Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Haematologica ; 98(1): 129-35, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22875626

RESUMEN

Patients with ß-thalassemia require iron chelation therapy to protect against progressive iron overload and non-transferrin-bound iron. Some patients fail to respond adequately to deferoxamine and deferasirox monotherapy while others have side effects which limit their use of these drugs. Since combining deferiprone and deferoxamine has an additive effect, placing all patients into net negative iron balance, we investigated the possibility that combining deferasirox and deferoxamine would lead to similar results. We conducted 34-day metabolic iron balance studies in six patients in whom the relative effectiveness of deferasirox (30 mg/kg/day) and deferoxamine (40 mg/kg/day) was compared, alone and in combination. Patients consumed fixed low-iron diets; daily urinary and stool iron excretion were determined by atomic absorption. Red blood cell transfusions were given prior to each drug treatment to minimize the effects of ineffective erythropoiesis. Serial safety measures, hematologic parameters, serum chemistries, ferritin levels and urinalyses were determined. All patients were in negative iron balance when treated with deferoxamine alone while four of six patients remained in positive balance when deferasirox monotherapy was evaluated. Daily use of both drugs had a synergistic effect in two patients and an additive effect in three others. Five of six patients would be in negative iron balance if they used the combination of drugs just 3 days a week. No significant or drug-related changes were observed in the blood work-ups or urinalyses performed. We conclude that supplementing the daily use of deferasirox with 2 - 3 days of deferoxamine therapy would place all patients into net negative iron balance thereby providing a convenient way to tailor chelation therapy to the individual needs of each patient.


Asunto(s)
Benzoatos/administración & dosificación , Deferoxamina/administración & dosificación , Triazoles/administración & dosificación , Talasemia beta/tratamiento farmacológico , Talasemia beta/metabolismo , Adulto , Deferasirox , Quimioterapia Combinada , Femenino , Humanos , Hierro/sangre , Hierro/orina , Quelantes del Hierro/administración & dosificación , Masculino
2.
Am J Hematol ; 88(8): 652-6, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23640778

RESUMEN

Cardiovascular magnetic resonance (CMR) and hepatic magnetic resonance imaging (MRI) have become reliable noninvasive tools to monitor iron excess in thalassemia major (TM) patients. However, long-term studies are lacking. We reviewed CMR and hepatic MRI T2* imaging on 54 TM patients who had three or more annual measurements. They were managed on various chelation regimens. Patients were grouped according to their degree of cardiac siderosis: severe (T2*, <10 msec), mild to moderate (T2* = 10-20 msec), and no cardiac siderosis (T2*, >20 msec). We looked at the change in cardiac T2*, liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) at years 3 and 5. In patients with severe cardiac siderosis, cardiac T2* (mean ± SD) improved from 6.9 ± 1.6 at baseline to 13.6 ± 10.0 by year 5, mean ΔT2* = 6.7 (P = 0.04). Change in cardiac T2* at year 3 was not significant in the severe group. Patients with mild to moderate cardiac siderosis had mean cardiac T2* of 14.6 ± 2.9 at baseline which improved to 26.3 ± 9.5 by year 3, mean ΔT2* = 1.7 (P = 0.01). At baseline, median LICs (mg/g dry weight) in patients with severe, mild-moderate, and no cardiac siderosis were 3.6, 2.8, and 3.3, whereas LVEFs (mean ± SD) (%) were 56.3 ± 10.1, 60 ± 5, and 66 ± 7.6, respectively. No significant correlation was noted between Δ cardiac T2* and Δ LIC, Δ cardiac T2*, and Δ LVEF at years 3 and 5. Throughout the observation period, patients with no cardiac siderosis maintained their cardiac T2* above 20 msec. The majority of patients with cardiac siderosis improve cardiac T2* over time with optimal chelation.


Asunto(s)
Cardiopatías , Corazón , Hemosiderosis , Hígado , Miocardio/metabolismo , Talasemia beta , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Corazón/diagnóstico por imagen , Corazón/fisiopatología , Cardiopatías/diagnóstico por imagen , Cardiopatías/etiología , Cardiopatías/metabolismo , Cardiopatías/fisiopatología , Hemosiderosis/diagnóstico por imagen , Hemosiderosis/etiología , Hemosiderosis/fisiopatología , Humanos , Quelantes del Hierro/administración & dosificación , Hígado/diagnóstico por imagen , Hígado/metabolismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Radiografía , Volumen Sistólico , Talasemia beta/complicaciones , Talasemia beta/diagnóstico por imagen , Talasemia beta/tratamiento farmacológico , Talasemia beta/metabolismo , Talasemia beta/fisiopatología
3.
Am J Hematol ; 85(10): 802-5, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20806230

RESUMEN

Thalassemia is an inherited blood disorder that requires lifelong adherence to a complicated and burdensome medical regimen which could potentially impact emotional functioning of patients. The importance of understanding and promoting healthy emotional functioning is crucial not only to psychological well-being, but also to physical health as it has been shown to impact adherence to medical regimens [1-4]. The current study aimed to [1] determine the prevalence of depressive and anxiety symptoms in adolescent and adult patients with thalassemia; and [2] explore possible demographic, medical, and psychosocial correlates of these symptoms in 276 patients (14-58 years old, M age = 27.83; 52% female). Overall, most patients did not report experiencing significant symptoms of anxiety and depression (33% of participants indicated experiencing symptoms of anxiety and 11% symptoms of depression). Females and older patients were more likely to experience these symptoms than males and younger patients. Symptoms of anxiety and depression were positively associated with self-report of difficulty with adherence and negatively associated with quality of life. Given these findings, regular screening for anxiety and depression symptoms could help to identify at-risk individuals to provide them with appropriate psychological support with the goal of improving both emotional and physical health.


Asunto(s)
Ansiedad/epidemiología , Depresión/epidemiología , Talasemia/psicología , Adolescente , Adulto , Ansiedad/etnología , Ansiedad/etiología , Pueblo Asiatico/psicología , Transfusión Sanguínea/psicología , Canadá/epidemiología , Terapia por Quelación/psicología , Depresión/etnología , Depresión/etiología , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Calidad de Vida , Riesgo , Factores Sexuales , Talasemia/epidemiología , Talasemia/etnología , Talasemia/terapia , Reino Unido/epidemiología , Estados Unidos/epidemiología , Población Blanca/psicología , Adulto Joven
5.
PLoS One ; 7(3): e32345, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22479321

RESUMEN

Preclinical and clinical studies demonstrate the feasibility of treating ß-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human ß-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human ß-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human ß-globin through a novel mechanism that links the rate of transcription of the transgenic ß-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+) cells isolated from patients affected by ß-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A) and concurrently reducing the sickling tetramer (Hb S).Our results suggest two major findings. First, we discovered that for the purpose of expressing the ß-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from ß-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these clinical trials, before patients undergo myeloablation and bone marrow transplant.


Asunto(s)
Anemia de Células Falciformes/terapia , Terapia Genética/métodos , Hemoglobinas/metabolismo , Talasemia beta/terapia , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/genética , Animales , Ancirinas/genética , Antígenos CD34/metabolismo , Secuencia de Bases , Diferenciación Celular/genética , Línea Celular Tumoral , Células Cultivadas , Células Precursoras Eritroides/metabolismo , Expresión Génica , Técnicas de Transferencia de Gen , Vectores Genéticos/genética , Hemoglobinas/genética , Humanos , Elementos Aisladores/genética , Lentivirus/genética , Ratones , Datos de Secuencia Molecular , Mutación , Células 3T3 NIH , Globinas beta/genética , Talasemia beta/sangre , Talasemia beta/genética
6.
Ann N Y Acad Sci ; 1202: 134-40, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20712784

RESUMEN

Lentiviral-mediated beta-globin gene transfer successfully treated beta-thalassemic mice. Based on this result, clinical trials were initiated. To date, however, no study has investigated the efficacy of gene therapy in relation to the nature of the different beta-globin mutations found in patients. Most mutations can be classified as beta(0) or beta(+), based on the amount of beta-globin protein produced. Therefore, we propose that a screening in vitro is necessary to verify the efficacy of gene transfer prior to treatment of individual patients. We used a two-phase liquid culture system to expand and differentiate erythroid progenitor cells (ErPCs) transduced with lentiviral vectors. We propose the use of this system to test the efficiency of lentiviral vectors carrying the human beta-globin gene, to correct the phenotype of ErPCs from patients preparing for gene therapy. This new approach might have profound implications for designing gene therapy and for understanding the genotype/phenotype variability observed in Cooley's anemia patients.


Asunto(s)
Terapia Genética , Talasemia beta/genética , Talasemia beta/terapia , Animales , Células Cultivadas , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Humanos , Lentivirus/genética , Ratones , Mutación , Globinas beta/genética , Globinas beta/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA