Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
1.
Infection ; 40(1): 81-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21779887

RESUMO

A 59-year-old male with acute lymphoblastic leukemia developed sinus, tracheobroncheal, pulmonary, and intracerebral aspergillosis. All lesions except the intracerebral aspergillosis healed after combination antifungal treatment. Long-term voriconazole--but not posaconazole--therapy induced partial regression of the cerebral manifestations. At the time of writing, 3.5 years after the initial diagnosis, the patient is working half-time and suffers from a possible voriconazole-induced polyneuropathy.


Assuntos
Antifúngicos/uso terapêutico , Neuroaspergilose/tratamento farmacológico , Neuroaspergilose/microbiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/microbiologia , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/isolamento & purificação , Encéfalo/diagnóstico por imagem , Encéfalo/microbiologia , Encéfalo/patologia , Caspofungina , Cérebro/diagnóstico por imagem , Cérebro/microbiologia , Cérebro/patologia , Equinocandinas/administração & dosagem , Equinocandinas/uso terapêutico , Humanos , Laringe/diagnóstico por imagem , Laringe/microbiologia , Laringe/patologia , Lipopeptídeos , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Pulmão/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/microbiologia , Seios Paranasais/patologia , Doenças do Sistema Nervoso Periférico/microbiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Suécia , Tomografia Computadorizada por Raios X , Triazóis/administração & dosagem , Triazóis/uso terapêutico , Voriconazol
2.
Leukemia ; 21(3): 511-4, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17215854

RESUMO

Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor 'first dose' reactions. All 5 patients responded with a >or=2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4-7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2-12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/complicações , Idoso , Alemtuzumab , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/cirurgia , Anemia Hemolítica Autoimune/terapia , Anticorpos Monoclonais Humanizados , Antígenos CD/imunologia , Antígenos de Neoplasias/imunologia , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Sangue , Antígeno CD52 , Clorambucila/administração & dosagem , Clorambucila/uso terapêutico , Terapia Combinada , Ciclofosfamida/administração & dosagem , Avaliação de Medicamentos , Resistência a Medicamentos , Glicoproteínas/imunologia , Hemoglobinas/análise , Humanos , Imunossupressores/uso terapêutico , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/imunologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Esplenectomia , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vincristina/administração & dosagem
3.
Leukemia ; 7(9): 1324-7, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8371582

RESUMO

The effect of human recombinant erythropoietin (rhEPO) was investigated in 29 anemic patients with myelodysplastic syndromes (MDS). A rhEPO dosage of 150 U/kg was administered subcutaneously three times weekly for a minimum of 6 weeks. Seven out of 27 evaluable patients (26%) had an effective clinical response to therapy by increasing hemoglobin concentrations by more than 15 g/l (reaching at least 105 g/l) or by eliminating transfusion requirements. Six out of the seven patients responded within four weeks. Three of the responders successfully continued rhEPO treatment 15 months or more. To determine whether it may be possible to predict response to rhEPO, various clinical parameters were examined. Responders were found to be significantly different from non-responders in five aspects: They had less elevated baseline serum EPO levels (92 +/- 33 versus 515 +/- 108 U/l, mean +/- SEM; p = 0.023) and were more often transfusion-independent (71% versus 20% of non-responders; p = 0.022). Furthermore, responders were more often females (71% versus 40% in the non-responding group; p = 0.025), of subtype RA rather than RAEB (four patients and one patient, respectively, compared to seven and nine patients in the non-responding group; p = 0.025), and they predominantly displayed normal karyotypes or a 5q- aberration (86% versus 47%; p = 0.005). We conclude, that rhEPO treatment can reduce anemia in MDS and that certain pre-treatment clinical parameters may be used to predict response.


