RESUMO
PURPOSE: To correlate the presence of p53 mutations and initial characteristics, response to chemotherapy, and survival in newly diagnosed Burkitt's lymphoma (BL) and Burkitt's acute lymphoblastic leukemia (L3 ALL). PATIENTS AND METHODS: Forty-eight patients with newly diagnosed BL or L3 ALL, most of whom were treated with very intensive regimens, including early CNS disease treatment, were studied. Detection of p53 mutations was made by single-strand conformation polymorphism (SSCP) analysis of exons 5 to 8 of the gene, and mutations were determined by direct sequencing of exons with abnormal SSCP findings. Comparison of outcome between mutated and nonmutated cases was made in all patients and also after excluding five patients who received therapeutic regimens considered as suboptimal and one patient who died of AIDS while in complete remission (CR), as those six patients had no p53 mutations. RESULTS: A point mutation was found in nine patients (19%), and consisted of a missense mutation in seven and a chain-terminating mutation in two. SSCP, sequence, and cytogenetic analysis strongly suggested that eight of nine patients with mutations had retained the normal p53 allele, which had been lost in the remaining patient. These findings were confirmed by fluorescence-in-situ hybridization (FISH) with a p53-specific probe in two patients, including the one who had lost the normal p53 allele. Unexpectedly, mutations were significantly less frequent in patients with disseminated disease, ie, L3 ALL or stage IV BL (four of 35, 11%), than in more localized forms, ie, BL stage I, II, or III (five of 13, 38%) (P = .03). CR rates were similar in mutated (78%) and nonmutated cases (78%). The actuarial disease-free interval (DFI) after 12 months and actuarial survival rates after 24 months were 49% and 66%, respectively, in patients with mutations, and 73% and 48%, respectively, those without mutations. The differences were not significant. CONCLUSION: Our findings suggest that, contrary to what is seen in most other neoplasias, p53 mutations in newly diagnosed BL and L3 ALL are not associated with extensive tumor mass or poor response to intensive therapeutic regimens. It is hypothesized that this difference with most tumors could be due to the fact that p53 mutations in BL and L3 ALL are generally associated with persistence of a normal residual p53 allele, contrary to what is observed in the majority of tumors.
Assuntos
Linfoma de Burkitt/genética , Genes p53/genética , Mutação Puntual , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Análise Atuarial , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sequência de Bases , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Taxa de SobrevidaRESUMO
BACKGROUND: Pentoxifylline (PTX), a methylxantine phosphodiesterase inhibitor commonly used to treat peripheral vascular disease, has been shown to decrease the production of proinflammatory cytokines and reactive oxygen species and to reduce the toxic effects of cyclosporine. Thus, administration of PTX to transplant patients, as an adjunct to immunosuppressive therapy, could prevent numerous posttransplantation complications. METHODS: One hundred forty consecutive patients receiving cadaveric kidney grafts were registered in a randomized double-blind study comparing PTX at a dose of 800 mg/day, then 1200 mg/day, versus placebo during the first 6 months after transplantation. All patients were followed up for 1 year. RESULTS: Rejection episodes were validated as the only independent risk factor for graft loss in this study. We compared graft survival rates in each group according to the presence or absence of acute rejection. Acute rejection reduced graft survival in the control group (graft survival rate at 1 year, 59% vs. 97%, P < 0.001), but this adverse effect was blunted in the PTX group (72% vs. 89%, NS). This improvement was confirmed by multivariate analysis for risk factors, with graft survival rates being described at best as the interaction between rejection and treatment (PTX vs. placebo, P = 0.045). CONCLUSION: Although PTX does not modify the incidence of any posttransplant complications, it weakens the consequences of rejection on graft survival.
Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim , Pentoxifilina/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Vasodilatadores/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Transplante de Rim/patologia , Transplante de Rim/fisiologia , Masculino , Análise Multivariada , Placebos , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de TempoAssuntos
Hipertensão Portal/etiologia , Transplante de Rim , Complicações Pós-Operatórias , Adulto , Azatioprina/uso terapêutico , Infecções por Citomegalovirus/etiologia , Varizes Esofágicas e Gástricas/etiologia , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Hepacivirus/isolamento & purificação , Prótese de Quadril , Humanos , Hipertensão Portal/fisiopatologia , Transplante de Rim/imunologia , Transplante de Rim/patologia , Masculino , Metilprednisolona/uso terapêutico , Reação em Cadeia da Polimerase , Diálise Renal , Esplenectomia , Fatores de TempoAssuntos
Rejeição de Enxerto/terapia , Transplante de Rim/imunologia , Muromonab-CD3/efeitos adversos , Obstrução da Artéria Renal/etiologia , Trombose/etiologia , Adulto , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Humanos , Transplante de Rim/patologia , Transplante de Rim/fisiologia , Masculino , Metilprednisolona/uso terapêutico , Muromonab-CD3/uso terapêutico , Prednisona/uso terapêutico , Transplante HomólogoRESUMO
This study, which included 153 heart transplant patients, was designed to determine whether the cytomegalovirus (CMV) status of both donor and recipient may influence graft rejection. The follow-up was 1 year and they all received the same triple-drug immunosuppressive regimen with induction (antilymphocyte serum). There was no difference in the total rejection rate, but an increase in repeated rejection rate was shown in transplant recipients with hearts from CMV seropositive donors (P < 0.05). These data strongly suggest the impact of CMV in enhancement but not in induction of rejection. To prevent iterative rejection in the CMV seropositive donor group, antiviral therapy could be proposed during enhancement of antirejection therapy.
Assuntos
Infecções por Citomegalovirus/complicações , Rejeição de Enxerto/etiologia , Transplante de Coração/efeitos adversos , HumanosRESUMO
Ischemia/reperfusion has been implicated in the mechanism of delayed graft function (DGF). Pentoxifylline (PTX) has been shown to suppress TNF alpha (released by activated macrophages, inhibiting subsequent superoxide anion release from neutrophil activation. In addition, PTX decreases cyclosporine (CsA) induced renal endothelial release and vasoconstriction. Thus, administration of PTX to renal transplant patient could be an excellent approach to prevent DGF and vascular toxicity of CsA in the early graft period. One hundred-and-forty consecutive patients receiving cadaveric kidney transplantation were registered in a randomized double-blind study comparing PTX vs. a placebo. PTX had no demonstrable effect on the incidence of DGF, on the rapidity of the renal function recovery, and on the ability to use higher doses of CsA in the first month post-graft.
Assuntos
Isquemia/prevenção & controle , Transplante de Rim/fisiologia , Pentoxifilina/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Vasodilatadores/uso terapêutico , Adulto , Cadáver , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Transplante de Rim/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Placebos , Superóxidos/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vasoconstritores/efeitos adversosRESUMO
We describe the case of a 60 year old man with primary amyloidosis, who suffered from peripheral neuropathy and cardiomyopathy and who presented with recurrent right pleural effusion. For this reason, he was admitted to hospital for thoracoscopic examination with pleurodesis. Macroscopic examination of the parietal pleura revealed a diffuse inflammation and light brown deposits that where covered with nodules. Biopsy specimens confirmed the amyloid deposition. This macroscopic appearance is described for the first time, and suggests that a local pleural synthesis of amyloid substance may occur during the course of systemic amyloidosis.