Keloids are classically regarded as scars that `outgrow the boundary of the original injury'. Ambiguous data concerning certain characteristics of keloid fibroblasts (such as proliferation rates and collagen production), however, have served only to confuse researchersT. he lack of an in vivo model and of detailed clinical accounts are added problems. In this study, a murine granulomatous tissue resolution model was used to investigate the profile of a number of cytokines suspectedto be involved in the aetiology of keloids. The results obtained from these experiments were then extrapolated to clarify the observations made in keloids. The results of these extrapolated comparisons revealed elevated levels of interleukin (IL)-4, IL-10, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF)-ß in keloid samples and decreasedle vels of interferon (IFN)-y and IL-2. The murine model was also used to investigate the implications of the low levels of IFN-y known to be present in the serum of keloid patients and shown here to be present in clinical samples. The results were found to support the hypothesis that the addition of IFN-y reduces the fibrosis so typical of keloids by rectifying the abnormality of the absence of IFNy content. The same model was used to provide evidence that the inhibition of VEGF activity in resolving wounds may halt the development of keloid lesions. The immunohistochemical profiles of cellular proliferation, apoptosis, lymphokines and cytokines for resolution (and, to a certain extent, the model) were used to compare with the abnormally resolved wounds which were available as clinical samples. Immunohistochemistry was also employed to describe the cellular nature of the clinical tissue samples in detail and to facilitate the development of the following hypothesis for keloid formation and propagation: lymphocytes migrate to the site of an (alleged) endogenous antigen present in the skin. The nature of these lymphocytes is characteristic of a type 2 immune response, they produce IL-4 (and IL-10) which in turn inhibit(s) the production of IFN-y and IL-2. Aside from this immunological response, wound resolution is taking place: fibroblasts are producing PDGF, EGF and TGF-ß to aid matrix remodelling and collagen synthesis. The provisional matrix is being vascularised by the action of VEGF, to allow the replenishment of nutrients; regression of blood vessels occurs through the action of an apoptosis-dependent mechanism, as does the 'normalisation' of fibroblastic populations. The keloid scar continues to grow after the cessation of resolution because the immune response to the 'endogenous' antigen continues and the lymphocytes continue to migrate to the site of the wound and continue to stimulate fibroblast proliferation and collagen production through the release of IL-4.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-10-19Bitstream added on 2014-06-13T19:27:13Z : No. of bitstreams: 1 oliveirajunior_b_me_botfm_prot.pdf: 1921358 bytes, checksum: 7c77f1984d2b8ff6d426ffda01962318 (MD5) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / Keloids are common forms of abnormal scar resulting from abnormal responses to wounding that can originate after trauma or other injuries of the skin. They can be induced by surgery, tear, tattooing, burning, injection, bite, vaccine, as well as dematosis (supurative hydradenite) or foreign body reaction. Morfologicaly keloids are characterized by means of cellular hyperplasia, produced by intrinsecaly normal polyclonal fibroblasts that answer to abnormal extracelular signal. Keloid once a time formed is not radiosensitive, and in these circunstances the fibrotic tissue will suffer little or no change with radiation. On other side the ionizing irradiation can produce some degrees of regression in keloid just formed. The fibroblasts in a recent scar of an individual that forms keloid, are higly responsive. Recent keloids are rich in fibroblasts. Trott13 considered that the way of irradiation action in fibroblasts is based on the inhibition of proliferation and acceleration on differenciation of these cells. To the patients keloid is not only a cosmetic problem. Keloid scars can itch, hurt, as well as do some clothes intolerance, many times having more importance that the aesthetic aspect. The surgery alone has disappointed results, with recurrence rates in order of 50-80%. These results leadead a variety of treatments: criotherapy, laser therapy, intra lesional injection of cortisones and others. The modality that reached better results with minimum recurrence rates was percutaneous radiotherapy after surgery, with 2-36% of recurrence rates. After the 70's decade, the use of Sr90 (betatherapy) was diffused in keloids treatment, and some authors started the use of low energy electron beam with encouraging results and minimum side effects. Our study compared the use of Sr90 (betatherapy) with electron beam irradiation and we conclude... (Complete abstract click electronic access below)

