Seham M. Ragab

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and tumor necrosis factor-alpha (TNF-α) and their relation to premature atherosclerosis in β-thalassemia children

Abstract Background/Objectives Beta (β)-thalassemia adults are prone to premature atherosclerosis but data about this complication among thalassemia children are few. Lipoprotein-associated phospholipase A2 (Lp-PLA2) and tumor necrosis factor-α (TNF-α) are inflammatory markers that could be implicated in atherosclerotic process. We investigated Lp-PLA2 and TNF-α levels in β-thalassemia children and their relation to subclinical atherosclerosis. Methods Twenty-two β-thalassemia major (TM), 20 β-thalassemia intermedia children, and 30 age- and sex-matched healthy controls were included. Lipid profile (by colorimetric assay), serum ferritin, TNF-α, and plasma Lp-PLA2 levels (by enzyme-linked immunosorbent assay technique) were estimated. Carotid intima-media thickness (cIMT) was measured by high-resolution ultrasound. Results Both patient groups exhibited anti-atherogenic lipid profile except increased serum triglycerides. They had significantly higher plasma Lp-PLA2 and serum TNF-α compared to the controls (P < 0.001). Elevated cIMT was documented in 57% of the thalassemia children and was higher among hepatitis C (HCV) positive patients. Serum ferritin, TNF-α, and plasma Lp-PLA2 levels were significantly higher in patients with premature atherosclerosis. cIMT correlated significantly with serum ferritin, TNF-α, and plasma Lp-PLA2 in both patient groups. Among TM children, serum ferritin had significant positive correlation with serum TNF-α and plasma Lp-PLA2. The elevation of both markers was not related to HCV infection. Conclusions Premature atherosclerosis is common among young thalassemia children. Lp-PLA2 and TNF-α are significantly increased in thalassemia children and show strong correlations with cIMT, suggesting that both of them may be appreciated as modulating factors in carotid atherosclerosis pathophysiological process among these children.

HER2/neu Expression: A Predictor for Differentiation and Survival in Children With Wilms Tumor

Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expression could be implicated in the development of many tumors. The clinico-demographic and pathological data of 28 Wilms tumor patients were , reviewed. The tissue samples were examined by light Microscopy then immunohistochemical staining for HER2/neu expression. Additional 28 normal surrounding renal tissue specimens were included. There was significant differences between HER2/neu positive and HER2/neu negative Wilms tumors in relation to stage, histological phase and epithelial differentiation (P > 0.05 for all). The overall survival advantage was noticed if Wilms tumor was at early stages (I and II) (Log-rank = 13.23 and P > 0.001), homologous epithelial differentiation (Log-rank = 6.01 and P = 0.04), as well as HER2/neu positive tumors (Log-rank = 6.14 and P = 0.013). A statistical significant trend toward a longer recurrence free survival was, noticed if Wilms tumor was at early stages (Log-rank = 21.22, P > 0.0000) and if HER2/neu positive (Log-rank = 8.53, P = 0.004). HER2/neu expression in Wilms tumor could be a marker for epithelial and homologous differentiation and its expression could be a good predictor for overall survival and longer recurrence free survival.

Tissue factor-positive monocytes expression in children with sickle cell disease: clinical implication and relation to inflammatory and coagulation markers.

Hemostatic abnormalities are well documented in sickle cell disease (SCD). Nevertheless, whether these perturbations could contribute to sickle vasculopathy is still not clear. We evaluated monocytes tissue factor (TF) expression in children with SCD correlating the results with the clinical state and some inflammatory and coagulation markers. The study included 24 children with SCD in steady state, 24 in painful crisis and 20 healthy age and sex-matched children as controls. Complete blood count, prothrombin time (%), activated partial thromboplastin time, fibrinogen, D-dimer, thrombin–antithrombin complex and quantitative C-reactive protein were assayed. TF expression on monocytes was analyzed by flow cytometry. TF-positive monocytes were significantly higher in both patient groups compared with the controls, being higher in painful crisis group (2.06 ± 0.64, 8.01 ± 1.53, 13.5 ± 4.3 for the controls, steady state and painful crisis groups, respectively). Among painful crisis group, TF expression on monocytes was positively correlated with the pain rate, reticulocytes (%) and three out of six markers of inflammation and coagulation (C-reactive protein, D-dimer and fibrinogen) with inverse correlation with hemoglobin and the red blood cells count. TF-positive monocytes were more expressed in SCD both in steady state and in painful crisis, being significantly higher in painful crisis. This expression was significantly related to the pain rate as well as to markers of hemolysis, inflammation and coagulation among patients in painful crisis. These results confirm the substantial role played by TF-positive monocytes in the pathogenesis of SCD painful crisis.

Haptoglobin genotypes polymorphism as a risk factor for subclinical atherosclerosis in beta-thalassemia major children; a single center Egyptian study

Abstract Background/Objectives Haptoglobin (Hp) is an antioxidant protein. Its genotypic polymorphism had been proposed to influence vascular complications among diabetics, but no data are available about this association among thalassemia patients so far. We have investigated the assumption of an association between Hp genotypes and subclinical atherosclerosis among beta-thalassemia major (TM) children. Methods One hundred beta-TM children and 70 matched healthy controls were included. Serum ferritin level and fasting lipid profile were assayed. Haptoglobin genotyping was determined by amplification gel electrophoresis. Carotid intima media thickness (cIMT) was measured using high resolution ultrasound. Results The relative distribution of the three Hp genotypes among thalassemia group and the control group were 18 and 14.3% for Hp1-1; 38 and 37.1% for Hp2-1; and 44 and 48.6% for Hp2-2 respectively. There was no significant difference between patients and controls regarding Hp genotypes distribution. Hp2-2 genotype TM children had significantly higher cIMT compared to other genotypes (P < 0.0001). Elevated cIMT was significantly represented in Hp2-2 genotype patients (P < 0.0001) who had higher serum ferritin compared to their counterparts (P < 0.05). Hp2-2 patients were five times more likely to suffer from subclinical atherosclerosis than Hp1-1 and six times than Hp2-1 genotype patients (P = 0.008 and 0.001, respectively); a difference that persisted significant after adjustment for some risk factors compared to Hp2-1 patients (OR 3.96; P = 0.02). Conclusions Hp2-2 genotype is a significant predictor for premature atherosclerosis in TM children and confers them an increased risk for iron overload.

The effect of zinc supplementation on growth and development in preterm neonates

Objective This study aimed to show the effect of zinc supplementation on growth and development in preterm neonates in the first 6 months of life. Background Preterm infants have impaired zinc status because of low body stores as 60% of fetal zinc is acquired during the third trimester of pregnancy in addition to their limited capacity to absorb and retain micronutrients, coupled with increased endogenous losses associated with organ immaturity. Patients and methods The present study was carried out in the Department of Obstetrics in Nasr City Health Insurance Hospital on 80 healthy preterm infants between 32 and 36 weeks of age divided into two groups: a zinc-supplemented group fed with breast milk, and supplemented with multivitamins and zinc (2 mg/kg/day) since the first day of life, and a non-zinc-supplemented group fed breast milk with multivitamins only (without zinc supplementation). Both groups were followed for 6 months for growth with assessment of development by the Age and Stage Questionnaire at 4 and 6 months of corrected age and serum levels of zinc, alkaline phosphatase, and hemoglobin at corrected age of 3 and 6 months. Results The zinc-supplemented group showed a significant increase ( P There was a highly significant increase in the serum zinc levels of the zinc-supplemented group compared with the non-zinc-supplemented group, in addition to a significant positive correlation between zinc level and both weight and length at 3 and 6 months of age. Also, the developmental score of the zinc-supplemented group was significantly higher ( P Conclusion Zinc supplementation in the first 6 months of life was found to be an effective enhancer for both the growth and the development of preterm infants.

Impact of beta thalassemia on maxillary sinuses and sino-nasal passages: A case control study

OBJECTIVES Skeletal changes among beta (β) thalassemia children are well documented, but without available data regarding sino-nasal passages alterations. The authors investigated the maxillary sinuses and sino-nasal passages changes in β-thalassemia children and correlated such changes with the amount of transfused red cells and the erythroid marrow activity. METHODS Clinical analyses including otorhinolaryngical examination (ORL) were obtained in twenty β-thalassemia children and 20 matched healthy controls. Hemoglobin (Hb), serum ferritin, soluble transferrin receptor (sTfR) levels and bone mineral density of the lumbar spine (BMD ls) were assayed. The two groups were analyzed for the CT image parameters: bone thickness, anterior and posterior choanae diameters, extramedullary hematopoiesis and chronic rhinosinusitis (CRS) RESULTS: Nasal congestion/obstruction was identified in 14 (70%) children. Eight patients (40%) had criteria of chronic rhinosinusitis. In comparison with the normal controls, the increase in the roof, floor, medial, anterior, lateral and posterior maxillary bony walls thickness was significantly higher (1.26, 2.46, 2.6, 2.9, 3.23 and 5.34-folds, respectively). The mean posterior choanae horizontal, vertical diameters and their surface area were significantly reduced in the patients compared to the controls. The mean anterior maxillary wall bone thickness directly correlated with sTfR (P=0.047) while that of the posterior wall correlated inversely with Hb level (P=0.013). The mean vertical posterior choanae diameter had positive correlation with the amount of transfused red cells (P=0.001) and negative correlation with sTfR (P=0.001). The Hounsfield unit of maxillary sinus wall had direct relation with BMDls (P=0.003) CONCLUSIONS: Thalassemia children are at risk of different folds increase of maxillary sinuses walls thicknesses utmost at posterior and lateral walls. Other sino-nasal morbidities include diminished posterior choanal diameter, nasal obstruction and CRS. Certain morbidities had relations to the erythroid marrow activity and the transfusion adequacy.

Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study

Background: 6-mercaptopurine (6-MP) is an essential component of pediatric acute lymphoblastic leukemia (ALL) maintenance therapy. Individual variability in this drug-related toxicity could be attributed in part to genetic polymorphism thiopurine methyltransferase (TPMT). Aim: To investigate the frequency of common TPMT polymorphisms in a cohort of Egyptian children with ALL and the possible relation between these polymorphisms and 6-MP with short-term complications. Materials and Methods: This study included 25 children. Data related to 6-MP toxicity during the maintenance phase were collected from the patients′ files. DNA was isolated and genotyping for TPMT G460A, and A719G mutations were performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Twenty (80%) of the included 25 patients had a polymorphic TPMT allele. TPMTFNx013A was the most frequent (14/25, 56%), 8 patients were homozygous and 6 were heterozygous. TPMTFNx013C mutant allele was found in 4 patients (16%) in the heterozygous state while 2 patients (8%) were found to be heterozygous for TPMTFNx013B mutant allele. TPMT mutant patients, especially homozygous, were at greater risk of 6-MP hematological toxicity without significant difference regarding hepatic toxicity. Conclusions: TPMT polymorphism was common among the studied group and was associated with increased risk of drug toxicity. A population-based multi-center study is required to confirm our results.

Evaluation of serum and urine fetuin-A levels in children with acute lymphoblastic leukemia during and after high-dose methotrexate therapy: Relation to toxicity.

Background/objectives: Fetuin-A is a multifunctional protein with its urine level was considered as a marker of acute kidney injury. We investigated the serum and urine fetuin-A in acute lymphoblastic leukemia (ALL) children during and after high-dose methotrexate (HDMTX). Methods: Twenty-two ALL children and 20 matched healthy controls were included. Liver transaminases, serum creatinine, estimated glomular filtration rate (eGFR), creatinine clearance (CrCl), serum β2 microglobulin (B2M), and serum and urine fetuin-A levels were assayed pre and 4 months after the consolidation. Among a subgroup of 15 patients, the investigations were performed 42 hours after the start of the second and the fourth HDMTX infusions. Results: HDMTX was well tolerated. During HDMTX, there was significant decline in serum fetuin-A together with significant rise of urine fetuin-A and B2M levels compared to the control and to the pre-consolidation levels, changes that persisted 4 months after the consolidation despite recovery of the significantly altered renal functions. The second HDMTX-related serum fetuin-A level directly correlated with eGFR and CrCl (r = 0.86, P < 0.0001 and r = 0.67, P = 0.016, respectively). Four months after consolidation, urine fetuin-A directly correlated with serum creatinine (r = 0.54, P = 0.004) and inversely correlated with the eGFR (r = −0.66, P < 0.0001). Conclusion: Significant disturbance in serum and urinary fetuin-A levels, which was related to renal functions, had occurred during HDMTX and persisted for at least 4 months after the consolidation. Serum and urine fetuin-A could be sensitive markers for subtle renal dysfunction in ALL children.

Lipid profiles in β thalassemic children

Objectives To study the pattern of serum lipids in β thalassemic children. Background β Thalassemia is a common chronic hemolytic anemia in Egypt. Iron overload is a common sequelae in these patients. Abnormal lipid profile patterns have been suggested to occur in thalassemic patients. Materials and methods Forty-two children with β thalassemia (22 thalassemia major and 20 thalassemia intermedia) were included in the present study with 30 matched controls. Complete blood count, kidney function tests (serum creatinine, blood urea), liver function tests (alanine aminotransferase, aspartate aminotransferase), serum ferritin, and 12-h overnight fasting Serum lipid profiles including total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) triglycerides were performed for patients and controls. Results The thalassemic children had significantly higher platelets count, WBCs count, serum ferritin, alanine aminotransferase, aspartate aminotransferase, and serum triglyceride levels, with significantly lower Hb level, RBCs count, total cholesterol, HDL-C, LDL-C levels, and LDL/HDL ratio compared with the control group. Conclusion β Thalassemic children are at risk of developing disturbed lipid profile patterns that could place them at risk for atherosclerosis and thromboembolic events.

The role of soluble transferrin receptor in iron overload in children with chronic hemolytic anemia

Objectives The current study was conducted to study the pathophysiology of iron overload in children with chronic hemolytic anemia (thalassemia major, thalassemia intermedia, and sickle cell anemia) and to assess the utility of soluble transferrin receptor (sTfR) for the evaluation of iron overload. Background Iron overload is a major complication of repeated blood transfusion in patients with chronic hemolytic anemia. sTfR, one of the main regulators of cellular iron homeostasis, is the truncated form of the tissue receptor. Patients and methods Sixty children with chronic hemolytic anemia (20 thalassemia major, 20 thalassemia intermedia, and 20 sickle cell anemia) were included, together with 20 age-matched and sex-matched controls. Clinical evaluation was performed for each child. Complete blood count along with serum ferritin and sTfR levels (using the ELISA technique) was assessed for both patients and controls. Results Both serum ferritin and sTfR levels were significantly higher in patients (2109±1350 ng/dl and 4.5±1.1 μg/ml, respectively) compared with controls and in patients with thalassemia major compared with those with thalassemia intermedia and those with sickle cell disease. Serum ferritin and sTfR levels were significantly correlated with age and with each other. Each of them negatively correlated with age at disease onset, time space between blood transfusions, and with hemoglobin level. Conclusion The sTfR level could contribute to and be used for the evaluation of iron overload in children with thalassemia and sickle cell disease.