This small exploratory study was designed to test the hypothesis that thin melanoma lesions contain nuclei of two similar phenotypes, in different proportions. In lesions likely to progress to metastatic disease, one of these phenotypes predominates. Histopathological sections from 18 cases of thin melanomas which did not progress to metastasis, and from 10 cases which did progress were imaged and digitized at high resolution, with a total of 2084 and 1148 nuclei, respectively, recorded. Five karyometric features were used to discriminate between nuclei from indolent and from potentially metastatic lesions. For each case, the percentage of nuclei classified by the discriminant function as having come from a potentially metastatic lesion was determined and termed as case classification criterion. Standard histopathological criteria, such as ulceration and high mitotic index, indicated in this material the need for intensive therapy for only one of the 10 participants, as compared with 7/10 identified correctly by the karyometric measure. Using a case classification criterion threshold of 40%, the overall accuracy was 86% in the test set. The proportion of nuclei of an aggressive phenotype may lend itself as an effective prognostic clue for thin melanoma lesions. The algorithm developed in this training set appears to identify those patients at high risk for metastatic disease, and demonstrates a basis for a further study to assess the utility of prognostic clues for thin melanomas.

Intraductal papillary mucinous neoplasms (IPMN) are pancreatic lesions with uncertain biologic behavior. This study sought objective, accurate prediction tools, through the use of quantitative histopathological signatures of nuclear images, for classifying lesions as chronic pancreatitis (CP), IPMN, or pancreatic carcinoma (PC). Forty-four pancreatic resection patients were retrospectively identified for this study (12 CP; 16 IPMN; 16 PC). Regularized multinomial regression quantitatively classified each specimen as CP, IPMN, or PC in an automated, blinded fashion. Classification certainty was determined by subtracting the smallest classification probability from the largest probability (of the three groups). The certainty function varied from 1.0 (perfectly classified) to 0.0 (random). From each lesion, 180 +/- 22 nuclei were imaged. Overall classification accuracy was 89.6% with six unique nuclear features. No CP cases were misclassified, 1/16 IPMN cases were misclassified, and 4/16 PC cases were misclassified. Certainty function was 0.75 +/- 0.16 for correctly classified lesions and 0.47 +/- 0.10 for incorrectly classified lesions (P = 0.0005). Uncertainty was identified in four of the five misclassified lesions. Quantitative histopathology provides a robust, novel method to distinguish among CP, IPMN, and PC with a quantitative measure of uncertainty. This may be useful when there is uncertainty in diagnosis.

Made available in DSpace on 2016-01-26T12:51:21Z (GMT). No. of bitstreams: 1 marceloalexandredematos_tese.pdf: 620885 bytes, checksum: c68d7436fd634ab933f278d73ae00cac (MD5) Previous issue date: 2008-05-13 / To evaluate the effects on the placenta of the administration to rats during embryogenesis, of sodium cyclamate or aspartame. Method: Administration of respectively, 14 mg/kg of aspartame via an orogastric sound to a group of rats during their tenth to fourteenth day of pregnancy, of 60 mg/Kg of sodium cyclamate intraperitonially to another group, and of equivalent volumes of saline by the same routes to controls. On the twentieth day of pregnancy five foetuses of each group were aleatorily selected for study. Karyometry was used to evaluate nuclear parameters of the decidua, spongy layers and chorionic villi of the placenta. Results: Weights of foetuses and placentas, as well as lengths of umbilical cords were lower in treated rats, compared to control. While no changes were observed in the decidual layer of the cyclamate-treated group, this layer was altered by aspartame treatment. Nuclear parameters in the spongy layer and chorionic villi were altered in both, cyclamate and aspartame-treated groups. Conclusions: The study numerically demonstrated placenta intoxication by sodium cyclamate or aspartame, and consequent repercussion on foetuses of the use of these substances during pregnancy. / Avaliar os efeitos do ciclamato de sódio na placenta de ratas com sua administração no período da embriogênese. Método: Foi administrado por sonda orogástrica nas ratas de um grupo tratado a dose de 14 mg/Kg de aspartame, e nas ratas do outro grupo tratado a dose de 60 mg/Kg de ciclamato de sódio por via intraperitoneal, do décimo ao décimo quarto dia de gestação, e volume equivalente de solução salina no grupo controle, pela mesma via. No vigésimo dia de prenhez, 5 fetos de cada grupo foram escolhidos ao acaso para estudo. A técnica de cariometria foi utilizada para avaliação dos parâmetros nucleares das células das camadas decídua, esponjosas e das vilosidades coriônicas da placenta. Resultados: O peso dos fetos tratados e de suas placentas, e o comprimento do cordão umbilical, foram menores do que o grupo controle. Não ouveram alterações na camada decídua do grupo tratado com ciclamato de sódio, enquanto tal camada mostru-se alterada no tratamento com aspartame. Foram alterados parâmetros nucleares nas camadas esponjosas e vilosidades coriônicas do grupo tratado com ciclamato de sódio, e do grupo tratado com aspartame. Conclusão: Este estudo demonstrou numéricamente a intoxicação placentária com o ciclamato de sódio e com aspartame, e a conseqüente repercussão fetal com o uso destas substâncias durante a gravidez.

