Search results for "IRON OVERLOAD"
showing 10 items of 40 documents
Myocardial scarring by delayed enhancement cardiovascular magnetic resonance in thalassaemia major
2009
Background: Cardiovascular magnetic resonance (CMR) by delayed enhancement (DE) enables visualisation of myocardial scarring, but no dedicated studies are available in thalassaemia major. Objective: To investigate the prevalence, extent, clinical and instrumental correlates of myocardial fibrosis or necrosis by DE CMR in patients with thalassaemia major. Patients: 115 Patients with thalassaemia major consecutively examined at an MRI laboratory. Methods: DE images were acquired to quantify myocardial scarring. Myocardial iron overload was determined by multislice multiecho T2*. Cine images were obtained to evaluate biventricular function. Results: DE areas were present in 28/115 patients (24…
Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation
2014
This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum fe…
Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassemia major patients: a randomised clinical trial
2009
A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone–deferoxamine (DFO–DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8–12 h) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg, administered 7 d/week during a 5-year follow-up. The main outcome measures were differences between multiple observations of serum ferritin concentrations. Secondary outcomes were survival analysis, adverse events, and costs. Consecutive thalassaemia patients (275) were assessed for eligibility; 213 of these…
Standardized T2* map of normal human heart in vivo to correct T2* segmental artefacts.
2007
A segmental, multislice, multi-echo T2* MRI approach could be useful in heart iron-overloaded patients to account for heterogeneous iron distribution, demonstrated by histological studies. However, segmental T2* assessment in heart can be affected by the presence of geometrical and susceptibility artefacts, which can act on different segments in different ways. The aim of this study was to assess T2* value distribution in the left ventricle and to develop a correction procedure to compensate for artefactual variations in segmental analysis. MRI was performed in four groups of 22 subjects each: healthy subjects (I), controls (II) (thalassemia intermedia patients without iron overload), thala…
Preferential patterns of myocardial iron overload by multislice multiecho T2* CMR in thalassemia major patients.
2010
T*(2) multislice multiecho cardiac MR allows quantification of the segmental distribution of myocardial iron overload. This study aimed to determine if there were preferential patterns of myocardial iron overload in thalassemia major. Five hundred twenty-three thalassemia major patients underwent cardiac MR. Three short-axis views of the left ventricle were acquired and analyzed using a 16-segment standardized model. The T*(2) value on each segment was calculated, as well as the global value. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. Significant segmental variability was found in the 229 patients with significant myocardial iron overload (glob…
Influence of myocardial fibrosis and blood oxygenation on heart T2* values in thalassemia patients
2009
Purpose To determine whether T2* measurements quantifying myocardial iron overload in thalassemia patients are influenced by myocardial fibrosis and blood oxygenation. Materials and Methods Multislice multiecho T2* was performed in 94 thalassemia patients in order to quantify myocardial iron overload. The left ventricle was automatically segmented into a 16-segment standardized heart model, and the T2* value on each segment as well as the global T2* were calculated. Delayed enhanced cardiovascular magnetic resonance (DE-CMR) images were obtained to detect myocardial fibrosis. The blood oxygenation was assessed by the noninvasive measurement of partial pressure of oxygen (pO2). Results Myoca…
Effects of waterborne iron overload and simulated winter conditions on acute physiological stress response of whitefish, Coregonus lavaretus
2003
Two-year-old whitefish (Coregonus lavaretus) were exposed for 30 days to episodic iron overload in iron-rich humic water (5%) supplemented with inorganic iron (5 mg FeL(-1)). Two parallel laboratory exposures were performed, one under conditions simulating winter and the other under conditions simulating spring. After exposure, some of the fish were subjected to acute handling stress in the form of a short air challenge to reveal possible modification of the primary and secondary stress responses. In whitefish sampled without additional handling, iron accumulated in the liver (under spring conditions) and gills (under winter and spring conditions); plasma catecholamine and beta-estradiol (b…
Iron, oxidative stress, and redox signaling in the cardiovascular system.
2014
The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation-reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are invo…
Treatment of hepatitis C virus infection with direct-acting antiviral drugs is safe and effective in patients with hemoglobinopathies
2017
Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chron…
Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic ir…
2014
Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighte…