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Sysmex XE-5000 är en automatiserad cellräknare som utför mätningar enligt olikamätprinciper, de två som tillämpats i projektet är RF/DC(Radio Frequency/DirectCurrent) samt Flödescytometri med halvledarlaser. RF/DC bygger på förändringari radiofrekventa resistansen och likspänningsresistansen. Förändringar i denradiofrekventa resistansen (RF) ger information om densiteten i cellernas inre(exempelvis kärnans storlek) och förändringar i likspänningsresistensen (DC) gerinformation om blodcellernas storlek. Flödescytometri definierar ett mått påcellers fysiologiska och kemiska egenskaper. Detektion av cellerna sker genom attde bestrålas med en laserstråle samtidigt som de passerar en och en i instrumentet.Informationen som fås ut från flödescytometri inkluderar spritt ljus ochfluorescens. Sysmex XE-5000 arbetar med flera olika felmeddelanden, så kalladelarm. Ett eller flera larm indikerar att det finns en ökad risk för förekomst avabnormala celler och kan enbart uteslutas genom en manuell differentialräkning. Istudien har tre larm, vilka indikerar närvaron av onormala leukocyter, undersökts:”Blasts?”, ”Atypical Lympho?” och ”Abn Lympho/L_Blasts?”. Syftet medprojektet är att jämföra nuvarande beräkningar med en ny mjukvara (eMM) förlarmen och utvärdera om de ger ett mindre antal falskt positiva larm frånhematologiinstrumentet Sysmex XE-5000. Prover med något av ovanstående larmvaldes ut och analyserades först med nuvarande inställningar på instrumentet ochdärefter med de nya beräkningarna för eMM. Resultatet visar på att antalet falsktpositiva prover minskar och även att antalet dubblettlarm minskar. / Sysmex XE-5000 is an automated cell counter that performs measurements withdifferent principles. The two applied in this project are RF/DC (RadioFrequency/Direct Current) and Flow cytometry with semiconductor laser. RF/DCis based on changes in radio frequency resistance and direct current voltage.Changes in RF provide information about the density of the cell’s internalstructure (e.g. the nucleus) and changes in DC provide information about the sizeof the blood cells. Flow Cytometry define as physiological and chemicalproperties of the cell. Detection of cells is achieved by the irradiation with a laserbeam while passing through one by one. The information obtained from flowcytometry includes scattered light and fluorescence. Sysmex XE-5000 works withseveral different error messages, so-called alarm. One or more alarm indicates thatthere is an increased risk for the presence of abnormal cells and this can only beruled out by a manual differential count. In this study three alarms, which indicatethe presence of abnormal white blood cells, were analyzed: “Blasts?”, AtypicalLympho?” and “Abn Lympho/L_Blasts?”. The project aims to compare thecurrent calculations with the new software (eMM) for the alarms and evaluate ifthey provide a smaller number of false positive alarms from the hematologyinstrument Sysmex XE-5000. Samples with one or two of the alarms wereselected and analyzed with the current settings and then with the new settings foreMM. The result showed that the number of false-positive samples was reducedand that the number of duplicate alarms decreased.

Recent events throughout the world and in the US lend support to the belief that another terrorist attack on the US is likely, perhaps probable. Given the potential for large numbers of casualties to be produced by a blast using conventional explosives, it is imperative that health systems across the nation consider the risks in their jurisdictions and take steps to better prepare for the possibility of an attack. Computer modeling and simulation offers a viable and useful methodology to better prepare an organization or system to respond to a large scale event. The real question, given the shortage, and in some areas absence, of experiential data, could computer modeling and simulation be used to predict the resource requirements generated by this type of event and thus prepare a health system in a defined geographic area for the possibility of an event of this nature? Research resulted in the identification of variables that surround a health system at risk, the development of a computer model to predict the injuries that would be seen in an injured survivor population and the medical resources required to care for this population. Finally, methodologies were developed to modify the existing model to match unique health system structures and processes in order to assess the preparedness of a specific geographic location or health system. As depicted in this research, computer modeling and simulation was found to offer a viable and usable methodology for a defined geographic region to better prepare for the potential of a large scale blast event and to care for the injured survivors that result from the blast. This can be done with relatively low cost and low tech approach using existing computer modeling and simulation software, making it affordable and viable for even the smallest geographic jurisdiction or health system.

