José Barbot - Academia.edu (original) (raw)
Papers by José Barbot
A decisao de transfundir reveste-se actualmente de um grau de responsabilidade elevada que exige ... more A decisao de transfundir reveste-se actualmente de um grau de responsabilidade elevada que exige o maximo rigor e ponderacao possiveis.Os autores fizeram uma analise da pratica transfusional na UCI do Hospital Maria Pia. Foi avaliada a situacao clinica pre e pos-transfusional de53 recem-nascidos (RN), que no periodo compreendido entre 1 de Fevereiro de 1994 e 1 de Fevereiro de 1995, foram transfundidos na Unidade deCuidados Intensivos (UCI) do Hospital de Criancas Maria Pia, num total de 190 internados (53% por motivos cirurgicos e 47% por motivos medicos).Sao analisados os valores medios de hemoglobina pre e pos-transfusional, assim como os motivos de ordem clinica que interferiram na decisao detransfusao, em 3 grupos diferentes elaborados segundo a idade gestacional.A variacao dos sinais vitais pre'e pos-transfusionais foi analisada em todos os RN, bem como grau de espoliacao iatrogenica nos RN transfundidospor motivos medicos.A adequacao das transfusoes realizadas foi avaliad...
Nascer e Crescer, 2012
Introduction: The paroxysmal cold hemoglobinuria is a rare form of presentation of autoimmune hem... more Introduction: The paroxysmal cold hemoglobinuria is a rare form of presentation of autoimmune hemolytic anemia. Case report: We describe the case of a 23 months -old child with jaundice and dark urine of sudden onset. There was reference to upper respiratory infection a week earlier. He presented severe anemia with hemoglobinuria. DHL was rised and the direct Coombs test was positive with specifi c anti -C3d. The positive of Donath -Landsteiner proof, to demonstrate the biphasic nature of the autoantibody, confi rmed the diagnosis of paroxysmal cold hemoglobinuria. Conclusion: With this case report the authors aim to highlight the importance of recognizing this condition and the character of intravascular hemolysis, so that quicker diagnosis and treatment can be made.
Blood, 2013
Fanconi anaemia (FA) is an inherited disorder characterized by chromosomal instability, progressi... more Fanconi anaemia (FA) is an inherited disorder characterized by chromosomal instability, progressive bone marrow failure and increased incidence of haematological and non-haematological malignancies. Mutations in 16 FA genes have been identified which disrupt a DNA repair complex, resulting in increased chromosomal fragility. However, the phenotype is variable even amongst patients from the same family and with the same mutation. This raises the possibility that other factors, such as epigenetic modifications, may affect the disease phenotype. Epigenetic changes play an important role in oncogenesis of several haematological malignancies and solid tumours. These changes may be pharmacologically manipulated with DNA hypomethylating agents and histone deacetylase inhibitors. The aim of our project was to explore whether the epigenetic profiles in FA differ from non-FA individuals and whether these could be manipulated to alter the disease phenotype. To assess whether epigenetic pattern...
Nascer e Crescer
Introduction: Children with nephrotic syndrome (NS) have an increased risk of thromboembolic comp... more Introduction: Children with nephrotic syndrome (NS) have an increased risk of thromboembolic complications.
Haematologica, 2001
The close association between cerebrovascular disease and APLA has been observed in well-controll... more The close association between cerebrovascular disease and APLA has been observed in well-controlled prospective studies in young patients. 5 In the newborn period there are few case reports that associate newborn infarction and maternal APLA. 6-9 Theoretically APLA ...
Pediatric Neurology, 2003
The aim of this study was to identify hereditary and acquired risk-factors as they are related to... more The aim of this study was to identify hereditary and acquired risk-factors as they are related to the occurrence of stroke in children. We identified 21 children with stroke. A search of the Factor V Leiden mutation, the Factor II G20210A variant, and the thermolabile variant of methylenetetrahydrofolate reductase was performed in patients and in a control group (n ؍ 115). We identified risk factors of acquired and/or hereditary nature for stroke in 19 of 21 children. Eleven children had three or more risk factors, seven had two risk factors, and one child had only one risk factor. We found three carriers (14.3%) of the Factor V Leiden mutation, two carriers (9.5%) of the Factor II G20210A variant, eleven (52.4%) thermolabile variant of methylenetetrahydrofolate reductase heterozygote carriers, and one (4.8%) homozygotes for this variant. Frequencies of the Factor V Leiden mutation and the Factor II variant were higher in patients than in controls, suggesting that these variants are associated with an increased risk of stroke in childhood. Homozygosity for the thermolabile variant of methylenetetrahydrofolate reductase was equally frequent amongst patients and controls. Our study confirms that stroke in children is commonly associated with a combination of multiple risk factors, both genetic and acquired, and that the Factor V Leiden mutation and the Factor II G20210A variant are predisposing factors for this situation.
Pediatric Hematology and Oncology, 2004
Clinical and Laboratory Haematology, 2004
We evaluate a technique for genotyping HNA-1a,-1b and-1c antigens, resorting to fluorescence-prim... more We evaluate a technique for genotyping HNA-1a,-1b and-1c antigens, resorting to fluorescence-primed allele-specific polymerase chain reaction (FPAS-PCR), and determine the frequency of the different genotypes in a normal Portuguese population. Our results indicate that the FPAS-PCR system is a reliable and simple tool for genotyping the neutrophil Fcc receptor IIIB antigens. The HNA-1a,-1b and-1c gene frequencies of 42.98, 84.21 and 6.14%, respectively, found in this study are similar to those reported for other white populations.
European Journal of Pediatrics, 2000
European Journal of Haematology, 2005
O despiste de ferropenia pré operatório numa população pediátrica, pode constituir uma oportunida... more O despiste de ferropenia pré operatório numa população pediátrica, pode constituir uma oportunidade para detectar e corrigir estadios deficitários de ferro, susceptíveis de provocar sequelas a médio/longo prazo. Com o objectivo de detectar estas situações, fomos ...
Acta Pediatrica …, 2000
Resumo Os autores apresentam o caso de uma jovem de 15 anos de idade, sexo feminino, com antecede... more Resumo Os autores apresentam o caso de uma jovem de 15 anos de idade, sexo feminino, com antecedentes de infecções do tracto urinario de repetição e com malformações congênitas esqueléticas e hipoplasia renal direita, orientada para estudo de bicitopenia ( ...
Clinical Biochemistry, 2011
This study aimed to evaluate the relationship between erythropoiesis and inflammation, in Heredit... more This study aimed to evaluate the relationship between erythropoiesis and inflammation, in Hereditary Spherocytosis (HS) clinical outcome. Design and methods: We studied 26 controls and 82 HS patients presenting mild (n =49) and severer (n = 33) HS forms. We evaluated plasma levels of EPO, sTfR, ferritin, iron, folic acid, vitamin B12, TNF-α, IFN-γ, elastase and lactoferrin; leukocyte and reticulocyte counts and RPI were determined. Results: All HS patients showed significantly higher EPO, sTfR, reticulocytes and RPI but only mild HS presented normal hemoglobin levels; the positive significant correlations between EPO and sTfR, reticulocytes and RPI observed in mild HS were not observed in severer HS patients. HS patients presented with higher levels of neutrophils, TNF-α, IFN-γ, elastase, lactoferrin and ferritin. Conclusions: Our data show HS as a disease linked to enhanced erythropoiesis that is disturbed in the more severe forms, to which inflammation may contribute, at least in part.
British Journal of Haematology, 2010
British Journal of Haematology, 2001
We report the results of 10 years of prophylactic fresh-frozen plasma (FFP) infusion therapy in a... more We report the results of 10 years of prophylactic fresh-frozen plasma (FFP) infusion therapy in a 14-year-old girl with chronic relapsing thrombotic thrombocytopenic purpura (TTP), in whom a severe congenital von Willebrand factor (VWF)-cleaving protease deficiency has been documented. Severe haemolytic crises triggered by infections were prevented and her present renal and neurological functions have been preserved. Sequential measurements of protease activity and platelet count after FFP infusion led us to conclude tentatively that 5% may be sufficient to degrade very large and adhesive VWF multimers.
Blood Cells, Molecules, and Diseases, 2006
We describe the molecular study in a cohort of 120 Portuguese patients with the clinical diagnosi... more We describe the molecular study in a cohort of 120 Portuguese patients with the clinical diagnosis of Gilbert syndrome and in one with the diagnosis of Crigler-Najjar syndrome type II, as well as a prenatal diagnosis of Crigler-Najjar syndrome type I. Among the 120 unrelated patients with Gilbert syndrome, 110 were homozygous for the [TA]7 allele ([TA]7/[TA]7), and one patient was a compound heterozygote for two different insertions ([TA]7/[TA]8). The remaining 9 patients were heterozygous for the TA insertion ([TA]6/[TA]7). Additional studies in these 9 patients revealed heterozygosity for the c.674T>G, c.488 _ 491dupACCT and c.923G>A mutations, in 1, 1 and 4 patients, respectively. The patient with Crigler-Najjar syndrome type II was a compound heterozygote for [TA]7 and the c.923G>A mutation. The undocumented polymorphisms c.-1126C>T and c.997-82T>C were also detected in the course of this study. Prenatal diagnosis in a family with a boy previously diagnosed as Crigler-Najjar syndrome type I and homozygosity for the c.923G>A mutation revealed that the fetus was unaffected. Homozygosity for the [TA] insertion was found to be the most frequent cause of GS in our population. Identification of further mutations in the UGT1A1 gene was also seen to contribute significantly towards diagnosis.
Blood, 2011
Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer pred... more Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. To investigate the origin, functional role, and clinical impact of FANCA mutations, we determined a FANCA mutational spectrum with 130 pathogenic alleles. Some of these mutations were further characterized for their distribution in populations, mode of emergence, or functional consequences at cellular and clinical level. The world most frequent FANCA mutation is not the result of a mutational “hot-spot” but results from worldwide dissemination of an ancestral Indo-European mutation. We provide molecular evidence that total absence of FANCA in humans does not reduce embryonic viability, as the observed frequency of mutation carriers in the Gypsy population equals the expected by Hardy-Weinberg equilibrium. We also prove that long distance Alu-Alu recombination can cause Fanconi anemia by originating large interstitial deletions involving FANCA and 2 adjacent genes. Finally, we...
![Research paper thumbnail of [The molecular basis of dominantly inherited beta-thalassemia]](https://attachments.academia-assets.com/105260670/thumbnails/1.jpg)
](Acta medica portuguesa, 1999
In this study, we sought to clarity the molecular basis of a dominant inherited beta-thalassemia,... more In this study, we sought to clarity the molecular basis of a dominant inherited beta-thalassemia, found in heterozygosity in a northern Portuguese family with thalassemia intermedia. We characterized: i) the alpha-globin gene cluster structure; ii) the beta-globin gene cluster haplotype; and iii) the beta-thalassemia mutation. The alpha-globin gene cluster was structurally normal. The G-->T transversion at codon 121 of the beta-globin gene was found in the affected individuals in association with Orkin's haplotype V. This is an uncommon, though ubiquitous, mutation. Which has also been found, in association with different haplotypes, in several distant populations. It has only been observed in this three-generation family, in the Portuguese population. We suggest a mechanism to explain the genotype/phenotype correlation.
A decisao de transfundir reveste-se actualmente de um grau de responsabilidade elevada que exige ... more A decisao de transfundir reveste-se actualmente de um grau de responsabilidade elevada que exige o maximo rigor e ponderacao possiveis.Os autores fizeram uma analise da pratica transfusional na UCI do Hospital Maria Pia. Foi avaliada a situacao clinica pre e pos-transfusional de53 recem-nascidos (RN), que no periodo compreendido entre 1 de Fevereiro de 1994 e 1 de Fevereiro de 1995, foram transfundidos na Unidade deCuidados Intensivos (UCI) do Hospital de Criancas Maria Pia, num total de 190 internados (53% por motivos cirurgicos e 47% por motivos medicos).Sao analisados os valores medios de hemoglobina pre e pos-transfusional, assim como os motivos de ordem clinica que interferiram na decisao detransfusao, em 3 grupos diferentes elaborados segundo a idade gestacional.A variacao dos sinais vitais pre'e pos-transfusionais foi analisada em todos os RN, bem como grau de espoliacao iatrogenica nos RN transfundidospor motivos medicos.A adequacao das transfusoes realizadas foi avaliad...
Nascer e Crescer, 2012
Introduction: The paroxysmal cold hemoglobinuria is a rare form of presentation of autoimmune hem... more Introduction: The paroxysmal cold hemoglobinuria is a rare form of presentation of autoimmune hemolytic anemia. Case report: We describe the case of a 23 months -old child with jaundice and dark urine of sudden onset. There was reference to upper respiratory infection a week earlier. He presented severe anemia with hemoglobinuria. DHL was rised and the direct Coombs test was positive with specifi c anti -C3d. The positive of Donath -Landsteiner proof, to demonstrate the biphasic nature of the autoantibody, confi rmed the diagnosis of paroxysmal cold hemoglobinuria. Conclusion: With this case report the authors aim to highlight the importance of recognizing this condition and the character of intravascular hemolysis, so that quicker diagnosis and treatment can be made.
Blood, 2013
Fanconi anaemia (FA) is an inherited disorder characterized by chromosomal instability, progressi... more Fanconi anaemia (FA) is an inherited disorder characterized by chromosomal instability, progressive bone marrow failure and increased incidence of haematological and non-haematological malignancies. Mutations in 16 FA genes have been identified which disrupt a DNA repair complex, resulting in increased chromosomal fragility. However, the phenotype is variable even amongst patients from the same family and with the same mutation. This raises the possibility that other factors, such as epigenetic modifications, may affect the disease phenotype. Epigenetic changes play an important role in oncogenesis of several haematological malignancies and solid tumours. These changes may be pharmacologically manipulated with DNA hypomethylating agents and histone deacetylase inhibitors. The aim of our project was to explore whether the epigenetic profiles in FA differ from non-FA individuals and whether these could be manipulated to alter the disease phenotype. To assess whether epigenetic pattern...
Nascer e Crescer
Introduction: Children with nephrotic syndrome (NS) have an increased risk of thromboembolic comp... more Introduction: Children with nephrotic syndrome (NS) have an increased risk of thromboembolic complications.
Haematologica, 2001
The close association between cerebrovascular disease and APLA has been observed in well-controll... more The close association between cerebrovascular disease and APLA has been observed in well-controlled prospective studies in young patients. 5 In the newborn period there are few case reports that associate newborn infarction and maternal APLA. 6-9 Theoretically APLA ...
Pediatric Neurology, 2003
The aim of this study was to identify hereditary and acquired risk-factors as they are related to... more The aim of this study was to identify hereditary and acquired risk-factors as they are related to the occurrence of stroke in children. We identified 21 children with stroke. A search of the Factor V Leiden mutation, the Factor II G20210A variant, and the thermolabile variant of methylenetetrahydrofolate reductase was performed in patients and in a control group (n ؍ 115). We identified risk factors of acquired and/or hereditary nature for stroke in 19 of 21 children. Eleven children had three or more risk factors, seven had two risk factors, and one child had only one risk factor. We found three carriers (14.3%) of the Factor V Leiden mutation, two carriers (9.5%) of the Factor II G20210A variant, eleven (52.4%) thermolabile variant of methylenetetrahydrofolate reductase heterozygote carriers, and one (4.8%) homozygotes for this variant. Frequencies of the Factor V Leiden mutation and the Factor II variant were higher in patients than in controls, suggesting that these variants are associated with an increased risk of stroke in childhood. Homozygosity for the thermolabile variant of methylenetetrahydrofolate reductase was equally frequent amongst patients and controls. Our study confirms that stroke in children is commonly associated with a combination of multiple risk factors, both genetic and acquired, and that the Factor V Leiden mutation and the Factor II G20210A variant are predisposing factors for this situation.
Pediatric Hematology and Oncology, 2004
Clinical and Laboratory Haematology, 2004
We evaluate a technique for genotyping HNA-1a,-1b and-1c antigens, resorting to fluorescence-prim... more We evaluate a technique for genotyping HNA-1a,-1b and-1c antigens, resorting to fluorescence-primed allele-specific polymerase chain reaction (FPAS-PCR), and determine the frequency of the different genotypes in a normal Portuguese population. Our results indicate that the FPAS-PCR system is a reliable and simple tool for genotyping the neutrophil Fcc receptor IIIB antigens. The HNA-1a,-1b and-1c gene frequencies of 42.98, 84.21 and 6.14%, respectively, found in this study are similar to those reported for other white populations.
European Journal of Pediatrics, 2000
European Journal of Haematology, 2005
O despiste de ferropenia pré operatório numa população pediátrica, pode constituir uma oportunida... more O despiste de ferropenia pré operatório numa população pediátrica, pode constituir uma oportunidade para detectar e corrigir estadios deficitários de ferro, susceptíveis de provocar sequelas a médio/longo prazo. Com o objectivo de detectar estas situações, fomos ...
Acta Pediatrica …, 2000
Resumo Os autores apresentam o caso de uma jovem de 15 anos de idade, sexo feminino, com antecede... more Resumo Os autores apresentam o caso de uma jovem de 15 anos de idade, sexo feminino, com antecedentes de infecções do tracto urinario de repetição e com malformações congênitas esqueléticas e hipoplasia renal direita, orientada para estudo de bicitopenia ( ...
Clinical Biochemistry, 2011
This study aimed to evaluate the relationship between erythropoiesis and inflammation, in Heredit... more This study aimed to evaluate the relationship between erythropoiesis and inflammation, in Hereditary Spherocytosis (HS) clinical outcome. Design and methods: We studied 26 controls and 82 HS patients presenting mild (n =49) and severer (n = 33) HS forms. We evaluated plasma levels of EPO, sTfR, ferritin, iron, folic acid, vitamin B12, TNF-α, IFN-γ, elastase and lactoferrin; leukocyte and reticulocyte counts and RPI were determined. Results: All HS patients showed significantly higher EPO, sTfR, reticulocytes and RPI but only mild HS presented normal hemoglobin levels; the positive significant correlations between EPO and sTfR, reticulocytes and RPI observed in mild HS were not observed in severer HS patients. HS patients presented with higher levels of neutrophils, TNF-α, IFN-γ, elastase, lactoferrin and ferritin. Conclusions: Our data show HS as a disease linked to enhanced erythropoiesis that is disturbed in the more severe forms, to which inflammation may contribute, at least in part.
British Journal of Haematology, 2010
British Journal of Haematology, 2001
We report the results of 10 years of prophylactic fresh-frozen plasma (FFP) infusion therapy in a... more We report the results of 10 years of prophylactic fresh-frozen plasma (FFP) infusion therapy in a 14-year-old girl with chronic relapsing thrombotic thrombocytopenic purpura (TTP), in whom a severe congenital von Willebrand factor (VWF)-cleaving protease deficiency has been documented. Severe haemolytic crises triggered by infections were prevented and her present renal and neurological functions have been preserved. Sequential measurements of protease activity and platelet count after FFP infusion led us to conclude tentatively that 5% may be sufficient to degrade very large and adhesive VWF multimers.
Blood Cells, Molecules, and Diseases, 2006
We describe the molecular study in a cohort of 120 Portuguese patients with the clinical diagnosi... more We describe the molecular study in a cohort of 120 Portuguese patients with the clinical diagnosis of Gilbert syndrome and in one with the diagnosis of Crigler-Najjar syndrome type II, as well as a prenatal diagnosis of Crigler-Najjar syndrome type I. Among the 120 unrelated patients with Gilbert syndrome, 110 were homozygous for the [TA]7 allele ([TA]7/[TA]7), and one patient was a compound heterozygote for two different insertions ([TA]7/[TA]8). The remaining 9 patients were heterozygous for the TA insertion ([TA]6/[TA]7). Additional studies in these 9 patients revealed heterozygosity for the c.674T>G, c.488 _ 491dupACCT and c.923G>A mutations, in 1, 1 and 4 patients, respectively. The patient with Crigler-Najjar syndrome type II was a compound heterozygote for [TA]7 and the c.923G>A mutation. The undocumented polymorphisms c.-1126C>T and c.997-82T>C were also detected in the course of this study. Prenatal diagnosis in a family with a boy previously diagnosed as Crigler-Najjar syndrome type I and homozygosity for the c.923G>A mutation revealed that the fetus was unaffected. Homozygosity for the [TA] insertion was found to be the most frequent cause of GS in our population. Identification of further mutations in the UGT1A1 gene was also seen to contribute significantly towards diagnosis.
Blood, 2011
Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer pred... more Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. To investigate the origin, functional role, and clinical impact of FANCA mutations, we determined a FANCA mutational spectrum with 130 pathogenic alleles. Some of these mutations were further characterized for their distribution in populations, mode of emergence, or functional consequences at cellular and clinical level. The world most frequent FANCA mutation is not the result of a mutational “hot-spot” but results from worldwide dissemination of an ancestral Indo-European mutation. We provide molecular evidence that total absence of FANCA in humans does not reduce embryonic viability, as the observed frequency of mutation carriers in the Gypsy population equals the expected by Hardy-Weinberg equilibrium. We also prove that long distance Alu-Alu recombination can cause Fanconi anemia by originating large interstitial deletions involving FANCA and 2 adjacent genes. Finally, we...
Acta medica portuguesa, 1999
In this study, we sought to clarity the molecular basis of a dominant inherited beta-thalassemia,... more In this study, we sought to clarity the molecular basis of a dominant inherited beta-thalassemia, found in heterozygosity in a northern Portuguese family with thalassemia intermedia. We characterized: i) the alpha-globin gene cluster structure; ii) the beta-globin gene cluster haplotype; and iii) the beta-thalassemia mutation. The alpha-globin gene cluster was structurally normal. The G-->T transversion at codon 121 of the beta-globin gene was found in the affected individuals in association with Orkin's haplotype V. This is an uncommon, though ubiquitous, mutation. Which has also been found, in association with different haplotypes, in several distant populations. It has only been observed in this three-generation family, in the Portuguese population. We suggest a mechanism to explain the genotype/phenotype correlation.