Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (p. 175-193).

Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-11-13Bitstream added on 2014-06-13T20:01:40Z : No. of bitstreams: 1 cabral_vp_dr_jabo.pdf: 464248 bytes, checksum: 83473e8d960d8d22d0470e9cf4817b9e (MD5) / Cesumar / Com o trabalho, propõe-se apresentar um modelo experimental de prolapso da glândula da terceira pálpebra em cães, valendo-se, para tal, da ressecção do retináculo glandular periorbitário e de estudos macro e microscópicos, bem como das intercorrências clínicas, quanto à produção lacrimal. As variáveis foram estudadas em bulbos dos olhos com glândulas prolapsadas, em outros com glândulas sepultadas cirurgicamente e em bulbo do olhos que passaram por exérese glandular. Mediante análise dos resultados constatou-se que a produção lacrimal diminuiu, comparativamente às glândulas normais não prolapsadas, notadamente naqueles casos em que as glândulas prolapsadas não foram sepultadas. Glândulas prolapsadas apresentaram-se maiores, quanto ao comprimento, à largura e à espessura. Microscopicamente, glândulas prolapsadas não sepultadas cirurgicamente, exibiram alterações inflamatórias glandulares e ductais em maior intensidade. Das glândulas prolapsadas, 84,2% assim permaneceram, permitindo que fossem estudadas quanto às variáveis concebidas. / The work proposes to present an experimental model of prolepsis of the third eyelid gland in dogs, using for such a thing the resection of the periorbital glandular support and macro and rnicroscopic studies, as well as the c1inical intercurrences, related to the lacrimal production. The variables weíe studied in the eyes bulb with prolapsed glands, in others with surgically buried glands and eyes bulb that passed by glandular exerese. Through the results analysis, it was evidenced that the lacrimal production diminished, when compared with the normal ones not prolapsed, mainly in those cases where the prolapsed glands were not buried. Prolapsed glands are presented bigger, in relation to their length, width and thickness. Microscopically, prolapsed glands that were not buried surgically, showed glandular and duct inflammatory changes in higher intensity. Qut of the prolapsed glands, 84.2% remained in the same way, allowing that they were studied in relation to the conceived variables.

Orientador: José Luiz Laus / Banca: Aline Adriana Bolzan / Banca: Cristiane dos Santos Honsho / Banca: Marcia Rita Fernandes Machado / Banca: Cintia Lucia Maniscalco / Resumo: Com o trabalho, propõe-se apresentar um modelo experimental de prolapso da glândula da terceira pálpebra em cães, valendo-se, para tal, da ressecção do retináculo glandular periorbitário e de estudos macro e microscópicos, bem como das intercorrências clínicas, quanto à produção lacrimal. As variáveis foram estudadas em bulbos dos olhos com glândulas prolapsadas, em outros com glândulas sepultadas cirurgicamente e em bulbo do olhos que passaram por exérese glandular. Mediante análise dos resultados constatou-se que a produção lacrimal diminuiu, comparativamente às glândulas normais não prolapsadas, notadamente naqueles casos em que as glândulas prolapsadas não foram sepultadas. Glândulas prolapsadas apresentaram-se maiores, quanto ao comprimento, à largura e à espessura. Microscopicamente, glândulas prolapsadas não sepultadas cirurgicamente, exibiram alterações inflamatórias glandulares e ductais em maior intensidade. Das glândulas prolapsadas, 84,2% assim permaneceram, permitindo que fossem estudadas quanto às variáveis concebidas. / Abstract: The work proposes to present an experimental model of prolepsis of the third eyelid gland in dogs, using for such a thing the resection of the periorbital glandular support and macro and rnicroscopic studies, as well as the c1inical intercurrences, related to the lacrimal production. The variables weíe studied in the eyes bulb with prolapsed glands, in others with surgically buried glands and eyes bulb that passed by glandular exerese. Through the results analysis, it was evidenced that the lacrimal production diminished, when compared with the normal ones not prolapsed, mainly in those cases where the prolapsed glands were not buried. Prolapsed glands are presented bigger, in relation to their length, width and thickness. Microscopically, prolapsed glands that were not buried surgically, showed glandular and duct inflammatory changes in higher intensity. Qut of the prolapsed glands, 84.2% remained in the same way, allowing that they were studied in relation to the conceived variables. / Doutor

No description available.

