Role of RANKL/OPG and L-carnitine systems in osteopenia/osteoporosis in children with B-thalassemia major

Bone disease in beta TM in the form of low bone mass remains a frequent, debilitating and poorly understood problem, even among well transfused and chelated patients. Receptor activator of nuclear factor kB ligand [RANKL] is a regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor and with antagonist binding protein osteoprotegerin [OPG]. L-carnitine enhanced osteoblasric activity as well. The objective is to define the role of RANKUOPG and L-carnitine systems-related bone loss in attempt for better management of osteopenialosteoporosis in beta TM children. The study included 69 I3TM children [45 males and 24 females, mean age 8.72 +/- 3. 70 ys and weight 22.84 +/- 7.04kg] attended the Children University Hospital [January-September 2008]. The patients were subdivided into 2 groups; one [n=34] received iron chelating [DFO] and the other group [n=35] did not receive any chelating drug. Fifteen healthy matched age, sex and BMI were included as controls. Serum OPG, sRANKL, L-carnitine, calcium, inorganic phosphorus and free fatty acids were measured by ELIZA and spectrophotometer. BMD, BMC and Z-score were measured by DEXA in 25 patients. There was a significantly lower serum level of OPG, L-carnitine and significantly higher sRANKL, sRANKL/OPG ratio, FFAs in patients than controls and in patients receiving DFO than those not receiving chelation. DEXA bone scanning detected osteopenia/osteoporosis in 12%and 88%of patients [mean Z score-3.38 +/- 1.19] with significantly higher osteoporosis in patients receiving DFO; more obvious in pelvis, L-spine, and femoral neck. L-carnitine correlated negatively with sRANKL, and positively with OPG. sRANKL correlated negatively with OPG. Z-score correlated negatively with age and positively with OPG. In conclusion, Reduced osteoblas tic activity and enhancing osteoclastic resorption are the basic mechanisms of bone loss in beta TM through decrease in L-carnitine and disturbed RANKL/OPG pathway. Recombinant OPG, L-carnitine and anti-RANKL supplement may be future agents that help in management of beta TM osteopenia/osteoporosis. Chelation with DFO seems to affect the bone density in such patients

Fetal cardiovascular hemodynamics in diabetic and hypertensive pregnancies

Fetal echocardiography is a useful technique in the evaluation of the fetal cardiovascular system. The purpose of this work was to evaluate fetal cardiac anatomy and function in two of the most common medical problems seen in pregnancy, diabetes mellitus and chronic maternal hypertension. In this cross sectional study, 60 fetuses between 20-30 weeks of gestation were included. Twenty of them were fetuses of diabetic mothers [FODMs], 20 fetuses of hypertensive mothers [FOHMs] and the remaining twenty were normal fetuses of matchable gestational age as controls. Transabdominal fetal echocardiography was obtained and the cardiac diameters and thickness were measured. The systolic function [stroke volume and cardiac output] and the diastolic function [E/A ratio] were obtained. There was a significant increase in cardiac diameters and thickness in FODMs and decrease in diameters in FOHMs. The pulmonary and aortic blood flow velocities were significantly faster in FODMs and slower in FOHMs. The diastolic functions were impaired in all patients. The stroke volume and cardiac output were significantly higher in FODMs and lower for the right ventricule in FOHMs than controls. Fetal echocardiographic examination showed significant changes in both cardiac anatomy and function in FODMs and FOHMs. The practical value of this non invasive technique is in need for further prospective comparative studies with the well established methods in obstetric decision making

Six months follow-up study of cardiac performance using antioxidants in beta - thalassemic patients

The present study was designed to evaluate the cardiac performance in beta-thalassemic patients before and after 2, 4 and 6 months of antioxidants therapy. Fifty-eight children with beta-thalassemia were involved in the study. Their age ranged from 2 - 13 years. All the patients have a history of multiple blood transfusions. Twenty healthy children of matching age and sex were taken as control. Echocardiography was performed to all patients and control. All patients were given desferrioxamine. They were divided into four groups according to the type of therapy either desferrioxamine alone or combined with vitamin E, beta-carotene or vitamin D. A follow up study with echocardiography was done to all patients. Echocardiography detected a significant increase in LA and RV diameters, RVAW, IVS and LVPW thickness and E/A ratio and a significant decrease in FS% in patients than control. After the use of combined desferrioxamine with antioxidants, a significant improvement in cardiac diameters, thicknesses, FS% and E/A ratio occurred. However these results were not obtained after combined desferrioxamine and vitamin D therapy. The imbalance between free radicals and antioxidants can lead to severe myocardial impairment in beta- thalassemic patients. The use of antioxidants like combined vitamin E and combined beta-carotene with desferrioxamine could stop this impairment. The use of combined vitamin D therapy with desferrioxamine my add more myocardial damage, so it is not advised to be given

Effect of hemodialysis on ECG in children with chronic renal failure

Hemodialysis [HD] may expose patients with chronic renal failure [CRF] to arrhythmia and sudden cardiac death. The aim of the present was to evaluate the effect of HD on ECG parameters in children with CRF. Forty children with CRF on regular HD and without relevant heart disease were selected. A standard ECG was performed, both before and at 15 minutes after the end of HD session. The measurements of the amplitude of P, Q, T waves, R and S waves in leads V1 and V6, PR and RR interval, ST segment and QRS amplitude, duration and axis were performed. The QT and QTc interval and dispersion were measured. Laboratory investigations including hemoglobin level, blood urea, serum creatinine and serum electrolytes [sodium, calcium, phosphorus and magnesium] were estimated before and after dialysis session. After dialysis, there was a significant increase in the amplitudes of P, Q and QRS waves and a significant decrease in T wave amplitude than pre-dialysis. There was also a significant increase in the amplitude of R and S waves in leads V1 and V6 and a significant decrease in the QRS duration. QT and QTc interval and dispersion increased after dialysis. There was a significant positive correlation between the T wave amplitude and both the body weight and systolic blood pressure as well as between the systolic blood pressure and QRS duration