Assuntos
Eritropoetina/uso terapêutico , Síndromes Mielodisplásicas/terapia , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária/terapia , Transfusão de Sangue , Deleção Cromossômica , Cromossomos Humanos Par 5 , Eritropoetina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/genética , Valor Preditivo dos Testes , Prognóstico , Proteínas Recombinantes/uso terapêutico , Fatores Sexuais
4.
Leukemia ; 18(1): 41-7, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14574334

RESUMO

Bmf is a BH3-only Bcl-2 family member that is normally sequestered to myosin V motors by binding to the dynein light chain 2 (DLC2). Certain damage signals release Bmf, which then binds prosurvival Bcl-2 proteins and triggers apoptosis. Here, two novel isoforms of human Bmf, Bmf-II and Bmf-III, were identified and cloned from cDNA derived from B-chronic lymphocytic leukemia (B-CLL) cells. Bmf-II and Bmf-III were characterized as two splice variants, lacking the BH3 domain but retaining the DLC2 binding domain. Bmf (here called Bmf-I) expression in HeLa cells induced apoptosis and reduced colony formation in contrast to Bmf-II and Bmf-III, which had no effect on apoptosis and instead increased colony formation. While bmf-I mRNA was expressed in many cell types, expression was higher in B lymphoid cells and bmf-II and bmf-III were mainly detected in B-CLL and normal B cells. bmf-I mRNA was upregulated in normal and leukemic B cells, while bmf-III mRNA was downregulated only in B-CLL cells by serum deprivation. We show that Bmf is regulated by transcriptional activation and alternative splicing and conclude that the relative levels of Bmf isoforms may have a role in regulating growth and survival in B cells and leukemic B-CLL cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Apoptose , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Regulação Neoplásica da Expressão Gênica , Leucemia Linfocítica Crônica de Células B/metabolismo , Processamento Alternativo , Linfócitos B/metabolismo , Sequência de Bases , Células Cultivadas , Meios de Cultura Livres de Soro , DNA Complementar/genética , DNA Complementar/metabolismo , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Dados de Sequência Molecular , Isoformas de Proteínas , RNA Mensageiro/metabolismo , Homologia de Sequência do Ácido Nucleico , Transcrição Gênica , Transfecção
5.
Leukemia ; 15(12): 1868-77, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11753607

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent activator of the cell death pathway and exerts tumoricidal activity in vivo with minimal toxicity. In order to investigate the therapeutic potential of TRAIL in B chronic lymphocytic leukemia (B-CLL) we have analyzed the expression of TRAIL receptors (TRAIL-Rs) in leukemic cells from B-CLL patients and their in vitro sensitivity to apoptosis induced by recombinant human TRAIL. We have found TRAIL-R1 and -R2 death receptor, and TRAIL-R3 and -R4 decoy receptor mRNA expression in most of the 57 B-CLL patients studied (R1 82%, R2 100%, R3 96% and R4 82%). TRAIL-R1 and R2 proteins were expressed on the surface and within the cells, whereas R3 and R4 decoy receptors were almost exclusively expressed in the cytoplasm. Despite TRAIL death receptor expression, B-CLL cells were relatively resistant to induction of apoptosis by recombinant human TRAIL (300 ng/ml). However, the susceptibility to TRAIL-induced apoptosis was increased by treatment of B-CLL cells with actinomycin D (Act D). Western blot analysis showed higher constitutive expression of the long form of FLICE-inhibitory protein (FLIP(L)) in B-CLL as compared to normal tonsillar B cells. Act D treatment down-regulated both long and short FLIP expression, which was correlated with the increase in B-CLL sensitivity to TRAIL. Although the surface TRAIL death receptor expression was up-regulated both by cell culture and by Act D treatment, the changes were not correlated with a gain in susceptibility to TRAIL. In addition, neither decoy receptors nor Bcl-2 expression were affected by Act D. Our findings suggest the possible involvement of FLIP in regulating TRAIL-mediated apoptosis in B-CLL.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Transporte/efeitos dos fármacos , Dactinomicina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Leucemia Linfocítica Crônica de Células B/patologia , Glicoproteínas de Membrana/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Sinergismo Farmacológico , Feminino , Proteínas Ligadas por GPI , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Receptores do Fator de Necrose Tumoral/metabolismo , Membro 10c de Receptores do Fator de Necrose Tumoral , Ligante Indutor de Apoptose Relacionado a TNF , Receptores Chamariz do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/genética
6.
Leukemia ; 17(9): 1827-33, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12970783