Objetivos: a) descrever um novo método de medida do contorno palpebral superior, b) medir o grau de assimetria interocular do contorno em sujeitos normais, c) quantificar a assimetria interocular do contorno após cirurgia de ptose com conjuntivo-müllerectomia (CMM) e avanço aponeurótico via anterior (VANT), realizadas por dois cirurgiões. Casuística e Métodos: a) dois observadores independentes usaram o programa NIH Image J, com plugin Bézier para extrair o contorno palpebral de fotografias de 29 olhos de sujeitos normais. A concordância entre as duas extrações foi aferida pelo coeficiente percentual de superposição (CPS) de duas linhas, bem como pelo gráfico de Bland-Altman para as diferenças entre a localização do ponto mais alto dos contornos (pico) e pelo coeficiente de correlação Lin, que mensura o quanto as medidas se aproximam da linha de igualdade; b) foi medido o contorno palpebral direito e esquerdo de uma amostra de 75 pessoas normais, com idades variando entre 19 e 73 anos, com média = 44,6 ± 15,7 DP. A amostra foi analisada como um todo e também quando dividida em dois grupos: Grupo 1 (G1) (n=39, idade média =30,2 anos ± 4,5 DP) e Grupo 2 (G2) (n=38, idade média =58,6 anos ± 8,2 DP). O grau de concordância do contorno palpebral direito e esquerdo foi estimado pela mensuração do CPS para toda a extensão da pálpebra, bem como para as porções medial e lateral em relação ao centro da pupila. A assimetria da posição do pico dos contornos também foi quantificada; c) foram analisadas as fotos de 38 pacientes consecutivos portadores de ptose involucional operados bilateralmente por dois cirurgiões distintos (C1, n=20 e C2, n=18) com CMM e VANT (o mesmo número de pacientes em cada técnica). Resultados: a) As curvas de Bézier foram ajustadas a todos os contornos palpebrais com alta reprodutibilidade, o CPS médio = 96,1% ± 1.7 DP. As diferenças entre a posição do pico do contorno foram de +0.5 e -0.5, em torno da média = 0. O coeficiente de Lin foi igual a 0.96; b) os contornos palpebrais foram ajustados por funções parabólicas com coeficiente de determinação médio de 0,99. A assimetria média dos CPS foi de 5.5% sem diferenças significativas entre os segmentos lateral e medial e entre G1 e G2. O valor médio da localização dos picos foi de -0.48 mm (lateral ao centro pupilar) ± 0,06 EP. A média da assimetria desse parâmetro foi de 0,43 mm ± 0,04 EP; c) a assimetria média dos contornos após a CMM foi de 5.3% para C1 e 5.9% para C2. Esse grau de assimetria não foi diferente do observado no grupo controle. Após a correção VANT, esses valores foram, respectivamente, 10.4% e 10.8%, significativamente maiores do que os observados na população normal. Conclusões: As curvas de Bézier possibilitam a extração do contorno palpebral superior com excelente reprodutibilidade. Na pessoas normais, todos os contornos são bem ajustados por curvas parabólicas com picos situados discretamente lateral ao centro pupilar. O contorno é melhor simetrizado com a CMM do que com a VANT. / Purposes: a) to describe a new test of upper eyelid contour measurement, b) to quantify the asymmetry of the interocular of lid contour in normal subjects, c) to measure the interocular contour asymmetry after ptosis surgery with conjunctivaMüllerectomy (CMM) and aponeurotic surgery anterior approach (AAS). Casuistic and Methods: a) two independent observers used the NHIJ image software with a Bézier plugin to extract the lid contour of 29 photos of normal eyes. The agreement of the two lid contours was measured with the coefficient percentage overlapping of superimposing two lines (PCLS) as well by computing the differences of the contour peak location with the Bland and Altman plot and Lin correlation coefficient; b) The right and left lid contours of a sample of normal subjects (n = 75) with ages ranging from 19 and 73 years was measured. The sample was analyzed as a whole and also divided into two age groups G1 (n=39, mean age = 30.2 ± 4,5 SD) and G2 (mean age = 58.6 years ± 8,2 SD). The degree of agreement of the two contours was estimated by the CLS for the whole extension of the lid and for the medial and portions relative to the pupil center. The contour peak asymmetry was also quantified; c) the photos of 28 patients with involutional ptosis who underwent bilateral surgery by 2 different surgeons (C1, n=20 and C2, n=18) with CMM and AAS (equal number of patients with each technique). Results: a) The Bézier curves were adjusted with high concordance between observers for all lid contours. The mean CLS was 96.1% ± 1.7 SD. The peak contour differences (+0.5 to -0.5 mm) were equally distributed around the mean value = 0. The mean Lin coefficient of concordance was 0.96; b) all lid contours were adjusted to parabolic functions with a mean coefficient of determination = 0.99. The mean asymmetry of the contours estimated by the CLS was 5.5%. The mean value of the peak location was - 0.48 mm ± 0,06 SE (lateral to the pupil center) without significant differences between the medial and lateral portions of the lids and between G1 and G2. The mean asymmetry of this parameter was de 0,43 mm ± 0,04 EP; c) The mean contour asymmetry following CMM was 5.3% for C1 and 5.9% for C2, these values were not different from the observed in the control group. After ptosis correction with AAS these values were respectively 10.4% and 10.8% significantly greater than observed in the normal population. Conclusions: The Bézier curves allow the extraction of the upper lid contours with excellent concordance between observers. In the normal population all contours are well adjusted with parabolic function with the peak contour localized slightly lateral to the pupil center. CMM allow a better symmetry of lid contour than AAS.

OBJETIVO: Avaliar a eficácia e segurança da imunoterapia tópica com imiquimode creme 5% no tratamento do carcinoma basocelular nodular periocular. MÉTODOS: Pacientes com carcinoma basocelular confirmado por biopsia e com contraindicação clínica para a cirurgia reconstrutiva devido ao alto risco ou que recusaram a cirurgia por razões estéticas ou fobia foram incluídos no estudo. O tratamento foi iniciado após treinamento do paciente e de acompanhante. A posologia foi de 5 vezes por semana por 8 a 16 semanas. Acompanhamento quinzenal foi realizado durante a vigência do tratamento com questionário, exame biomicroscópico, medida da acuidade visual e documentação fotográfica. As características clínicas das lesões foram mensuradas através do software ImageJ. Após 12 semanas do fim da terapia, uma nova biópsia na região da lesão foi guiada por fotografia. O seguimento dos pacientes foi semestral, após fim do tratamento, com biópsias anuais da região até o presente momento. RESULTADOS: 19 foram tratadas. A taxa de cura histológica foi de 89,5% após três meses do final do tratamento, e de 84,2% nos três anos de seguimento (39,5 meses). A taxa de cura histológica em três anos foi de 100% para lesões menores que 10 mm, e de 81,8% para lesões maiores que 10 mm. De uma forma geral, os efeitos colaterais da medicação foram mais frequentes durante as oito primeiras semanas de tratamento. Quanto menor foi a distância da lesão à margem palpebral, maior foi chance de o paciente desenvolver ectrópio no tratamento (p = 0,045). Assim, como quanto maior foi a inflamação, maior foi a chance de desenvolver ectrópio, dor e edema durante o tratamento (p = 0,017, p = 0,016 e p = 0,044, respectivamente). CONCLUSÕES: Imiquimode creme 5% mostrou-se eficaz para o tratamento alternativo do carcinoma basocelular periocular, principalmente em lesões menores que 10 mm. Em adição, demonstrou um interessante efeito neoadjuvante sobre as lesões maiores que 10 mm que não foram curadas. Mostrou-se um tratamento seguro; entretanto, um cuidado maior deve ser dado às lesões próximas à margem palpebral devido ao maior risco de complicações e desenvolvimento de ectrópio / Objective: to evaluate the efficacy and safety of topical administration of 5% imiquimod cream in the treatment of periocular nodular basal cell carcinoma (BCC). Methods: Patients with periocular nodular basal cell carcinoma confirmed by biopsy and clinical contraindication to reconstructive surgery due to high risk or who decline surgery for aesthetic reasons or phobia were included in the study. The medication was applied once a day, five days a week for 8-16 weeks. Treatment was initiated after provision of patient and caretaker training. During treatment, patients were followed up twice a month with questionnaires, biomicroscopic examinations, measurement of visual acuity and photographic documentation. The clinical characteristics of the tumors were registered with the software ImageJ. Twelve weeks after the end of treatment, an image-guided biopsy of the tumor site was performed. Patients have since been attending follow-up visits every six months, and biopsies of the region are performed annually. Results: 19 tumors were treated with imiquimod. The average histological cure rate was 89.5% after 3 months at the end of the treatment and 84.2% after 3 years of follow-up (39.5 months). The 3-year histological cure rate was 100% for smaller tumors and 81.8% for larger tumors (>10 mm). In general, drug-related side effects were more frequent during the first 8 weeks of treatment. The smaller the distance between tumor and lid margin, the greater the probability of developing ectropion during treatment (p=0.045). Likewise, the more severe the inflammation, the greater the probability of developing ectropion, pain and edema during treatment (p=0.017, p=0.016 and p=0.044 respectively). Conclusion: Topical administration of 5% imiquimod cream was found to be an efficacious and relatively safe alternative treatment for periocular BCC, especially for tumors smaller than 10 mm, with interesting neoadjuvant effects on uncured tumors larger than 10 mm. However, special care is required when treating tumors near the eyelid margin due to the risk of complications and development of ectropion

OBJETIVO: Avaliar a eficácia e segurança da imunoterapia tópica com imiquimode creme 5% no tratamento do carcinoma basocelular nodular periocular. MÉTODOS: Pacientes com carcinoma basocelular confirmado por biopsia e com contraindicação clínica para a cirurgia reconstrutiva devido ao alto risco ou que recusaram a cirurgia por razões estéticas ou fobia foram incluídos no estudo. O tratamento foi iniciado após treinamento do paciente e de acompanhante. A posologia foi de 5 vezes por semana por 8 a 16 semanas. Acompanhamento quinzenal foi realizado durante a vigência do tratamento com questionário, exame biomicroscópico, medida da acuidade visual e documentação fotográfica. As características clínicas das lesões foram mensuradas através do software ImageJ. Após 12 semanas do fim da terapia, uma nova biópsia na região da lesão foi guiada por fotografia. O seguimento dos pacientes foi semestral, após fim do tratamento, com biópsias anuais da região até o presente momento. RESULTADOS: 19 foram tratadas. A taxa de cura histológica foi de 89,5% após três meses do final do tratamento, e de 84,2% nos três anos de seguimento (39,5 meses). A taxa de cura histológica em três anos foi de 100% para lesões menores que 10 mm, e de 81,8% para lesões maiores que 10 mm. De uma forma geral, os efeitos colaterais da medicação foram mais frequentes durante as oito primeiras semanas de tratamento. Quanto menor foi a distância da lesão à margem palpebral, maior foi chance de o paciente desenvolver ectrópio no tratamento (p = 0,045). Assim, como quanto maior foi a inflamação, maior foi a chance de desenvolver ectrópio, dor e edema durante o tratamento (p = 0,017, p = 0,016 e p = 0,044, respectivamente). CONCLUSÕES: Imiquimode creme 5% mostrou-se eficaz para o tratamento alternativo do carcinoma basocelular periocular, principalmente em lesões menores que 10 mm. Em adição, demonstrou um interessante efeito neoadjuvante sobre as lesões maiores que 10 mm que não foram curadas. Mostrou-se um tratamento seguro; entretanto, um cuidado maior deve ser dado às lesões próximas à margem palpebral devido ao maior risco de complicações e desenvolvimento de ectrópio / Objective: to evaluate the efficacy and safety of topical administration of 5% imiquimod cream in the treatment of periocular nodular basal cell carcinoma (BCC). Methods: Patients with periocular nodular basal cell carcinoma confirmed by biopsy and clinical contraindication to reconstructive surgery due to high risk or who decline surgery for aesthetic reasons or phobia were included in the study. The medication was applied once a day, five days a week for 8-16 weeks. Treatment was initiated after provision of patient and caretaker training. During treatment, patients were followed up twice a month with questionnaires, biomicroscopic examinations, measurement of visual acuity and photographic documentation. The clinical characteristics of the tumors were registered with the software ImageJ. Twelve weeks after the end of treatment, an image-guided biopsy of the tumor site was performed. Patients have since been attending follow-up visits every six months, and biopsies of the region are performed annually. Results: 19 tumors were treated with imiquimod. The average histological cure rate was 89.5% after 3 months at the end of the treatment and 84.2% after 3 years of follow-up (39.5 months). The 3-year histological cure rate was 100% for smaller tumors and 81.8% for larger tumors (>10 mm). In general, drug-related side effects were more frequent during the first 8 weeks of treatment. The smaller the distance between tumor and lid margin, the greater the probability of developing ectropion during treatment (p=0.045). Likewise, the more severe the inflammation, the greater the probability of developing ectropion, pain and edema during treatment (p=0.017, p=0.016 and p=0.044 respectively). Conclusion: Topical administration of 5% imiquimod cream was found to be an efficacious and relatively safe alternative treatment for periocular BCC, especially for tumors smaller than 10 mm, with interesting neoadjuvant effects on uncured tumors larger than 10 mm. However, special care is required when treating tumors near the eyelid margin due to the risk of complications and development of ectropion

Subciliary and transconjunctival approaches are commonly used to enter the orbital floor. Although both surgical approaches have been used for decades, there is no consensus regarding the most appropriate incision to prevent postoperative lower eyelid complications. The aim of this study was to compare the frequencies of lower eyelid complications after subciliary versus transconjunctival approaches to orbital floor fractures. The investigator implemented a retrospective cohort study and enrolled a sample consisting of subjects who had orbital floor repair. The predictor variable was two different surgical methods, subciliary or transconjunctival approch. The primary outcome variable was postoperative lower eyelid complications (ectropion, entropion, and eyelid retraction). Other variables were demographic backgrounds, anatomical consideration, or time to surgery. The samples were composed of 346 patients (98 [28.3%] females; 225 [65%] underwent a subciliary approach) with a mean age of 42.7 ± 21.1 years. The subciliary approach was significantly linked to the higher rates of ectropion and the lower rates of entropion at 7 days and 6 months postoperatively. There was no statistically significant difference in the frequency of eyelid retraction between both groups. In the setting of orbital floor fractures, these results suggest that the use of the subciliary approach increases the frequency of ectropion, while the transconjunctival approach increases the frequency of entropion. Consequently, the selection should be based on an individual patient basis and surgeon’s preference.

No description available.

Desmosomes are intercellular junctions that anchor intermediate filaments to the sites of intercellular contacts. They are critical for maintaining the integrity of tissues that experience constant mechanical and structural stresses, like the skin and heart. Perturbation of desmosomal adhesion can lead to devastating epidermal and myocardial diseases. However, little is known about the regulators of desmosomes and the role of desmosomes in cell signalling events. Recent work has suggested that iASPP, an inhibitor of the p53 family of proteins, localises at the intercalated discs where desmosomes reside. However, its role at the desmosomes has remained elusive. Thus, in this thesis, it was investigated whether iASPP is a dual function protein that links desmosome adhesion to gene expression and if desmosome-related diseases develop in the absence of iASPP. iASPP was found to be a novel regulator of desmosomes, co-localising with them by physically interacting with the desmosomal components desmoplakin and K5 intermediate filaments. Loss of iASPP resulted in increased phosphorylation and solubilisation of desmoplakin, leading to the formation of K5 aggregates. This culminated in disrupted intercellular adhesion and enhanced cellular migration. Consistent with the role of iASPP in the maintenance of desmosomal adhesion integrity, focal palmoplantar keratoderma was observed in iASPP-deficient mice — a disorder often associated with desmosome dysfunction. This was accompanied by disrupted intracellular signalling, as exemplified by the disrupted expression of differentiation markers; an increase in the thickness of cell layers expressing differentiation marker K1 was noted, and K5 and K6 cells were ectopically expressed throughout the diseased palmoplantar epidermis. Impaired intercellular adhesion and migration had consequences for wound healing, as iASPP-deficient mice exhibited delayed wound closure. Furthermore, defects in eyelid closure in iASPP-deficient mice were found to be due to increased apoptosis. The localisation of apoptotic cells at the leading edge of the eyelid epidermis implied that apoptosis might have occurred due to a loss of cell-matrix or cell-cell contact, i.e. anoikis. Taken together, these results suggest that iASPP is involved in pathological (palmoplantar keratoderma), physiological (wound healing) and developmental processes (embryonic eyelid closure) through its regulation of desmosomes and their dynamics. Therefore, iASPP represents a new candidate gene in cutaneous disorders and could be implicated in a variety of epidermal and myocardial diseases.