Orientador: Hamilton da Rosa Pereira / Banca: Hamilton Ometto Stolf / Banca: José Roberto Fígaro Caldeira / Resumo: Resumo completo, clicar acesso eletrônico abaixo / Abstract: Keloids are common forms of abnormal scar resulting from abnormal responses to wounding that can originate after trauma or other injuries of the skin. They can be induced by surgery, tear, tattooing, burning, injection, bite, vaccine, as well as dematosis (supurative hydradenite) or foreign body reaction. Morfologicaly keloids are characterized by means of cellular hyperplasia, produced by intrinsecaly normal polyclonal fibroblasts that answer to abnormal extracelular signal. Keloid once a time formed is not radiosensitive, and in these circunstances the fibrotic tissue will suffer little or no change with radiation. On other side the ionizing irradiation can produce some degrees of regression in keloid just formed. The fibroblasts in a recent scar of an individual that forms keloid, are higly responsive. Recent keloids are rich in fibroblasts. Trott13 considered that the way of irradiation action in fibroblasts is based on the inhibition of proliferation and acceleration on differenciation of these cells. To the patients keloid is not only a cosmetic problem. Keloid scars can itch, hurt, as well as do some clothes intolerance, many times having more importance that the aesthetic aspect. The surgery alone has disappointed results, with recurrence rates in order of 50-80%. These results leadead a variety of treatments: criotherapy, laser therapy, intra lesional injection of cortisones and others. The modality that reached better results with minimum recurrence rates was percutaneous radiotherapy after surgery, with 2-36% of recurrence rates. After the 70's decade, the use of Sr90 (betatherapy) was diffused in keloids treatment, and some authors started the use of low energy electron beam with encouraging results and minimum side effects. Our study compared the use of Sr90 (betatherapy) with electron beam irradiation and we conclude... (Complete abstract click electronic access below) / Mestre

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13291号 / 論医博第2189号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 小池 薫, 教授 妻木 範行 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Made available in DSpace on 2014-06-11T19:31:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-12-16Bitstream added on 2014-06-13T19:41:49Z : No. of bitstreams: 1 oliveirajunior_b_dr_botfm.pdf: 616970 bytes, checksum: 156878e124f2d8e1dc946e551816e468 (MD5) / Universidade Estadual Paulista (UNESP) / Existem diversas modalidades de tratamento para queloides que isoladamente apresentam resultados desapontadores. O tratamento combinado de excisão cirúrgica e irradiação pós-operatória com elétrons é efetiva para a qualidade da cicatriz e redução da taxa de recidiva. Avaliar comparativamente dois esquemas de tratamento utilizando feixes de elétrons em termos de probabilidade de cura e efeitos colaterais na área irradiada. Este é um estudo clínico, fase III, prospectivo, randomizado, realizado na Faculdade de Medicina de Botucatu-UNESP, no período 2008 a 2010, incluindo pacientes, no pós-operatório imediato de ressecção de queloides, divididos nos grupos G1 e G2 que receberam tratamento radioterápico com elétrons de um Acelerador Linear, 30 Gy/10 frações para G1 e 32 Gy/16 frações para G2. O seguimento foi de 18 meses. Os resultados foram avaliados através de observação feita por dois avaliadores independentes e questionário aplicado aos participantes do estudo. Fizeram parte do estudo 43 pacientes, 21 no grupo G1 e 22 no grupo G2. No grupo G1 52,4%% apresentaram bons resultados e 47,6% de recidivas. No grupo G2, 91% de bons resultados e 9% de recidivas. O esquema 32 Gy/16 frações e superior ao esquema 30 Gy/10 frações, com melhor resposta terapêutica e menos efeitos colaterais / There are many different treatments for keloids that alone show disappointing results. The combined treatment of surgical excision and irradiation post- operative with electrons is effective for the quality of the scar and reduction of the rate of recurrence. To compare two treatments using different quantity of electron beams in terms of the probability of cure and side effects in the area irradiated. This is a clinical study, fase III, prospective, randomized, carried out at the Faculdade de Medicina de Botucatu, UNESP, in the period 2008 to 2010, including patients, in the immediate postoperative period of resection of keloids, divided in G1 and G2. Patients received radiotherapy with electrons of a Linear Accelerator, 30 Gy/10 fractions for G1 and 32 Gy/16 fractions for G2. The follow-up was 18 months. The results were assessed by means of observation made by two independent evaluators and the questionnaire applied to participants of the study. The study involved 43 patients, 21 in group G1 and 22 in group G2. In group G1 52.4 %% showed good results and 47.6 % of relapses. In group G2, 91% of good results and 9% of relapses. The scheme 32 Gy/16 fractions showed better response to treatment and less side effects