RESUMO

In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels

Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Tioguanina/uso terapêutico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Anemia Refratária com Excesso de Blastos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transformação Celular Neoplásica , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Tioguanina/efeitos adversos
7.
Cell Prolif ; 34(6): 369-78, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11737001

RESUMO

Intracellular nitric oxide levels may differ in resting and stimulated cells and contribute to the regulation of cell survival and proliferation through a variety of mechanisms and effects. We exposed two B-cell lines to a range of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) concentrations in order to examine their susceptibility to exogenous nitric oxide and the participation of nitric oxide as modulator of cell proliferation. Although both FLEB and NALM-6 decreased their levels of thymidine incorporation, only NALM-6 cells were induced to undergo G1 arrest, phosphatidyl serine exposure and DNA fragmentation when cultured in the presence of 250 microm SNAP. This higher sensitivity of NALM-6 coincided with initially low cyclin E protein levels which were increased 7.8-fold after culture for 24 h with 250 microm SNAP. In contrast, there was no difference in cyclins A and D3, Bcl-2 and actin levels, neither at the beginning nor at the end of the 24 h culture. Our study reveals that FLEB and NALM-6 exhibit different response to the same concentration of nitric oxide, that nitric oxide can simultaneously induce cell cycle alterations and apoptosis, and further suggests an association between these two processes, with the involvement of cell cycle regulatory molecules.


Assuntos
Apoptose , Ciclina E/biossíntese , Leucemia/metabolismo , Leucemia/patologia , Óxido Nítrico/metabolismo , Penicilamina/análogos & derivados , Actinas/biossíntese , Linfócitos B/patologia , Western Blotting , Ciclo Celular , Separação Celular , Ciclina A/biossíntese , Ciclina D3 , Ciclinas/biossíntese , Fragmentação do DNA , Citometria de Fluxo , Fase G1/efeitos dos fármacos , Penicilamina/farmacologia , Fosfatidilserinas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Timidina/metabolismo , Fatores de Tempo , Células Tumorais Cultivadas
8.
Semin Oncol ; 30(2): 226-30, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12720141

RESUMO

Waldenstrom's macroglobulinemia (WM) is in the World Health Organization (WHO) classification considered to be a clinical syndrome rather than a specific pathologic diagnosis. The clinical manifestations associated with WM relate to direct tumor infiltration, hyperviscosity, and deposition of IgM in various tissues. The indications for and choice of treatment vary considerably and no generally accepted prognostic models exist. The clinical features, treatment, and prognosis of 72 patients with WM seen at one British (n = 36) and one Swedish (n = 36) academic center were therefore compared. Significantly more patients presented with a low albumin concentration (< v > 40 g/L, P <.001), anemia (hemoglobin < v > 120 g/L; P <.001), thrombocytopenia (< v > 150 x 10(9)/L; P <.05), hepatomegaly (P <.001), splenomegaly (P <.01), and lymphadenopathy (P <.01), at St Bartholomew's Hospital (SBH) in comparison to the Karolinska Hospital (KH). Fifty-six percent of SBH patients received chemotherapy immediately following diagnosis as compared to 14% at KH. The median overall survival of all patients was 6.3 years; 4.2 years and 11.0 years at SBH and KH, respectively (P <.001). In univariate analysis, anemia (hemoglobin < 120 g/L) and albumin < 35 g/L (but not <40 g/L) at diagnosis predicted a worse overall survival. The presence of hepatomegaly and/or splenomegaly and/or lymphadenopathy was significantly associated with anemia (P <.001) and hypoalbuminaemia (P <.001). The mean Morel score (including age, albumin, and cytopenias) of patients treated at SBH (2.6) was significantly higher than that of KH patients (1.6; P <.001). These findings illustrate the clinical heterogeneity of WM, most probably explained by differences in referral patterns, and in addition, indicate the need for establishing standard criteria for diagnosis, response to treatment, and prognostic features.


Assuntos
Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/mortalidade
9.
Br J Pharmacol ; 120(4): 702-6, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9051311

RESUMO

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.


Assuntos
Colo/metabolismo , Mucosa Gástrica/metabolismo , Óxido Nítrico/biossíntese , Nervo Vago/fisiologia , Animais , Colo/inervação , Estimulação Elétrica , Feminino , Masculino , Microdiálise , Contração Muscular , Músculo Liso/inervação , Músculo Liso/metabolismo , Nitratos/análise , Nitritos/análise , Coelhos , Estômago/inervação
10.
J Appl Physiol (1985) ; 61(4): 1358-62, 1986 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3781951

RESUMO

The purpose of this study was to evaluate the effect of long-term anemia and subsequent retransfusion of erythrocytes on various circulatory parameters. Anemia was induced in nine healthy male subjects by repeated venesections. The stored blood was retransfused after 9 wk (range 8-11 wk). Exercise tests were performed before venesection in the control state (C), in the anemic state (A), and 48 h after retransfusion (R). Hemoglobin concentration levels were 146 +/- 10 g/l in C, 110 +/- 7 g/l in A, and 145 +/- 9 g/l in R. Maximal O2 uptake was 4.55 +/- 0.6, 3.74 +/- 0.7, and 4.45 +/- 0.6 l/min in C, A, and R, respectively. A decrease in heart rate of 7 beats/min (P less than 0.01) and in cardiac output of 2 l/min (P less than 0.05) at maximal exercise occurred in the anemic state compared with control values. These decreases were not reversed but, rather, were further accentuated after retransfusion. The adaptive response to submaximal exercise (cycling at 150-175 W) in anemia was mediated to the amount of 50% by an increase in cardiac output (mainly an increase in heart rate) and 50% was due to increased O2 extraction in the peripheral tissue. In conclusion, long-term anemia was found to decrease the heart rate and cardiac output at maximal exercise. Furthermore the close correlation between hemoglobin concentration and maximal O2 uptake in humans is confirmed.


Assuntos
Anemia/fisiopatologia , Circulação Sanguínea , Transfusão de Sangue , Esforço Físico , Débito Cardíaco , Hemodinâmica , Hemoglobinas/análise , Humanos , Masculino , Consumo de Oxigênio
11.
Int J Hematol ; 62(2): 117-20, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8590772

RESUMO

A 78-year-old male with Waldenström's macroglobulinemia was after 23 years of conservative treatment given fludarabine phosphate in 1993 because of disease progression. Three weeks after the third fludarabine course he presented with a 5-day-history of watery diarrhoea, nausea and vomiting. Stool cultures were negative but a semiquantitative electron microscopy method demonstrated massive amounts of astrovirus (> 10(14) particles/ml). Symptomatic treatment was given but since his condition deteriorated, high-dose intravenous immunoglobulin (IvIg) treatment, 0.4 g/kg for four days was initiated. Within twenty-four hours all symptoms disappeared and the patient was discharged after a few days. A stool sample collected after two weeks demonstrated 10(7) particles/ml and after four weeks no astrovirus could be detected. The association between fludarabine and this opportunistic infection and the potential role of high dose IvIg treatment are discussed.


Assuntos
Gastroenterite/terapia , Imunização Passiva , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Mamastrovirus , Infecções Oportunistas/terapia , Úlcera Péptica/complicações , Vidarabina/análogos & derivados , Viroses/terapia , Macroglobulinemia de Waldenstrom/complicações , Idoso , Gastroenterite/complicações , Gastroenterite/virologia , Humanos , Masculino , Mamastrovirus/isolamento & purificação , Infecções Oportunistas/complicações , Infecções Oportunistas/virologia , Vidarabina/uso terapêutico , Viroses/complicações , Viroses/virologia , Macroglobulinemia de Waldenstrom/tratamento farmacológico
12.
Leuk Lymphoma ; 27(5-6): 429-38, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9477124

RESUMO

Interleukin-2 (IL-2) activates natural killer (NK)-cells to destroy leukemic blasts from patients with acute myelogenous leukemia (AML), but even aggressive regimens of IL-2 fail to prevent relapse or prolong remission time in AML. Results obtained in studies of NK-cell-mediated killing of AML blasts show that monocytes inhibit IL-2-induced lysis of AML blasts in vitro. Histamine, a biogenic amine, prevents the monocyte-derived, inhibitory signal; thereby, histamine and IL-2 synergize to induce killing of AML blasts. Here we present updated results of a post-consolidation trial in which histamine (0.5-0.7 mg s.c. bid) has been administered together with IL-2 (1 micro/kg s.c. bid) to 22 AML patients (aged 29-79, mean 59) in repeated courses of three weeks, continued until relapse or until a disease-free remission of 24 months. Low-dose therapy with cytarabine and thioguanine was given between the initial courses of histamine/IL-2. In 13 patients, treatment according to this protocol was started in first complete remission (CR1). The mean remission time in CR1 patients is 19 (median 14) months, and 9/13 remain in CR. Nine patients have entered the protocol in CR2 (n=6), CR3 (n=2), or CR4 (n=1). The mean remission time in CR2-4 is 19 (median 21) months, and 6/9 patients remain in CR. Seven out of seven evaluable patients have achieved a duration of CR which exceeds that of the foregoing remission. Histamine has been well tolerated, and 21/22 CR patients have treated themselves at home throughout the trial. We conclude that the putative benefit of histamine treatment in AML should be the focus of a randomized trial.


Assuntos
Histamina/uso terapêutico , Imunoterapia/métodos , Interleucina-2/uso terapêutico , Leucemia Mieloide Aguda/terapia , Subpopulações de Linfócitos , Monócitos/fisiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comunicação Celular , Sinergismo Farmacológico , Feminino , Humanos , Interleucina-2/fisiologia , Células Matadoras Ativadas por Linfocina/fisiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Med Sci Sports Exerc ; 18(2): 156-61, 1986 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3702642

RESUMO

The purpose of the present study was to evaluate the effects of iron deficiency on enzyme activities and endurance. Iron deficiency was induced in 9 healthy male subjects by repeated venesections. After a period of 9 wk (range, 8-11 wk) when the subjects had become iron deficient as defined by laboratory parameters, blood was retransfused to reestablish the control hemoglobin concentration. In this state it was possible to evaluate the effect of iron deficiency isolated from anemia. In samples secured by muscle biopsies, glycolytic, oxidative, and iron depending enzymes were analyzed in the control (C) and anemic (A) states and after retransfusion (R). There were no significant changes in the maximal activities of any of the enzymes studied. The capillary/fiber ratio remained unchanged between C (1.92) and R (1.94). Times to exhaustion on treadmill tests were 49 min, 11 s in C, 26 min, 33 s in A, and 52 min, 3 s in R. Vo2max was 4.55 1 X min-1 in C, 3.74 1 X min-1 in A, and 4.45 1 X min-1 in R. An artificially induced iron deficiency defined by conventional laboratory parameters did not affect endurance when transfusion of red blood cells was performed in order to exclude the influence of a low hemoglobin concentration. A 4-wk period of severely depleted or absent tissue iron stores did not affect the maximal activities of various enzymes in human skeletal muscle.


Assuntos
Deficiências de Ferro , Músculos/enzimologia , Resistência Física , Adulto , Anemia Hipocrômica/sangue , Anemia Hipocrômica/fisiopatologia , Transfusão de Sangue Autóloga , Capilares/anatomia & histologia , Transfusão de Eritrócitos , Hemoglobinas/metabolismo , Humanos , Lactatos/sangue , Ácido Láctico , Masculino , Músculos/irrigação sanguínea , Consumo de Oxigênio , Fatores de Tempo
14.
Eur J Obstet Gynecol Reprod Biol ; 91(1): 41-2, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10817877

RESUMO

Acute promyelocytic leukaemia (APL) is characterised by a life-threatening hemorrhagic diathesis which is attributed to a DIC-like coagulopathy. This report describes the problems of childbirth in two patients with untreated APL. It is concluded that caesarean section can be performed without major complications. A prerequisite is an active treatment of the coagulopathy and a close collaboration between the obstetrician and the haematologist.


Assuntos
Cesárea , Leucemia Promielocítica Aguda/terapia , Complicações Neoplásicas na Gravidez/terapia , Adulto , Antineoplásicos/uso terapêutico , Transplante de Medula Óssea , Terapia Combinada , Feminino , Humanos , Leucemia Promielocítica Aguda/complicações , Equipe de Assistência ao Paciente , Gravidez , Transplante de Células-Tronco , Transplante Autólogo , Tretinoína/uso terapêutico
15.
Angiology ; 45(1): 43-8, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8285383

RESUMO

This study evaluates the effect of stepwise lowering of the hemoglobin (Hb) concentration on maximal walking distance (MWD) and hemodynamics in patients with intermittent claudication. The results in a study group (n = 6) were compared with those of a control group (n = 6) whose members were not subjected to venesections. An average decrease of Hb concentration from 151 +/- 4 to 121 +/- 3 g/L did not significantly influence MWD, the result being 282 +/- 62 meters before venesections and 255 +/- 54 meters after three to five (mean four) repeated venesections. Transcutaneous oxygen pressure was measured at the dorsum of the foot before and after exercise and did not change with a gradual decrease of the Hb concentration. Maximal heart rate, painfree walking distance, ankle pressure, and blood lactate concentration were also unchanged. An average venesection volume of about 1.4 liters whole blood within fourteen days, without isovolemic replacement, did not change the blood volume, which was 5.1 +/- 0.4 liters before and 5.0 +/- 0.5 liters after venesections. In conclusion, hemodilution accomplished by venesections did not have a clinically or physiologically beneficial effect in patients with severe intermittent claudication. However, hemodynamics and clinical symptoms were not affected by a considerable decrease in the arterial oxygen content within the normal Hb concentration range.


Assuntos
Sangria , Hemodiluição , Hemodinâmica/fisiologia , Hemoglobinas/análise , Claudicação Intermitente/fisiopatologia , Claudicação Intermitente/terapia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Caminhada
17.
Br J Cancer ; 97(6): 769-77, 2007 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-17726463

RESUMO

B-cell chronic lymphocytic leukaemia (B-CLL) is characterised by the progressive accumulation of monoclonal CD5(+) B cells. In a previous study, we have analysed the expression profile of apoptosis-regulating genes using a cDNA-based microarray and found overexpression of the antiapoptotic bcl-2 family member, bfl-1, in B-CLL cells with an apoptosis-resistant phenotype. In this study, bfl-1 mRNA levels have been determined by competitive PCR in an extended population of B-CLL patients to characterise its role in disease progression and development of chemoresistance. bfl-1 levels were significantly higher in patients with no response (NR) to last chemotherapy than in patients responding (partial response (PR)) to last chemotherapy (P<0.05) and in patients who had not required treatment (P<0.05). We found no correlation between bfl-1 mRNA levels and disease progression, IGHV mutational status or other clinical parameters. In addition, bfl-1 mRNA levels were inversely correlated with apoptotic response to in vitro fludarabine treatment of B-CLL cells. Specific downregulation of bfl-1 using siRNA induced apoptosis in resistant cells. Our data suggest that bfl-1 contributes to chemoresistance and might be a therapeutic target in B-CLL.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Vidarabina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Regulação para Cima/efeitos dos fármacos , Vidarabina/administração & dosagem , Vidarabina/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-3698991

RESUMO

The purpose of the present study was to examine to what degree a reduction in systemic oxygen transport capacity influences the absolute and relative levels (% of maximal oxygen uptake) of submaximal blood lactate accumulation. Anemia was induced by repeated venesections in eight healthy males. After 9-10 weeks of anemia, hemoglobin concentration [Hb] was restored by retransfusion of packed erythrocytes. The [Hb] values obtained were, before venesections, in control (C) = 145 +/- 10, in the anemic state (A) = 110 +/- 8, and after retransfusion (R) = 143 +/- 8 g X l-1 respectively. In all states, muscle biopsies were taken and measurements made of VO2max and VO2 at a running velocity corresponding to a blood lactate concentration of 4 mM (upsilon Hla 4.0). In the A condition Vo2max decreased by 19% as compared to C (P less than 0.01). upsilon Hla 4.0 was 14% lower in A as compared to C and R (p less than 0.01). VO2 at upsilon Hla 4.0 was 13% lower in A as compared to C (P less than 0.01). However, VO2 at upsilon Hla 4.0 expressed as a percentage of VO2max was increased (P less than 0.01) in the anemic state, the values obtained being C = 83.3%, A = 89.8% and R = 84.8%. Ventilation at upsilon Hla 4.0 was higher in A as compared to C and R (P less than 0.05). R and C values were not significantly different for any of the values presented above. The maximal activity of citrate synthase in muscle did not differ between the three different conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Anemia/sangue , Lactatos/sangue , Esforço Físico , Adulto , Humanos , Masculino , Concentração Osmolar , Consumo de Oxigênio
19.
Clin Physiol ; 14(4): 385-91, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7955936

RESUMO

Transcutaneous oxygen pressure (TcPO2) measurements were performed on 10 male patients with moderate-to-severe intermittent claudication. The TcPO2 electrode was attached to the dorsum of the foot. TcPO2 response to a standardized treadmill exercise test was evaluated, as was the reproducibility of TcPO2 measurements at rest and during exercise. Reproducibility was assessed using a similar exercise test within 2-5 days. Treadmill exercise induced a marked decrease in TcPO2 in all patients, from 9.3 +/- 0.9 to 2.8 +/- 2.0 kPa. Maximal walking distance was 280 +/- 127 m at the first treadmill test and 272 +/- 113 m at the second. Blood lactate and heart rates at rest and at end of exercise were also unchanged. TcPO2 at rest was highly reproducible, but considerable variation was found for measurements during and after exercise. This variation was most obvious for measurements during exercise and no direct or reproducible relation was found between ischaemic calf pain and TcPO2 values. Post-exercise measurements were slightly more reproducible and somewhat easier to assess. In contrast to standard TcPO2 measurements, total exercise-induced ischaemia expressed as area under the post-exercise TcPO2 curve was highly reproducible. In summary, our results with TcPO2 measurements in patients with intermittent claudication showed a marked exercise-induced decrease in all patients. However, the variation in TcPO2 values when the test was repeated after 2-5 days under stable clinical and circulatory conditions limits its application as a quantitative measure of lower-limb ischaemia. Thus, measurements of area under the TcPO2 curve might be preferred for this purpose.


Assuntos
Monitorização Transcutânea dos Gases Sanguíneos , Claudicação Intermitente/sangue , Oxigênio/sangue , Idoso , Teste de Esforço , Frequência Cardíaca/fisiologia , Humanos , Claudicação Intermitente/fisiopatologia , Isquemia , Lactatos/sangue , Ácido Láctico , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Caminhada
20.
Acta Physiol Scand ; 129(1): 47-54, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3565043

RESUMO

Increasing the haemoglobin concentration ([Hb]) improves the oxygen transport capacity but it also increases the viscosity of the blood. The influence of changes in [Hb] and viscosity on submaximal exercise capacity and maximal aerobic power was investigated in eight healthy males in varying states of training and with a normal resting [Hb] ([Hb]r), ranging from 123 to 178 g l-1. The subjects were venesected five times (450 ml per unit) and exercise tests were performed in the anaemic state. After 5-7 weeks, when [Hb] had returned to the 'normal' value, a stepwise re-transfusion of three to five units of blood was performed with exercise tests after each transfusion. The [Hb]r was 137 +/- 15 g l-1 in the anaemic state (A) and 170 +/- 16 g l-1 after the last re-transfusion (LT). The VO2max rose from 3.94 +/- 0.35 in A to 4.68 +/- 0.30 l min-1 after LT. Individual regression lines for [Hb] and VO2max revealed a mean increase in VO2max of 19 +/- 6 ml min-1 per g l-1 change in [Hb]. This value did not differ between individuals with high and low normal [Hb]. Furthermore, in intra-individual comparisons the relationship between [Hb] and VO2max in high and low individual [Hb] ranges was not found to be statistically different despite a 40% increase in the in vitro viscosity from the anaemic to the polycythaemic state.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Anemia/fisiopatologia , Hemoglobinas/metabolismo , Consumo de Oxigênio , Esforço Físico , Policitemia/fisiopatologia , Respiração , Adulto , Viscosidade Sanguínea , Hemodinâmica , Humanos , Lactatos/sangue , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA