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1.
Br J Haematol ; 189(5): 976-981, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32128787

RESUMO

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.


Assuntos
Androgênios/uso terapêutico , Transtornos da Insuficiência da Medula Óssea/tratamento farmacológico , Adolescente , Adulto , Androgênios/efeitos adversos , Transtornos da Insuficiência da Medula Óssea/sangue , Transtornos da Insuficiência da Medula Óssea/genética , Transtornos da Insuficiência da Medula Óssea/terapia , Canadá/epidemiologia , Linhagem da Célula , Criança , Pré-Escolar , Terapia Combinada , Danazol/efeitos adversos , Danazol/uso terapêutico , Progressão da Doença , Substituição de Medicamentos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Oximetolona/efeitos adversos , Oximetolona/uso terapêutico , Pancitopenia/tratamento farmacológico , Pancitopenia/etiologia , Sistema de Registros , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Resultado do Tratamento , Virilismo/induzido quimicamente
3.
J Pediatr Hematol Oncol ; 41(3): 229-232, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29668547

RESUMO

Fanconi anemia (FA) is an autosomal recessive, progressive bone marrow failure disorder characterized by congenital defects and marked cancer predisposition. Hematopoietic stem cell transplant is the therapy of choice for FA patients with progressive pancytopenia. These patients receive multiple transfusions for cytopenias. Oxymetholone has been used with variable success to improve cytopenias. Eltrombopag has been shown to induce bilineage or trilineage hematopoiesis in aplastic anemia and patients with myelodysplastic marrow. We report a case of FA where eltrombopag in conjunction with oxymetholone induced trilineage hematopoiesis and eliminated transfusion requirement before transplant, thereby enhancing favorable outcome after hematopoietic stem cell transplant.


Assuntos
Benzoatos/farmacologia , Anemia de Fanconi/terapia , Hematopoese/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas , Hidrazinas/farmacologia , Pirazóis/farmacologia , Quimioterapia Combinada , Anemia de Fanconi/complicações , Humanos , Oximetolona/uso terapêutico , Pancitopenia/etiologia
4.
Hematology Am Soc Hematol Educ Program ; 2017(1): 96-101, 2017 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-29222242

RESUMO

Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.


Assuntos
Doenças da Medula Óssea/terapia , Doenças Genéticas Inatas/terapia , Androgênios/efeitos adversos , Androgênios/uso terapêutico , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/metabolismo , Doença Hepática Induzida por Substâncias e Drogas , Danazol/efeitos adversos , Danazol/uso terapêutico , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Terapia Genética , Humanos , Leucina/uso terapêutico , Oximetolona/efeitos adversos , Oximetolona/uso terapêutico , Quercetina/uso terapêutico , Transplante de Células-Tronco , Síndrome , Virilismo/induzido quimicamente
5.
Leuk Res ; 50: 21-28, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27639703

RESUMO

Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS. Increased bone marrow angiogenesis and VEGF concentrations are adverse prognostic features in all of these patients. In this study, 69 patients were treated in two groups: hypomethylating agents or supportive care with oxymetholone±pyridoxine. We evaluated the MVD and VEGF expression of paraffin-embedded bone marrow samples from patients. We also investigated the relationship between angiogenesis-related biomarkers including MVD, VEGF expression, and clinical factors. The patient median age was 65 years, and the median follow-up duration was 28 months. MVD assessment among subtypes of WHO MDS classification showed that the MVD of RCUD was significantly lower than in other types (p=0.02). However, there was no significant difference in VEGF expression according to the subtype of MDS. Although MVD and VEGF expression did not differ between risk groups based on the IPSS, the low risk group tended to have lower expression of angiogenesis-related biomarkers. MDS patients receiving hypomethylating agents had significantly lower MVD expression in responders than in non-responders (6.13±3.38 vs. 9.89±2.10, respectively, p=0.039). In a consecutive evaluation at the time of diagnosis and 3 months after the initial treatment, the group with a decrease or no change of MVD had a higher response rate compared to that in the group with an increase of MVD (92.9% vs. 58.8%, respectively, p=0.045). Adverse prognostic factors included older age, MDS type other than RCUD, a higher IPSS risk group, and abnormal cytogenetics. Although angiogenesis-related markers did not demonstrate any significant prognostic association with survival, MVD (≥10n/mm2) and a strong expression of VEGF seemed to be associated with lower survival rate. These data suggested that the MVD value might be helpful in predicting responsiveness to treatment, especially in MDS patients treated with hypomethylating agents. Although angiogenesis-related markers including VEGF did not demonstrate a significant association with survival outcomes, we observed that high MVD and strong VEGF expression seemed to be associated with lower survival rate. Therefore, biologic markers related to angiogenesis might have a potential as prognostic factors for MDS patients.


Assuntos
Imunossupressores/uso terapêutico , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/diagnóstico , Neovascularização Patológica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Exame de Medula Óssea , Humanos , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Neovascularização Patológica/diagnóstico por imagem , Oximetolona/uso terapêutico , Prognóstico , Piridoxina/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/análise , Adulto Jovem
6.
Stem Cell Reports ; 4(1): 90-102, 2015 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-25434823

RESUMO

Androgens are widely used for treating Fanconi anemia (FA) and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged Fancd2(-/-) mice were used to assess the therapeutic efficacy of oxymetholone (OXM) and its mechanism of action. Eighteen-month-old Fancd2(-/-) mice recapitulated key human FA phenotypes, including reduced bone marrow cellularity, red cell macrocytosis, and peripheral pancytopenia. As in humans, chronic OXM treatment significantly improved these hematological parameters and stimulated the proliferation of hematopoietic stem and progenitor cells. RNA-Seq analysis implicated downregulation of osteopontin as an important potential mechanism for the drug's action. Consistent with the increased stem cell proliferation, competitive repopulation assays demonstrated that chronic OXM therapy eventually resulted in stem cell exhaustion. These results expand our knowledge of the regulation of hematopoietic stem cell proliferation and have direct clinical implications for the treatment of bone marrow failure.


Assuntos
Ciclo Celular/efeitos dos fármacos , Anemia de Fanconi/genética , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Osteopontina/genética , Oximetolona/farmacologia , Transcrição Gênica/efeitos dos fármacos , Animais , Contagem de Células Sanguíneas , Medula Óssea/patologia , Ciclo Celular/genética , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Anemia de Fanconi/tratamento farmacológico , Anemia de Fanconi/patologia , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Regulação da Expressão Gênica , Hematopoese/efeitos dos fármacos , Hematopoese/genética , Humanos , Camundongos , Camundongos Knockout , Oximetolona/uso terapêutico , Pancitopenia/sangue , Pancitopenia/genética , Pancitopenia/patologia , Análise de Sequência de RNA , Fatores de Tempo
7.
Cochrane Database Syst Rev ; (10): CD006881, 2014 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-25300168

RESUMO

BACKGROUND: Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial. OBJECTIVES: The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD. SEARCH METHODS: We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014. SELECTION CRITERIA: All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently. AUTHORS' CONCLUSIONS: We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.


Assuntos
Androgênios/uso terapêutico , Anemia/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Adulto , Anemia/sangue , Anemia/etiologia , Colesterol/sangue , Eritropoetina/uso terapêutico , Hematócrito , Humanos , Nandrolona/análogos & derivados , Nandrolona/uso terapêutico , Decanoato de Nandrolona , Oximetolona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
8.
Best Pract Res Clin Haematol ; 27(2): 175-85, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25189728

RESUMO

Anaemia is a common finding at diagnosis in myelofibrosis, and becomes a symptomatic problem in most patients with time. There are several treatment options for specific anaemia treatment, none of which has been tested in large, randomized, controlled trials. However, as myelofibrosis is not a disease with spontaneous remissions, even non-randomized trials carry weight. In this survey, the existing evidence will be analysed, both for the commonly used treatments like erythropoiesis-stimulating agents, androgens and thalidomide and for the new drugs in the area, and conclusions will be drawn concerning standard clinical anaemia treatment in myelofibrosis, which according to evidence from studies has a 40-50% chance of response in patients with not too advanced disease.


Assuntos
Androgênios/uso terapêutico , Anemia/tratamento farmacológico , Hematínicos/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Talidomida/uso terapêutico , Anemia/complicações , Anemia/patologia , Transfusão de Sangue , Eritropoetina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Interferons/uso terapêutico , Lenalidomida , Nitrilas , Oximetolona/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas , Talidomida/análogos & derivados
9.
J Korean Med Sci ; 25(11): 1676-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21060762

RESUMO

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-α. The patient developed progressive, severe anemia after the use of erythropoietin-α. As the anemia did not improve after the administration of either other erythropoietin-α products or erythropoietin-ß, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-α at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-α can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.


Assuntos
Anticorpos/sangue , Eritropoetina/análogos & derivados , Eritropoetina/imunologia , Hematínicos/uso terapêutico , Aplasia Pura de Série Vermelha/tratamento farmacológico , Adulto , Anemia/tratamento farmacológico , Anemia/etiologia , Anticorpos/imunologia , Células da Medula Óssea/patologia , Darbepoetina alfa , Hipersensibilidade a Drogas/imunologia , Eritropoetina/efeitos adversos , Eritropoetina/uso terapêutico , Feminino , Glomerulonefrite por IGA/complicações , Hematínicos/efeitos adversos , Hematínicos/imunologia , Humanos , Falência Renal Crônica/complicações , Oximetolona/uso terapêutico , Proteínas Recombinantes , Aplasia Pura de Série Vermelha/induzido quimicamente , Aplasia Pura de Série Vermelha/imunologia
11.
Int J Hematol ; 91(5): 770-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20524094

RESUMO

The clinical course of non-severe aplastic anemia is variable, and risk factors related to disease progression are not well known. We reviewed clinical and laboratory data of the patients who were diagnosed with non-severe aplastic anemia from 1997 to 2007 at Seoul National University Hospital and analyzed the clinical course and outcomes in these patients. We defined non-severe aplastic anemia as hypocellular marrow with cytopenia in the peripheral blood, which does not meet the criteria for severe aplastic anemia (at least two of the following: ANC < 500/microl, platelet < 20,000/microl or reticulocyte < 20,000/microl). Among a total of 96 patients, 53 (55.2%) were male and the median age was 37.6 years old. As much as 41.7% (40) of the patients were initially asymptomatic. Sixty-two patients who were treated with oxymetholone, ATG/ALG, cyclosporin or other agents after initial diagnosis showed significantly lower levels of initial hemoglobin, red blood cell count and platelet count than those who did not receive any treatment. During the follow-up period, 18 patients progressed to severe aplastic anemia. Their median age was 29.9 years and the median progression time was 18 months. Initial white blood cell count and absolute neutrophil count in the evolution group tended to be lower than in the other group. The patients whose thrombocytopenia did not respond to treatment showed markedly higher frequency of progression to severe aplastic anemia. Treatment itself and responsiveness in reticulocyte and absolute neutrophil count were not correlated with their clinical courses. Sixteen patients showed overall improvement, whereas three patients developed secondary hematologic disease, acute myeloid leukemia, myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria. Non-severe aplastic anemia has a relatively indolent and mild clinical course. However, 18.8% of the study population progressed to severe disease. White blood cell and absolute neutrophil count at diagnosis and treatment responsiveness of thrombocytopenia were associated with disease progression. Careful monitoring and early management are needed for patients at risk.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Androgênios/uso terapêutico , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/epidemiologia , Ciclosporina/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Oximetolona/uso terapêutico , Prognóstico , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-152646

RESUMO

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-alpha. The patient developed progressive, severe anemia after the use of erythropoietin-alpha. As the anemia did not improve after the administration of either other erythropoietin-alpha products or erythropoietin-beta, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-alpha at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-alpha can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.


Assuntos
Adulto , Feminino , Humanos , Anemia/tratamento farmacológico , Anticorpos/sangue , Células da Medula Óssea/patologia , Hipersensibilidade a Drogas/imunologia , Eritropoetina/análogos & derivados , Eritropoetina/efeitos adversos , Glomerulonefrite por IGA/complicações , Hematínicos/efeitos adversos , Falência Renal Crônica/complicações , Oximetolona/uso terapêutico , Aplasia Pura de Série Vermelha/induzido quimicamente
13.
Ann Allergy Asthma Immunol ; 100(1 Suppl 2): S19-22, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18220148

RESUMO

OBJECTIVE: To provide a summary of the literature regarding the use of attenuated androgens during the past 40 to 50 years for the treatment of hereditary angioedema (HAE). DATA SOURCES: MEDLINE and PubMed were searched to identify studies involving the treatment of HAE with androgens. STUDY SELECTION: Studies were selected based on their relevance to the use of androgens for the treatment of HAE. RESULTS: Attenuated androgens have proven successful for the short- and long-term treatment of HAE. Adverse effects are still concerning, and their use in children and pregnant women must be undertaken with great caution. Scheduled monitoring of liver function tests and lipid profiles in patients treated with these medications is critical. CONCLUSIONS: Attenuated androgens have been successful in the short- and long-term treatment of HAE, and they are still the most frequently used medications in the United States for the treatment of this disease. There is a lack of readily available options for the treatment of acute HAE attacks apart from the administration of fresh frozen plasma or safe prophylactic therapies; however, several appropriate agents currently in clinical trials in the United States appear promising.


Assuntos
Androgênios/uso terapêutico , Angioedemas Hereditários/tratamento farmacológico , Androgênios/síntese química , Criança , Ensaios Clínicos como Assunto , Danazol/uso terapêutico , Antagonistas de Estrogênios/uso terapêutico , Feminino , Humanos , Masculino , Oximetolona/uso terapêutico , Estanozolol/uso terapêutico
14.
Mol Cell Biochem ; 287(1-2): 193-9, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16532255

RESUMO

Oxymetholone is a 17alpha -alkylated anabolic-androgenic steroid. This drug can stimulate bone marrow cells and increase the blood cells in the peripheral blood vessels. It has been used for the treatment of anemia caused by low red cell production. Since oxymetholone has hematopoietic effect, we studied radioprotective effects of this drug in mice. In this study, we determined percentage of survival, dose-reduction factor (DRF) and hematological parameters in irradiated mice which treated with or without oxymetholone. Oxymetholone administrated at different doses 80, 160, 320, 640 mg/kg by gavages at 24 h before 8 Gy gamma irradiation. At 30 days after treatment, the following percentage of animals survival in each group was as: 80 mg/kg, 50%; 160 mg/kg, 50%; 320 mg/kg, 55%; 640 mg/kg, 75% and vehicle, 15%. Percentage of survival increased in all of treated groups statistically compared with irradiated-vehicle group. In the groups treated by oxymetholone, maximum protection was realized at 640 mg/kg. In order to calculate the DRF for oxymetholone, mice were exposed to whole-body gamma irradiation with dose ranges between 5.83 and 11.23 Gy. The probit line for oxymetholone-treated mice was shifted to the right with a DRF of 1.14. In mice exposed to whole-body gamma-irradiation (4 Gy), an oral administration of 640 mg/kg oxymetholone ameliorated radiation-induced decreases in circulating platelets and erythrocytes, but had a less effect on total number of WBC. These results demonstrate that oxymetholone stimulates myelopoiesis and thrombocytopenia and enhances survival in mice after ionizing radiation.


Assuntos
Raios gama , Sistema Hematopoético/efeitos dos fármacos , Oximetolona/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/mortalidade , Protetores contra Radiação/uso terapêutico , Animais , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/efeitos da radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Avaliação Pré-Clínica de Medicamentos , Sistema Hematopoético/citologia , Camundongos , Mielopoese/efeitos dos fármacos , Oximetolona/administração & dosagem , Protetores contra Radiação/administração & dosagem , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente
15.
J Pediatr Hematol Oncol ; 27(10): 565-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16217263

RESUMO

A 13-year-old girl with a history of Fanconi anemia developed acute myeloid leukemia of the M7 subtype with a 45,XX,-7 karyotype, which is rare in M7 subtype. Treatment protocols were set up, but she died of sepsis and osteomyelitis during induction.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 7 , Anemia de Fanconi/genética , Leucemia Megacarioblástica Aguda/genética , Monossomia , Adolescente , Anabolizantes/uso terapêutico , Quimioterapia Combinada , Anemia de Fanconi/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Oximetolona/uso terapêutico
16.
Haematologica ; 88(11): ECR33, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14607765

RESUMO

Littoral cell angioma (LCA) is a rare benign tumour of the spleen. We describe a patient with aplastic anaemia who, following multiple treatments with rabbit and horse Anti-Thymocyte Globulin and anabolic steroids developed marked splenomegaly and hypersplenism. LCA was diagnosed post splenectomy. This is the first case of LCA associated with aplastic anaemia and its treatment.


Assuntos
Anemia Aplástica/complicações , Hemangioma/complicações , Neoplasias Esplênicas/complicações , Anemia Aplástica/tratamento farmacológico , Animais , Soro Antilinfocitário/efeitos adversos , Transfusão de Sangue , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Feminino , Hemangioma/induzido quimicamente , Cavalos , Humanos , Hiperesplenismo/etiologia , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Oximetolona/efeitos adversos , Oximetolona/uso terapêutico , Coelhos , Esplenectomia , Neoplasias Esplênicas/induzido quimicamente , Linfócitos T
17.
HIV Clin Trials ; 4(3): 150-63, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12815555

RESUMO

BACKGROUND: Despite highly active antiretroviral therapy (HAART), chronic involuntary weight loss still remains a serious problem in the care of HIV patients due to various alterations in energy metabolism and endocrine regulation. Previous studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant growth hormone (rGH) have shown partial restoration of lean body mass (LBM), but these treatments have largely not been sufficiently studied in eugonadal individuals. METHOD: A double-blind, randomized, placebo-controlled trial of 89 HIV-positive eugonadal women and men with wasting assigned to the anabolic steroid oxymetholone (50 mg bid or tid) or placebo for 16 weeks was performed. Body weight, bioimpedance measurements, quality of life parameters, and appetite were analyzed. RESULTS: Oxymetholone led to a significant weight gain of 3.0 +/- 0.5 and 3.5 +/- 0.7 kg in the tid and bid groups, respectively (p <.05 for each treatment versus placebo), while individuals in the placebo group gained an average of 1.0 +/- 0.7 kg. Body cell mass (BCM) increased in the oxymetholone bid group (3.8 +/- 0.4 kg; p <.0001) and in the oxymetholone tid group (2.1 +/- 0.6 kg; p <.005). Significant improvements were noted in appetite and food intake, increased wellbeing, and reduced weakness by self-examination. The most important adverse event was liver-associated toxicity. Overall, 43% of patients in the tid group, 25% of patients in the bid oxymetholone group, and 8% in the placebo group had a greater than 5 times baseline increase for ALT, AST, or gamma GT, while other adverse events were not increased over placebo. CONCLUSION: Oxymetholone can be considered an effective anabolic steroid in eugonadal male and female patients with AIDS-associated wasting. The bid (100 mg/day) regimen appeared to be equally effective to the tid (150 mg/day) regimen in terms of weight gain, LBM, and BCM and was associated with less liver toxicity.


Assuntos
Infecções por HIV/complicações , Síndrome de Emaciação por Infecção pelo HIV/complicações , Síndrome de Emaciação por Infecção pelo HIV/tratamento farmacológico , Oximetolona/uso terapêutico , Adulto , Idoso , Apetite/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Método Duplo-Cego , Feminino , Síndrome de Emaciação por Infecção pelo HIV/sangue , Hormônios/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Oximetolona/administração & dosagem , Oximetolona/efeitos adversos , Oximetolona/farmacologia , Qualidade de Vida
19.
Hematol J ; 4(1): 3-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12692514

RESUMO

A number of inherited (constitutional/genetic) disorders are characterized by bone marrow (BM) failure/aplastic anaemia (AA) usually in association with one or more somatic abnormality. Occasionally, these patients may present with AA alone and be labelled to have idiopathic AA. In recent years, there have been significant advances in the genetics of Fanconi anaemia (FA), dyskeratosis congenita (DC) and other BM failure syndromes. This is facilitating accurate diagnosis and beginning to unravel their pathophysiology. Furthermore, these advances are also providing important insights into normal haemopoiesis and how this might become defective in some patients presenting with the more common idiopathic AA. Indeed, a link between DC and idiopathic AA and in turn to defective telomerase has now been established. This advance also suggests that treatments directed at correction of telomerase activity might benefit AA patients who do not respond to conventional therapy.


Assuntos
Anemia Aplástica/genética , Adolescente , Adulto , Anemia Aplástica/etiologia , Anemia Aplástica/patologia , Medula Óssea/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/fisiologia , Criança , Pré-Escolar , Cromossomos Humanos/ultraestrutura , Cromossomos Humanos X/genética , Mecanismo Genético de Compensação de Dose , Disceratose Congênita/sangue , Disceratose Congênita/complicações , Disceratose Congênita/terapia , Anemia de Fanconi/complicações , Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Anemia de Fanconi/terapia , Heterogeneidade Genética , Fatores de Crescimento de Células Hematopoéticas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Proteínas Nucleares/fisiologia , Oximetolona/uso terapêutico , Prednisolona/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos
20.
AIDS ; 17(5): 699-710, 2003 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-12646793

RESUMO

BACKGROUND: Despite highly active antiretroviral therapy (HAART), chronic involuntary weight loss still remains a serious problem in the care of HIV patients. Various alterations in energy metabolism and endocrine regulation have been found to cause loss of lean body mass (LBM) and body cell mass (BCM). Previous studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant growth hormone (rGH) have shown partial restoration of LBM, but these treatments have largely been ineffective in eugonadal individuals. STUDY DESIGN: Double-blind, randomized, placebo-controlled trial of 89 HIV-positive women and men with wasting assigned to the anabolic steroid oxymetholone [50 mg twice (BID) or three times daily (TID)] or placebo for 16 weeks followed by open-label treatment. STUDY ENDPOINTS: Body weight, bioimpedance measurements, quality of life parameters and appetite. RESULTS: Oxymetholone led to a significant weight gain of 3.0 +/- 0.5 and 3.5 +/- 0.7 kg in the TID and BID groups, respectively (P < 0.05 for each treatment versus placebo), whereas individuals in the placebo group gained an average of 1.0 +/- 0.7 kg. Body cell mass increased in the oxymetholone BID group (3.8 +/- 0.4 kg; P < 0.0001) and in the oxymetholone TID group (2.1 +/- 0.6 kg; P < 0.005), corresponding to 12.4 and 7.4% of baseline BCM, respectively. Significant improvements were noted in appetite and food intake, increased well-being and reduced weakness by self-examination. The most important adverse event was liver-associated toxicity. Overall, 35% of patients in the TID, 27% of patients in the BID oxymetholone group and no patients in the placebo group had a greater than five times baseline increase for alanine aminotransferase during the double-blind phase of the study. CONCLUSIONS: Oxymetholone can be considered an effective anabolic steroid in eugonadal male and female patients with AIDS-associated wasting. The BID (100 mg/day) regimen appeared to be equally effective as the TID (150 mg/day) regimen in terms of weight gain, LBM and BCM and was associated with less, but still significant liver toxicity.


Assuntos
Anabolizantes/uso terapêutico , Síndrome de Emaciação por Infecção pelo HIV/tratamento farmacológico , Oximetolona/uso terapêutico , Adulto , Idoso , Anabolizantes/efeitos adversos , Apetite/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Oximetolona/efeitos adversos , Qualidade de Vida , Testosterona/sangue , Aumento de Peso/efeitos dos fármacos
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