Correlation of vascular endothelial growth factor with the severity of thalassemia intermedia.

Several lines of evidence indicate that thalassemia intermedia is associated with disturbances in vascular endothelial cell proliferation. In addition, autopsy studies of thalassemia intermedia reported obstructive lesions in the pulmonary artery in 44% of cases, especially splenectomized patients, and a recent in-vivo study reported increased level of vascular endothelial growth factor (VEGF) in thalassemia intermedia. The aim of the present study was to determine whether VEGF levels are correlated with the severity of the disease. Blood samples were collected from 21 patients with thalassemia intermedia and assayed for VEGF by a two-site enzyme-linked immunosorbent assay. A significant correlation was noted between VEGF levels and patient age (P = 0.0022, r = 0.82), presence of splenomegaly (P = 0.004, r = 0.79) and hepatomegaly (P = 0.023, r = 0.82). VEGF levels were also significantly correlated with both left ventricular end-diastolic diameter and left ventricular end-systolic diameter (P = 0.02, r = 0.84 and P = 0.01, r = 0.86, respectively). The study indicates that VEGF levels may be related to the clinical severity of thalassemia intermedia, as expressed by the degree of hepatomegaly and splenectomy and cardiac indexes. Further and larger studies are needed to confirm these observations.

Use of sirolimus and low-dose calcineurin inhibitor in lung transplant recipients with renal impairment: results of a controlled pilot study.

BACKGROUND: Renal failure induced by calcineurin-inhibitor agents is a common complication of lung transplantation. Sirolimus, a macrolide immunosuppressant with a distinct mechanism of action, may prevent renal failure but was found to have a high infectious and toxicity rate in the only relevant study conducted so far. The aim of the present prospective pilot study was to assess the benefit of sirolimus combined with low-dose calcineurin inhibitors in this patient population. METHODS: Sixteen lung transplant recipients with post-transplantation renal dysfunction were allocated to receive the standard immunosuppression regimen or a combination sirolimus/low-dose calcineurin-inhibitor regimen. Target trough levels of sirolimus were 4 to 8 ng/mL. Tacrolimus was tapered down to target trough levels of 4 to 8 ng/mL and cyclosporine to 80 to 120 ng/mL. Duration of follow-up was 18 months. RESULTS: At the end of follow-up, the sirolimus group showed a significant improvement in creatinine clearance (42.6 mL/min vs. 32.5 mL/min, P= 0.05), whereas the control group showed a significant reduction (32.3 mL/min vs. 40.3 mL/min, P= 0.02). The difference between the groups was statistically significant (P < 0.0001). Acute rejection episodes occurred in 2 patients in the sirolimus group and 1 patient in the control group (P= NS). Pneumonia developed in 6 study patients and 4 controls; all responded to antibiotics. CONCLUSION: Sirolimus combined with low-dose calcineurin inhibitors appears to be a safe and effective alternative immunosuppressive therapy to sirolimus alone in lung transplant recipients with renal failure. Graft function is preserved, and infection and drug toxicity rates are low.