Assuntos
Linfoma de Células B , Linfoma Difuso de Grandes Células B , Neoplasias do Mediastino , Humanos , Linfoma de Células B/patologia , Doxorrubicina/uso terapêutico , Polietilenoglicóis/uso terapêutico , Neoplasias do Mediastino/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
ß-thalassemia patient treated with thalidomide: dimensional reduction of EMH foci (MRI evaluation) and reduction of hematological responce at follow-up.
Assuntos
Doenças Hematológicas , Hematopoese Extramedular , Talassemia alfa , Talassemia beta , Humanos , Talassemia beta/complicações , Talassemia beta/tratamento farmacológico , Talidomida/uso terapêutico , EritropoeseRESUMO
The basilic/brachial (BBV), internal jugular (IJV), and subclavian veins (SCV) are commonly used as central venous catheter (CVC) sites. A BBV approach [peripherally inserted central catheter (PICC)] is increasingly used for short- to intermediate-term CVCs for acute leukemias undergoing cytotoxic intensive regimens. In this retrospective study, the catheterization of the BBV, IJV, and SCV in patients with previously untreated acute leukemia was assessed. The primary outcome was the composite incidence of catheter-related symptomatic deep-vein thrombosis (sDVT) and bloodstream infection (BSI) from catheterization up to 30 days later. In a 10-year period, 336 CVC were inserted in the BBV (n = 115), IJV (n = 111), and SCV (n = 110) in 336 patients suffering from AML (n = 201) and ALL (n = 135) and undergoing induction chemotherapy. The primary outcome events were 8, 20, and 27 in the BBV, SCV and IJV cohorts (2.6, 6.9, and 9.6 per 1000 catheter-days, respectively; p = 0.002). The primary outcome risk was significantly higher in the IJV-cohort than in the BBV-cohort (HR, 3.6; 95% CI, 1.6 to 7.9; p = 0.001) and in the SCV-cohort than in the BBV-cohort (HR, 2.6; 95% CI, 1.2 to 5.9; p = 0.02). PICC was a valid CVC for the induction chemotherapy of acute leukemia for the lowest risk of sDVT and BSI.
RESUMO
We describe a patient with an unusual combination of hypersideremia (700 microg/dL), hypertransferrinemia (570 mg/dL), hyperferritinemia (800 microg/L), and monoclonal gammopathy of undetermined significance (MGUS), in which the monoclonal immunoglobulin showed specific transferrin-binding activity. Liver histology revealed hepatic iron overload, prominent in periportal hepatocytes, suggesting intestinal iron hyperabsorption. We demonstrate that low urinary hepcidin, likely due to impaired iron delivery to erythroid cells via the transferrin cycle pathway over time, may be the mechanism for iron loading. We suggest that MGUS associated with monoclonal antibodies with antitransferrin activity should be added to the list of acquired causes of hemochromatosis.
Assuntos
Hemocromatose/imunologia , Hemossiderose/imunologia , Paraproteinemias/sangue , Transferrina/imunologia , Autoanticorpos/sangue , Hemocromatose/diagnóstico , Hemocromatose/patologia , Hemossiderose/diagnóstico , Hemossiderose/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Ferroportin is encoded by the SLC40A1 gene and mediates iron export from cells by interacting with hepcidin. SLC40A1 gene mutations are associated with an autosomal type of genetic iron overload described as haemochromatosis type 4, or HFE4 (Online Mendelian Inheritance in Man number 606069), or ferroportin disease. We report three families with this condition caused by novel SLC40A1 mutations. Denaturing high-performance liquid chromatography was employed to scan for the SLC40A1 gene. A D181V (A846T) mutation in exon 6 of the ferroportin gene was detected in the affected members of an Italian family and shown to have a de novo origin in a maternal germinal line. This mutation was associated with both parenchymal and reticuloendothelial iron overload in the liver, and with reduced urinary hepcidin excretion. A G80V (G543T) mutation in exon 3 was found in the affected members of an Italian family with autosomal hyperferritinaemia,. Finally, a G267D (G1104A) mutation was identified in exon 7 in a family of Chinese descent whose members presented with isolated hyperferritinaemia. Ferroportin disease represents a protean genetic condition in which the different SLC40A1 mutations appear to be responsible for phenotypic variability. This condition should be considered not only in families with autosomal iron overload or hyperferritinaemia, but also in cases of unexplained hyperferritinaemia.
Assuntos
Proteínas de Transporte de Cátions/genética , Hemocromatose/genética , Mutação , Adolescente , Adulto , Peptídeos Catiônicos Antimicrobianos/urina , Sequência de Bases , Criança , China/etnologia , Cromatografia Líquida de Alta Pressão , Feminino , Ferritinas/sangue , Genótipo , Hemocromatose/metabolismo , Hepcidinas , Humanos , Ferro/análise , Ferro/metabolismo , Itália , Fígado/química , Fígado/metabolismo , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Alinhamento de SequênciaRESUMO
BACKGROUND AND OBJECTIVES: During the last decade new approaches to the treatment of pulmonary arterial hypertension (PH) have increased symptomatic relief and prolonged survival. PH is a common sequel of the hemoglobinopathies, thalassemia and sickle cell anemia, but the use of standard oral treatment options, such as calcium channel blockers, endothelin receptor antagonists, and long-term anticoagulation therapy, is limited because of toxicity and poor effectiveness. Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5) which promotes selective smooth muscle relaxation in lung vasculature and has been utilized successfully in the treatment of PH. The primary objective of this study was to evaluate the efficacy of sildenafil treatment in the control of PH in patients with hemoglobinopathies. DESIGN AND METHODS: In this study patients with hemoglobinopathies (thalassemia intermedia n=4; thalassemia major n=2; sickle thalassemia n=1) suffering from severe PH were treated with sildenafil citrate (50 mg b.i.d.) for periods ranging from 4 to 48 months. RESULTS: A significant decrease in pulmonary pressure and improvement in exercise capacity and functional class were observed in all patients. No significant adverse events were reported. INTERPRETATION AND CONCLUSIONS: These data, in a small group of patients, indicate that sildenafil citrate is effective in the treatment of PH in hemoglobinopathies that cannot be treated with alternative oral drugs and is well tolerated long-term at a daily dose of 100 mg, though studies including more patients may uncover toxicities and limitations of efficacy.