Study of some pathophysiological factors in children with acquired aplastic anaemia

Aplastic anaemia [AA] is a heterogenous disease including different pathophysiological conditions, characterized by severely diminished numbers of bone marrow [B.M] haematopiotic cells resulting in failure of the marrow to produce mature blood elements, this study aimed to determine the role of apoptosis, tumour necrosis factor alpha [TNFalpha.] and granulocytes-macrophage colony stimulating factor [GM-CSF] in the pathogensis of AA. Thirty five cases diagnosed as acquired A.A, Twenty cases newly diagnosed, 8 cases in partial remission and 7 cases in complete remission were studied. Twenty age and sex matched children were taken as control group.Mononuclear cell apoptosis was estimated using flowcytometry by TUNEL method.Serum level of TNFa. and GM-CSF were estimated using ELISA technique. The result of this study revealed significant increase of mononuclear cell apoptosis and TNFalpha in newly diagnosed cases of AA and in cases with partial remission more than in control group. Also there was an insignificant increase of apoptosis in the cases in complete remission than in control group. Serum GM-CSF was significantly reduced in all cases of aplastic anaemia except cases in complete remission when compared with control group.There was inverse correlation between mononuclear cell apoptosis,TNFalpha, and GM-CSF [r - 0.52, - 0.55 respectively, p <0.001] In conclusion increase the rate of mononuclear cell apoptosis,TNF-alpha and decreased level of GM-CSF play a role in pathophysiology of B.M failure and their follow up may be one of the important parameters to assure complete recovery

Evaluation of iron deposition and oxidative stress on renal function in children with beta-thalassemia major

Beta-Thalassemia is the commonest form of hemoglobinopathy in Egypt. Shortened red cell life span, rapid iron turnover and tissue deposition of excess iron are major factors responsible for functional and physiological abnormalities found in various forms of thalassemia. Increased deposition of iron had been found in renal parenchyma of thalassemic patients, but no systematic study of the effect of the deposits on renal functions has been available. The purpose of .this study is to describe the functional abnormalities of the kidney in patients with Beta- thalassemia and provide evidence that increased oxidative stress might be one of the factors responsible for the damage. Urine and serum samples from 40 patients with Beta-thalassemia were studied comparing with 10 age matched healthy controls. The patients were dividied into two groups: 22 with severe anaemia [hematocrite [Hct] < 25%] and 18 with moderate anaemia [Hct > 25%]. The result of this study showed that there was significant increase in serum iron, ferritin, urinary malondialedehyde [MDA] an indicator of lipid perioxidiation] and urinary B2 microglobulin [B[2]M]-level in all patients compared with normal children. Decrease in the ability to concentrate urine was detected by reduction in specific gravity in all thalassmic patients. Patients with severe anaemia had significantly higher serum iron, ferritin, urinary MDA and urinary B[2]M than those with moderate anaemia. There was positive correlation between MDA with level of serum ferritin and B[2]M .In conclusion the data indicated that patients have high prevelance of proximal tubular and medullary defects, we also demonstrate that the defects corrleate with the disease severity suggesting that oxidative stress might play a major role in the pathogenesis. Frequent urinary B[2]M estimation is recommended for early detection of tubular abnormalities