this thesis as an alternative to a very common method in tissue deform simulation, the mass-spring method, reviewing a comparison based on computational resources. To achieve a method definition were analyzed fields of study involving deformation methods, point-based models and SPH as platforms to build and deploy the proposed method for this thesis. To show the characteristics for this developed deformation method was realized the implementation and tests based on deformation models and real time interaction on a simulation environment that includes a breast deformation, taking in account the comparison to mass-spring, number of points of the cloud model and multiple properties
63

Características da neo formação dos tecidos moles periimplantares e periodontais após excisão cirúrgica de margem / Characterization of soft tissue neo formation around implants and teeth after margin surgical excision

Sukekava, Flávia 10 September 2008 (has links)
O presente estudo descreve as características da cicatrização de tecido mole ao redor de dentes e implantes, em 5 cães beagle, após remoção cirúrgica. Os terceiros e quartos pré-molares inferiores bilateralmente foram extraídos. Três meses após, 2 implantes de titânio Osseospeed foram instalados em cada quadrante inferior, juntamente com a instalação imediata do conector na região dos pré-molares extraídos previamente. Três meses após a instalação dos implantes, quatro áreas contendo um implante e um dente foram determinadas e identificadas em cada cão. Uma área foi aleatoriamente escolhida em cada animal para receber a cirurgia ressectiva na face vestibular do dente e do implante. Na face lingual não foi executado qualquer procedimento ficando esta face como lado controle. As 3 áreas remanescentes foram tratadas de maneira idêntica e os animais foram ortotanasiados e forneceram biópsias representando os seguintes intervalos de cicatrização 1, 2, 4 e 12 semanas. As biópsias foram preparadas para análise histological e morfométrica. Foi observado que em 12 semanas a altura da mucosa periimplantar e da gengiva foram similares ao lado controle. Além disso, a análise morfométrica demonstrou que no intervalo 12 semanas o volume de feixes de fibras colágenas, fibroblastos, estruturas vasculares e tecido residual não foi similar entre o grupo de implantes comparando grupo teste com grupo controle. O presente experimento demonstrou que a cicatrização do tecido mole ao redor de implantes parece ser mais lenta que ao redor de dentes. / The current presentation will describe a study in the dog features characteristic of soft tissue healing after ressective surgery at teeth and implants. Five beagle dogs were used. In both quadrants of the mandible, the third and fourth premolars were extracted. Three months later, two titanium fixtures Osseospeed were installed and abutment connection performed in each mandibular quadrant at the premolar region of the edentulous ridge. Following additional 3 months of healing, four regions containing each implant and an adjacent tooth were identified in each dog. One region was randomly selected and soft tissue ressective surgery was performed at the buccal aspect. The lingual soft tissues were not included in the experimental surgical procedure and were regarded as control sites. The remaining three regions were treated in an identical manner and the dogs sacrificed to provide biopsies representing healing intervals of 1, 2, 4 and 12 weeks. The biopsies were prepared for histological and morphological analyses. It was observed that at the 12-weeek interval the height of the soft tissue both at the gingival and implant mucosa was similar to the one at the control site. Furthermore, the morphometric analyses demonstrated that the 12-week interval the volume of collagen fibers, fibroblasts, vessels and residual tissue in the healing tissues was not similar between the gingival and periimplant mucosa also differed from the control sites regarding the vascular content. The present experiment demonstrated that soft tissue healing around implants seems to be slower than around tooth.
64

Características da neo formação dos tecidos moles periimplantares e periodontais após excisão cirúrgica de margem / Characterization of soft tissue neo formation around implants and teeth after margin surgical excision

Flávia Sukekava 10 September 2008 (has links)
O presente estudo descreve as características da cicatrização de tecido mole ao redor de dentes e implantes, em 5 cães beagle, após remoção cirúrgica. Os terceiros e quartos pré-molares inferiores bilateralmente foram extraídos. Três meses após, 2 implantes de titânio Osseospeed foram instalados em cada quadrante inferior, juntamente com a instalação imediata do conector na região dos pré-molares extraídos previamente. Três meses após a instalação dos implantes, quatro áreas contendo um implante e um dente foram determinadas e identificadas em cada cão. Uma área foi aleatoriamente escolhida em cada animal para receber a cirurgia ressectiva na face vestibular do dente e do implante. Na face lingual não foi executado qualquer procedimento ficando esta face como lado controle. As 3 áreas remanescentes foram tratadas de maneira idêntica e os animais foram ortotanasiados e forneceram biópsias representando os seguintes intervalos de cicatrização 1, 2, 4 e 12 semanas. As biópsias foram preparadas para análise histological e morfométrica. Foi observado que em 12 semanas a altura da mucosa periimplantar e da gengiva foram similares ao lado controle. Além disso, a análise morfométrica demonstrou que no intervalo 12 semanas o volume de feixes de fibras colágenas, fibroblastos, estruturas vasculares e tecido residual não foi similar entre o grupo de implantes comparando grupo teste com grupo controle. O presente experimento demonstrou que a cicatrização do tecido mole ao redor de implantes parece ser mais lenta que ao redor de dentes. / The current presentation will describe a study in the dog features characteristic of soft tissue healing after ressective surgery at teeth and implants. Five beagle dogs were used. In both quadrants of the mandible, the third and fourth premolars were extracted. Three months later, two titanium fixtures Osseospeed were installed and abutment connection performed in each mandibular quadrant at the premolar region of the edentulous ridge. Following additional 3 months of healing, four regions containing each implant and an adjacent tooth were identified in each dog. One region was randomly selected and soft tissue ressective surgery was performed at the buccal aspect. The lingual soft tissues were not included in the experimental surgical procedure and were regarded as control sites. The remaining three regions were treated in an identical manner and the dogs sacrificed to provide biopsies representing healing intervals of 1, 2, 4 and 12 weeks. The biopsies were prepared for histological and morphological analyses. It was observed that at the 12-weeek interval the height of the soft tissue both at the gingival and implant mucosa was similar to the one at the control site. Furthermore, the morphometric analyses demonstrated that the 12-week interval the volume of collagen fibers, fibroblasts, vessels and residual tissue in the healing tissues was not similar between the gingival and periimplant mucosa also differed from the control sites regarding the vascular content. The present experiment demonstrated that soft tissue healing around implants seems to be slower than around tooth.
65

Deformação de tecidos moles para simuladores médicos: uma abordagem sem malha / Soft tissue deformation for medical simulators: a meshless approach

Hipólito Douglas França Moreira 03 December 2015 (has links)
Esta dissertação de mestrado propõe o estudo e a implementação de um método de deformação usando modelos tridimensionais sem o uso de malhas baseado na técnica Smoothed Particles Hydrodynamics (SPH), que consiste num sistema de resolução de equações diferenciais para aplicação de conceitos físicos para simular deformação de tecidos moles. A opção pelo método sem malha para processo de deformação é apresentado nesta dissertação como alternativa a um dos métodos mais comuns em simulação de deformação de tecidos, o método massa-mola, explorando questões referentes ao uso de recursos computacionais. Para chegada a definição do método foram analisados os temas envolvendo métodos de deformação, modelos baseados em pontos e o SPH como plataformas para alcançar o desenvolvimento do método proposto pela dissertação. Como forma de comprovar as propriedades do método desenvolvido foi realizada a implementação e testes levando em consideração os modelos de deformação e a interação em tempo real num ambiente de simulação que contempla a deformação de uma mama, levando em conta a comparação com o método massa-mola, o uso de recursos do próprio método em função do aumento de detalhe e do uso de objeto com múltiplas propriedades / This master thesis proposes a study and implementation of deformation method using tridimensional models without edge composed meshes based on Smoothed Particles Hydrodynamics (SPH) technique, that consists on diferential equation solving system to reproduce physical concepts to simulate soft tissue deformation. The option for a meshless method to deformation process is shown in this thesis as an alternative to a very common method in tissue deform simulation, the mass-spring method, reviewing a comparison based on computational resources. To achieve a method definition were analyzed fields of study involving deformation methods, point-based models and SPH as platforms to build and deploy the proposed method for this thesis. To show the characteristics for this developed deformation method was realized the implementation and tests based on deformation models and real time interaction on a simulation environment that includes a breast deformation, taking in account the comparison to mass-spring, number of points of the cloud model and multiple properties
66

Avaliação da reprodutibilidade intra e interobservador da segmentação manual dos sarcomas de partes moles em imagens de ressonância magnética / Evaluation of intra and interobserver reproducibility of manual segmentation of soft-tissue sarcomas in magnetic resonance images

Oliveira, Larissa Santos 29 May 2017 (has links)
Os sarcomas de partes moles constituem um grupo diverso de neoplasias que podem surgir nos tecidos conjuntivos praticamente de qualquer região do corpo. A ressonância magnética (RM) é atualmente o exame de escolha para detecção, estadiamento regional e acompanhamento desses tumores. A segmentação das lesões a partir das imagens de RM da rotina permite extrair dados quantitativos, que tem potencial para adicionar informações a análise. O propósito do estudo é avaliar a reprodutibilidade da segmentação manual de sarcomas de partes moles em imagens de RM de pacientes com diagnóstico definitivo confirmado por meio da histopatologia. Como objetivo secundário foi realizada a comparação da segmentação manual e semiautomática a fim de validar a segmentação semiautomática como método alternativo para segmentação desses tumores. Foi estudada uma coorte retrospectiva de 15 pacientes consecutivos com diagnóstico confirmado de sarcoma de partes moles acompanhados em nosso serviço, no período de janeiro de 2006 até janeiro de 2016, com imagens de RM adquiridas previamente ao tratamento e disponíveis para análise no formato DICOM. Foi utilizado o software 3D Slicer para realizar as segmentações pelos métodos manual e semiautomático. Três radiologistas fizeram as segmentações de forma independente e às cegas para permitir avaliação interobservador. Os resultados obtidos demonstram haver alta reprodutibilidade intraobservador com coeficiente de similaridade de Dice entre as segmentações variando de 0,849 a 0,979 e as distâncias Hausdorff variando de 3,53 mm a 20,96 mm e uma boa reprodutibilidade interobservador com coeficientes de similaridade de Dice variando de 0,741 a 0,972 e distâncias Hausdorff variando de 5,83 a 60,84 mm. Foi encontrada uma concordância substancial entre as segmentações realizadas pelo método semiautomático quando comparadas com as segmentações realizadas pelo método manual com coeficientes de similaridade de Dice variando de 0,871 a 0,973 e distâncias Hausdorff variando de 5,43 mm a 31,75 mm. Em relação ao tempo de segmentação não houve diferença estatisticamente significativa do método semiautomático quando comparado ao método manual (p>0,05). Também foram calculados os volumes obtidos nas diferentes segmentações e houve concordância quase perfeita entre as duas segmentações manuais realizadas pelo radiologista 1, entre as segmentações realizadas pelo radiologista 1 e pelo radiologista 2, entre as segmentações realizadas pelo radiologista 1 e pelo radiologista 3, e entre a segmentação manual e semiautomática realizadas pelo radiologista 1, sendo obtidos coeficientes de correlação intraclasse (ICC) entre 0,9927 e 0,9990. Os resultados obtidos demonstram boa reprodutibilidade intra e interobservador da segmentação manual utilizando o software 3D Slicer validando dessa forma esse método como ferramenta confiável para servir de padrão de referência em futuros estudos quantitativos desses tumores. Foi encontrada concordância quase perfeita entre as segmentações realizadas pelo método semiautomático quando comparadas com as segmentações realizadas pelo método manual, mas nossos resultados não demonstraram diferença significativa de tempo de segmentação do método semiautomático em relação ao método manual. / Soft tissue sarcomas constitute a diverse group of neoplasms that can arise in the connective tissues from virtually any region of the body. Magnetic resonance imaging (MRI) is currently the examination of choice for detection, regional staging and followup of these tumors. The segmentation of the lesions from the routine MR images allows the extraction of quantitative data, which has the potential to add information to the analysis. The purpose of the study is to evaluate the reproducibility of manual segmentation of soft tissue sarcomas in MRI images of patients with definitive diagnosis confirmed by histopathology. As a secondary objective, a comparison of manual and semiautomatic segmentation was performed to validate semiautomatic segmentation as an alternative method for segmentation of these tumors. We studied a retrospective cohort of 15 consecutive patients with confirmed diagnosis of soft tissue sarcoma accompanied at our service from January 2006 to January 2016 with MR images acquired prior to treatment and available for analysis in the DICOM format. The software was used 3D Slicer to perform segmentation by manual and semiautomatic methods. Three radiologists did the segmentations independently and blindly to allow inter-observer evaluation. The results obtained show high intraobserver reproducibility with Dice similarity coefficient between the segmentations ranging from 0.849 to 0.979 and Hausdorff distances ranging from 3.53 mm to 20.96 mm and good interobserver reproducibility with Dice similarity coefficients ranging from 0.741 to 0.972 and Hausdorff distances varying from 5.83 to 60.84 mm. A substantial agreement was found between the segmentations performed by the semiautomatic method when compared to the segmentations performed by the manual method with Dice similarity coefficients ranging from 0.871 to 0.973 and Hausdorff distances ranging from 5.43 mm to 31.75 mm. Regarding the segmentation time, there was no statistically significant difference of the semiautomatic method when compared to the manual method (p> 0.05). The volumes obtained in the different segmentations were also calculated and there was almost perfect agreement between the two manual segmentations performed by the radiologist 1, between the segmentations performed by radiologist 1 and radiologist 2, between the segmentations performed by radiologist 1 and radiologist 3, and between The manual and semi-automatic segmentation performed by the radiologist 1, and intraclass correlation coefficients (ICC) between 0.9927 and 0.9990 were obtained. The results obtained demonstrate good intra and interobserver reproducibility of the manual segmentation using 3D Slicer software, thus validating this method as a reliable tool to serve as a reference standard in future quantitative studies of these tumors. Almost perfect agreement was found between the segmentations performed by the semiautomatic method when compared to the segmentations performed by the manual method, but our results did not show a significant difference in segmentation time of the semiautomatic method in relation to the manual method.
67

3D facial analysis: unaffected parents of individuals with cleft lip/palate

Defay, David Kay 01 May 2011 (has links)
The purpose of this work is to study phenotypic craniofacial traits of unaffected parents of individuals with nonsyndromic cleft lip with or without palate (NSCL/P). In order to evaluate these craniofacial traits, three dimensional photographs were obtained and landmarked to compare the sample of unaffected parents with a control sample. The sample was comprised of 40 unaffected fathers, 25 control males, 84 unaffected mothers, and 34 control females. Twenty-four three-dimensional landmarks were exported for analysis for each subject. For the purposes of this study, nine euclidean distances were subjected to a discriminant function analysis to evaluate their ability to discriminate between an unaffected parent and a control. In both the male and female analysis, certain craniofacial measurements correctly and significantly discriminated between unaffected parents and controls. It appears that certain facial traits are subclinical markers for enhanced genetic susceptibility to nonsyndromic cleft lip with or without palate.
68

Risk Factors and Outcomes for Bloodstream Infections Among Patients with Skin Infections

Rybak, Michael Rybak 01 January 2016 (has links)
Acute bacterial skin and skin structure infections (ABSSSI) are common infections within the local community, and they result in higher morbidity and health care costs. While risk factors for skin and soft tissue infections have been previously evaluated, risk factors associated with secondary bloodstream infections (BSI) has not been investigated, especially in an intercity patient population with limited health care resources. In this case control investigation, 392 patients consisting of 196 cases (ABSSSI + BSI) and 196 controls (ABSSSI) were investigated to determine risk for BSI. Both sociodemographic and underlying conditions were evaluated. According to bivariate analysis of cases and controls, individuals with ABSSSI + BSI were significantly older (p < 0.001), more often male (p = 0.008), and had a higher percentage of abnormal symptoms, such as elevated temperature, white blood cell count, and acute renal failure on hospital admission (p < 0.001). Individuals with ABSSSI + BSI also had a higher percentage of chronic renal failure (p = 0.002), diabetes (p = 0.005), congestive heart failure (p = 0.012), intravenous drug use (p =0.012), and a history of prior hospitalization (p < 0.001). Several of these factors remained statistically significant by logistic regression analysis, such as male gender aOR of 1.85, 95% CI 1.11-3.66; acute renal failure aOR 2.08, 95% CI 1.18-3.67; intravenous drug use aOR 4.38, 2.22-8.62; and prior hospitalization aOR 2.41, 95% CI 1.24-4.93. This study contributes to positive social change by identifying patient characteristics that are associated with ABSSSI-related BSI, thus providing health care providers the ability to improve patient outcomes in this underserved patient population.
69

A comparison of physiotherapy and RICE self treatment advice for early management of ankle sprains

Lopes, Justin Unknown Date (has links)
Ankle sprains are one of the most common musculoskeletal injuries. Physiotherapy treatment and advice to rest, use ice, use compression, and elevate the ankle (RICE advice) is believed to speed up the functional recovery and enhance healing associated with acute ankle sprains. However, there is limited evidence to support the efficacy of RICE treatment. This study investigated whether physiotherapy (including RICE advice) was as effective as RICE advice alone in improving the time to recovery in a clinical situation.The evidence for RICE advice was reviewed along with the different treatment modalities currently used by physiotherapists in New Zealand for acute ankle sprain. This review highlighted the low number and poor quality of studies investigating RICE and early intervention physiotherapy management for ankle sprains. RICE principals appear to be relatively inexpensive and somewhat effective for pain relief and may reduce further tissue damage in the acute stage of Grade I and II ankle sprains. Evidence extrapolated from studies investigating the use of post surgical ice appears to support the use of ice in the acute stage of an ankle sprain to minimise bleeding and oedema. The intermittent application of ice is more effective for pain relief in the acute phase than sustained icing. Physiotherapy interventions such as TENS for pain relief and bracing for the support of Grade II - III ankle sprains have been shown to be beneficial for pain relief in the acute phase. A need for further high quality, randomised controlled trials (RCT's) was identified.Subsequently a RCT was conducted with 28 participants to investigate the difference between (a) early intervention physiotherapy management combined with RICE advice, and (b) self management RICE advice without physiotherapy.Twenty eight individuals (males n = 22, females n = 6), between the ages of 16 and 40 with acute ankle sprains, who met the inclusion criteria, were approached by physiotherapists working on this project and invited to participate. Dependant variables were pain, function, swelling, compliance and medication use up to Day 11 post injury. Swelling, pain and function were measured over three assessments on Days 1, 3 and 11, using volumetric analysis, a visual analogue scale (VAS) and a functional question derived from a validated functional questionnaire respectively. Medication use and compliance were elicited from information gathered in a participant home diary. Both groups were similar on Day 1 in respect to their initial pain, swelling, the number of participants who were referred for X-rays, and the time taken to present to the physiotherapist. However the RICE group had significantly higher function scores (p = 0.042). The RICE group also had a significantly higher use of medication on Day 1 (p = 0.035) and Day 11 (p = 0.048). For both groups there was a statistically significant decrease in swelling (p = 0.003), pain scores (p = 0.000), and an increase in function scores (p = 0.000) in relation to time over the eleven days of assessment. The physiotherapy group had significantly improved function scores (p = 0.042) from Day 1 to Day 11 compared to the RICE group. There were no significant differences between groups for swelling, pain scores, and their first day of documented non-compliance. The within day range of error in the volumetric measurements was within 189.9 ml and 1.2 ml. Three trials were conducted per person within a Day session. The first volumetric analysis was significantly less than the subsequent two measurements (p = 0.040).It was concluded that, in the early stage of an ankle injury both physiotherapy and RICE, and RICE advice alone, resulted in significant improvements in swelling, pain and function. Early intervention physiotherapy was significantly better at improving the functional ability of participants by Day 11. Early intervention physiotherapy may also identify complications associated with ankle sprains.Despite its limitations this research could potentially lead to changes in the standard treatment protocols for soft tissue ankle injuries. Implementation of self management RICE by patients in the acute stage would initially reduce the cost of physiotherapy treatments, and may lead to equal improvements in pain and swelling outcomes. However, it appears that physiotherapy may lead to better functional outcomes which would reduce the costs associated with time off work, and rehabilitation. It is important to note that these findings are based on a small sample size and on Grade I or II ankle ligament sprains, and that treatment for more severe ankle injuries may be better with physiotherapy, or surgery, rather than self management RICE by patients. Findings contribute to the growing body of 'best practice' evidence for health practitioners. Keywords: Acute soft tissue injuries, ankle, sprain, early intervention, physiotherapy, RICE, volumetric measurement.
70

Gene profiling in soft tissue sarcoma: predictive value of EGFR in sarcoma tumour progression and survival

Das Gupta, Paromita, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW January 2007 (has links)
Despite improvements in the clinical management of soft tissue sarcomas (STS), 50% of patients will die of metastatic disease that is largely unresponsive to conventional chemotherapeutic agents. The aims of this study were to identify genes and pathways that are dysregulated in progressive and metastatic STS. In addition to this, cell lines from fresh tumours were initiated and established, thus increasing the repository of cell lines available for functional studies. Recent advances in the understanding of the molecular biology of STS have thus far not resulted in the use of molecular markers for clinical prognostication. Identifying novel genes and pathways will lead to molecular diagnostic methods to better stratify prognostic groups and could identify cellular targets for more efficacious treatments. Gene expression profiling of sarcoma cell lines of increasing metastatic potential revealed over-expression of genes involved in the epidermal growth factor (EGF) and transforming growth factor beta (TGFb) pathways. Factors involved in invasion and metastasis such as integrins and MMPs were over-expressed in the cell lines with higher metastatic potential. The developmental Notch pathway and cell cycle regulators were also dysregulated. NDRG1 was significantly over-expressed in the high grade sarcoma cell line, a novel finding in sarcomas. The expression of EGFR, NDRG1 and other genes from the above pathways was validated using quantitative RT-PCR in real time (qRT-PCR). A tissue microarray (TMA) comprising STS of varying tumour grades was constructed for high throughput assessment of target proteins. EGFR, its activated form and its signal transducers were investigated using immunohistochemistry (IHC). Activated EGFR (HR 2.228, p < 0.001) and phosphorylated Akt (HR 2.032, p = 0.003) were found to be independent predictors of overall survival and both correlated with tumour grade. Of the several STS cultures initiated and maintained, two of these cell lines were fully characterised in terms of cytogenetics, telomerase and alternate lengthening of 5 telomeres (ALT) status, KIT and TP53 mutation and the expression of certain biomarkers using both qRT-PCR and IHC. In summary, transcript profiling identified several potential biomarkers of tumour progression and metastasis in STS. Crucially, activated EGFR and pAkt were found in a cohort of STS samples to correlate with clinical outcome, identifying them as potential diagnostic and therapeutic targets in the treatment of STS. Activated EGFR can be used as a diagnostic marker for patient selection, as well as for target effect monitoring. Furthermore, the cell lines established in this project will serve as valuable tools in future preclinical studies.

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