RESUMO
Malignant lymphoma and other lymphoproliferative disorders represent a group of malignant hemopathies where immunotherapy has allowed spectacular progresses over the last ten years. The recent W.H.O. classification, based upon tumor immunology, and cytogenetical anomalies, allows a better identification of each lymphoma and the comparison of homogeneous populations within various clinical studies. The increase in the incidence of non-Hodgkin lymphoma is related to the aging of the population as well as to other factors that are still to be analysed - a real challenge for the future. We have tried to offer an overview of the latest therapeutical advances while focusing on the major role of general practitioner. The most frequency askeed questions will be discussed.
Assuntos
Drogas em Investigação/uso terapêutico , Clínicos Gerais , Linfoma/terapia , Papel do Médico , Humanos , Linfoma/patologia , Padrões de Prática Médica , Terapias em Estudo/métodosRESUMO
We describe a symptomatic Plasmodium falciparum infection in a 29-year-old Guinean man receiving Infliximab for one year and without recent travel. The reactivation of submicroscopic malaria following the inhibition of TNF-alpha by infliximab is suspected.
Assuntos
Infliximab/efeitos adversos , Malária Falciparum/etiologia , Adulto , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Masculino , Plasmodium falciparum , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
This study investigates the pathophysiology of mucormycosis caused by Rhizopus, which has been reported in 46 dialysis patients, while treated with deferoxamine (DFO). This drug aggravates mucormycosis, which we experimentally induced in guinea pigs and which lead to a shortened animal survival (P < or = 0.01). The drug's effect on Rhizopus is not mediated through the polymorphonuclear cells. Fe.DFO, the iron chelate of DFO, abolishes the fungistatic effect of serum on Rhizopus and increases the in vitro growth of the fungus (P < or = 0.0001). This effect is present at Fe.DFO concentrations > or = 0.01 microM, at which fungal uptake of radioiron from 55Fe.DFO is observed. A 1,000-fold higher concentration of iron citrate is required to achieve a similar rate of radioiron uptake and of in vitro growth stimulation as observed with Fe.DFO. These in vitro effects of Fe.DFO (1 microM) in serum on radioiron uptake and on growth stimulation are more striking for Rhizopus than for Aspergillus fumigatus and are practically absent for Candida albicans. For these three fungal species, the rates of radioiron uptake from 55Fe.DFO and of growth stimulation in the presence of Fe.DFO in serum are directly related (r = 0.886). These results underscore the major role of Fe.DFO in the pathogenesis of DFO-related mucormycosis. Pharmacokinetic changes in uremia lead to a prolonged accumulation of Fe.DFO after DFO administration, which helps explain the increased sensitivity of dialysis patients to DFO-related mucormycosis.
Assuntos
Desferroxamina/efeitos adversos , Desferroxamina/farmacologia , Mucormicose/etiologia , Neutrófilos/fisiologia , Diálise Renal , Rhizopus/crescimento & desenvolvimento , Animais , Fenômenos Fisiológicos Sanguíneos , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candidíase/fisiopatologia , Cobaias , Humanos , Técnicas In Vitro , Mucormicose/fisiopatologia , Neutrófilos/microbiologia , Rhizopus/citologia , Rhizopus/efeitos dos fármacos , Esporos Fúngicos/fisiologiaRESUMO
This case report describes the evolution of a mycosis fungoides into a Sézary syndrome. The originality of the case consists in the appearance of ascitis with Sézary cells during the leukemic phase. It is the second report of a such case. Mycosis fungoides and its leukemic variant, the Sézary syndrome, are primary cutaneous T-cell lymphomas. Their incidence is low. The treatments are topical in the early stages and systemic during the advanced stages. New immunomodulating treatments are in development. The existing therapeutic agents unfortunately do not improve the prognosis of the disease today.
Assuntos
Ascite/etiologia , Síndrome de Sézary/complicações , Neoplasias Cutâneas/complicações , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Prognóstico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
A new method for measuring the uptake of Staphylococcus aureus by human polymorphonuclear neutrophils (PMN) using flow cytometry (FCM) is described. Bacteria were labeled with fluorescein isothiocyanate (FITC) and incubated with PMN in a suspension assay. At the end of the assay, phagocytosis was arrested by the addition of cold paraformaldehyde. Thereafter, phagocytosis was quantitated by FCM, using crystal violet to distinguish adherent versus ingested bacteria. The method was validated in multiple samples by reference to our microscopic technique; correlations of phagocytic indices were in good agreement. The FCM method was also found to be reproducible and provided a mean to detect low phagocyte values. Another feature of the approach is that FCM readings can be delayed without any appreciable alterations in the results.
