RESUMEN
We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.
Asunto(s)
Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Ceftazidima/uso terapéutico , Cefalosporinas/uso terapéutico , Fiebre/complicaciones , Fiebre/tratamiento farmacológico , Neoplasias Hematológicas/complicaciones , Neutropenia/complicaciones , Neutropenia/tratamiento farmacológico , Amicacina/administración & dosificación , Amicacina/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Bacteriemia/diagnóstico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Cefepima , Ceftazidima/administración & dosificación , Ceftazidima/efectos adversos , Cefalosporinas/administración & dosificación , Cefalosporinas/efectos adversos , Farmacorresistencia Microbiana , Quimioterapia Combinada , Femenino , Enfermedades Gastrointestinales/microbiología , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , Masculino , Enfermedades Cutáneas Bacterianas/diagnóstico , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones Urinarias/diagnósticoRESUMEN
Human autorosette-forming cells (auto-RFC), which represent a T4/leu 3a+ cell subset, were investigated for their functional role in T-cell activation. Peripheral blood lymphocytes from healthy subjects either remained unfractionated or were separated into recovered or depleted auto-RFC populations. The phytohemagglutinin P stimulation of these three cell suspensions induced normal levels of proliferation, whereas the pokeweed mitogen activation was significantly decreased in the auto-RFC-depleted population compared to the auto-RFC-recovered subset or unfractionated cells. All three cell suspensions produced IL-2 in response to PHA stimulation. However the levels of lymphokine released were significantly lower in the recovered auto-RFC fraction than in the depleted auto-RFC. After activation, using anti-Tac antibodies, the synthesis of IL-2 receptors was evidenced in all the cell fractions regardless of the presence or absence of auto-RFC. In addition, both auto-RFC absorbed IL-2 activity from a reference supernatant. Taken together, these data suggest that auto-RFC can be expanded by T-cell mitogens, and that once activated, they express IL-2 receptors, but represent a minor source of IL-2 production.
Asunto(s)
Activación de Linfocitos , Formación de Roseta , Linfocitos T/inmunología , Separación Celular , Humanos , Técnicas de Inmunoadsorción , Interleucina-2/biosíntesis , Interleucina-2/metabolismo , Fitohemaglutininas/farmacología , Mitógenos de Phytolacca americana/farmacología , Receptores Inmunológicos/biosíntesis , Receptores de Interleucina-2 , Linfocitos T/clasificación , Linfocitos T/metabolismoRESUMEN
Spontaneous rosette formation in humans is restricted to a subpopulation of the circulating T cells. We have previously shown that the interaction between lymphocytes and autologous red blood cells (auto-RBC) is not mediated by a self-recognition mechanism, since allogeneic (allo-) RBC bind to T cells through the same receptors. In this work, we have extended these observations to thymocytes. Using a mixed-rosette assay in which one type of erythrocyte was identified by FITC labeling, we have shown that almost all the thymocytes which attached auto-RBC could also fix allo-RBC. However, as for the peripheral blood lymphocytes (PBL), binding of human RBC to thymocytes occurred with varying affinities according to the erythrocyte's origin. In order to further study the specificity of the erythrocyte to lymphocyte binding in rosette formation, PBL were mixed with auto-RBC and erythrocytes of xenogeneic (xeno-) origin. Although very disparate incidences of rosettes were found according to the species from which the RBC were derived, most of the autorosetting lymphocytes also had receptors for xeno-RBC. In addition, preincubation of PBL with monoclonal antibody OKT11A (directed against the sheep RBC receptors on T cells) completely abrogated rosette formation with all the erythrocytes tested (human auto- and allo-, sheep, pig, and rabbit) except mouse RBC. Taken together these data strongly suggest that human auto- or allo-, as well as sheep or some other xeno-RBC, bind to T lymphocytes by a single receptor and that the combining sites are expressed with different densities or varying affinities depending upon the RBC's origin. Therefore, spontaneous autorosettes may represent T lymphocytes having high-affinity receptors for sheep RBC.
Asunto(s)
Eritrocitos/metabolismo , Receptores de Antígenos de Linfocitos T/análisis , Formación de Roseta , Linfocitos T/metabolismo , Animales , Anticuerpos Monoclonales/fisiología , Unión Competitiva , Cobayas , Humanos , Ratones , Ratas , Receptores de Antígenos de Linfocitos T/inmunología , Formación de Roseta/métodos , Ovinos , Especificidad de la Especie , Porcinos , Linfocitos T/clasificación , Linfocitos T/inmunología , Timo/metabolismoRESUMEN
Spontaneous autorosette formation has been described as being restricted to a subpopulation of the circulating helper/inducer T cell subset. In order to study the specificity of the binding between human lymphocytes and autologous red blood cells (auto-RBC), we have investigated the relationship between autorosette forming cells (auto-RFC) and rosettes formed with allogeneic (allo-) or xenogeneic (xeno-) RBC. Using a mixed rosette assay in which the origin of the erythrocytes was assessed by the FITC labeling of one type of erythrocyte, we have shown that auto-RFC and allo-RFC belong to the same T cell subset, and that the T cells which rosette with auto-RBC can also bind xenogeneic (pig, sheep, rabbit) RBC, although a disparate incidence of rosettes is found depending upon the origin of the erythrocytes. Whether T lymphocytes co-expressed distinct receptors for RBC of different species was then investigated. Preincubation of lymphocytes with monoclonal antibody OKT11A (directed against the T cell receptors for sheep RBC) completely abrogated rosette formation with auto- or allo-RBC, indicating that auto- and allo-RBC interact with the lymphocytes by their receptors for sheep RBC. Therefore, the auto-RFC may represent T lymphocytes having high affinity receptors for sheep RBC.
Asunto(s)
Formación de Roseta , Linfocitos T/inmunología , Anticuerpos Monoclonales , Eritrocitos/inmunología , Humanos , Receptores Inmunológicos/inmunología , Linfocitos T/clasificación , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
The relationship between autorosettes and allorosettes was investigated using a mixed rosette assay in which the origin of the erythrocytes was assessed by the fluorescein isothiocyanate (FITC) labeling of one type of erythrocyte. The data show that auto- and allorosettes belong to the same T-cell subset: in most of the subjects, the percentages of T cells binding autologous red blood cells (auto-RBC) are equivalent to those binding allogeneic RBC (allo-RBC); the percentage of rosettes formed after the simultaneous addition of auto- and allo-RBC is similar to that of autorosettes alone or allorosettes alone; and nearly 80% of the rosetting cells bind both types of RBC as directly visualized in the mixed rosette assay. The experiments in which the lymphocytes are rosetted first with one type of RBC, and then with the other type support the finding that auto- and allo-RBC may bind to the lymphocytes through a single receptor which exhibits a varying affinity for RBC according to their origin.
Asunto(s)
Eritrocitos/inmunología , Formación de Roseta , Linfocitos T/inmunología , Fluoresceínas , Humanos , Especificidad de la EspecieRESUMEN
Autologous rosette-forming cells (auto-RFC) were characterized with monoclonal antibodies to various cell surface antigens using a technique combining immunofluorescence and rosette formation. In peripheral blood, auto-RFC were T cells (Leu 1+/OKT3+) the majority being derived from the helper/inducer subset (Leu 3a+/OKT4+). A small proportion of the circulating auto-RFC were Leu 2a+/OKT8+ and virtually none of them bore T10, T6, and DR antigens or peanut agglutinin (PNA) receptors. In the elderly, the percentages of Leu 3a+ auto-RFC increased significantly along with the augmentation of the Leu 3a+ circulating pool. After Con A stimulation of peripheral blood lymphocytes the autorosette population was expanded and therefore their phenotype was again that of helper cells. In the thymus, high levels of autorosettes are found (30 to 50%). Simple or double labeling of the rosetting cells with various monoclonal antibodies permitted the confirmation of the existence of distinct thymocyte subpopulations and moreover to identify the location of the auto-RFC in the intrathymic differentiation scheme. Nearly 70% of the rosetting cells were derived from common thymocytes, those cells defined by the coexpression of T10, T6, T4, and T8 antigens whether or not they were also stained by OKT3 antibodies. The remaining auto-RFC were found with similar frequency among the T4+ and T8+ mature thymocytes. In the spleen low percentages of auto-RFC were found and the majority resided in the Leu 3a+/OKT4+ population, similarly to peripheral blood autorosettes. Taken together, these data suggest that the expression of autologous erythrocyte receptors is acquired in the thymus and is gradually lost during T-cell maturation.
Asunto(s)
Envejecimiento , Antígenos de Superficie/análisis , Formación de Roseta , Linfocitos T/inmunología , Adulto , Anciano , Animales , Anticuerpos Monoclonales/inmunología , Diferenciación Celular , Femenino , Humanos , Activación de Linfocitos , Masculino , Ratones , Persona de Mediana Edad , Fenotipo , Receptores de Antígenos de Linfocitos T/análisis , Bazo/citología , Bazo/inmunología , Bazo/fisiología , Linfocitos T/citología , Linfocitos T/fisiología , Timo/citología , Timo/inmunología , Timo/fisiologíaRESUMEN
The phenotype of autorosette forming cells (A-RFC) in the peripheral blood of normal subjects was analyzed. Using a fluorescent technique in which the rosetting cells are labeled with different monoclonal antibodies directed against various cell surface antigens, we demonstrated that A-RFC are T cells, the majority of which belong to the helper/inducer subset. Nevertheless, about 10% of the A-RFC bear the Leu 2a antigens, which are specific for cytotoxic/suppressor T cells. On the other hand, no autorosettes were identified by OKT6 or anti-DR antibodies. When autologous and allogeneic red blood cells were added simultaneously to lymphocytes, 78% mixed rosettes were formed, suggesting a lack of specificity in autorosette formation. A functional role for A-RFC in the autologous mixed lymphocyte reaction (A-MLR) is demonstrated by the fact that the removal of A-RFC from the responder population abrogated the proliferative response in A-MLR. Therefore, despite their non restriction, A-RFC may represent an autoreactive T cell subset.