INTRODUCTION: The implementation of open posterior component separation (PCS) surgery has led to improved outcomes for complex hernias. While the PCS technique has been shown to decrease recurrence rates, and provide a feasible option to repair hernias in nontraditional locations, there is still significant postoperative pain associated with the laparotomy and extensive abdominal wall manipulation. Systemic opioids and thoracic epidural analgesia (TEA) are both commonly utilized, either together or independently, as postoperative analgesic regimens. The benefits of TEA have been studied following a variety of surgeries, however to date no study has been performed to investigate its efficacy in this particular surgery. The aim of this study is to evaluate the benefits of TEA following open PCS. We hypothesized that the incorporation of TEA in a patients postoperative analgesic regimen would show an advantage in time to bowel recovery. METHODS: An electronic medical record query was done to identify patients who had undergone an open PCS. Once this list was compiled, a retrospective chart review was performed and patients receiving TEA (either alone or combined with systemic opioids) were compared to patients receiving only systemic opioids. The primary endpoint compared time to resumption of a full diet, given by the patients postoperative day (POD). Secondarily, time to resumption of a liquid diet, postoperative length of stay (LOS), intensive care unit (ICU) admission rate, ICU LOS, and rates of several postoperative complications were all recorded and compared. A post-hoc analysis was also performed using the same endpoints. This analysis compared cohorts of patients receiving TEA and avoiding all systemic opioids, to patients who received systemic opioids (whether alone or combined with TEA). RESULTS: Based on inclusion parameters, 101 patients met criteria for analysis. In the initial analysis, 62 patients received TEA with or without systemic opioids, and 39 patients received only systemic opioids. In comparing these groups, there was no statistically significant difference in time to full diet (TEA 2.6 ± 1.7 vs Systemic opioids 3.1 ± 2.1 [mean POD ± SD]; P=0.21). In addition, no differences were found in the secondary outcomes of time to liquid diet, ICU admission, ICU LOS, or postoperative complications. In the post-hoc analysis, the 37 patients that received only TEA, were compared against 64 patients that received systemic opioids (either with or without TEA). In this comparison, the group receiving only TEA was found to have a statically shorter time to bowel recovery compared to patients receiving systemic opioids (TEA alone 2.2 ± 1.0 vs Systemic opioids 3.2 ± 2.2, P=0.0033). This subgroup (TEA only) also showed statically shorter time to liquid diet and a decreased postoperative LOS. CONCLUSION: For patients undergoing an open PCS, the inclusion of TEA in the postoperative analgesic regimen did not shorten return of bowel function. However, when TEA was utilized and systemic opioids were avoided, time to bowel recovery and hospital LOS were both significantly shortened.

<p> Bayesian filtering refers to the process of sequentially estimating the current state of a complex dynamic system from noisy partial measurements using Bayes' rule. This thesis considers Bayesian filtering as applied to an important class of state estimation problems, which is describable by a discrete-time nonlinear state-space model with additive Gaussian noise. It is known that the conditional probability density of the state given the measurement history or simply the posterior density contains all information about the state. For nonlinear systems, the posterior density cannot be described by a finite number of sufficient statistics, and an approximation must be made instead.</p> <p> The approximation of the posterior density is a challenging problem that has engaged many researchers for over four decades. Their work has resulted in a variety of approximate Bayesian filters. Unfortunately, the existing filters suffer from possible divergence, or the curse of dimensionality, or both, and it is doubtful that a single filter exists that would be considered effective for applications ranging from low to high dimensions. The challenge ahead of us therefore is to derive an approximate nonlinear Bayesian filter, which is theoretically motivated, reasonably accurate, and easily extendable to a wide range of applications at a minimal computational cost.</p> <p> In this thesis, a new approximate Bayesian filter is derived for discrete-time nonlinear filtering problems, which is named the cubature Kalman filter. To develop this filter, it is assumed that the predictive density of the joint state-measurement random variable is Gaussian. In this way, the optimal Bayesian filter reduces to the problem of how to compute various multi-dimensional Gaussian-weighted moment integrals. To numerically compute these integrals, a third-degree spherical-radial cubature rule is proposed. This cubature rule entails a set of cubature points scaling linearly with the state-vector dimension. The cubature Kalman filter therefore provides an efficient solution even for high-dimensional nonlinear filtering problems. More remarkably, the cubature Kalman filter is the closest known approximate filter in the sense of completely preserving second-order information due to the maximum entropy principle. For the purpose of mitigating divergence, and improving numerical accuracy in systems where there are apparent computer roundoff difficulties, the cubature Kalman filter is reformulated to propagate the square roots of the error-covariance matrices. The formulation of the (square-root) cubature Kalman filter is validated through three different numerical experiments, namely, tracking a maneuvering ship, supervised training of recurrent neural networks, and model-based signal detection and enhancement. All three experiments clearly indicate that this powerful new filter is superior to other existing nonlinear filters. </p> / Thesis / Doctor of Philosophy (PhD)

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Introdução: Os ependimomas são tumores gliais raros e compreendem o terceiro tumor do sistema nervoso central mais frequente na infância. Apesar dos avanços terapêuticos, cerca de 50% dos pacientes desenvolvem recidiva local e 40% dos pacientes vão ao óbito. Uma das causas do insucesso das terapias é a alta heterogeneidade do tumor e a inconsistência do diagnóstico histológico. Em 2015, foi publicada pela primeira vez a caracterização molecular de ependimomas, sendo descrito nove subgrupos tumorais com perfis clínicos, demográficos e moleculares distintos. Objetivo: Estabelecer e padronizar a classificação molecular em amostras de ependimomas pediátricos e correlacionar a classificação com dados clínicos dos pacientes. Casuística e Métodos: Foram estudados 65 casos de ependimomas, diagnosticados no período entre 2001 a 2016 e provenientes do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto e de São Paulo e do Centro Infantil Boldrini-Campinas. Vinte e seis casos eram ependimomas supratentoriais, classificados com base na presença de fusões gênicas C11orf95-RELA, YAP1-MAMLD1 e YAP1-FAM118B utilizando RT-PCR seguida por sequenciamento de Sanger. Trinta e nove casos de fossa posterior foram classificados em Grupos A, B ou não A e B através do perfil de expressão proteica e gênica dos marcadores: LAMA2, NELL2 e TNC utilizando imuno-histoquímica e PCR quantitativo em tempo real, respectivamente. Resultados: Dentre os ependimomas supratentoriais foram identificadas três amostras primárias e cinco amostras recidivadas com presença de fusão RELA, média de idade de 7 anos (variação de 2,6-13,7 anos), predominância do sexo masculino e grau de ressecção cirúrgica completa. Já a fusão YAP1- MAMLD1 foi identificada em quatro casos, diagnosticados em crianças mais novas, média de idade de 0,9 anos (variação de 0,75-2 anos). Adicionalmente, foi encontrado um caso variante em ependimoma supratentorial, denominado fusão C11orf95-LOC-RELA. Dentre os casos de ependimoma de fossa posterior, foram identificadas 26 amostras primárias e sete recidivas sugestivas de pertencerem ao Grupo A (LAMA2+/ NELL2 -) e seis amostras do Grupo não-A e não-B (LAMA2 +/ NELL2 + e LAMA2 -/NELL2-). Entre os pacientes considerados Grupo A, 90% (24/28) apresentaram marcação positiva para TNC, indicando serem tumores de pior prognóstico. A expressão gênica de LAMA2 e NELL2 apresentou correlação negativa e os genes TNC e LAMA2 uma correlação positiva, p<0,01 e p<0,05, respectivamente. Em ependimoma de fossa posterior Grupo A, os pacientes submetidos às ressecções completa e incompleta apresentaram diferença significativa na sobrevida global (5 anos) de 71,2% ± 14,5% versus 21,4% ± 17,8%, p< 0,01 e na SLE (2 anos) 63,5% ± 14,8% versus 25% ± 15.3%, p <0.001. Conclusões: De acordo com os resultados obtidos foi possível estabelecer a classificação molecular em uma casuística brasileira, seguindo os padrões descritos na literatura. Dados gerados a partir dessa padronização serão de fundamental importância para melhoria da estratificação tumoral, contribuindo tanto para determinação de estratégicas terapêuticas subgrupo-específicas, quanto na busca de novos alvos terapêuticos. / Introduction: Ependymomas are rare glial cell-derived tumors and comprise the third most frequent central nervous system tumor in childhood. Despite the therapeutic advances, about 50% of patients develop local recurrence and 40% of patients go to death. One of the causes of the failure of the therapies is the high tumor heterogeneity and the inconsistency of the histological diagnosis. In 2015, the molecular characterization of ependymomas was published for the first time, and nine