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1.
Semin Hematol ; 52(4): 279-86, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26404440

RESUMO

Macrocytic anemia, defined as a mean cell volume (MCV) ≥100 fL in adults, has a narrow differential diagnosis that requires evaluation of the peripheral blood smear as well as additional laboratory testing taken in conjunction with clinical information that includes patient history and physical examination findings. This review is an update on the approach to a patient with macrocytic anemia with attention paid to the differentiation of megaloblastic and non-megaloblastic macrocytic anemias. Critical to the determination of the diagnosis is the judicious use of laboratory testing and the evaluation of those findings in conjunction with the patient medical, surgical, and medication history.


Assuntos
Anemia Macrocítica/diagnóstico , Diferenciação Celular , Diagnóstico Diferencial , Índices de Eritrócitos , Humanos , Megaloblastos/patologia
2.
Acta Haematol ; 133(3): 287-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25472687

RESUMO

Microparticles (MPs) are present in healthy subjects and their concentration increases in patients at high risk of thrombosis. We evaluated 10 patients with sickle cell anemia (SCA) treated with hydroxyurea (HU) and 13 SCA patients without this treatment. MP concentrations were determined by flow cytometry. Coagulation was evaluated using the thrombin-antithrombin complex (TAT) and D-dimers. Total MP concentrations were increased in the HU-treated group (265 × 10(6)/ml vs. 67.45 × 10(6)/ml; p = 0.0026), as well as MPs derived from RBC (67.83 × 10(6)/ml vs. 26.31 × 10(6)/ml; p = 0.05), monocytes (51.31 × 10(6)/ml vs. 9.03 × 10(6)/ml; p = 0.0084), monocytes with tissue factor (TF) expression (2.27 × 10(6)/ml vs. 0.27 × 10(6)/ml; p = 0.0058), endothelium (49.42 × 10(6)/ml vs. 7.23 × 10(6)/ml; p = 0.007) and endothelium with TF (1.42 × 10(6)/ml vs. 0.26 × 10(6)/ml; p = 0.0043). Furthermore, the concentrations of TAT (7.56 vs. 10.98 µg/l; p = 0.014) and D-dimers (0.65 vs. 1.29 µg/ml; p = 0.007) were reduced with HU. The MP elevation may suggest a direct cytotoxic effect of HU. Another explanation is a cell surface increase secondary to a megaloblastic process, resulting in increased vesicle release. In our opinion, the known benefits of HU on SCA patients, along with the reduction in coagulation activation, surpass its potential detrimental effect on MPs. Future studies should elucidate the role of MPs and demonstrate their significance in different contexts.


Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/administração & dosagem , Micropartículas Derivadas de Células/metabolismo , Fibrinólise/efeitos dos fármacos , Hidroxiureia/administração & dosagem , Adulto , Anemia Falciforme/patologia , Animais , Antitrombinas/sangue , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Megaloblastos/metabolismo , Megaloblastos/patologia , Monócitos/metabolismo , Monócitos/patologia , Tromboplastina/biossíntese
4.
Dtsch Med Wochenschr ; 137(34-35): 1693-6, 2012 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-22893049

RESUMO

HISTORY AND ADMISSION FINDINGS: A previously healthy 66-year-old women presented with onset of general weakness, shortness of breath and significant weight loss. Due to appearance of jaundice, biliary obstruction had been ruled out by a CAT scan previous to the patients presentation in our practice. INVESTIGATIONS: The laboratory tests already arranged by the patients general practitioner showed a pronounced pancytopenia with megaloblastic anemia and hyperbilirubinemia. The bone marrow aspiration revealed a hypercellular bone marrow with megaloblastic erythropoiesis. The diagnosis of pernicious anemia was confirmed by the low cobalamin (vitamin B12) serum level and the presence of atrophic gastritis. TREATMENT: Pernicious anemia was treated with intramuscular injection of Cyanocobalamin (1000 µg) which resulted in an immediate reticulocytosis and a widely normalized blood cell count and bilirubin level four weeks after initiation of treatment. CONCLUSION: The differential diagnosis of megaloblastic anemia covers a wide spectrum of diseases with different etiology. This case report demonstrates an example of a pernicious anemia with atypical and foudroyant clinical course.


Assuntos
Doenças Autoimunes/diagnóstico , Gastrite Atrófica/diagnóstico , Icterícia/etiologia , Pancitopenia/etiologia , Idoso , Anemia Macrocítica/tratamento farmacológico , Anemia Macrocítica/etiologia , Doenças Autoimunes/tratamento farmacológico , Biópsia , Medula Óssea/patologia , Diagnóstico Diferencial , Índices de Eritrócitos , Feminino , Gastrite Atrófica/tratamento farmacológico , Gastroscopia , Humanos , Infusões Intravenosas , Icterícia/tratamento farmacológico , Megaloblastos/efeitos dos fármacos , Megaloblastos/patologia , Pancitopenia/tratamento farmacológico , Ultrassonografia , Vitamina B 12/administração & dosagem
5.
J Cell Physiol ; 225(2): 385-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20533375

RESUMO

The coelomic cavity is part of the extraembryonic mesoderm, surrounding amniotic cavity, embryo, and yolk sac in the early gestation. It is now believed to represent an important transfer interface and a reservoir of nutrients for the embryo. Coelocentesis by ultrasound-guided transvaginal puncture offers an easier access to the early human embryo, from 28 days post-fertilization. However, despite some studies about its biochemical composition being reported, our knowledge about the presence of cellular elements and their quality in this compartment are still limited. Here we studied human coelomic fluids sampled from 6.6 (48 days) to 10 weeks of gestation, demonstrating the presence of functional embryonic erythroid precursors, that is, megaloblasts in the coelomic cavity. The ease of access of the coelomic cavity could allow the development of novel strategies for diagnostic or therapeutic purposes by ultrasound imaging and ultrasound-guided puncture.


Assuntos
Líquidos Corporais/citologia , Embrião de Mamíferos/citologia , Megaloblastos/fisiologia , Antígenos CD/metabolismo , Embrião de Mamíferos/fisiologia , Citometria de Fluxo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Antígenos Comuns de Leucócito , Reação em Cadeia da Polimerase/métodos , Receptores da Transferrina/metabolismo , Saco Vitelino/fisiologia , Globinas épsilon/genética , Globinas épsilon/metabolismo , gama-Globinas/genética , gama-Globinas/metabolismo
6.
Intern Med ; 47(8): 737-42, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18421190

RESUMO

OBJECTIVE: Several reports of bone marrow dysplasia in patients with systemic lupus erythematosus (SLE) have been published. However, the reports are restricted primarily to descriptions of the erythroid lineage; no follow-up studies have been reported, and the clinical significance of the dysplasias is unknown. Therefore, in the present study, the dysplasias noted in bone marrow aspirates obtained from SLE patients were characterized. PATIENTS AND METHODS: The smears of bone marrow aspirates obtained from 17 SLE patients who had bone marrow aspiration due to cytopenia (WBC < 1,500/microl, or Hb < 10.5 g/dl, or platelet count < 10 x 10(4)/microl) were examined retrospectively. Of the 17 patients, 4 had a repeat bone marrow aspiration during follow-up. Clinical and laboratory data were obtained from the medical records. RESULTS: Of the 17 SLE patients, 12 had dysplasias, including: erythroid cell multinuclearity (trinuclear or more) (5 patients), megaloblastoid changes (4), pseudo-Pelger abnormalities (6), annular nuclear myeloid cells (2), separated nuclear megakaryocytes (4), and micromegakaryocytes (5). In the 4 patients who had follow-up bone marrow aspiration, these dysplasias were correlated with disease activity; some abnormalities disappeared with remission of SLE. Diffuse proliferative glomerulonephritis (3 patients) and cerebral lupus/neuropsychiatric lupus (4 patients) were seen only in patients with dysplasia. CONCLUSION: This study found that bone marrow dysplasia can be observed in all lineage cells of SLE patients, and that the dysplasia is reversible during the course of the disease. The presence of dysplasias appears to be associated with disease severity.


Assuntos
Doenças do Desenvolvimento Ósseo/etiologia , Doenças do Desenvolvimento Ósseo/patologia , Medula Óssea/patologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Adolescente , Adulto , Biópsia por Agulha Fina , Criança , Feminino , Humanos , Masculino , Megacariócitos/patologia , Megaloblastos/patologia , Pessoa de Meia-Idade , Células Mieloides/patologia , Remissão Espontânea , Estudos Retrospectivos , Índice de Gravidade de Doença
7.
Cytometry B Clin Cytom ; 74(2): 104-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18044723

RESUMO

BACKGROUND: Megaloblastic anemias are characterized by several hematopoietic cells with dysplastic nuclear morphology. The analyses of DNA ploidy and cell cycle of these cells are important to understand the property of such diseases. METHODS: As laser scanning cytometry (LSC) is a useful tool to evaluate the morphology of the cells fixed on the slide glass together with the quantitative analysis of the fluorescence information of each cell by rapid scanning of the specimens, the authors examined the DNA ploidy and cell cycle of six cases with megaloblastic anemia using LSC. RESULTS: Giant neutrophilic series such as giant metamyelocytes and giant band cells were found to have extraordinarily higher DNA ploidy, while hypersegmented neutrophils represented the normal diploid pattern like normal neutrophils. As to megaloblasts, cell cycle analysis showed that the proportion of the cells in S phase was increased as compared with the case of normal erythroblasts. CONCLUSIONS: The present study clearly demonstrates the abnormal aspects of the hematopoietic cells with megaloblastic anemia from the viewpoint of the DNA ploidy and cell cycle analyzed by the use of LSC.


Assuntos
Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/genética , Células da Medula Óssea/patologia , Ciclo Celular/genética , Aberrações Cromossômicas , Citometria de Varredura a Laser/métodos , Ploidias , Anemia Megaloblástica/sangue , Núcleo Celular/patologia , DNA/genética , Células Gigantes/patologia , Células Precursoras de Granulócitos/patologia , Células HL-60 , Células-Tronco Hematopoéticas/patologia , Humanos , Megaloblastos/patologia , Neutrófilos/patologia , Fase S/genética
8.
Leukemia ; 21(4): 668-77, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17301818

RESUMO

Multilineage dysplasia was advanced by the World Health Organization to increase prognostic accuracy in myelodysplastic syndromes (MDS) classification. We performed a structured cytomorphological examination of bone marrow (BM) in 221 low-grade MDS patients, this in conjunction with strict guidelines for cytopenias. A dysplasia scoring system was developed utilizing dysplastic changes, which were associated with worse outcome on univariate and multivariate analysis corrected for the International Prognostic Scoring System (IPSS). Dysplasia >or=10% in one BM lineage and one cytopenia constituted the low-risk category UCUD or Unilineage Cytopenia and Unilineage Dysplasia. The high-risk category comprised patients with cytopenia in >or=2 lineages and dysplasia in >or=2 BM lineages, namely MCMD or Multilineage Cytopenia and Multilineage Dysplasia. Intermediate-risk patients had one cytopenia and multilineage dysplasia, or cytopenia in >or=2 lineages and unilineage BM dysplasia, designated UCMD/MCUD or Unilineage Cytopenia and Multilineage Dysplasia/Multilineage Cytopenia and Unilineage Dysplasia. This system utilizing cytopenia-dysplasia scoring at diagnosis enabled comprehensive categorization of low-grade MDS cases that predicted for overall as well as leukemia-free survival. Cytopenia-dysplasia categorization added additional prognostic values to the lower risk IPSS categories. This suggests that a standardized dysplasia scoring system, used in conjunction with cytopenia, could improve diagnostic and prognostic sub-categorization of MDS patients.


Assuntos
Megaloblastos/patologia , Síndromes Mielodisplásicas/classificação , Análise de Variância , Medula Óssea/patologia , Células da Medula Óssea/patologia , Cariotipagem , Análise Multivariada , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Análise de Sobrevida , Organização Mundial da Saúde
11.
Med Princ Pract ; 14 Suppl 1: 2-14, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16103708

RESUMO

OBJECTIVE: Megaloblastosis (i.e., megaloblastic transformation of erythroid precursor cells in the bone marrow) is the cytomorphological hallmark of megaloblastic anemia resulting from vitamin B12 and folate deficiency. It is characterized by a finely stippled lacy pattern of nuclear chromatin, which is believed to be an expression of deranged cellular DNA synthesis. However, the molecular basis of these cytomorphological aberrations still remains obscure. The current presentation describes the results of our studies on some molecular events associated with the development of megaloblastosis. METHODS: Transmission electron microscopy was used to study megaloblasts as well as DNA fibers extracted from megaloblastic and normoblastic bone marrows with and without treatment with proteinase K during the extraction procedure; cellular DNA synthesis in bone marrow cultures was studied by incorporation of 3H-thymidine and deoxyuridine suppression test, while histone biosynthesis in bone marrow cells was studied by in vitro incorporation of 3H-tryptophan, 3H-lysine and 3H-arginine into histones. RESULTS: Derangement of DNA synthesis occurred due to an impaired de novo pathway of thymidylate synthesis in both vitamin-B12- and folate-deficient human megaloblastic bone marrows as well as in the bone marrows of rhesus monkeys and rats with experimentally induced folate deficiency. Interestingly, folate-deficient monkeys developed frank megaloblastic bone marrows, but folate-deficient rats did not. On the other hand, megaloblastic changes in the bone marrow of human patients with myelodysplastic syndrome and erythroleukemia were not associated with this DNA synthetic abnormality. Biosynthesis of predominantly arginine-rich histones in megaloblastic bone marrows was markedly reduced as compared to normoblastic bone marrows, which was consistently associated with elongation and despiralization of chromosomes and finely stippled nuclear chromatin in megaloblasts. CONCLUSION: The impaired biosynthesis of predominantly arginine-rich nuclear histones appeared to be a common molecular event (a denominator) underlying the development of megaloblastosis with or without abnormal DNA synthesis.


Assuntos
Anemia Megaloblástica/genética , Anemia Megaloblástica/patologia , Histonas/genética , Megaloblastos/patologia , Adolescente , Adulto , Anemia Megaloblástica/sangue , Anemia Megaloblástica/etiologia , Animais , Estudos de Casos e Controles , Criança , Análise Citogenética , DNA/biossíntese , Feminino , Deficiência de Ácido Fólico/fisiopatologia , Marcadores Genéticos , Código das Histonas , Histonas/sangue , Humanos , Macaca mulatta , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Wistar , Supressão Genética , Deficiência de Vitamina B 12/fisiopatologia
13.
Leuk Res ; 29(2): 119-21, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15607356

RESUMO

In erythroleukaemia megaloblastic changes can co-exist with leukaemic changes in the marrow. The cause of the disease must therefore be such as can cause megaloblastosis and at the same time be mutagenic. Failure of the thymidylate synthelase reaction, the commonest cause of megaloblastic anaemia, can be eliminated in erythroleukaemia because (a) the dU suppression test is normal in the disease and (b) failure of the thymidylate synthelase reaction is not mutagenic. The deamination of both cytosine and adenine is mutagenic but the deamination of cytosine alone is apparent and the nucleotide of cytosine is the prime mutagenic nucleotide in leukaemia and cancer. Megaloblastic changes can result from an inadequate supply of any one of the four nucleotides that enter into the composition of DNA and it is suggested that an inadequate supply of the mutagenic nucleotide of cytosine, possibly through impaired synthesis, could cause both the megaloblastic and leukaemic changes in erythroleukaemia.


Assuntos
Leucemia Eritroblástica Aguda/etiologia , Medula Óssea/enzimologia , Medula Óssea/metabolismo , Medula Óssea/patologia , DNA/metabolismo , Humanos , Leucemia Eritroblástica Aguda/patologia , Megaloblastos/metabolismo , Megaloblastos/patologia , Mutagênese , Nucleotídeos/metabolismo , Timidilato Sintase/metabolismo
14.
Indian J Pathol Microbiol ; 46(2): 228-30, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15022920

RESUMO

Refractory anemia with excess blasts in transformation (RAEB-t) in young adults is a rare entity. RAEB-t presenting with megaloblastic erythropoiesis should be differentiated from nutritional B12 and folic acid deficiency and from acute erythroleukemia. We report two cases in the present article.


Assuntos
Anemia Refratária com Excesso de Blastos/patologia , Adulto , Anemia Refratária com Excesso de Blastos/sangue , Anemia Refratária com Excesso de Blastos/diagnóstico , Eritropoese , Deficiência de Ácido Fólico/diagnóstico , Humanos , Leucemia Eritroblástica Aguda/diagnóstico , Masculino , Megaloblastos/patologia , Deficiência de Vitamina B 12/diagnóstico
16.
Sante ; 9(5): 301-4, 1999.
Artigo em Francês | MEDLINE | ID: mdl-10657774

RESUMO

We report three cases of pernicious anemia diagnosed in women in Africa. All three women had macrocytic anemia with megaloblasts evident on medullogram. The patients had neurological signs of combined sclerosis and the presence of megaloblasts confirmed the diagnosis of pernicious anemia. All were successfully treated parenterally with vitamins. This disease seems to be underdiagnosed in Africa given the number of cases reported in previous studies.


Assuntos
Anemia Perniciosa/diagnóstico , Adulto , Idoso , Anemia Perniciosa/tratamento farmacológico , Anemia Perniciosa/patologia , Feminino , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico/diagnóstico , Deficiência de Ácido Fólico/tratamento farmacológico , Humanos , Megaloblastos/patologia , Esclerose , Transtornos das Sensações/diagnóstico , Vitamina B 12/uso terapêutico , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico
18.
Br J Haematol ; 95(1): 73-6, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8857941

RESUMO

Four patients with congenital dyserythropoiesis characterized by marked macrocytosis, little or no anaemia, and vitamin B12- and folate-independent megaloblastic erythropoiesis are reported. Their erythroblasts also showed various dysplastic changes but not those diagnostic for congenital dyserythropoietic anaemia (CDA) types I or III. The haematological features of the four patients, who included two siblings, resemble those of a previously reported patient and together these patients form a recognizable subgroup within those cases of CDA not belonging to CDA types I-III. In two of the cases studied, and possibly a third, the inheritance was as an autosomal recessive character.


Assuntos
Eritropoese , Doenças Hematológicas/congênito , Adulto , Anemia Diseritropoética Congênita/diagnóstico , Criança , Eritropoese/fisiologia , Feminino , Ácido Fólico/fisiologia , Doenças Hematológicas/patologia , Humanos , Masculino , Megaloblastos/patologia , Vitamina B 12/fisiologia
19.
Med Pediatr Oncol ; 26(4): 249-53, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8600336

RESUMO

Two children who had the Rothmund-Thomson syndrome and developed osteosarcoma are reported. The 10 previously reported cases are reviewed. The osteosarcomas developed at a younger age than normally expected and 66% occurred in the tibia/fibula. Four of the five patients for whom information was available showed undue sensitivity to cancer chemotherapy agents with prolonged myelosuppression and severe mucositis. It is recommended that doxorubicin in particular should be given with extreme caution in such patients.


Assuntos
Neoplasias Ósseas/complicações , Osteossarcoma/complicações , Síndrome de Rothmund-Thomson/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Eritropoese/efeitos dos fármacos , Humanos , Masculino , Megaloblastos/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Rádio (Anatomia)/patologia , Síndrome de Rothmund-Thomson/patologia , Tíbia/patologia
20.
Br J Haematol ; 91(4): 783-94, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8547119

RESUMO

In order to develop a non-isotopic quantitative assay of granulocyte colony-stimulating factor (G-CSF) receptors on human or murine cells, we devised a flow-cytometric assay using cells stained with biotin-labelled G-CSF (b-G-CSF) and a streptavidin-RED670 conjugate. For quantification, we applied the Kolmogorov-Smirnov test and calculated the D value. The D value was evaluated from the degree of shift in two fluorescence profiles according to the increase of fluorescence intensity due to the specific binding of b-G-CSF to G-CSF receptors. A good correlation was observed between the number of G-CSF receptors obtained by the radioisotopic binding assay and the number calculated from the D value by the flow-cytometric assay. Then, expression of G-CSF receptors on human bone marrow cells, peripheral blood granulocytes and blast cells from patients with acute myeloid leukaemia (AML) were studied. G-CSF receptors was expressed on CD34+CD33-, CD34+CD33+ and CD34-CD33+ cells in the following order: CD34-CD33+ > CD34+CD33+ > CD34+CD33- cells, indicating that the receptors increased with maturation. The receptor levels of CD34-CD33+ cells in bone marrow were apparently lower than those of CD34-CD33+ cells in peripheral blood granulocytes. On the other hand, an abnormal expression pattern of G-CSF receptors was noted in AML blast cells.


Assuntos
Leucemia Mieloide/metabolismo , Megaloblastos/química , Receptores de Fator Estimulador de Colônias de Granulócitos/metabolismo , Doença Aguda , Diferenciação Celular/fisiologia , Separação Celular , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Granulócitos/química , Granulócitos/imunologia , Humanos , Leucemia Mieloide/patologia , Megaloblastos/imunologia , Ligação Proteica , Ensaio Radioligante , Estatísticas não Paramétricas
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