Made available in DSpace on 2016-01-26T12:51:12Z (GMT). No. of bitstreams: 1 veraluciafugitadossantos_tese.pdf: 270025 bytes, checksum: 8c9d7e6ebc77bbe636dd22a57632946e (MD5) Previous issue date: 2006-10-31 / Objective: To evaluate the effects of sodium cyclamate on fetal growth and on testicular cells of rat fetuses treated during embryogenesis. Method: From the tenth to the thirteenth day of pregnancy, 50 mg/Kg sodium cyclamate was administered via intraperitoneally in rats participating in the Treated Group. An equal volume of distilled water was similarly administered to rats of a Control Group. The fetuses were removed on the twentieth day by laparotomy, when 5 fetuses were randomly selected from the both Treated and Control Groups. Using karyometry, the nuclear parameters of the testicular cells were evaluated in respect to gonocytes, Sertoli cells and Leydig cells. Results: The mean fetal and placental weights of the animals from the Treated Group were lower than those of the Control Group, with a similar result seen in respect to the length of the umbilical cord. No changes were seen in the nuclei of the gonocytes. In relation to the Sertoli cells, differences were observed in the lowest diameter, mean diameter, volume, area, volume:area ratio and perimeter. No nuclear alterations were identified in the Leydig cells. Conclusions: This study identified alterations in fetal growth and in the testicular cells of rat fetuses caused by the administration of sodium cyclamate during the gestational period. / Objetivo: Avaliar os efeitos do ciclamato de sódio sobre o crescimento fetal e nas células testiculares de fetos de ratas tratadas durante a embriogênese. Método: Do décimo ao décimo terceiro dia de prenhez, foi administrado por via intraperitoneal, 50 mg/Kg de ciclamato de sódio nas ratas participantes do grupo tratado e, pela mesma via, igual volume de água destilada nas ratas do grupo controle. A laparotomia para a retirada dos fetos foi realizada no vigésimo dia da gestação, onde foram selecionados aleatoriamente cinco fetos das ratas tratadas e cinco das ratas controle. Por meio da cariometria, foi realizada a avaliação dos parâmetros nucleares de células testiculares dos fetos: gonócitos, células de Sertoli e células de Leydig. Resultados: As médias dos pesos fetal e placentário dos animais componentes do grupo tratado foram menores que os do grupo controle; sendo o mesmo resultado observado para o comprimento do cordão umbilical. Nos núcleos dos gonócitos não foram verificadas alterações. Nas células de Sertoli as modificações foram notadas nos seguintes parâmetros nucleares: diâmetro menor, diâmetro médio, volume, área, relação volume/área e no perímetro. Nas células de Leydig não foram registradas alterações nucleares. Conclusões: O desenvolvimento desta pesquisa possibilitou a observação de alterações no crescimento fetal e células testiculares de fetos de ratas, causadas pelo uso de ciclamato de sódio durante o período gestacional.

Orientador: Konradin Metze / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-10T11:27:03Z (GMT). No. of bitstreams: 1 Valladao_MariaLuizadeCastroRamos_M.pdf: 884922 bytes, checksum: 2e058daa788641932fbfccd1408d3d69 (MD5) Previous issue date: 2007 / Resumo: O Tumor Venéreo Transmissível Canino (TVTC) é uma neoplasia muito comum em caninos com livre acesso as ruas. O TVTC pode provocar metástases que levam o animal à morte. A presente tese realizou estudo exploratório e prospectivo em 100 caninos portadores de TVTC de ocorrência natural. Foram anotados dados clínicos como raça, sexo, idade, peso corporal e escore na Escala de Desempenho Karnofsky Adaptada (EDKA), bem como amostras citológicas. O objetivo do estudo foi elaborar fatores prognósticos relacionados à sobrevida e fatores preditivos da resposta da monoterapia com vincristina. Os resultados demonstraram que o a idade, o peso corporal do cão e o escore na EDKA são fatores independentes prognósticos da sobrevida durante o tratamento. Cães com escore na EDKA abaixo de 50 tiveram um péssimo prognóstico de sobrevida. O tempo de interrupção do tratamento, época do ano em que se iniciou o tratamento, área do núcleo e a "rugosidade" da cromatina em preparações citológicas mostraram ser fatores independentes preditivos do sucesso da terapia. A sobrevida durante a terapia depende do estado clínico do animal, enquanto a resposta terapêutica depende tanto de características da neoplasia como de fatores ambientais externos que modificam o estado clínico do animal / Abstract: The veneral transmissible tumor of dogs (CTVT) is a common neoplasia in free roaming dogs. Since this tumor may metastasize it is a possible tread for the animals. In a prospective exploratory study based on 100 dogs with naturally occuring CTVT we collected data on breed, sex, age, weight, tumor size and the score on a modified Karnofsky Performance Scale, as well cytologic smears. The objective of the investigation was study to elaborate prognostic factors related to survival and predicitive factors related to the response to vincristine monochemotherapy. Age, sex and the Karnofsky score showed to be independent prognostic factors for survival during chemotherapy. A score below 50 indicated poor survival. Time of interruption of the treatment, season of the year, nuclear area and "roughness" of the cromatin in cytologic preparations showed to be independent prognostic factors for the success of therapy. Thus survival during therapy depends on the performance status of the dog, whereas therapy success depends both on tumor characteristics and external factors modificating the animals performance / Mestrado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Mestre em Fisiopatologia