Assuntos
Citometria de Fluxo , Fluoresceínas , Formaldeído , Fagocitose , Polímeros , Staphylococcus aureus/imunologia , Tiocianatos , Fluoresceína-5-Isotiocianato , Violeta Genciana/farmacologia , Humanos , Neutrófilos/imunologiaRESUMO
In view of the increasing need to assess the proliferative activity of hematologic malignancies, slide-based methods to quantify the proliferating cell nuclear antigen (PCNA) were developed and evaluated. Two techniques to evaluate this antigen were adapted to the infiltration level of the disease. The first one is particularly appropriate to massive invasion and is based on the alkaline phosphatase-antialkaline phosphatase complex (APAAP)method. The second one is reversed for reduced infiltration and uses a double immunofluorescence labeling. One is specific for the target cell to be identified and the other one is specific for the PCNA. These techniques permit an easy and accurate routine evaluation of cell cycle marker expression in hematologic malignancies.
Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/análise , Medula Óssea/patologia , Leucemia/patologia , Mieloma Múltiplo/patologia , Proteínas Nucleares/análise , Divisão Celular , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Cinética , Leucócitos Mononucleares/patologia , Antígeno Nuclear de Célula em ProliferaçãoRESUMO
We report the case of a 70 years old woman who developed a thrombotic thrombocytopenic purpura. Despite a treatment with corticoids and high doses IV gammaglobulins, the patient developed seizures. Treatment with plasma exchanges combined with plasma infusions allowed recovery. The authors review the clinical and biological aspects as well as the pathogeny of the disease. The authors insist on the importance of the plasma exchanges in the treatment of this disease.
Assuntos
Púrpura Trombocitopênica Trombótica/terapia , Idoso , Contagem de Células Sanguíneas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Infecções/complicações , Neoplasias/complicações , Troca Plasmática , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/etiologiaRESUMO
OBJECTIVES: The aim of our study was to evaluate the clinical values of anti-beta2 glycoprotein I antibodies (anti-beta2GPI) IgG and IgM comparing with lupus anticoagulant (LA), anticardiolipin antibodies (aCL) in the two clinical groups of antiphospholipid syndrome (APS), vascular thrombosis (VT) and pregnancy morbidity (PM). METHODS: Eighty patients who fulfilled the APS clinical criteria, VT nâ=â34; PM nâ=â40, both VT and PM nâ=â6 were included. LA, aCL and three anti-beta2GPI ELISA kits were tested. RESULTS: Sensitivities of LA, aCL and anti-beta2GPI assays were found respectively 62, 26 and 41% in VT, and 28, 28 and 30% in PM. The sensitivity for the APS diagnosis could reach to 63% using triple tests. The presence of LA (P<0·01, ORâ=â4·3) or anti-beta2GPI IgG alone (P<0·05, ORâ=â8·4) was significantly associated with VT. IgM isotype was found more frequent in PM (92%) than in VT (57%) among all positive anti-beta2GPI cases. CONCLUSION: Both IgG and IgM anti-beta2GPI assays were useful when clinical features of APS presented, even its standardization is ongoing. A decreased by half sensitivity of LA in PM compared with that in VT underlines the importance of adding anti-beta2GPI in PM of APS, especially IgM isotype although recent review questioned its significance.
Assuntos
Síndrome Antifosfolipídica/diagnóstico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Complicações na Gravidez/diagnóstico , Trombose/diagnóstico , beta 2-Glicoproteína I/imunologia , Adulto , Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Biomarcadores/sangue , Feminino , Humanos , Inibidor de Coagulação do Lúpus/sangue , Masculino , Valor Preditivo dos Testes , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia , Trombose/sangue , Trombose/imunologiaAssuntos
Antineoplásicos Fitogênicos/efeitos adversos , Hipertensão Pulmonar/induzido quimicamente , Linfoma Relacionado a AIDS/tratamento farmacológico , Paclitaxel/efeitos adversos , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Homossexualidade Masculina , Humanos , Masculino , Paclitaxel/uso terapêutico , Derrame Pericárdico , Derrame PleuralRESUMO
Accurate measurements of bacteria concentrations are required in numerous studies; they raise methodological problems that complicate, for instance, the investigations of polymorphonuclear neutrophil functions. We propose a new flow cytometric method of determining bacteria concentrations by comparison with a standardized fluorescent latex bead solution. Relative counts of beads and bacteria are established in a system using both fluorescence and light scatter for the two types of particles. On the one hand, the latex bead size (0.98 microns in diameter) permits counting on traditional hematological counters and, on the other, a flow cytometric detection with the same conditions for bacteria. The reproducibility of the study of bacteria concentration measurements gave a coefficient of variation of < 5%.
Assuntos
Bactérias , Neutrófilos/fisiologia , Técnicas Bacteriológicas , Citometria de Fluxo/métodos , Humanos , Látex , MicroesferasRESUMO
Increased risk that patients with iron overload who are undergoing dialysis will have bacteremia caused by Yersinia enterocolitica has previously been shown. Iron overload is known to increase the virulence of Y. enterocolitica. Whether alterations of the phagocyte defense against this organism are also involved has not yet been determined. We compared neutrophil defense against a serum-resistant strain of Y. enterocolitica in three groups of individuals: nine patients receiving hemodialysis who had iron overload (group 1), nine patients receiving hemodialysis who did not have iron overload (group 2), and 10 healthy controls (group 3). Y. enterocolitica phagocytosis and killing were studied in the presence of autologous or pooled normal human serum. Phagocytosis was significantly decreased in group 1 compared with that in the other two groups. The use of normal serum for opsonization did not improve the phagocytosis function. Killing was moderately decreased in the group 1, but only in the presence of autologous serum. We conclude that in patients with iron overload who are undergoing dialysis, the high frequency of Yersinia bacteremia is attributable not only to increased virulence of this microorganism but also to disturbances of the mechanisms specifically involved in the neutrophil defense against Yersinia invasion.
Assuntos
Atividade Bactericida do Sangue , Ferro/sangue , Neutrófilos/fisiologia , Diálise Renal/efeitos adversos , Yersinia enterocolitica/fisiologia , Humanos , Fagocitose , Fatores de TempoRESUMO
Protein aggregates, red cell or white cell fragments are known to interfere with platelet counts in automated blood analysers, both by aperture impedance and optical technologies. When a falsely high value is suspected, interference by pseudo-platelet particles can be confirmed by systematic examination of stained blood films. The method that best avoids these sources of interference is the reference, immunological platelet count. We describe a case of treated malaria with a false normal platelet count. The blood smear revealed small red cells, infected by trophozoites of Plasmodium falciparum, that interfered with the platelet count. The Cell Dyn 4000 shows different patterns of interference by infected red cells in its impedance and optical counts, and thrombocytopenia was suspected immediately. This was confirmed by a phase-contrast microscopic platelet count.
Assuntos
Malária/sangue , Contagem de Plaquetas/métodos , Adulto , Anticorpos Monoclonais/análise , Plaquetas/imunologia , Eritrócitos/microbiologia , Eritrócitos/patologia , Reações Falso-Positivas , Humanos , Masculino , Contagem de Plaquetas/instrumentação , Contagem de Plaquetas/normasRESUMO
Treatment of average-risk acute lymphoblastic leukaemia (ALL) in children consists of 6 months of intensive chemotherapy followed by 18 months of maintenance therapy. Polymorphonuclear leucocyte (PMN) functions from children with ALL were studied in order to evaluate and compare the toxicity of the initial intensive treatment with the toxicity of the subsequent less intensive maintenance treatment. H2O2 and O2- production, evaluated by chemiluminescence, were significantly decreased during the intensive period but returned to normal values when maintenance therapy began. In contrast, bactericidal activity against Gram-positive and Gram-negative microorganisms remained at low levels throughout the treatment but returned to normal values in patients off chemotherapy. PMN from patients on maintenance therapy exhibited an excess of morphological changes associated with apoptosis. This was confirmed by standard two-colour flow cytometry which revealed an increase in the number of hypodiploid cells, and increased expression of membrane phosphatidylserine together with a drastic reduction in the expression of the Fcgamma receptor IIIB (CD16). These defective PMN were differentially sensitive to the effects of granulocyte colony stimulating factor (G-CSF): G-CSF induced similar increase in chemiluminescence in control and patient PMN; GSF partially corrected the defective bactericidal activity; G-CSF did not affect the accelerated PMN apoptosis. These observations indicate that ALL children undergoing chemotherapy present PMN defective functions which are partially sensitive or even resistant to G-CSF.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Neutrófilos/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adolescente , Sobrevivência Celular , Criança , Pré-Escolar , Escherichia coli/imunologia , Humanos , Medições Luminescentes , Ativação de Neutrófilo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Explosão Respiratória , Staphylococcus aureus/imunologiaRESUMO
The aims of the present study are: first, to assess the toxic role of serum from thalassemic patients in phagocytosis of PMN from healthy controls, and second, to seek to determine whether serum and cellular disturbances of polymorphonuclear neutrophils (PMN) phagocytosis, observed in thalassemic patients, can be prevented and/or corrected by use of desferrioxamine (DFX). Two kinds of in vitro incubations--without or with DFX--were performed. PMN or serum from thalassemic patients or from healthy controls was used. First, a phagocytosis defect of 3 different bacteria species was induced in PMN from healthy controls by incubation in thalassemic serum. Second, DFX could prevent, already at 1 microM, the phagocytic defect induced in normal PMN by the incubation with thalassemic serum, with disappearance of the toxic role of thalassemic serum at higher concentrations. Third, improvement of the phagocytosis defect of PMN from thalassemic patients was also observed at 1 microM of DFX for the 3 bacteria species. Normalization was obtained at higher concentrations for gram-negative bacteria. In vivo studies revealed, after a 3 hr subcutaneous infusion of DFX into 3 thalassemic patients, an improvement of the phagocytosis results and a decrease of the Prussian Blue reactivity of the PMN. It is concluded first that an iron-mediated defect in phagocytosis can be induced in normal neutrophils by incubation in serum from thalassemic patients, and second that a precautious and intensive chelation therapy seems to be advantageous for increasing PMN defense against infectious agents. Special care must nevertheless be taken in order to detect rapidly opportunistic (such as Yersinia) infections.
Assuntos
Desferroxamina/farmacologia , Neutrófilos/fisiologia , Fagocitose/efeitos dos fármacos , Talassemia/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neutrófilos/efeitos dos fármacos , Disfunção de Fagócito Bactericida/etiologia , Disfunção de Fagócito Bactericida/prevenção & controle , Talassemia/sangue , Talassemia/patologiaRESUMO
Iron overload increases the risk of bacterial infection in dialysis patients, partly by impairing functions of the polymorphonuclear granulocytes (PMNs). PMN defence was studied sequentially in haemodialysis patients with transfusional haemosiderosis, treated for 6 +/- 1.5 months (n = 8) to 13 +/- 1.7 months (n = 4) with recombinant human erythropoietin (rHuEpo). Over this period, signs of iron overload (increased serum ferritin and serum iron) improved, and stainable iron disappeared in PMNs. Simultaneously, phagocytosis of Yersinia enterocolitica by PMNs improved. The decrease in serum ferritin was significantly related to the improved phagocytosis. Killing of Y. enterocolitica by PMNs also improved. It is anticipated that rHuEpo therapy in iron-overloaded dialysis patients could decrease the incidence of bacterial infection by improving PMN functions in these patients.
Assuntos
Atividade Bactericida do Sangue/efeitos dos fármacos , Eritropoetina/uso terapêutico , Ferro/sangue , Neutrófilos/fisiologia , Diálise Renal/efeitos adversos , Adulto , Idoso , Infecções Bacterianas/prevenção & controle , Feminino , Hemossiderose/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fagocitose/efeitos dos fármacos , Proteínas Recombinantes/uso terapêutico , Yersinia enterocolitica/imunologiaRESUMO
The phagocytosis of blood polymorphonuclear cells (PMNs) was measured by cytofluorometry in 22 patients with inflammatory rheumatic diseases before and after a 60-day treatment with 45 mg zinc daily or a placebo, and the values were compared with those obtained in a group of healthy subjects. Plasma zinc was lower than controls before supplementation and phagocytosis assessed by the percentage of PMNs exhibiting phagocytic activity was significantly impaired. Zinc supplementation increased the percentage of phagocytic PMNs and the mean phagocytic activity, particularly in subjects with initial low phagocytosis. The impairment of PMN phagocytosis could therefore be corrected by zinc supplementation, but the clinical consequence of this stimulant effect remains unknown.
Assuntos
Gluconatos/uso terapêutico , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Doenças Reumáticas/tratamento farmacológico , Zinco/uso terapêutico , Administração Oral , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Método Duplo-Cego , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/imunologia , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/imunologiaRESUMO
The susceptibility to infections was recorded in 13 patients with beta thalassaemia major (T.P.). The following parameters were also investigated in their polymorphonuclear neutrophils (PMN): nitro blue tetrazolium (NBT) reduction, heated yeast and Escherichia coli phagocytosis, Escherichia coli killing and myeloperoxydase activity. These results were compared to those obtained in healthy controls (H.C.). The Perls's reaction was performed on PMN and graded according to a scoring system with the aim of quantifying the iron intoxication of PMN. Phagocytosis and Perls's reaction of PMN from H.C. were also studied after 20 h of incubation with thalassaemic serum. 6 T.P. out of 13 developed septicaemia during their lifetime and in all 9 septicaemic episodes were noted. Phagocytosis was greatly impaired, disclosing both cellular and serum abnormalities. The mean percentage of Perls's positive PMN was 13% in T.P., contrasting with the constant negative reaction in H.C. The incubation of PMN from H.C. with serum from T.P. induced the simultaneous appearance of a phagocytosis defect and of a positive Perl's reaction. It was concluded that in beta thalassaemia major the phagocytosis of PMN was altered due to a combination of serum and cellular abnormalities and that both may be related to the iron overload.
Assuntos
Ferro/metabolismo , Neutrófilos/fisiologia , Talassemia/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Infecções/etiologia , Masculino , Neutrófilos/metabolismo , Fagocitose , Talassemia/sangue , Talassemia/complicaçõesRESUMO
To analyze the toxicity associated to chemotherapy upon granulocytes, different functional assays were performed, within days of drug exposure and at time of bone marrow recovery, on polymorphonuclear neutrophils (PMN) from children with cancer. There were no significant postchemotherapy changes in the expression of the different receptors studied nor in the phagocytosis of Staphylococcus aureus 42D. By contrast, a significant decrease was observed in H2O2 production in PMN recently exposed to chemotherapy with both cytofluorometric and chemiluminescence assays. There was also a decrease in the production of O2- and in chemotaxis; finally, the intracellular killing of S. aureus 42D and Escherichia coli was reduced. In patients having recovered from drug-induced bone marrow aplasia, PMN functions were found to be normal except for bactericidal activity which was still defective. The observations indicate that, in patients exposed to chemotherapy, some PMN functions are transiently altered, whereas microorganism cell killing is continuously impaired.
Assuntos
Antineoplásicos/efeitos adversos , Granulócitos/efeitos dos fármacos , Granulócitos/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia , Adolescente , Atividade Bactericida do Sangue/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Quimiotaxia de Leucócito/efeitos dos fármacos , Criança , Pré-Escolar , Escherichia coli/imunologia , Feminino , Granulócitos/imunologia , Humanos , Peróxido de Hidrogênio/metabolismo , Técnicas In Vitro , Masculino , Neoplasias/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/fisiologia , Fagocitose/efeitos dos fármacos , Receptores de Complemento/efeitos dos fármacos , Receptores de Complemento/metabolismo , Receptores de IgG/efeitos dos fármacos , Receptores de IgG/metabolismo , Explosão Respiratória/efeitos dos fármacos , Staphylococcus aureus/imunologia , Superóxidos/metabolismoRESUMO
Granulocyte colony-stimulating factor (G-CSF) has important direct and priming effects on different functions of normal mature polymorphonuclear leukocytes (PMNL). Previous study has shown an alteration in respiratory burst and bactericidal activities of PMNL harvested from children with cancer treated with chemotherapy. The present study evaluates the possibility that recombinant human (rh) G-CSF could correct these defective functions in vitro. Free radical formation in defective PMNL was enhanced by rhG-CSF to a level similar to that found in normal PMNL primed by rhG-CSF. The defective bactericidal activity against Escherichia coli and Staphylococcus aureus was also corrected. This bactericidal activity was not different from that observed in normal PMNL primed by rhG-CSF. In conclusion, correction of the altered free radical-formation pathway by rhG-CSF in these cells contributed to the restoration of normal bactericidal activity against both gram-positive and gram-negative microorganisms.