tumor subgroups with distinct clinical, demographic and molecular profiles were described. Aim: To establish and standardize molecular classification in pediatric ependymoma samples and to correlate the classification with clinical data of the patients. Methods: We studied 65 cases of ependymomas, diagnosed between 2001 and 2016, from the Clinics Hospital of the Medical School of Ribeirão Preto and São Paulo and the Boldrini Children\'s Center-Campinas. Twenty-six cases were supratentorial ependymomas, classified based on the presence of gene fusions C11orf95- RELA, YAP1-MAMLD1 and YAP1-FAM118B using RT-PCR followed by Sanger sequencing. Thirty-nine posterior fossa cases were classified into Groups A, B or non A and B through the protein and gene expression profile of the markers: LAMA2, NELL2 and TNC using immunohistochemistry and quantitative real-time PCR, respectively. Results: Among the supratentorial ependymomas, three primary samples and five relapsed samples with RELA fusion, mean age of 7 years (range of 2.6-13.7 years), male predominance, and degree of complete surgical resection were identified. The YAP1-MAMLD1 fusion was identified in four cases, diagnosed in younger children, mean age 0.9 years (range of 0.75-2 years). In addition, a variant case was found in supratentorial ependymoma, called fusion C11orf95- LOC-RELA. Twenty-six primary samples and seven recurrences suggestive of Group A (LAMA2 + / NELL2-) and six non-A and non-B Group samples (LAMA2 + / NELL2 + and LAMA2 - / NELL2-). Among the patients considered Group A, 90% (24/28) presented positive staining for TNC, indicating that tumors had a worse prognosis. The gene expression of LAMA2 and NELL2 presented negative correlation and the TNC and LAMA2 genes had a positive correlation, p <0.01 and p <0.05, respectively. In the group A posterior fossa ependymoma, patients submitted to complete and incomplete surgical presented a significant difference in overall survival (5 years) of 71.2% ± 14.5% versus 21.4% ± 17.8%, p <0 , 01 and in SLE (2 years) 63.5% ± 14.8% versus 25% ± 15.3%, p <0.001. Conclusions: According to the results obtained, it was possible to establish the molecular classification in a Brazilian cohort, following the standards described in the literature. Data generated from this standardization will be of fundamental importance for the improvement of tumor stratification, contributing both to the determination of subgroup-specific therapeutic strategies and to the search for new therapeutic targets.

Neste estudo, foram descritos os aspectos clínicos e resultados visuais em indivíduos com evidência sorológica e sinais clínicos de toxoplasmose ocular. Os sujeitos foram examinados com lâmpada de fenda, exame de oftalmoscopia indireta, tendo registros fotográficos com retinografia e tomografia de coerência óptica. Duzentos e sessenta e sete participantes foram incluídos no estudo (n = 350 olhos). A forma de toxoplasmose ocular foi considerada primária em 52 indivíduos (19,5%), recorrente ativa em 89 (33,3%) e inativa em 126 (47,2%). A maioria dos olhos apresentou uma lesão (n=169; 48,3%), enquanto que 149 olhos (42,6%) apresentaram duas a quatro lesões e 32, cinco ou mais lesões (9,1%). As lesões centrais estiveram presentes em 127 olhos (36,3%), periféricas em 178 (50,9%), enquanto que lesões centrais e periféricas em 45 (12,6%). A maioria dos indivíduos apresentou sorologia para toxoplasma gondii (T. gondii) IgG + IgM- (n=245; 91,8%), enquanto que apenas 22 (8,2%) foram T. gondii IgG + IgM +. Do total de olhos afetados em que a acuidade visual foi medida (n=314), a maioria (n=160; 50,9%) apresentou melhor acuidade visual corrigida final >20/40, e 25,8% (n=81) foram considerados cegos (<20/400). Lesões múltiplas, de localização central e com tamanho maior que um diâmetro de disco óptico foram consideradas fator de risco para pior prognóstico visual. A membrana epirretiniana (n=21; 7,1%) e opacidade vítrea (n=20; 6,8%) foram as principais causas de complicações observadas. A taxa de incidência de complicações foi de 0,41 complicações/ano, e foram verificadas 0,13 reativações/ano. O estudo demonstrou altas taxas de déficit visual, devendo ser realizados novos estudos para o desenvolvimento de novas modalidades terapêuticas para diminuir o impacto da doença como causa de cegueira e deficiência visual. / In this study, we describe the clinical aspects clinical aspects and visual outcomes in individuals with serological evidence and clinical signs of ocular toxoplasmosis. The subjects were examined with a slit lamp, indirect ophthalmoscopy examination, having photographic records with retinography and optical coherence tomography. Two hundred and sixty -seven subjects were included in the study (n=350 eyes). The form of ocular toxoplasmosis was considered primary active in 52 subjects (19.5%), recurrent active in 89 subjects (33.3%) and inactive in 126 (47.2%). Most eyes presented only one lesion (n=169; 48.3%), whereas 149 individuals (42,6%) had 2-4 lesions, and 32 had five or more lesions (9.1%). Central lesions only were present in 127 eyes (36,3%), peripheral in 178 (50,9%%), while concomitant central and peripheral were present in 45 (12.6%). Most subjects had T. gondii IgG+ IgMserology (n=245; 91.8%), whereas only 22 (8,2%) were T. gondii IgG+ IgM+. From the total of affected eyes which visual acuity was measured (n=314), most (n=160; 50,9%) had better final corrected visual acuity> 20/40 and 25.8% (n = 81) were considered blind (<20/400). Multiple, centrally located lesions of greater size than an optic disc diameter were considered risk factor for a worse visual prognosis. The epiretinal membrane (n=21; 7.1%) and vitreous opacity (n=20; 6.8%) were the main causes of complications seen. The incidence rate of complications was 0,41 complications/year, and it was verified 0,13 reactivations/year. The study demonstrated a high rate of visual impairment, and studies for the development of novel therapeutic modalities should be performed to reduce the impact of the disease as a cause of blindness and visual impairment.

O objetivo primário deste estudo foi identificar parâmetros anatômicos que permitissem ao cirurgião, durante o ato cirúrgico, localizar com o auxílio de fluoroscopia o centro de inserção do ligamento cruzado posterior (LCP) na tíbia. O objetivo secundário foi propor ao cirurgião um método reprodutível e seguro para realizar a perfuração do túnel tibial na cirurgia de reconstrução do LCP. Vinte joelhos de cadáveres frescos congelados foram, inicialmente, submetidos à tomografia computadorizada de alta resolução (TC). Os joelhos foram, a seguir, dissecados e a inserção tibial do LCP digitalizada por um sistema de rastreamento óptico. A digitalização óptica da inserção do LCP resultou em modelos tridimensionais que permitiram localizar o centroide virtual dessa inserção. Paralelamente à analise virtual, inseriu-se um fio de Kirschner (FK) no centro anatômico da inserção tibial do LCP sob visualização direta. Foi realizado exame fluoroscópico no plano sagital desta tíbia e o ponto correspondente à inserção do FK foi registrado na imagem. Os locais definidos como o centro do LCP, nos dois métodos, foram plotados em uma linha imaginária paralela à faceta tibial de inserção do mesmo. Para fins de referência, essa linha foi dividida em uma escala centesimal, tendo o seu ponto zero correspondente à margem anterior/proximal da faceta e o ponto 100, correspondente à margem posterior/distal da faceta. O centro do LCP esteve situado em um ponto correspondente a 70% da distância, a partir da borda anterior/proximal da faceta do LCP, quando tomada como referência uma imagem de fluoroscopia em perfil do joelho (plano sagital). Essa medida mostrou ser reprodutível e pode ser um parâmetro útil para orientar a perfuração e inserção do fio guia tibial na confecção do túnel tibial nas cirurgias de reconstrução do LCP. / The primary objective of this study was to determine the center of the anatomical tibial insertion of the posterior cruciate ligament in cadaver knees and correlate this point to anatomical references as seen on fluoroscopic images of the same specimens. We aimed to describe a reproducible and safe method to place the tibial tunnel at the most anatomical position during posterior cruciate ligament reconstructions. Twenty fresh frozen cadaver knees were initially submitted to a high-resolution computadorized tomography (CT). Then, the knees were dissected and the PCL tibial insertion was digitalized with an optical tracking system. The optical digitalization of the PCL insertion resulted in tridimensional models that allowed the identification of the virtual centroid of this insertion. After the virtual analysis by CT scan, a Kirschner wire was inserted at the anatomical center of the PLC tibial insertion under direct visualization. Fluoroscopic views of the tibia on the sagittal plane were acquired and the correspondent point of the Kirschner wire insertion was registered. The points defined as the posterior cruciate ligament center by the two methods were plotted in an imaginary line parallel to the tibial facet of the PCL insertion. As a reference, this line was divided in a centesimal scale, with the zero point corresponding to the anterior/proximal margin of the facet and the 100-point, corresponding to the posterior/distal margin of the facet. The PCL center was found in one point corresponding to approximately 70% of the distance from the anterior/proximal border of the PCL facet when a lateral fluoroscopic image of the knee was utilized as a reference (sagittal plane). This measure was found to be consistently reproducible and may be a useful parameter to guide the positioning of the tibial guide wire during tibial tunnel drilling in posterior cruciate ligament reconstructions.

O ácido retinóico (AR) é sintetizado a partir de oxidações sucessivas do retinol. A última etapa de oxidação é catalisada pelas enzimas RALDHs. O estabelecimento da polaridade ântero-posterior (AP) do coração é crítico para a demarcação das regiões de efluxo (ventrículos) e de influxo (átrios). Nosso grupo propõe que uma onda caudo-rostral (CR) de RALDH2 seja o mecanismo responsável por esta padronização em vertebrados. Para testar o papel da sinalização pelo AR na padronização AP do peixe zebra, manipulamos sua via com o inibidor das enzimas RALDHs, DEAB, com AR e com um inibidor da enzima CYP26 (IC), que cataboliza o AR. Os tratamentos com DEAB durante o período da onda de RALDH2 produziram átrios reduzidos, enquanto que os tratados com AR e com IC apresentam o domínio atrial expandido. Animais tratados com DEAB e AR em um estágio posterior a onda não mostraram diferença significativa ao controle. Estes dados sugerem uma forte correlação entre o evento da onda e a padronização das câmaras cardíacas, semelhante ao que ocorre nos demais amniotos. / The retinoic acid (RA) is synthetized by successive oxidations of retinol. The last oxidation step is catalyzed by the RALDHs enzymes. The establishment of the anteroposterior (AP) polarity is critical for the demarcation of outflow (ventricle) and inflow (atrium) regions. Our group proposes that a caudorostral (CR) wave of RALDH2 is the mechanism responsible for this patterning in vertebrates. In order to test the role of the RA signaling in zebrafish AP patterning, we manipulated its pathway with a RALDH enzymatic inhibitor, DEAB, with RA and with a CYP26 (IC) enzymatic inhibitor, that catabolises the RA. The DEAB treatments during the manifestation of the RALDH wave produced reduced atriums; meanwhile, the treatments with RA and IC presented an atrium expansion. Animals treated with DEAB and RA during a stage posterior to the wave did not present any significant difference. These data suggest a strong correlation between the wave event and the cardiac chamber patterning, similar to the mechanism observed in others amniotes.

Introdução: Dentre as anomalias congênitas obstrutivas do trato urinário a Válvula de Uretra Posterior (VUP) apresenta elevado risco para a sobrevida do recém-nascido e é a causa mais comum de doença renal crônica terminal na infância. Seu tratamento envolve múltiplas especialidades e necessita seguimento no longo prazo. Com esses aspectos torna-se imperativo a permanente reavaliação de condutas. Objetivo: Descrever os aspectos clínicos e evolutivos dos pacientes portadores de Válvula de Uretra Posterior buscando avaliar a necessidade de adequações ao protocolo de atendimento. Casuística e Métodos: Constituída por 68 pacientes portadores de VUP atendidos no HCFMRP-USP no período entre 1990 e 2015. Foram revistos os dados relativos ao nascimento, encaminhamento, exames complementares, cirurgias realizadas e evolução clínica. Resultados: houve predomínio da raça branca (76,5%) e procedentes da DRS XIII (82,4%). A maioria das crianças vieram encaminhadas de outros hospitais (80,9%), alguns já submetidos à derivação urinária. Quanto à idade ao encaminhamento, 52,7% chegaram após o primeiro ano de vida embora o diagnóstico tenha sido feito em 76,5% antes do primeiro ano. Avaliação ultrassonográfica pré-natal foi realizada em 40 gestantes (48,8%) e oligoâmnio observado em16/40 (40,0%). Dentre os exames complementares para diagnóstico e seguimento ambulatorial ressaltamos a urografia excretora (16,2%), cintilografia renal (70,6%) e renograma (29,4%). Uretrocistografia foi realizada em todos os pacientes. Quanto aos principais procedimentos, derivação vesico-amniótica intrauterina foi realizada em 3 pacientes, cateterismo vesical de demora em 20, derivação alta em 4 pacientes, vesicostomia em 33, ressecção parcial do colo vesical em 9 e cauterização da VUP em 67. Dez pacientes foram transplantados. Discussão e Conclusões: os resultados apresentados são comparáveis àqueles divulgados na literatura pelas melhores instituições quanto ao diagnóstico, procedimentos cirúrgicos e evolução. O que fica evidente são as condições sócioeconômicas e culturais do nosso País onde a obtenção de melhores resultados terapêuticos tropeça em questões sociais e educacionais, necessitando de ações conjuntas visando educação continuada e organização social. Exame pré-natal adequado, diagnóstico precoce e rápido encaminhamento a centros que possam absorver estes pacientes são cruciais para a melhor evolução clínica. O protocolo mínimo de assistência deve ser objeto de difusão aos profissionais de saúde de diferentes especialidades visando o reconhecimento do quadro clínico. É desejável a inclusão, no protocolo de atendimento, de exames laboratoriais com capacidade prognóstica relacionada à evolução para doença renal crônica. / Introduction: Among congenital anomalies of the urinary tract, the posterior urethral valve (PUV) has a high risk for newborn´s mortality and is the most frequent cause of terminal chronic kidney disease in children. Its treatment involves multidisciplinary approach and long-term follow-up is necessary. Therefore, it is mandatory to permanently re-evaluate conducts. Objective: To describe the clinical and evolutive aspects of patients with PUV, aiming to evaluate the need for care protocol adjustments. Patients and Methods: The records of 68 boys with PUV who were treated at HCFMRP-USP between 1990 and 2015 have been reviewed. The data analyzed consisted of information regarding birth, age at referral, complementary exams, surgeries and clinical evolution. Results: There was a predominance of Caucasian (76.4%) and patients have been referred from region DRS XIII (82.4%). Most of the children have already been referred from other hospitals (80.8%), and some of them were already submitted to urinary diversion. Regarding the age of referral, 52.7% arrived after the first year of life, although the children were diagnosed before the first year of life in 70,6% of the cases. Prenatal ultrasound evaluation has been performed in 40 pregnant women (48.8%) and oligohydramnios was found in 16/40 (40,0%). Concerning the complementary exams for diagnosis and outpatient follow-up we highlighted excretory urography (16.2%), renal scintigraphy (70,6%) and renogram (29,4%). Voiding cistourethrography was performed in all patients. Regarding the main procedures, intrauterine vesico-amniotic shunt was performed in 3 patients, temporary drainage of urinary tract with vesical catheterization in 20, higher diversion in 4 patients, vesicostomy in 33, partial resection of the bladder neck in 9 and ablation during cystoscopy of the VUP in 67 patients. Ten patients were submitted to transplantation. Discussion and Conclusions: the results presented are comparable to those published in the literature by the best institutions regarding diagnosis, surgical procedures and patient evolution. What has become evident are the socioeconomic and cultural conditions of our country, where obtaining better therapeutic results stumbles on social and educational issues, requiring joint actions aimed continuing education and social organization. Proper prenatal examination, early diagnosis and early referral to institutions that can absorb these patients are crucial for the best clinical outcome. The minimum protocol of assistance should be disseminated to health professionals of different specialties in order to recognize the clinical picture. It is desirable to include, in the attendance protocol, laboratory tests with prognostic capabilities regarding evolution to chronic kidney disease.

Este trabalho investiga a influência de polimorfismos na região promotora do gene das metaloproteases 1, 3 e 8 na fisiopatogenia da insuficiência primária do tendão tibial posterior. A amostra de 150 pacientes selecionados é dividida em grupo-teste: 50 pacientes com diagnóstico clínico e anatomopatológico de tendinopatia do tendão tibial posterior e grupo-controle: 100 pacientes com tendão tibial posterior íntegro. O DNA dos voluntários é obtido a partir de células epiteliais da mucosa bucal mediante a extração com acetato de amônia. As técnicas de PCR e RFLP são utilizadas para análise dos genótipos. A análise estatística dos resultados é realizada pelo teste do qui-quadrado com nível de significância de 5%. Os resultados mostram que os polimorfismos -1607 da MMP-1 e -799 da MMP-8 estão relacionados com risco maior para tendinopatia primária do tendão tibial posterior, enquanto o polimorfismo -1612 da MMP-3 parece não influenciar essa tendinopatia / The aim of this study was to investigate the influence of polymorphisms in the promoter region of the gene of metalloproteinases 1, 3 and 8 in physiopatology of primary posterior tibial tendon insufficiency. The sample of 150 selected patients was divided into test group: 50 patients undergoing surgical procedures and pathological diagnosis of degenerative lesions of the posterior tibial tendon, and control group: 100 patients with posterior tibial tendon intact and no signs of degeneration. The DNA of the volunteers was obtained from oral mucosa epithelial cells, by extraction with ammonium acetate. PCR and RFLP were used for analysis of genotypes. Statistical analysis of results was performed by Chi-squared test with significance level of 5%. The results show that polymorphisms -1607 of MMP-1 and -799 of the MMP-8 are associated with increased risk for primary tendinopathy of the posterior tibial tendon, while the -1612 polymorphism of MMP-3 does not influence this tendinopathy

Introdução: A discrepância no comprimento dos membros inferiores (DCMI) está associada a alterações biomecânicas na marcha e a uma grande variedade de desordens ortopédicas, que incluem uma possível sobrecarga do tendão tibial posterior. Neste sentido, hipotetizamos que há associação entre a presença de DCMI e disfunção do TTP. Objetivo: O presente estudo foi realizado para comparar a frequência e a magnitude de DCMI em um grupo com e outro sem disfunção do tendão tibial posterior (DTTP), bem como para relacionar características clínicas com a presença da doença. Modelo do estudo: Estudo caso-controle. Método: O estudo envolveu 118 pacientes com diagnóstico de DTTP atendidos entre janeiro de 2009 e setembro de 2012 e 118 voluntários controles pareados por gênero e raça. Através de escanometria radiográfica ou tomográfica, a frequência da DCMI, assim como a média da DCMI absoluta e a média da DCMI relativa foram comparadas entre os dois grupos. Resultados: A prevalência da DCMI e as médias da DCMI absoluta e da DCMI relativa foram significativamente maiores no grupo de casos (94,9%, 5,64 mm e 7,36% respectivamente) do que no grupo controle (79,7%, 3,28 mm e 4,18% respectivamente) (p<0.001). Conclusões: Os resultados deste estudo demonstram haver uma relação entre a DCMI e a presença de DTTP. Devido a importantes alterações biomecânicas geradas pela DCMI, esta é possivelmente um fator predisponente para o desenvolvimento da DTTP. / Background: Leg length discrepancy (LLD) is associated with a variety of orthopedic disorders and biomechanical gait changes that involve possible overload of the posterior tibial tendon (PTT). In view of the biomechanical disturbances induced by LLD, an association may exist between LLD and PTT dysfunction (PTTD). Purpose: To compare the frequency and magnitude of LLD between subjects with and without PTTD and ascertain whether associations exist between clinical features and presence of dysfunction. Study design: Casecontrol study. Methods: A total of 118 patients with a diagnosis of PTTD were seen between January 2009 and September 2012 and compared to 118 sex- and race-matched volunteers. The frequency of LLD, the mean absolute LLD and the mean relative LLD were measured by conventional (radiographic) or CT scanography and compared between cases and controls. Results: The prevalence of LLD and mean absolute and relative LLD values were significantly greater in the case group (94.9%, 5.64 mm and 7.36% respectively) than in the control group (79.7%, 3.28 mm and 4.18% respectively) (p<0.001). Conclusion: The findings of this study demonstrate a relationship between LLD and PTTD. In light of the major biomechanical changes it induces, LLD may be a predisposing factor for development of PTTD.