O eritrovírus humano (parvovírus), gênero Erytrovírus, é o único representante da família Parvoviridae responsável por um amplo espectro de doenças. Estudos recentes têm demonstrado variações entre o eritrovírus e orientam a reclassificação destas variantes em três genótipos distintos: genótipos 1, 2 e 3. O papel do eritrovírus na etiopatogenia de doenças hematológicas em humanos permanece incerto. Este estudo teve como objetivo principal avaliar a relação etiopatogênica dos genótipos do eritrovírus e as citopenias de origem desconhecida. Materiais e Métodos: Participaram do estudo 285 indivíduos procedentes do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Destes, 120 apresentavam citopenias de origem desconhecida (grupo 1 Casos), 45 eram doadores de medula óssea (grupo 2 Controles Saudáveis) e 120 eram pacientes com doenças oncohematológicas crônicas (grupo 3 Controles com Neoplasias Hematológicas). A pesquisa do vírus foi realizada pelo método de semi-nested PCR (Reação em Cadeia da Polimerase) em amostras de medula óssea e de sangue periférico. As fitas complementares foram seqüenciadas diretamente do produto da PCR. Amostras de plasma de todos os indivíduos incluídos no estudo foram testadas para presença de anticorpos IgG e IgM específicos contra o eritrovírus por ensaio imunoenzimático. Resultados: Dos 40 indivíduos com resultado positivo na PCR em amostra da medula óssea, o genótipo 1 foi encontrado em 22 (55%), o genótipo 2 em 5 (12,5%), o genótipo 3 em 13 (32,5%). Quando comparadas as freqüências de positividade entre os casos e controles (Grupo 1 VS Grupos 2 e 3), não encontramos diferença significativa com relação ao genótipo 1 (p=0, 192) nem com relação aos genótipos 2 e 3 (p= 0.143). A soroprevalência encontrada na amostra foi de 71%. Conclusão: Concluímos que a infecção isolada pelo eritrovírus, independente do genótipo encontrado, não tem relação etiopatogênica com as citopenias de origem desconhecida, uma vez que o vírus foi encontrado com a mesma freqüência nos casos e nos controles estudados / The human erythrovirus (parvovirus), genus Erytrovirus, is the only representative of the family Parvoviridae responsible for a broad spectrum of diseases. Recent studies have shown variations within the erythrovirus and guide the classification of these variants in three distinct genotypes: genotypes 1, 2 and 3. The role of the erythrovirus in the etiopathogenesis of hematological diseases in humans remains uncertain. This studys main objective was to evaluate the etiopathogenic relationship between the genotypes of the erythrovirus and the cyptopenias of unknown origins. Methods and Materials: 285 individuals coming from the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo participated in the study. Of these, 120 represented cytopenias of unknown origins (group one Cases), 45 were bone marrow donors (group two - Healthy Controls), and 120 were patients with chronic oncohematological diseases (group three Controls with Hematological Disorder). The research of the virus was done through the semi-nested PCR method (polymerase chain reaction) in bone marrow and peripheral blood samples. The complementary strands were sequenced directly from the product of the PCR. Plasma samples from all of the individuals included in the study were tested through immunosorbent assay for the presence of lgG and IgM antibodies specific to the eritrovírus. Results: Of the 40 individuals that had positive PCR bone marrow results, the genotype 1 was found in 22 (55%), the genotype 2 in 5 (12.5%), and genotype 3 in 13 (32.5%). When the frequency of positivity was compared between the cases and the controls (Group 1 vs. Groups 2 and 3), we did not find a significant difference in relation to genotype 1 (p=0.192), nor did we find a significant difference in relation to genotypes 2 and 3 (p=0.143). The overall seroprevalence found in the samples was 71%. Conclusion: We conclude that the infection isolated by the erytrovirus, independent of the genotype found, does not have a etiopathogenic relationship with the cytopenias of unknown origins, hence the virus was found with the same frequency in the cases and the controls studied

O eritrovírus humano (parvovírus), gênero Erytrovírus, é o único representante da família Parvoviridae responsável por um amplo espectro de doenças. Estudos recentes têm demonstrado variações entre o eritrovírus e orientam a reclassificação destas variantes em três genótipos distintos: genótipos 1, 2 e 3. O papel do eritrovírus na etiopatogenia de doenças hematológicas em humanos permanece incerto. Este estudo teve como objetivo principal avaliar a relação etiopatogênica dos genótipos do eritrovírus e as citopenias de origem desconhecida. Materiais e Métodos: Participaram do estudo 285 indivíduos procedentes do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Destes, 120 apresentavam citopenias de origem desconhecida (grupo 1 Casos), 45 eram doadores de medula óssea (grupo 2 Controles Saudáveis) e 120 eram pacientes com doenças oncohematológicas crônicas (grupo 3 Controles com Neoplasias Hematológicas). A pesquisa do vírus foi realizada pelo método de semi-nested PCR (Reação em Cadeia da Polimerase) em amostras de medula óssea e de sangue periférico. As fitas complementares foram seqüenciadas diretamente do produto da PCR. Amostras de plasma de todos os indivíduos incluídos no estudo foram testadas para presença de anticorpos IgG e IgM específicos contra o eritrovírus por ensaio imunoenzimático. Resultados: Dos 40 indivíduos com resultado positivo na PCR em amostra da medula óssea, o genótipo 1 foi encontrado em 22 (55%), o genótipo 2 em 5 (12,5%), o genótipo 3 em 13 (32,5%). Quando comparadas as freqüências de positividade entre os casos e controles (Grupo 1 VS Grupos 2 e 3), não encontramos diferença significativa com relação ao genótipo 1 (p=0, 192) nem com relação aos genótipos 2 e 3 (p= 0.143). A soroprevalência encontrada na amostra foi de 71%. Conclusão: Concluímos que a infecção isolada pelo eritrovírus, independente do genótipo encontrado, não tem relação etiopatogênica com as citopenias de origem desconhecida, uma vez que o vírus foi encontrado com a mesma freqüência nos casos e nos controles estudados / The human erythrovirus (parvovirus), genus Erytrovirus, is the only representative of the family Parvoviridae responsible for a broad spectrum of diseases. Recent studies have shown variations within the erythrovirus and guide the classification of these variants in three distinct genotypes: genotypes 1, 2 and 3. The role of the erythrovirus in the etiopathogenesis of hematological diseases in humans remains uncertain. This studys main objective was to evaluate the etiopathogenic relationship between the genotypes of the erythrovirus and the cyptopenias of unknown origins. Methods and Materials: 285 individuals coming from the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo participated in the study. Of these, 120 represented cytopenias of unknown origins (group one Cases), 45 were bone marrow donors (group two - Healthy Controls), and 120 were patients with chronic oncohematological diseases (group three Controls with Hematological Disorder). The research of the virus was done through the semi-nested PCR method (polymerase chain reaction) in bone marrow and peripheral blood samples. The complementary strands were sequenced directly from the product of the PCR. Plasma samples from all of the individuals included in the study were tested through immunosorbent assay for the presence of lgG and IgM antibodies specific to the eritrovírus. Results: Of the 40 individuals that had positive PCR bone marrow results, the genotype 1 was found in 22 (55%), the genotype 2 in 5 (12.5%), and genotype 3 in 13 (32.5%). When the frequency of positivity was compared between the cases and the controls (Group 1 vs. Groups 2 and 3), we did not find a significant difference in relation to genotype 1 (p=0.192), nor did we find a significant difference in relation to genotypes 2 and 3 (p=0.143). The overall seroprevalence found in the samples was 71%. Conclusion: We conclude that the infection isolated by the erytrovirus, independent of the genotype found, does not have a etiopathogenic relationship with the cytopenias of unknown origins, hence the virus was found with the same frequency in the cases and the controls studied

No description available.

Background: Haematotoxicity of conventional chemotherapies often results in delays of treatment or reduction of chemotherapy dose. To ameliorate these side-effects, patients are routinely treated with blood transfusions or haematopoietic growth factors such as erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF). For the latter ones, pharmaceutical derivatives are available, which differ in absorption kinetics, pharmacokinetic and -dynamic properties. Due to the complex interaction of cytotoxic effects of chemotherapy and the stimulating effects of different growth factor derivatives, optimal treatment is a non-trivial task. In the past, we developed mathematical models of thrombopoiesis, granulopoiesis and erythropoiesis under chemotherapy and growth-factor applications which can be used to perform clinically relevant predictions regarding the feasibility of chemotherapy schedules and cytopenia prophylaxis with haematopoietic growth factors. However, interactions of lineages and growth-factors were ignored so far. Results: To close this gap, we constructed a hybrid model of human granulopoiesis and erythropoiesis under conventional chemotherapy, G-CSF and EPO applications. This was achieved by combining our single lineage models of human erythropoiesis and granulopoiesis with a common stem cell model. G-CSF effects on erythropoiesis were also implemented. Pharmacodynamic models are based on ordinary differential equations describing proliferation and maturation of haematopoietic cells. The system is regulated by feedback loops partly mediated by endogenous and exogenous EPO and G-CSF. Chemotherapy is modelled by depletion of cells. Unknown model parameters were determined by fitting the model predictions to time series data of blood counts and cytokine profiles. Data were extracted from literature or received from cooperating clinical study groups. Our model explains dynamics of mature blood cells and cytokines after growth-factor applications in healthy volunteers. Moreover, we modelled 15 different chemotherapeutic drugs by estimating their bone marrow toxicity. Taking into account different growth-factor schedules, this adds up to 33 different chemotherapy regimens explained by the model. Conclusions: We conclude that we established a comprehensive biomathematical model to explain the dynamics of granulopoiesis and erythropoiesis under combined chemotherapy, G-CSF, and EPO applications. We demonstrate how it can be used to make predictions regarding haematotoxicity of yet untested chemotherapy and growth-factor schedules.

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-04, page: 2059. Adviser: George L. Delclos. Includes bibliographical references.

Background: Haematotoxicity of conventional chemotherapies often results in delays of treatment or reduction of chemotherapy dose. To ameliorate these side-effects, patients are routinely treated with blood transfusions or haematopoietic growth factors such as erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF). For the latter ones, pharmaceutical derivatives are available, which differ in absorption kinetics, pharmacokinetic and -dynamic properties. Due to the complex interaction of cytotoxic effects of chemotherapy and the stimulating effects of different growth factor derivatives, optimal treatment is a non-trivial task. In the past, we developed mathematical models of thrombopoiesis, granulopoiesis and erythropoiesis under chemotherapy and growth-factor applications which can be used to perform clinically relevant predictions regarding the feasibility of chemotherapy schedules and cytopenia prophylaxis with haematopoietic growth factors. However, interactions of lineages and growth-factors were ignored so far. Results: To close this gap, we constructed a hybrid model of human granulopoiesis and erythropoiesis under conventional chemotherapy, G-CSF and EPO applications. This was achieved by combining our single lineage models of human erythropoiesis and granulopoiesis with a common stem cell model. G-CSF effects on erythropoiesis were also implemented. Pharmacodynamic models are based on ordinary differential equations describing proliferation and maturation of haematopoietic cells. The system is regulated by feedback loops partly mediated by endogenous and exogenous EPO and G-CSF. Chemotherapy is modelled by depletion of cells. Unknown model parameters were determined by fitting the model predictions to time series data of blood counts and cytokine profiles. Data were extracted from literature or received from cooperating clinical study groups. Our model explains dynamics of mature blood cells and cytokines after growth-factor applications in healthy volunteers. Moreover, we modelled 15 different chemotherapeutic drugs by estimating their bone marrow toxicity. Taking into account different growth-factor schedules, this adds up to 33 different chemotherapy regimens explained by the model. Conclusions: We conclude that we established a comprehensive biomathematical model to explain the dynamics of granulopoiesis and erythropoiesis under combined chemotherapy, G-CSF, and EPO applications. We demonstrate how it can be used to make predictions regarding haematotoxicity of yet untested chemotherapy and growth-factor schedules.:Background; Methods; Results; Model predictions; Discussion; Conclusions