Orientador: Silvana Artioli Schellini / Banca: Hamilton da Rosa Pereira / Banca: Joel Carlos Lastoria / Banca: Eliermes Arraes Menezes / Banca: Bogdana Victoria Kadunc / Resumo: Existem diversas modalidades de tratamento para queloides que isoladamente apresentam resultados desapontadores. O tratamento combinado de excisão cirúrgica e irradiação pós-operatória com elétrons é efetiva para a qualidade da cicatriz e redução da taxa de recidiva. Avaliar comparativamente dois esquemas de tratamento utilizando feixes de elétrons em termos de probabilidade de cura e efeitos colaterais na área irradiada. Este é um estudo clínico, fase III, prospectivo, randomizado, realizado na Faculdade de Medicina de Botucatu-UNESP, no período 2008 a 2010, incluindo pacientes, no pós-operatório imediato de ressecção de queloides, divididos nos grupos G1 e G2 que receberam tratamento radioterápico com elétrons de um Acelerador Linear, 30 Gy/10 frações para G1 e 32 Gy/16 frações para G2. O seguimento foi de 18 meses. Os resultados foram avaliados através de observação feita por dois avaliadores independentes e questionário aplicado aos participantes do estudo. Fizeram parte do estudo 43 pacientes, 21 no grupo G1 e 22 no grupo G2. No grupo G1 52,4%% apresentaram bons resultados e 47,6% de recidivas. No grupo G2, 91% de bons resultados e 9% de recidivas. O esquema 32 Gy/16 frações e superior ao esquema 30 Gy/10 frações, com melhor resposta terapêutica e menos efeitos colaterais / Abstract: There are many different treatments for keloids that alone show disappointing results. The combined treatment of surgical excision and irradiation post- operative with electrons is effective for the quality of the scar and reduction of the rate of recurrence. To compare two treatments using different quantity of electron beams in terms of the probability of cure and side effects in the area irradiated. This is a clinical study, fase III, prospective, randomized, carried out at the Faculdade de Medicina de Botucatu, UNESP, in the period 2008 to 2010, including patients, in the immediate postoperative period of resection of keloids, divided in G1 and G2. Patients received radiotherapy with electrons of a Linear Accelerator, 30 Gy/10 fractions for G1 and 32 Gy/16 fractions for G2. The follow-up was 18 months. The results were assessed by means of observation made by two independent evaluators and the questionnaire applied to participants of the study. The study involved 43 patients, 21 in group G1 and 22 in group G2. In group G1 52.4 %% showed good results and 47.6 % of relapses. In group G2, 91% of good results and 9% of relapses. The scheme 32 Gy/16 fractions showed better response to treatment and less side effects / Doutor

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13386号 / 論医博第2218号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 妻木 範行, 教授 安達 泰治 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Os aplicadores de 90Sr+90Y utilizados no Brasil em betaterapia para prevenção de quelóide e pterígio são importados e suas características dosimétricas são obtidas através de tabelas e manuais dos fabricantes apenas de forma ilustrativa pelos fabricantes. A rotina exaustiva dos profissionais de física médica nos serviços de radioterapia muitas vezes não viabiliza a realização de procedimentos para confirmação destes parâmetros. Este trabalho apresenta o desenvolvimento de uma metodologia para dosimetria de aplicadores de betaterapia de 90Sr+90Y. O software MCNP5 que é baseado no método de Monte Carlo foi utilizado para simulação das curvas de porcentagem de dose profunda e perfis de distribuição de dose produzidos por estes aplicadores. As medidas experimentais da atenuação da radiação, perfil radial e axial, foram realizadas com uma mini-câmara de extrapolação, dosímetros termoluminescentes e filmes radiocrômicos. Os resultados das medidas experimentais foram comparados com os valores simulados. Ambas as curvas de porcentagem de dose profunda e os perfis de distribuição de dose radiais, teóricos e experimentais, apresentaram boa concordância, o que pode validar o uso do software MCNP5 para estas simulações, reforçando a viabilidade do uso deste método nos procedimentos de dosimetria destas fontes emissoras de radiação beta. / The 90Sr+90Y applicators, used in Brazil betatherapy for prevention of keloids and pterigium, are imported and their dosimetric features are obtained through charts and manuals provided only in an illustrated form by the manufacturers. The exhaustive routine of the medical physicists in the clinic often do not make possible the accomplishment of procedures for the confirmation of these parameters. This work presents the development of a methodology for the dosimetry of 90Sr+90Y betatherapy applicators. The MCNP5 software that is based on the Monte Carlo method was used for the simulation of the percentage depth dose curves and dose distribution profiles produced by these applicators. The experimental measurements of the radial and axial radiation attenuation, have been done with a mini-extrapolation chamber, thermoluminescent dosimeters and radiographic films. The experimental results have been compared with the simulated values. Both percentage depth dose curves and the radial dose profiles, the theoretical and the experimental ones, have presented good agreement, which may validate the use of the MCNP5 software for these simulations, confirming the viability of the usage of this method in procedures of beta emitter sources dosimetry.

