RESUMO
BACKGROUND: The general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms and QoL in COVID-19 survivors shortly after hospital discharge. METHODS: This was a cross-sectional analysis of a prospective study of hospitalized COVID-19 survivors followed up for 2 months after discharge. A battery of standardized instruments evaluating neurocognitive function, psychiatric morbidity and QoL (mental and physical components) was administered by telephone. RESULTS: Of the 229 screened patients, 179 were included in the final analysis. Amongst survivors, the prevalence of moderately impaired immediate verbal memory and learning was 38%, delayed verbal memory (11.8%), verbal fluency (34.6%) and working memory (executive function) (6.1%), respectively. Moreover, 58.7% of patients had neurocognitive impairment in at least one function. Rates of positive screening for anxiety, depression and post-traumatic stress disorder were 29.6%, 26.8% and 25.1%, respectively. In addition, 39.1% of the patients had psychiatric morbidity. Low QoL for physical and mental components was detected in 44.1% and 39.1% of patients respectively. Delirium and psychiatric morbidity were associated with neurocognitive impairment, and female gender was related with psychiatric morbidity. CONCLUSION: Hospitalized COVID-19 survivors showed a considerable prevalence of neurocognitive impairment, psychiatric morbidity and poor QoL in the short term. It is uncertain if these impacts persist over the long term.
Assuntos
COVID-19/psicologia , Transtornos Cognitivos/etiologia , Transtornos da Memória/etiologia , Qualidade de Vida , Sobreviventes/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Estudos Transversais , Depressão/etiologia , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/etiologia , Adulto JovemRESUMO
Transplantation using hematopoietic stem cells from umbilical cord blood (UCB) is a life-saving treatment option for patients with select oncologic diseases, immunologic diseases, bone marrow failure, and others. Often this transplant modality requires cryopreservation and storage of hematopoietic stem cells (HSC), which need to remain cryopreserved in UCB banks for possible future use. The most widely used cryoprotectant is dimethylsulfoxide (Me(2)SO), but at 37 degrees C, it is toxic to cells and for patients, infusion of cryopreserved HSC with Me(2)SO has been associated with side effects. Freezing of cells leads to chemical change of cellular components, which results in physical disruption. Reactive oxygen species (ROS) generation also has been implicated as cause of damage to cells during freezing. We assessed the ability of two bioantioxidants and two disaccharides, to enhance the cryopreservation of UCB. UCB was processed and subjected to cryopreservation in solutions containing different concentrations of Me(2)SO, bioantioxidants and disaccharides. Samples were thawed, and then analysed by: flow cytometry analysis, CFU assay and MTT viability assay. In this study, our analyses showed that antioxidants, principally catalase, performed greater preservation of: CD34+ cells, CD123+ cells, colony-forming units and cell viability, all post-thawed, compared with the standard solution of cryopreservation. Our present studies show that the addition of catalase improved the cryopreservation outcome. Catalase may act on reducing levels of ROS, further indicating that accumulation of free radicals indeed leads to death in cryopreserved hematopoietic cells.
Assuntos
Antioxidantes/farmacologia , Preservação de Sangue/métodos , Criopreservação/métodos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Catalase/farmacologia , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Dissacarídeos/farmacologia , Sangue Fetal/citologia , Sangue Fetal/efeitos dos fármacos , Citometria de Fluxo , Humanos , Células-Tronco/efeitos dos fármacos , Sacarose/farmacologia , Trealose/farmacologiaRESUMO
INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Nomogramas , Pirrolidinas/uso terapêutico , Trifluridina/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Intervalo Livre de Progressão , Pirrolidinas/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Espanha , Taxa de Sobrevida , Timina , Trifluridina/efeitos adversos , Uracila/efeitos adversos , Uracila/uso terapêuticoRESUMO
Bone marrow transplantation (BMT) is a therapeutic procedure that involves transplantation of hematopoietic stem cells (HSC). To date, there are three sources of HSC for clinical use: bone marrow; mobilized peripheral blood; and umbilical cord blood (UCB). Depending on the stem cell source or type of transplantation, these cells are cryopreserved. The most widely used cryoprotectant is dimethylsulfoxide (Me(2)SO) 10% (v/v), but infusion of Me(2)SO-cryopreserved cells is frequently associated with serious side effects in patients. In this study, we assessed the use of trehalose and sucrose for cryopreservation of UCB cells in combination with reduced amounts of Me(2)SO. The post-thawed cells were counted and tested for viability with Trypan blue, the proportion of HSC was determined by flow cytometry, and the proportion of hematopoeitic progenitor cells was measured by a colony-forming unit (CFU) assay. A solution of 30mmol/L trehalose with 2.5% Me(2)SO (v/v) or 60mmol/L sucrose with 5% Me(2)SO (v/v) produced results similar to those for 10% (v/v) Me(2)SO in terms of the clonogenic potential of progenitor cells, cell viability, and numbers of CD45(+)/34(+) cells in post-thawed cord blood cryopreserved for a minimum of 2 weeks. Thus, cord blood, as other HSC, can be cryopreserved with 1/4 the standard Me(2)SO concentration with the addition of disaccharides. The use of Me(2)SO at low concentrations in the cryopreservation solution may improve the safety of hematopoietic cell transplantation by reducing the side effects on the patient.
Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Sacarose/farmacologia , Trealose/farmacologia , Linhagem Celular , Sobrevivência Celular , Ensaio de Unidades Formadoras de Colônias , Dimetil Sulfóxido/farmacologia , Feminino , Humanos , Células K562 , GravidezRESUMO
INTRODUCTION: Retinopathy of prematurity (ROP) is the first cause of childhood blindness in Argentina and is reaching epidemic proportions. To gain greater insight into the issues involved in this epidemic, we analyzed the characteristics of the infants referred for treatment of very severe ROP to the Dr. Juan P. Garrahan Pediatric Hospital, located in the city of Buenos Aires. METHODS: We performed a retrospective study of patients referred for ROP from 01/01/96 to 12/31/03. Very severe ROP was defined as threshold disease or worse in both eyes, plus disease in zones 1 or 2, or Rush disease. Unusual patients were defined as those with very severe ROP with a gestational age (GA) of > 31 weeks or birth weight (BW) > 1500 g. Patients were divided into two groups according to the distance between the referring center and our hospital: group A consisted of those from nearby areas (
Assuntos
Países em Desenvolvimento , Retinopatia da Prematuridade , Argentina/epidemiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/terapia , Estudos RetrospectivosRESUMO
Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009-2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5-8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3-4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.
Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Atenção à Saúde/estatística & dados numéricos , Atenção à Saúde/tendências , Previsões , Saúde Global/estatística & dados numéricos , Saúde Global/tendências , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , América Latina , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation.
Assuntos
Saúde Global/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Inquéritos e Questionários , Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Humanos , Transplante de Células-Tronco de Sangue Periférico , Doadores de Tecidos , Transplante Haploidêntico , Transplante HomólogoRESUMO
Normal and leukemic blood cell progenitors depend upon the bone marrow (BM) stroma with which they communicate through soluble and membrane-anchored mediators, adhesive interactions and gap junctions (GJ). Regarding hematopoiesis, it is believed that it can be influenced by connexin expression, but the exact role of GJ in cell death and proliferation is not clear. Using flow cytometry, we monitored the division rate of leukemic cell lines, communicating and not communicating with stromal cell line through GJ. We found that GJ-coupled cells (i) did not proliferate; (ii) were kept in G0; and (iii) were protected from drug-induced apoptosis when compared to either total or uncoupled cell population. We conclude that GJ coupling between stroma and leukemic lymphoblasts prevents proliferation, keeping cells in a quiescent state, thus increasing their resistance to antimitotic drugs. Since GJ are particularly abundant in the sub-endosteal environment, which harbors blood stem cells, we also asked which cells within the normal human BM communicate with the stroma. Using a primary BM stroma cell culture, our results show that 80% of CD34+ progenitors communicate through GJ. We propose that blood cell progenitors might be retained in the low-cycling state by GJ-mediated communication with the hematopoietic stroma.
Assuntos
Apoptose , Células da Medula Óssea/citologia , Comunicação Celular , Junções Comunicantes/fisiologia , Leucemia/patologia , Células Estromais/fisiologia , Antígenos CD34/análise , Divisão Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Células-Tronco Hematopoéticas/química , Células-Tronco Hematopoéticas/fisiologia , Humanos , Metotrexato/toxicidade , Fase de Repouso do Ciclo Celular , Células Estromais/citologia , Células Estromais/ultraestruturaRESUMO
We describe a case of allograft rejection that occurred 23 months after successful bone marrow transplantation for severe aplastic anemia in a patient with paroxysmal nocturnal hemoglobinuria. The allograft rejection appears to have been induced by recombinant alpha-interferon (rINF-alpha) treatment for non-A, non-B hepatitis that developed 11 months after transplantation. During the 9 months of active hepatitis, the donor graft functioned normally; however, 3 months after rINF-alpha therapy was started, pancytopenia and a chimeric hematopoietic state developed. rINF-alpha was discontinued, cyclosporin A was reintroduced, and autologous bone marrow recovery followed. rINF-alpha treatment may be detrimental to some recipients of allogeneic bone marrow transplants.
