Serum thrombomodulin level in children with beta thalassaemia major

In recent years, it is suspected that vascular endothelial cells may have some role in vascular complications noted in thalassemic patients. Activated or injured endothelial cells release their protein constituents mainly thrombomodulin into the circulation. Thrombomodulin is considered the most important indicator of vascular endothelial injury. To study serum thrombomodulin level in children with B-thalassaemia major and its relation to the duration of disease and extent of iron overload. The present study was carried out on 35 patients with fl-thalassaemia major. They were divided according to the age into two groups. Group I: included 15 young children aged less than 10 years. Their mean disease duration was 5.5 years. Group II: included 20 older children and adolescents aged from 10 to 20 years. Their mean disease duration was 15.6 years. Ten apparently healthy children of matching age and sex served as control group. Estimation of serum levels of Thrombomodulin [TM] by ELISA. Echocardiography, two-dimensional, M-mode, and Doppler studies. Cardiomegaly was found in 7 [35%] patients of group II. Pulmonary hypertension was encountered only in 4 [20%] patients of group II. Thromboembolic manifestations [femoral deep vein thrombosis] were found in only 1 [5%] thalassaemic patient in group II. The serum TM level was significantly higher in both groups, in comparison with controls [F=10.36, p<0.001]. No significant difference was found between both thalassaemic groups [t=0.421, p=0.673]. Moreover, no significant difference was found between TM levels in splenectomized and non-splenectomized cases [t=0.62, p=0.541]. TM levels of both thalassemic groups showed no significant correlation with serum ferritin level [r=-0.02, p=0.914]. A significantly higher mean value of right ventricular wall thickness was encountered in group II thalassaemic patient as compared to group I [t=2, 57, P=0.019]. In conclusion, increased serum TM level in our polytransfused thalassaemic patients reflects a state of endothelial cell activation and/or injury in these patients. The statistically significant negative correlation between serum TM level and pulmonary acceleration time [r=-0.45, p=0.047], may point to the possible role of pulmonary vascular endothelium injury as a contributory factor in the pathogenesis of pulmonary hypertension in our thalassaemic patients

Study of caspase-3 level in relation to prognostic risk factors in children with acute lymphoblastic leukemia

Apoptosis refers to a biochemically regulated process of automated cell death mediated through a highly organized network of interacting proteases. Malignant transformation of hematopoietic progenitors into leukemic cells results in defects in the cell cycle regulation; including defects in apoptosis. Multiple mechanisms may account for why leukemic cells become resistant to chemotherapy. One common cause includes defects in the cell inherent programmed cell death [apoptosis]. This study was conduced on 20 children with newly diagnosed ALL and 10 controls. Our aim was to evaluate the level of caspase-3 among them and relate it to prognostic factors. It can be concluded that caspase-3 level after induction therapy proved to be a significant predictor of remission stage especially for B-ALL. CD10 positive cases also showed a significant difference between caspase-3 level before and after induction therapy. The same was demonstrated with low risk cases. We can also conclude that failure of caspase-3 level to increase after induction is associated with poor prognosis

Comparative study for the detection of 563 C-T G6PD mutation using restriction enzyme assay and amplification and refractory mutation system [ARMS]

G6PD deficiency is the most common enzyme disorder in humans and is characterized by considerable biochemical and molecular heterogeneity. The prevalence of G6PD deficiency in the Middle East varies greatly, ranging from 1% among Egyptians to 11.5% among Iranians. G6PD Mediterranean [563 C-T] mutation is probably the most common G6PD variant in the world. The relative frequency of this mutation ranges from 70% among Egyptians to 97% for Kurdish Jews. This study was conducted on 30 Egyptian pediatric G6PD-deficient patients. Quantitation of G6PD enzyme was performed before molecular analyses, during, and one month after the hemolytic attack. The frequency of the mutation was investigated using two methods; the reference method; RFLPs and ARMS technique. The aim of this study was to compare both methods. Both methods gave identical results, yet ARMS method is easier and less time consuming

Study of some autoantibodies in cases of lymphoproliferatve disease

lymphoproliferative disorders are usually complicated by autoimmune disorders, the aim of this work is to study the autoimmune profile in some cases of lymphoproliferative disease. Material and Sixty cases of B-lymphoproliferative disorders, forty-five cases of non-Hodgkin lymphoma [NHL] and fifteen chronic lymphocytic leukemia [CLL] were included in this study. The autoimmune profile including; anti-nuclear antibodies, anti-ds-DNA anti-cardiolipin antibodies, both IgG and IgM were evaluated. 42% percent of studied cases displayed one or more autoimmune marker positivity. A total thirteen out of sixty [22%] were postive for anti-nuclear antibodies; three out fifteen CLL cases [20%] and ten out of forty-five non-Hodgkin lymphoma cases [22%]. Two out of fifteen [13%] CLL cases and eight out of forty-five [18%] NHL cases were positive for anti-ds-DNA antibodies. Only thirty-eight cases were tested for anti-cardiolipin antibodies; three case were acL IgG positive and nine were acL IgM positive. Although there was a high percent of positive autoimmune marker, SLE was diagnosed clinically in only of the NHL cases [2.2%]. HCV seropositivity was tested to exclude HCV as a contributing factor for autoantibodies development. Causes of autoimmune phenomena in lymphoproliferative conditions are heterogeneous and the association may not necessarily causal; certain individuals may be genetically predisposed to develop both disorders i.e. that genetic factors disturbing the regulation of the immune system may predispose both to lymphoid neoplasms and to autoimmune disease

Study of the mutations in the NAD[p]H: quinone oxidoreductase in cases of chronic myeloid leukemia

NAD [p] H: quinone oxidoreductase NQO1 originally called DT-diaphorase is an enzyme that is able to detoxify a number of natural and synthetic compounds, including quinones and their derivatives. It is induced by synthetic antioxidants and cruciferous vegetables and protects cells against oxidative stress. The human NQO1gene is located on chromosome 16q22.1, a single nucleotide polymorphism [cytosine to thymine, [CT]] at position 609 in the NQO1 gene has been identified in a human colon cancer cell line with very low NQO1 activity. This variant produces a proline-to-serine substitution that inactivates the enzyme. People who are homozygous for the variant allele completely lack NQO1 activity, while heterozygote have low to intermediate activity compared with people with the wild type. The incidence of the polymorphism varies widely by race, and associations have been made between the presence of variant alleles and lung and urological cancers. NQO1 mutation had been identified as risk factor in AML and ALL but no avilable data in chronic myeloid leukemia. Our study included 21 chronic myeloid patients and 10 apparently healthy persons using PCR-RFLP technique to detect the NQO1 nutation. Among the cases 11[52.4%] were positive for the mutation compared to 1[10%] of control. A higher incidence of the mutation was noticed among patients in crisis stage. Conclusion from our data we noticed a high incidence of NQO1 mutation in cases of CML which may suggest an important role of this gene in the etiology and pathogenesis of chronic myeloid leukemia