Os aplicadores de 90Sr+90Y utilizados no Brasil em betaterapia para prevenção de quelóide e pterígio são importados e suas características dosimétricas são obtidas através de tabelas e manuais dos fabricantes apenas de forma ilustrativa pelos fabricantes. A rotina exaustiva dos profissionais de física médica nos serviços de radioterapia muitas vezes não viabiliza a realização de procedimentos para confirmação destes parâmetros. Este trabalho apresenta o desenvolvimento de uma metodologia para dosimetria de aplicadores de betaterapia de 90Sr+90Y. O software MCNP5 que é baseado no método de Monte Carlo foi utilizado para simulação das curvas de porcentagem de dose profunda e perfis de distribuição de dose produzidos por estes aplicadores. As medidas experimentais da atenuação da radiação, perfil radial e axial, foram realizadas com uma mini-câmara de extrapolação, dosímetros termoluminescentes e filmes radiocrômicos. Os resultados das medidas experimentais foram comparados com os valores simulados. Ambas as curvas de porcentagem de dose profunda e os perfis de distribuição de dose radiais, teóricos e experimentais, apresentaram boa concordância, o que pode validar o uso do software MCNP5 para estas simulações, reforçando a viabilidade do uso deste método nos procedimentos de dosimetria destas fontes emissoras de radiação beta. / The 90Sr+90Y applicators, used in Brazil betatherapy for prevention of keloids and pterigium, are imported and their dosimetric features are obtained through charts and manuals provided only in an illustrated form by the manufacturers. The exhaustive routine of the medical physicists in the clinic often do not make possible the accomplishment of procedures for the confirmation of these parameters. This work presents the development of a methodology for the dosimetry of 90Sr+90Y betatherapy applicators. The MCNP5 software that is based on the Monte Carlo method was used for the simulation of the percentage depth dose curves and dose distribution profiles produced by these applicators. The experimental measurements of the radial and axial radiation attenuation, have been done with a mini-extrapolation chamber, thermoluminescent dosimeters and radiographic films. The experimental results have been compared with the simulated values. Both percentage depth dose curves and the radial dose profiles, the theoretical and the experimental ones, have presented good agreement, which may validate the use of the MCNP5 software for these simulations, confirming the viability of the usage of this method in procedures of beta emitter sources dosimetry.

Made available in DSpace on 2015-07-22T20:50:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução: O estado nutricional geral do indivíduo influi na cicatrização. Estudos sobre o estado nutricional em cicatrização patológica, especialmente no quelóide, são raros, embora a correlação entre o desenvolvimento desta com o estado nutricional possa estar vinculado. Objetivo: Investigar o estado nutricional, ingestão alimentar e níveis séricos de cobre, manganês e zinco de pacientes portadores de quelóide. Métodos: Foram entrevistados 111 indivíduos oriundos do ambulatório do Setor de Cicatrizes Patológicas da Disciplina de Cirurgia Plástica da UNIFESP. Sessenta e um pertenceram ao grupo quelóide (GQ) e 50 ao grupo controle (GC). Primeiramente determinou-se o Índice de Massa Corporal (IMC) e a porcentagem de gordura corporal (%Gordura). Em seguinda, foi realizada a avaliação dietética a partir do Recordatório de 24 Horas e do registro alimentar de três dias. E, a seguir, a avaliação sérica dos minerais. Resultados: O IMC de ambos os grupos apresentou médias semelhantes; entretanto, a média de %Gordura foi superior no GQ (p<0,05). Não houve diferença significante da ingestão dos micronutrientes entre os grupos. Já os níveis séricos de cobre e manganês estiveram superiores e o de zinco esteve inferior no GQ (p<0,05). Conclusão: Os pacientes portadores de quelóide apresentaram maior %Gordura, menor nível sérico de zinco e maior nível sérico de cobre e manganês em relação aos pacientes portadores de cicatrizes normotróficas, apesar da ingestão alimentar desses micronutrientes não diferir entre os grupos. / Introduction: Studies on nutrition and keloid discuss the intake of macroand micronutrients. Regarding micronutrients, although the literature has already determined the association between trace elements and wound healing, studies about the relationship between them and the development of keloid are reduced. Objective: To investigate the nutritional status of patients with keloid, in relation to copper, manganese and zinc. Methods: 111 patients from the outpatient clinic of the Department of Pathological Scars of Plastic Surgery, UNIFESP were interviewed. Sixty-one belonged to keloid group (GQ) and 50 to control group (GC). Firstly, the body mass index (BMI) and percentage’s body fat (%Fat) were determined. Secondly, the dietary assessment was performed by the recall of 24 hours and 3 days of food records. After that, the patients were sent to the laboratory of the Association for Psychopharmacology Incentive Fund, which carried out the assessment of their serum minerals. Results: The BMI of both groups presented similar means, however, the average of %Fat was higher in GQ (p <0.05). As for dietary intake of copper, manganese and zinc, no statistically significant difference between the groups were found. In the other hand, serum levels of copper and manganese were higher and the level of zinc was lower in GQ (p <0.05). Conclusion: Patients with keloids have a higher %Fat, lower serum zinc and higher serum levels of copper and manganese in relation to patients with normotrophyc scars. / TEDE / BV UNIFESP: Teses e dissertações