Therapeutic efficacy of different iron chelators in Egyptian children with Beta Thalassemia with iron overload.

BACKGROUNDS: Beta thalassemia is a hereditary blood disorder characterized by reduced or absent beta chains of hemoglobin resulting in imbalanced globin chain synthesis with early destruction of RBCs and anemia. Patients with thalassemia major become transfusion- dependent with subsequent iron overload. Effective iron chelation therapy remains the main target of management of thalassemia major. OBJECTIVES: 'The aim of this work was to compare the efficacy of different iron chelating agents' in the treatment of ' iron overload in children with beta thalassemia major'. PATIENTS AND METHODS: 'The current study was conducted on 120 children with beta thalassemia major with serum ferritin level of more than 1000 ng/ml who were divided into 4 groups': Group A: 30 patients were treated with 8 hours intravenous infusion of Desferrioxamine, '40 mg/kg/day, 6 days per week for 6 months'. Group B: 30 patients were treated with subcutaneous infusion of Desferrioxamine, 40 mg/kg/day, 6 days per week 8-12 hours per day at night using Desferal pump for 6 months. Group C: 30 patients were treated with oral Deferiprone 75 mg/kg/day in three divided doses daily for 6 months. Group D: 30 patients were treated with oral Deferasirox 30 mg/kg/day in single dose on empty stomach daily for 6 months. 'For all patients laboratory investigations were carried out including complete blood count (CBC), measurement of serum ferritin, serum iron, TIBC (total iron binding capacity), liver enzymes and kidney functions'. RESULTS: There were significant reductions in 'serum ferritin and serum iron' after treatment in all studied groups with the highest reduction in group A, group B, group D and group C but without statistically significant differences between the four studied groups before and after chelation therapy. 'There were no significant differences in' the mean values of the parameters of CBC, liver enzymes and kidney functions between the studied groups before and after chelation therapy. CONCLUSION: From this study we concluded that there was significant reduction in serum ferritin and serum iron after chelation therapy in studied groups with the highest reduction in group A (IV Desferrioxamine), group B (SC Desferrioxamine), group D (oral Deferasirox) and group C (oral Deferiprone) with no statistically significant differences between the studied groups of patients before and after 6 months of regular chelation.

Regulated upon activation, normal T-cell expressed and secreted chemokine and interleukin-6 in rheumatic pulmonary hypertension, targets for therapeutic decisions.

BACKGROUND: Recent studies have highlighted the possible influence of chemokines and cytokines on several types of pulmonary arterial hypertension (PAH). Increasing interest has also been focussed on their role as a cause of post-cardiopulmonary bypass (CPB) organ dysfunction. HYPOTHESIS: Chemokines and cytokines are involved in the pathobiology of rheumatic PAH. METHODS: Serum levels of the chemokine, regulated upon activation, normal T-cell expressed and secreted (RANTES) and the cytokine interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) in 35 patients with rheumatic mitral valve disease and 10 matched healthy subjects (control group). Eleven patients (31.4%) had severe pulmonary hypertension. Subsequently, 23 patients underwent mitral valve replacement. The relation of RANTES and IL-6 circulating level with postoperative organ dysfunction was analysed through multiple organ dysfunction score (MODS). RESULTS: Patients with severe PAH have a significantly higher mean serum level of RANTES compared with other patients (6138.6+/-3543.8 pg/ml vs 1818.2+/-475.2 pg/ml, p=0.0003). The serum level of IL-6 in the patients was statistically different from that of the control (378+/-50.8 pg/ml vs 262+/-90.5 pg/ml, respectively, p=0.002). Patients who required postoperative inotropes had higher preoperative and post-CPB levels of both RANTES and IL-6. While patients with postoperative lung dysfunction had higher levels of IL-6 preoperatively and post-CPB and lower levels of RANTES post-CPB. CONCLUSIONS: RANTES and IL-6 should be investigated as potential therapeutic targets in the control of rheumatic PAH. Improved understanding of the contribution of RANTES and IL-6 to adverse postoperative complications can lead to improved patient outcome.