Assuntos
Transplante de Medula Óssea , Rejeição de Enxerto , Hemoglobinúria Paroxística/terapia , Hepatite Crônica/terapia , Interferon-alfa/efeitos adversos , Adulto , Transplante de Medula Óssea/efeitos adversos , Ciclosporina/uso terapêutico , Feminino , Hepatite Crônica/etiologia , HumanosRESUMO
We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 x 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3), acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transfusão de Linfócitos/normas , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Causas de Morte , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Efeito Enxerto vs Leucemia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Transfusão de Linfócitos/efeitos adversos , Transfusão de Linfócitos/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão/métodos , Prevenção Secundária , Quimeras de TransplanteRESUMO
A t(11;14)(p15;q11) was the sole chromosome abnormality observed in the malignant cells of a 10-year-old boy with acute leukemia. Morphologically, these cells were classified as L1 by the criteria of the French-American-British Working Group. Cytochemical analysis revealed that the leukemic cells were negative for Sudan Black B, periodic acid Schiff, and esterases, and positive for acid phosphatase. Immunophenotyping disclosed that the cells expressed a very immature antigenic profile [CD34+, CD7+, cytoplasmic CD3+, membrane CD3-, CD4-, and CD8-]. In spite of very intensive chemotherapy, complete remission was never induced, and the child died of progressive disease. The relationship of this case to other reported cases of acute leukemia arising from immature pluripotent hematopoietic cells is discussed.
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Leucemia-Linfoma de Células T do Adulto/genética , Translocação Genética , Antígenos CD/análise , Antígenos CD7 , Antígenos de Diferenciação de Linfócitos T/análise , Antígenos CD4/análise , Antígenos CD8/análise , Criança , Humanos , Imunofenotipagem , MasculinoRESUMO
The immunological reconstitution that follows bone marrow transplantation (BMT) was studied in 40 leukaemia patients: 19 with chronic myeloid leukaemia (CML), 12 with acute myeloid leukaemia (AML) and the remaining 9 with acute lymphoblastic leukaemia (ALL). The recovery of the CML group was slower than that of the ALL and AML groups. This difference was produced by the T cell compartment, as NK cell activity and B cell numbers did not differ significantly. Factors such as conditioning treatment and graft versus host disease (GVHD) prophylaxis were analysed. Our experience suggests that all leukaemia patients should not be considered as one group when analysing their immunological reconstitution, as factors related to the original disease may affect their outcome.
Assuntos
Transplante de Medula Óssea/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Linfócitos T/fisiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Células Matadoras Naturais/fisiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
Ex vivo expansion and manipulation of human mesenchymal stem cells are important approaches to immunoregulatory and regenerative cell therapies. Although these cells show great potential for use, issues relating to their overall nature emerge as problems in the field. The need for extensive cell quantity amplification in vitro to obtain sufficient cell numbers for use, poses a risk of accumulating genetic and epigenetic abnormalities that could lead to sporadic malignant cell transformation. In this study, we have examined human mesenchymal stem cells derived from bone marrow, over extended culture time, using cytogenetic analyses, mixed lymphocyte reactions, proteomics and gene expression assays to determine whether the cultures would retain their potential for use in subsequent passages. Results indicate that in vitro cultures of these cells demonstrated chromosome variability after passage 4, but their immunomodulatory functions and differentiation capacity were maintained. At the molecular level, changes were observed from passage 5 on, indicating initiation of differentiation. Together, these results lead to the hypothesis that human mesenchymal stem cells cultures can be used successfully in cell therapy up to passage 4. However, use of cells from higher passages would have to be analysed case by case.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco Mesenquimais/citologia , Células da Medula Óssea/citologia , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , Instabilidade Cromossômica , Cromossomos/fisiologia , Análise Citogenética , Perfilação da Expressão Gênica , Humanos , Linfócitos/imunologia , Linfócitos/metabolismo , ProteômicaRESUMO
Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Metilprednisolona/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Infliximab , Leucemia/mortalidade , Leucemia/cirurgia , Masculino , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Aberrações Cromossômicas , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Rearranjo Gênico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Criança , Pré-Escolar , Terapia Combinada , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgiaRESUMO
A multicentric randomized trial was undertaken to compare the toxicity of amphotericin B in 5% dextrose with that of amphotericin B in a fat emulsion (Intralipid) in cancer patients. Group 1 (n = 33) received amphotericin B diluted in 5% dextrose with premedication consisting of promethazine plus an antipyretic. Group 2 (n = 28) received amphotericin B diluted in 20% Intralipid without premedication. Amphotericin B was infused daily at a dose of 1 mg/kg of body weight over a 1-h period to members of both groups for empirical antifungal therapy (in neutropenic patients) or for the treatment of documented fungal infections. The majority of patients (80%) received empirical amphotericin B treatment. The two groups were comparable with regard to age, gender, underlying disease, and the following baseline characteristics: use of other nephrotoxic drugs and serum levels of potassium and creatinine. The median cumulative doses of amphotericin B were 240 mg in group 1 and 245 mg in group 2 (P = 0.73). Acute adverse events occurred in 88% of patients in group 1 and in 71% of those in group 2 (P = 0.11). Forty percent of the infusions in group 1 were associated with fever, compared to 23% in group 2 (P < 0.0001). In addition, patients in group 2 required less meperidine for the control of acute adverse events (P = 0.008), and fewer members of this group presented with hypokalemia (P = 0.004) or rigors (P < 0.0001). There was no difference in the proportions of patients with nephrotoxicity (P = 0.44). The success rates of empirical antifungal treatment were similar in the two groups (P = 0.9). Amphotericin B diluted in a lipid emulsion seems to be associated with a smaller number of acute adverse events and fewer cases of hypokalemia than amphotericin B diluted in 5% dextrose.
Assuntos
Anfotericina B/efeitos adversos , Emulsões Gordurosas Intravenosas/administração & dosagem , Glucose/administração & dosagem , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Idoso , Anfotericina B/administração & dosagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
Twenty-nine patients with severe aplastic anaemia (SAA) were submitted to bone marrow transplantation (BMT) and their immunological recovery analysed. Total lymphocyte counts, estimation of B lymphocytes, T lymphocytes and their subsets, natural-killer (NK) activity were performed. Cells with the CD8+ phenotype and NK activity were the first signs of immunological recovery, whereas the CD4+ subset recovered later in patients who suffered from acute graft versus host disease (GvHD) and infections. Acute and chronic GvHD, cirrhosis, rejection and HIV viral infection contributed to the persistence of the profound immunodeficiency status observed after BMT. Our results did not differ greatly from the others and confirmed that BMT may be performed in underdeveloped countries despite the difficulties it might pose.
Assuntos
Anemia Aplástica/imunologia , Anemia Aplástica/terapia , Transplante de Medula Óssea/imunologia , Adulto , Anemia Aplástica/epidemiologia , Linfócitos B/imunologia , Linfócitos B/patologia , Transplante de Medula Óssea/patologia , Brasil/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Masculino , Fenótipo , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
BACKGROUND: PBSC transplant provides 10 times more T cells than BMT However, the incidence and severity of acute GvHD is similar among recipients of both types of transplants. Studies in mouse models suggest that the similar clinical outcome in BMT and PBSCT is due to differences in the lymphokine profiles. METHODS: PBMC, PBMC from G-CSF mobilized donors (G-PBMC)and BM mononuclear cells (BM-MC) were analyzed by flow cytometry and ELISA to detect gamma-IFN and IL-4 production. Hematoxylin and eosin staining was used to identify morphology and annexin/propidium-iodide was used for apoptosis assays. RESULTS: We show decreased production of gamma-interferon (85%) and IL-4 (60%) in G-PBMC when compared with either PBMC or BM-MCT cells on ex vivo assays. Surprisingly, 85% of fresh G-PBMC is composed of low-density granulocytes (LDG), which undergo apoptosis after 48 h in culture. At this same time, gamma-IFN production from G-PBMC T cell was reverted. In vitro, G-CSF converts granulocytes into LDGs, able to inhibit T-cell function by H2O2 production, and not through immune-deviation towards a Th2-type phenotype. DISCUSSION: We show that the estimated numbers of Th1 and Th2 cells infused in BMT and PBSCT do not differ significantly. These findings are discussed with reference to the relatively low incidence of acute GvHD in PBSCT shown in the literature. We suggest that these results might depend on the high number of granulocytes and progenitors infused. The potential use of granulocytes as immunosupressive short-term therapy is now being investigated by our group using a mouse experimental model.