Myelodysplastic syndromes (MDS) are regarded as clonal disorders of haematopoietic stem cells (HSC). Recent evidence demonstrates that stromal microenvironment, in addition to HSC defects, plays a particular role via its direct contact with haematopoietic precursor cells (HPC). This thesis aims at evaluating the putative growth deficiencies of mesenchymal stromal cells (MSC) from MDS individuals compared with normal controls, exploring their adhesion profile, assessing the adhesion process-involved molecular substrates, and establishing correlations with their growth patterns and HPC dysfunctions. Functional assays revealed that MSC from MDS are intrinsically pathological, show a continuous decline of proliferation over a 14-day culture and a reduced clonogenic capacity in the absence of signals from HPC. MSC growth defects significantly correlate with decreased CD44 and CD49e expression. Moreover, stroma-dependent adhesion mechanisms control HPC clonogenic potential and CD49e might be one of the molecules involved in this process. Qualitative and quantitative abnormalities of focal adhesion (FA) proteins paxillin and pFAK [Y397] and of two regulatory proteins, HSP90αβ and p130CAS were identified via immunofluorescence analysis. Paxillin, pFAK [Y397] and HSP90αβ increased expression, besides its stronger nuclear colocalization in MSC from RAEB correlates with a consistent proliferative advantage and has a negative impact on HPC clonogenic capacity. These results open interesting opportunities, e.g. HPC-to-MSC interactions involve FA proteins signalling, and, as FAK is an HSP90αβ-client protein, it may enhance the utility of HSP90αβ inhibitors as adjuvant therapy in MDS

Les syndromes myélodysplasiques (SMD) sont considérés comme des maladies clonales des cellules souches hématopoïétiques (CSH). Le microenvironnement joue un rôle important par ses contacts direct avec les cellules progénitrices hématopoïétiques (CPH). Notre objectif était d'évaluer les défauts de croissance des cellules stromales mésenchymateuses (CSM) dans les MDS, d’explorer les molécules d’adhérence impliquées, et d'effectuer des corrélations avec leurs dysfonctionnements de croissance et les anomalies des CPH. Les CSM de MDS sont intrinsèquement pathologiques, montrant une baisse continue de la prolifération pendant 14 jours de culture et une capacité clonogénique réduite. Ces anomalies sont corrélés à une diminution des molécules d'adhérence CD44 et CD49e. Par ailleurs, le potentiel clonogénique des CPH est contrôlé par des mécanismes d'adhérence dépendant du stroma, CD49e pouvant être une des molécules impliquées. L’analyse en immunofluorescence des protéines d'adhérence focale (FA), paxilline et pFAK [Y397], et des deux protéines régulatrices, HSP90αβ et p130CAS permet l'identification d’anomalies qualitatives et quantitatives. Une expression accrue de paxilline, pFAK et HSP90αβ et leur forte co-localisation nucléaire dans les CSM d'anémie réfractaire avec excès de blastes (AREB) sont corrélées avec un avantage prolifératif et un impact négatif sur la capacité clonogénique de CPH. Ces résultats ouvrent des possibilités intéressantes : la signalisation via les protéines FA pourrait être impliquée dans les interactions HPC-MSC ; par ailleurs, FAK étant une protéine cliente d’HSP90, les inhibiteurs d’HSP90 sont une potentielle thérapie adjuvante dans les myélodysplasies / Myelodysplastic syndromes (MDS) are regarded as clonal disorders of haematopoietic stem cells (HSC). Recent evidence demonstrates that stromal microenvironment, in addition to HSC defects, plays a particular role via its direct contact with haematopoietic precursor cells (HPC). This thesis aims at evaluating the putative growth deficiencies of mesenchymal stromal cells (MSC) from MDS individuals compared with normal controls, exploring their adhesion profile, assessing the adhesion process-involved molecular substrates, and establishing correlations with their growth patterns and HPC dysfunctions. Functional assays revealed that MSC from MDS are intrinsically pathological, show a continuous decline of proliferation over a 14-day culture and a reduced clonogenic capacity in the absence of signals from HPC. MSC growth defects significantly correlate with decreased CD44 and CD49e expression. Moreover, stroma-dependent adhesion mechanisms control HPC clonogenic potential and CD49e might be one of the molecules involved in this process. Qualitative and quantitative abnormalities of focal adhesion (FA) proteins paxillin and pFAK [Y397] and of two regulatory proteins, HSP90αβ and p130CAS were identified via immunofluorescence analysis. Paxillin, pFAK [Y397] and HSP90αβ increased expression, besides its stronger nuclear colocalization in MSC from RAEB correlates with a consistent proliferative advantage and has a negative impact on HPC clonogenic capacity. These results open interesting opportunities, e.g. HPC-to-MSC interactions involve FA proteins signalling, and, as FAK is an HSP90αβ-client protein, it may enhance the utility of HSP90αβ inhibitors as adjuvant therapy in MDS

Anemia aplástica adquirida (AAA) é doença rara e seu diagnóstico diferencial inclui a Síndrome mielodisplásica hipocelular (SMD-h). A evolução de AAA para SMD/LMA (Síndrome mielodisplásica/Leucemia mieloide aguda) ocorre em até 15% dos casos. Este estudo propõe-se a comparar parâmetros histológicos e imuno-histoquímicos de pacientes adultos e crianças com AAA que evoluíram e não para SMD/LMA. Seu objetivo é avaliar a ocorrência dos critérios morfológicos/imunofenotípicos nas biópsias de medula óssea do grupo pediátrico (<19 anos) com o grupo de adultos, comparar esses critérios associados à evolução para SMD/LMA nestes dois grupos e verificar se estes critérios superpõem-se àqueles descritos na literatura na SMD-hipocelular do adulto e, mais recentemente, na SMD pediátrica (Citopenia refratária da infância - CRI). Espera-se trazer uma contribuição para a discussão da intersecção entre essas entidades e a AAA, estudando essa \"zona cinzenta\" do ponto de vista dos pacientes com AAA, particularmente aqueles que progrediram para SMD/LMA. Foram analisadas, retrospectivamente, 118 biópsias de medula óssea ao diagnóstico de AAA, idiopática ou não, realizadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 1993 e 2012. O diagnóstico de AAA foi estabelecido de acordo com critérios clássicos. A evolução de AAA para SMD ou LMA foi considerada na presença de: disgranulopoese ou dismegacariopoese acentuadas, mais de 15% de sideroblastos em anel, blastos em sangue periférico ou mais de 5% de blastos na medula óssea ao mielograma e/ou à biópsia de medula óssea ou na presença de estudo citogenético (FISH ou cariótipo) da medula óssea, apresentando monossomia ou deleção do braço longo do cromossomo 7. Todas as biópsias foram submetidas à análise morfológica e imuno-histoquímica (MPO, Glicoforina A, Fator VIII, CD34, CD117 e Ki-67) por dois hematopatologistas sem conhecimento prévio da evolução dos pacientes. As variáveis qualitativas nominais foram analisadas pelo teste exato de Fisher para verificar se houve desproporção significativa entre os grupos. As variáveis qualitativas ordinais foram analisadas para a diferença entre os grupos pelo teste de Mann-Whitney. O nível de significância adotado foi 5% (p=0,05). A correlação entre os valores de celularidade geral das amostras e seu índice proliferativo foi avaliada pelo teste não paramétrico Rô de Spearman. Setenta e um pacientes (60,2%) eram do gênero masculino com mediana de idade 24,4 anos (mínimo de 7 meses até 76 anos), 42 do grupo pediátrico e 76 adultos, e tempo de seguimento de 5,1 anos (de 1 mês a 22,1 anos). Doze (10,2%) (seis em cada grupo) pacientes evoluíram para SMD/LMA. Avaliação dos parâmetros morfológicos e imuno-histoquímicos mostrou distribuição irregular do tecido hematopoético em 59 (50%) casos, mediana de celularidade geral de 10% (de 1% a 40%), distúrbio de maturação da série granulocítica (critério 1) em três (2,5%) casos, localização anormal da eritropoiese em 13 (11%) casos, agregados de pelo menos 20 precursores eritroides (critério 2), em 54 (45,7%) casos, presença de formas jovens eritroides (proeritroblastos) (critério 3) em 32 (27,1%) casos, aumento do número de mitoses dos elementos eritroides (critério 4) em 24 (20,3%) casos, displasia de megacariócitos (micromegacariócitos, megacariócitos bi ou multinucleados e elementos hipo ou monolobados) (critério 5) em 15 (12,7%) casos, localização anormal de megacariócitos em quatro (3,3%) casos, megacariócitos CD34-positivos não foram identificados, blastos CD34-positivos em 11 (9,3%) casos, reticulogênese discretamente aumentada (grau 1) em três (2,5%) casos e índice proliferativo (Ki-67) com mediana de 30 (de 0% a 90%). Critérios descritos por Bennett e Orazi sugestivos de SMD-h (critérios 1 e/ou 5) foram detectados em 16 (13,6%) casos. Critérios descritos por Baumann et al. sugestivos de SMD da infância (critérios 2 + 3 com ou sem 4) foram observados em 30 (25,4%) casos. Não houve diferença estatística nos achados morfológicos/imuno-histoquímicos entre a população total, adultos e crianças que evoluíram e que não evoluíram para SMD/LMA, incluindo a presença de critérios Bennett e Orazi para SMD-h do adulto. Houve diferença quanto aos critérios de Baumann et al. para CRI, e o grupo que não evoluiu para SMD/LMA apresentou com mais frequência os critérios do que o que evoluiu (p=0,036), ao contrário do previamente suposto. No entanto, ao testar esta hipótese no grupo adulto separado do pediátrico, a diferença estatística não foi comprovada. Houve uma correlação estatisticamente significante entre os valores da celularidade geral das amostras e seu índice proliferativo (p < 0,001). Pacientes adultos e pediátricos com AAA, incluindo os que evoluíram para SMD/LMA, têm características morfológicas/imuno-histoquímicas semelhantes. Algumas alterações descritas por Baumann et al. para SMD pediátrica são também encontradas em casos pediátricos e de adultos com AAA. Além disso, o índice proliferativo pode ser aumentado em casos de AAA, este dado não tem correlação com a evolução para SMD/LMA. Alterações morfológicas/imuno-histoquímicas em biópsias de medula óssea em AAA não identificaram um grupo com maior risco de progressão para SMD/LMA em nossa casuística / Acquired Aplastic Anemia (AAA) is a rare disease which progresses to MDS / AML in up to 15% of cases. When this happens, hematopathologists are asked whether the diagnosis of hypocellular Myelodisplastic Syndrome (h-MDS) would not have been confused morphologically with aplastic anemia. This study aims to identify morphological/immunophenotypical findings that could predict this adverse prognosis in adults and children ( < 19y) diagnosed as AAA and verify if those criteria match with the ones described in literature in adult h-MDS and, more recently, in pediatric MDS (Refractory cytopenia of childhood - RCC), contributing to the discussion of this \"grey zone\". We retrospectively analyzed 118 patients/bone marrow (BM) biopsies at the moment of AAA diagnosis at Clinical Hospital of São Paulo Medical School from 1993 to 2012. Diagnosis of AAA was carried out according to classical criteria. Evolution to MDS or AML was considered in the presence of at least one of the findings: significant dysgranulopoiesis or dysmegakaryocytopoiesis, more than 15% ring sideroblasts, blasts in peripheral blood or more than 5% blasts in bone marrow smear and/or biopsy, or in the presence of monosomy or deletion of the long arm of chromosome 7 by cytogenetic analysis (FISH or karyotype) of the BM. All biopsies were submitted to morphological and immunophenotypic (MPO, Glycophorin A, Factor VIII, CD34, CD117 and Ki67) evaluation by two hematopathologists without previous knowledge about the evolution of the patients. Nominal qualitative variables were analyzed by using Fisher\'s exact test to check significant disproportion between the groups. The ordinal qualitative variables were analyzed for differences between groups by Mann-Whitney test. The significance level was 5% (p = 0.05). The correlation between the overall cellularity values of the samples and their proliferative index was evaluated by nonparametric Spearman Rô test. Seventy-one (60,2%) were male, median age 24.4 years (7 months to 76 years old), 42 belongs to the pediatric group and 76 to the adults group. Median follow-up was 5.1y (range, 1 month to 22.1 years). Twelve patients (12%) (6 in each group) progressed to MDS/AML. Evaluation of morphological/immunohistochemical parameters showed irregular distribution of hematopoietic tissue in 59 (50%) cases, median BM overall cellularity of 10% (range, 1 to 40%), marrow dysgranulopoiesis (criteria 1) in 3 (2,5%) cases, abnormal localization of erythropoiesis in 13 (11%) cases, clusters of at least 20 erythroid precursors (criteria 2) in 54 (45.7%) cases, increased number of proerythroblasts (criteria 3) in 32 (27,1%) cases, increased number of mitoses of the erythroid elements (criteria 4) in 24 (20,3%) cases, marrow dysplasia of megakaryocytes (micromegakaryocytes , two or more separeted nuclei, small round nuclei) (criteria 5) in 15 (12,7%) cases, abnormal localization of megakaryocytes in 4 (3,3%) cases, CD34-positive megakaryocytes were not identified, CD34-positive blast cells (criteria 6) in 11 (9,3%) cases, increment in reticulin fibers in 3 (2,5%) cases, and median proliferative index (Ki-67) 30 (range, 0 to 90%). Criteria described by Bennett and Orazi suggestive of h-SMD (criteria 1 and/or 5) were detected in 16 (13,6%) cases. Criteria described by Baumann et al suggestive of childhood MDS (criteria 2 + 3 with or without 4) were observed in 30 (25.4%) cases. There was no statistical difference in morphological/immunohistochemical findings among total population, adults and children who developed and did not develop MDS/AML, including the presence of Bennett and Orazi criteria for h-MDS. Regarding Baumann et al criteria were more frequently identified in the group that did not progress to MDS/AML than the one that did (p=0,036), the opposite of what was expected. But when the criteria were tested in pediatric and adults\' groups separately, the statistical significance was no longer observed. There was a statistical significant correlation between the overall cellularity values of the samples and their proliferative index (p=0,001). Adult and pediatric patients with AAA, including those that progress to MDS/AML, have similar morphological/immunohistochemical characteristics. Some changes described by Baumann et al for pediatric MDS are also found in pediatric and adults\' cases with AAA. In addition, the proliferative index may be increased in cases of AAA and this finding has no correlation with progression to MDS/AML. Morphological/immunohistochemical changes in bone marrow biopsies in AAA have failed to identify a group at higher risk for progression to MDS/AML in our series

Anemia aplástica adquirida (AAA) é doença rara e seu diagnóstico diferencial inclui a Síndrome mielodisplásica hipocelular (SMD-h). A evolução de AAA para SMD/LMA (Síndrome mielodisplásica/Leucemia mieloide aguda) ocorre em até 15% dos casos. Este estudo propõe-se a comparar parâmetros histológicos e imuno-histoquímicos de pacientes adultos e crianças com AAA que evoluíram e não para SMD/LMA. Seu objetivo é avaliar a ocorrência dos critérios morfológicos/imunofenotípicos nas biópsias de medula óssea do grupo pediátrico (<19 anos) com o grupo de adultos, comparar esses critérios associados à evolução para SMD/LMA nestes dois grupos e verificar se estes critérios superpõem-se àqueles descritos na literatura na SMD-hipocelular do adulto e, mais recentemente, na SMD pediátrica (Citopenia refratária da infância - CRI). Espera-se trazer uma contribuição para a discussão da intersecção entre essas entidades e a AAA, estudando essa \"zona cinzenta\" do ponto de vista dos pacientes com AAA, particularmente aqueles que progrediram para SMD/LMA. Foram analisadas, retrospectivamente, 118 biópsias de medula óssea ao diagnóstico de AAA, idiopática ou não, realizadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 1993 e 2012. O diagnóstico de AAA foi estabelecido de acordo com critérios clássicos. A evolução de AAA para SMD ou LMA foi considerada na presença de: disgranulopoese ou dismegacariopoese acentuadas, mais de 15% de sideroblastos em anel, blastos em sangue periférico ou mais de 5% de blastos na medula óssea ao mielograma e/ou à biópsia de medula óssea ou na presença de estudo citogenético (FISH ou cariótipo) da medula óssea, apresentando monossomia ou deleção do braço longo do cromossomo 7. Todas as biópsias foram submetidas à análise morfológica e imuno-histoquímica (MPO, Glicoforina A, Fator VIII, CD34, CD117 e Ki-67) por dois hematopatologistas sem conhecimento prévio da evolução dos pacientes. As variáveis qualitativas nominais foram analisadas pelo teste exato de Fisher para verificar se houve desproporção significativa entre os grupos. As variáveis qualitativas ordinais foram analisadas para a diferença entre os grupos pelo teste de Mann-Whitney. O nível de significância adotado foi 5% (p=0,05). A correlação entre os valores de celularidade geral das amostras e seu índice proliferativo foi avaliada pelo teste não paramétrico Rô de Spearman. Setenta e um pacientes (60,2%) eram do gênero masculino com mediana de idade 24,4 anos (mínimo de 7 meses até 76 anos), 42 do grupo pediátrico e 76 adultos, e tempo de seguimento de 5,1 anos (de 1 mês a 22,1 anos). Doze (10,2%) (seis em cada grupo) pacientes evoluíram para SMD/LMA. Avaliação dos parâmetros morfológicos e imuno-histoquímicos mostrou distribuição irregular do tecido hematopoético em 59 (50%) casos, mediana de celularidade geral de 10% (de 1% a 40%), distúrbio de maturação da série granulocítica (critério 1) em três (2,5%) casos, localização anormal da eritropoiese em 13 (11%) casos, agregados de pelo menos 20 precursores eritroides (critério 2), em 54 (45,7%) casos, presença de formas jovens eritroides (proeritroblastos) (critério 3) em 32 (27,1%) casos, aumento do número de mitoses dos elementos eritroides (critério 4) em 24 (20,3%) casos, displasia de megacariócitos (micromegacariócitos, megacariócitos bi ou multinucleados e elementos hipo ou monolobados) (critério 5) em 15 (12,7%) casos, localização anormal de megacariócitos em quatro (3,3%) casos, megacariócitos CD34-positivos não foram identificados, blastos CD34-positivos em 11 (9,3%) casos, reticulogênese discretamente aumentada (grau 1) em três (2,5%) casos e índice proliferativo (Ki-67) com mediana de 30 (de 0% a 90%). Critérios descritos por Bennett e Orazi sugestivos de SMD-h (critérios 1 e/ou 5) foram detectados em 16 (13,6%) casos. Critérios descritos por Baumann et al. sugestivos de SMD da infância (critérios 2 + 3 com ou sem 4) foram observados em 30 (25,4%) casos. Não houve diferença estatística nos achados morfológicos/imuno-histoquímicos entre a população total, adultos e crianças que evoluíram e que não evoluíram para SMD/LMA, incluindo a presença de critérios Bennett e Orazi para SMD-h do adulto. Houve diferença quanto aos critérios de Baumann et al. para CRI, e o grupo que não evoluiu para SMD/LMA apresentou com mais frequência os critérios do que o que evoluiu (p=0,036), ao contrário do previamente suposto. No entanto, ao testar esta hipótese no grupo adulto separado do pediátrico, a diferença estatística não foi comprovada. Houve uma correlação estatisticamente significante entre os valores da celularidade geral das amostras e seu índice proliferativo (p < 0,001). Pacientes adultos e pediátricos com AAA, incluindo os que evoluíram para SMD/LMA, têm características morfológicas/imuno-histoquímicas semelhantes. Algumas alterações descritas por Baumann et al. para SMD pediátrica são também encontradas em casos pediátricos e de adultos com AAA. Além disso, o índice proliferativo pode ser aumentado em casos de AAA, este dado não tem correlação com a evolução para SMD/LMA. Alterações morfológicas/imuno-histoquímicas em biópsias de medula óssea em AAA não identificaram um grupo com maior risco de progressão para SMD/LMA em nossa casuística / Acquired Aplastic Anemia (AAA) is a rare disease which progresses to MDS / AML in up to 15% of cases. When this happens, hematopathologists are asked whether the diagnosis of hypocellular Myelodisplastic Syndrome (h-MDS) would not have been confused morphologically with aplastic anemia. This study aims to identify morphological/immunophenotypical findings that could predict this adverse prognosis in adults and children ( < 19y) diagnosed as AAA and verify if those criteria match with the ones described in literature in adult h-MDS and, more recently, in pediatric MDS (Refractory cytopenia of childhood - RCC), contributing to the discussion of this \"grey zone\". We retrospectively analyzed 118 patients/bone marrow (BM) biopsies at the moment of AAA diagnosis at Clinical Hospital of São Paulo Medical School from 1993 to 2012. Diagnosis of AAA was carried out according to classical criteria. Evolution to MDS or AML was considered in the presence of at least one of the findings: significant dysgranulopoiesis or dysmegakaryocytopoiesis, more than 15% ring sideroblasts, blasts in peripheral blood or more than 5% blasts in bone marrow smear and/or biopsy, or in the presence of monosomy or deletion of the long arm of chromosome 7 by cytogenetic analysis (FISH or karyotype) of the BM. All biopsies were submitted to morphological and immunophenotypic (MPO, Glycophorin A, Factor VIII, CD34, CD117 and Ki67) evaluation by two hematopathologists without previous knowledge about the evolution of the patients. Nominal qualitative variables were analyzed by using Fisher\'s exact test to check significant disproportion between the groups. The ordinal qualitative variables were analyzed for differences between groups by Mann-Whitney test. The significance level was 5% (p = 0.05). The correlation between the overall cellularity values of the samples and their proliferative index was evaluated by nonparametric Spearman Rô test. Seventy-one (60,2%) were male, median age 24.4 years (7 months to 76 years old), 42 belongs to the pediatric group and 76 to the adults group. Median follow-up was 5.1y (range, 1 month to 22.1 years). Twelve patients (12%) (6 in each group) progressed to MDS/AML. Evaluation of morphological/immunohistochemical parameters showed irregular distribution of hematopoietic tissue in 59 (50%) cases, median BM overall cellularity of 10% (range, 1 to 40%), marrow dysgranulopoiesis (criteria 1) in 3 (2,5%) cases, abnormal localization of erythropoiesis in 13 (11%) cases, clusters of at least 20 erythroid precursors (criteria 2) in 54 (45.7%) cases, increased number of proerythroblasts (criteria 3) in 32 (27,1%) cases, increased number of mitoses of the erythroid elements (criteria 4) in 24 (20,3%) cases, marrow dysplasia of megakaryocytes (micromegakaryocytes , two or more separeted nuclei, small round nuclei) (criteria 5) in 15 (12,7%) cases, abnormal localization of megakaryocytes in 4 (3,3%) cases, CD34-positive megakaryocytes were not identified, CD34-positive blast cells (criteria 6) in 11 (9,3%) cases, increment in reticulin fibers in 3 (2,5%) cases, and median proliferative index (Ki-67) 30 (range, 0 to 90%). Criteria described by Bennett and Orazi suggestive of h-SMD (criteria 1 and/or 5) were detected in 16 (13,6%) cases. Criteria described by Baumann et al suggestive of childhood MDS (criteria 2 + 3 with or without 4) were observed in 30 (25.4%) cases. There was no statistical difference in morphological/immunohistochemical findings among total population, adults and children who developed and did not develop MDS/AML, including the presence of Bennett and Orazi criteria for h-MDS. Regarding Baumann et al criteria were more frequently identified in the group that did not progress to MDS/AML than the one that did (p=0,036), the opposite of what was expected. But when the criteria were tested in pediatric and adults\' groups separately, the statistical significance was no longer observed. There was a statistical significant correlation between the overall cellularity values of the samples and their proliferative index (p=0,001). Adult and pediatric patients with AAA, including those that progress to MDS/AML, have similar morphological/immunohistochemical characteristics. Some changes described by Baumann et al for pediatric MDS are also found in pediatric and adults\' cases with AAA. In addition, the proliferative index may be increased in cases of AAA and this finding has no correlation with progression to MDS/AML. Morphological/immunohistochemical changes in bone marrow biopsies in AAA have failed to identify a group at higher risk for progression to MDS/AML in our series

In last decades, with expansion of immunological and biological methods are developed new diagnostical and treatment processes, which enable stratification of patients into sanative groups and trend to individual therapy. Absolutely transparent are effects relevant to leukemia. Present treatment procedures enable not only longer survivance of patients, but often their stable sanation. In present time is in progress intesive research imunotherapy NK cells, which could be able to finish minimal residual disease after chemotherapeutical treatment, which is evoke by persistant malignant cells. Next advantage of this treatment procedure is elimination of system disease in cosequence of exactly pointed cure. In this work he attended in vitro testing to possibility of utilization imunotherapeutic treatment by NK cells acute and chronic myeloid leukemia and chronic lymfoblastic leukemia. Using flow cytometry methods we detected activation and inhibitory ligands which are recognized by NK cells on the cell surface of leukemia blasts. These are members of MHC complex HLA-E, molecules derived from MHC class I (MICA, MICB), UL16-binding proteins (ULBP-1, ULBP -2, ULBP -3, ULBP -4) and also Hsp70 protein according to the newest observation. We also atended to detection of expression inducible heat shock...

The need to protect marine structures from the high-intensity impulsive loads created by underwater explosions has stimulated renewed interest in the mechanical response of sandwich structures. The objective of this combined numerical and experimental study is to analyze the dynamic response of composite sandwich structures and develop material-structure-property relations and design criteria for improving the blast-resistance of marine structures. Configurations analyzed include polymer foam core structures with planar geometries. A novel experimental facility to generate high-intensity underwater impulsive loads and carry out in-situ measurements of dynamic deformations in marine structures is developed. Experiments are supported by fully dynamic finite-element simulations which account for the effects of fluid-structure interaction, and the constitutive and damage response of E-glass/polyester composites and PVC foams. Results indicate that the core-density has a significant influence on dynamic deformations and failure modes. Polymeric foams experience considerable rate-effects and exhibit extensive shear cracking and collapse under high-magnitude multi-axial underwater impulsive loads. In structures with identical masses, low-density foam cores consistently outperform high-density foam cores, undergoing lesser deflections and transmitting smaller impulses. Calculations reveal a significant difference between the response of air-backed and water-backed structures. Water-backed structures undergo much greater damage and consequently need to absorb a much larger amount of energy than air-backed structures. The impulses transmitted through water-backed structures have significant implications for structural design. The thickness of the facesheets is varied under the conditions of constant material properties and core dimensions. The results reveal an optimal thickness of the facesheets which maximizes energy absorption in the core and minimizes the overall deflection of the structure.