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   Table of Contents - Current issue
Coverpage
July-September 2018
Volume 43 | Issue 3
Page Nos. 97-150

Online since Monday, December 3, 2018

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ORIGINAL ARTICLES  

The abnormal iron homeostasis among Egyptian obese children and adolescents: relation to inflammation of obesity p. 97
Ehab K Emam, Marwa H.A Hamed, Dina A Fouad, Reham O Abd-Allah
DOI:10.4103/ejh.ejh_52_17  
Background Obesity is associated with low-grade inflammatory changes that increase Fe tissue storage and affect the level of circulating serum Fe, leading to tissue overload and decreased availability of Fe for hematopoiesis. Objectives The objectives of this study were to determine the relation between the low iron state and the chronic inflammation found in obese children and to assess the role of inflammatory markers in the detection of iron status. Design and setting This was a case–control study. This study was conducted in the outpatient and clinical nutrition clinics of Pediatric Hospital, Ain Shams University. Patients and methods This was a case–control study conducted on 50 obese children and adolescents over 1 year. They were divided into two subgroups: iron deficient and noniron deficient patients. The study also included 20 normal weight children and adolescents as controls. All patients were subjected to the obesity sheet, anthropometric measurements, complete blood picture, measurement of iron profile and high-sensitivity C-reactive protein (hs-CRP). Results There were significantly lower mean values of hemoglobin, serum iron, ferritin and transferrin saturation among obese than among nonobese children. The mean serum level of hs-CRP was significantly higher among obese children than controls, and, of the 50 obese patients, 62% had high levels. The mean serum level of hs-CRP among anemic obese patients was significantly higher than in the nonanemic obese group. The hs-CRP showed significant positive correlations with BMI and significant negative correlations with serum iron. Conclusion The chronic inflammation changes of obesity lead to a low iron state. Thus, regular follow-up of obese children by measuring serum hs-CRP, hemoglobin, and iron profile is mandatory.
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Evaluation of multiprobe fluoresence in-situ hybridization panel in the detection of common chromosomal abnormalities of acute myeloid leukemia p. 103
Amani F Sorour, Dalia A Nafea, Rania S Swelem, Eshraq M Soliman
DOI:10.4103/ejh.ejh_50_17  
Background Numerous recurrent chromosomal aberrations have been identified in acute myeloid leukemia (AML), and their detection has become essential for accurate diagnosis, classification, and prognosis of the disease. Fluorescence in-situ hybridization (FISH) provides a powerful technique complementary and even alternative to chromosome banding studies for the identification of selected chromosome aberrations. Aim Evaluation of the multiprobe FISH panel in the detection of common cytogenetic abnormalities in AML and to investigate their association with clinical diagnosis, chemotherapy, and prognosis. Patients and methods This study was conducted on 20 newly diagnosed AML patients. All patients were subjected to full history taking, clinical examination, laboratory investigations including complete blood count, bone marrow aspiration, immunophenotyping, and interphase FISH using cytocell multiprobe AML/myelodysplastic syndrome panel designed to detect AML/Eight-twenty-one (ETO), Promyelocytic leukaemia- Retinoic acid receptor alpha (PML-RARA), and core-binding factor beta/Myosin, heavy chain 11, smooth muscle (CBFβ/MYH11) translocations, mixed-lineage leukaemia (MLL) break apart, P53, 5q, 7q, and 20q deletions. Results Interphase FISH analysis showed 5q deletion in 8/20 (40%) cases, positive PML/RARA in 3/20 (15%) cases p53 deletion in 15/20 (75%) cases, positive AML1/ETO in 1/20 (5%) cases, no MLL break apart cases (0%), 7q deletion in 4/20 (20%) cases, positive CBFβ/MYH11 fusion gene in 4/20 (20%) cases, 20q deletion in 9/20 (45%) cases, and trisomy 8 in 7/20 (35%) cases. There was a statistically significant relationship between 5q deletion and prognosis (P=0.028). Conclusion Multiprobe FISH is more cost effective and time effective compared with traditional FISH. It is an efficient technique for the detection of cytogenetic aberrations AML, providing critical information for diagnosis and prognosis, and for monitoring the course of the disease.
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Signaling lymphocytic activation molecule family-1 (CD150) expression as a prognostic indicator in patients with chronic lymphocytic leukemia p. 109
Rasha A Elkholy, Alzahraa A Allam
DOI:10.4103/ejh.ejh_4_18  
Introduction Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy characterized by the accumulation of mature monoclonal CD5-positive B-lymphocytes in the peripheral blood, bone marrow, and secondary lymphoid tissues. It is characterized by remarkable clinical variability. CD150 is a multifunctional type I transmembrane glycoprotein; it has been suggested that CD150 expression modulates CLL response to chemokines and regulates autophagy. Aim The aim of this study was to determine the expression of CD150 in patients with CLL and its relation to the other well-established prognostic markers and also to determine its impact on patient survival. Patients and methods This case–control study was performed on 50 newly diagnosed CLL patients and 50 apparently healthy individuals as a control group. CD150 expression was measured by flow cytometry. Results This study has shown that CD150 expression was decreased in CLL patients compared with the control group, with great heterogeneity between CLL patients. There were negative correlations between CD49d, CD38, ZAP-70 expression, clinical staging of CLL patients, and CD150 expression, whereas there were positive correlation between hemoglobin level, platelets count, and CD150 expression. Patients with CD150 expression less than or equal to 6% of CD19-positive B-lymphocytes have shorter progression-free survival and overall survival and needed to start treatment early. Conclusion CD150 can be a useful tool in identifying B-CLL patient’s risk.
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Effect of homocysteine and folic acid on vaso-occlusive crisis in children with sickle cell disease p. 115
Ahmed A Raouf, Mona M Hamdy, Ahmed M Badr, Osama Shalaan, Moustafa Sakr, Abdel R.A Rahman
DOI:10.4103/ejh.ejh_1_18  
Introduction Vaso-occlusion is a determinant for most manifestations of sickle cell anemia (SCA). Elevated concentration of homocysteine contributes to thrombosis, a frequent event in SCA. Folic acid deficiency leads to increase in plasma homocysteine. The aim of study was to test whether children with SCA have elevated serum homocysteine with diminished folate level and to determine whether hyperhomocysteinemia has a correlation with the frequency of vaso-occlusive crisis. Patients and methods A case–control study was carried over a period of 1 year (January to December 2014) in the hematology clinic, Abo El-Reesh Hospital, Cairo University. A total of 50 patients with SCA were included together with 30 age-matched and sex-matched healthy children recruited from Menoufia Hospital. Venous blood samples were obtained from both groups to measure serum homocysteine and folic acid levels. Results The mean±SD of age of the patients and controls were 6.20±2.55 and 6.03±2.64 years, respectively. Homocysteine level was significantly higher in the patients group compared with control group, with a mean±SD of 44.68±9.096 and 18.81±3.76 µmol/l, respectively (P>0.01). Folic acid level was lower in the patients group than control group, with 12.02±2.76 and 14.68±2.99 ng/ml, respectively (P<0.05). Significant inverse correlation was found between homocysteine and folic acid (correlation coefficient −0.337 and P=0.017). A strong positive correlation between homocysteine level and the frequency of vaso-occlusive crisis was found (P=0.04). Conclusion Patients with sickle cell disease have high serum homocysteine with low folate levels. This hyperhomocysteinemia is positively correlated with the frequency of vaso-occlusive crisis.
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T helper 1/T helper 2-associated chemokine and chemokine receptor expression in immune thrombocytopenia p. 119
Nadia I Sewelam, Hanan Al-Wakeel, Zainab El Saadany, Rania Magdy, Nevin Fouad
DOI:10.4103/ejh.ejh_12_18  
Background Immune thrombocytopenia (ITP) is an acquired immune disorder. Chemokines have complicated role in different autoimmune disorders including ITP. C-C motif chemokine ligand 2 (CCL2) chemokine represents a T helper (Th)2 polarizing chemokine, whereas C-X-C motif chemokine receptor 3 (CXCR3) and C-C motif chemokine receptor 2 (CCR2) represent chemokine members with Th1 polarization effect on the immune system. ITP is associated with an imbalance in Th1/Th2 ratio and favors Th1 polarization. This study aimed to explore the role of CCL2 and its receptor CCR2 in addition to CXCR3 receptor gene expression in the pathogenesis and severity of ITP. Participants and methods Expression of CCL2, CCR2, and CXCR3 was assayed using real-time quantitative polymerase chain reaction in peripheral blood mononuclear cells of 21 normal healthy participants and 68 patients with ITP: 24 acute cases, 25 chronic responder cases, and 19 chronic non-responder cases. Results Acute ITP group showed a 1.85 median fold change in CCL2 gene expression from the control group. CCR2 and CXCR3 showed a higher median fold change from the control group in acute ITP (7.36 and 5.42, respectively) and in chronic non-responder patients (3.38 and 4.32, respectively), whereas the chronic responder patients showed the least changes (1.63 and 2.35, respectively). There was no significant difference in chemokine or chemokine receptors gene expression between different ITP groups (P>0.05). Statistically significant positive correlations were detected between CCL2 and CCR2 (r=0.453, P<0.001) and between CXCR3 and CCR2 (r=0.583, P<0.001) among patients with ITP. Conclusion CCR2 and CXCR3 but not CCL2 may have a role in ITP pathogenesis. Further studies investigating the role of the complicated chemokine network may help better understanding of ITP pathogenesis.
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Oxidative DNA damage and RUNX1-RUNX1T1 translocation induced by cigarette smoking as a potential risk factor for leukemogenesis p. 125
Mohammed M El-Khawanky, Ahmed M Solaiman, Basel A Abdel-Wahab
DOI:10.4103/ejh.ejh_16_18  
Background Cigarette smoking, one of the main causes of avertible morbidity and mortality, has a multitude of well-known side effects. Cigarette smoking contains large amounts of reactive oxygen species that induce oxidative DNA damage and increase the incidence of chromosomal aberrations and thus increases the incidence of oncogenesis. Aim The aim of this work is to study the hematological effects of smoking and its ability to induce DNA damage and specific RUNX1-RUNX1T1 gene translocation. Patients and methods The hematological studies and measurement of plasma concentration of 8-hydroxy-2’-deoxyguanosine (8-OHDG) (using enzyme-linked immunosorbent assay) and RUNX1-RUNX1T1 translocation t(8;21) (using reverse transcription-PCR) were conducted on two groups of participants one smoking and the other is a nonsmoking control group. Results Smokers group showed a highly significant (P≤0.001) increase in plasma 8-OHDG and with a significant correlation between 8-OHDG and hemoglobin concentrations. In addition, the incidence of translocation(8;21) was 8.3% in the smokers’ group with obvious myelodysplasia of peripheral white blood cells was detected in 29.2% of smoking persons.
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Gravin and survivin gene expression levels as possible therapeutic targets for acute myeloid leukemia in adult Egyptian patients p. 131
Hadeer A Abbassy, Dalia A Elneely, Ahmed A Shehata
DOI:10.4103/ejh.ejh_11_17  
Background Despite the recent progress in diagnosis and management, acute myeloid leukemia (AML) still remains a fatal hematologic malignancy, which invites the need for accurate predictors of clinical outcome. Objective The aim of the present study was to explore the possible prognostic importance of gravin and survivin gene expression in adult patients with de-novo AML by correlating their expression levels with response to induction therapy, disease-free survival (DFS), and overall survival (OS). Patients and methods This study was conducted on 105 patients with de-novo AML, and 45 age-matched and sex-matched patients were selected as a control group. RNA isolation from bone marrow aspirates or peripheral blood and cDNA preparation followed by quantitative real-time reverse transcription-PCR were done to assess expression of gravin and survivin. Results Gravin expression was markedly downregulated whereas survivin gene showed an overexpression in AML cases. There was a significant association between gravin and survivin expression levels with poor clinical outcome. OS and DFS were significantly lower in patients with low gravin and high survivin expression levels. Conclusion Survivin overexpression and gravin downregulation were significantly associated with adverse clinical outcome and tendency to chemoresistance in AML. The degree of their expression derangement has been found to be correlated with a lower complete remission rate and shorter OS and disease-DFS which renders them as future candidates for target through adjuvant immunotherapy.
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‘Gatekeeper’ mutation in patients with chronic myeloid leukemia resistant to imatinib therapy: effect on survival p. 138
Mohamed A.M El-Menoufy, Amel A El Naggar, Laila E.S Ziada
DOI:10.4103/ejh.ejh_18_18  
Background T315I is the most difficult type of point mutation that appears during treatment of chronic myeloid leukemia (CML). It represents kind of a ‘gatekeeper’ that controls access of small molecule inhibitors and confers resistance to the most known tyrosine kinase inhibitors. Aim The aim of the present study was to assess the characteristics of Egyptian patients with CML harboring T315I mutation and to evaluate its effect on the patients’ survival. Patients and methods A total of 45 patients with CML in chronic phase resistant to imatinib mesylate (IM) treatment were enrolled in this study. Allele-specific oligonucleotide-PCR was used to detect T315I BCR-ABL gene mutation in all patients at the time of IM resistance. Results T315I mutation was present in 11 (24.4%) patients. The level of resistance was heterogeneous. Responses were observed in two resistant T315+ patients with IM dose escalation and three patients who were shifted to second-generation tyrosine kinase inhibitor. There was no significant difference in patient characteristics and overall survival between T315I+ and T315I resistant patients. Overall survival is significantly associated with the duration of response and the phase of the disease at the time of resistance. Conclusion Evaluation of T315I mutation is recommended in all patients with CML, even in the early phase of the disease, which may be subsequently associated with resistance or progression of their disease in the future and requires the need for an alternative therapeutic option(s).
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CASE REPORT Top

Brucellosis associated with transient myelodysplastic features p. 145
Khalid Al-Hashmi, Fahad H Al-Ghafri, Anil Pathare
DOI:10.4103/ejh.ejh_8_18  
This case demonstrates transient dysplasia in two cell lines associated with brucellosis infection which completely resolved upon treatment. Brucellosis is an important public health problem in the Middle Eastern and Mediterranean cultures, where animal husbandry including cattle grazing is an integral part of daily life in rural areas. This is the first report to our knowledge of brucellosis causing transient myelodysplasia in a brucella endemic area.
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LETTER TO THE EDITOR Top

Screening of EPCR gene mutations in children with acute lymphoblastic leukemia p. 149
Dilara F.A Bali, Didem T Özkan, Emin Kürekçi, Nejat Akar
DOI:10.4103/ejh.ejh_13_18  
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