• Users Online: 362
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Reader Login
Export selected to
Endnote
Reference Manager
Procite
Medlars Format
RefWorks Format
BibTex Format
  Access statistics : Table of Contents
   2013| April  | Volume 38 | Issue 2  
    Online since June 20, 2014

 
 
  Archives   Previous Issue   Next Issue   Most popular articles   Most cited articles
 
Hide all abstracts  Show selected abstracts  Export selected to
  Viewed PDF Cited
ORIGINAL ARTICLES
Subcutaneous iron chelation therapy, oral iron chelation therapy, or both in patients with thalassemia?
Gihan M. Babrs, Mohammed A. Abd El-Hakeem
April 2013, 38(2):51-55
DOI:10.7123/01.EJH.0000427962.62047.43   
Background

This study aimed to compare the efficacy of different iron-chelating agents, namely deferoxamine (DFO), deferiprone (DFP), and deferasirox and combined DFO and DFP in reducing serum ferritin levels in thalassemic patients attending the Pediatric Hematology Clinic of the Children and Obstetrics and Gynecology Hospital, Minia University.

Patients and methods

A total of 57 patients with thalassemia major attending the Pediatric Hematology Clinic of Minia University were included in the study. They were classified into four groups according to type of chelation: the DFO group included 12 patients, the DFP group included 18 patients, the deferasirox group included 15 patients, and the combined DFO and DFP group included 12 patients. The patients were subjected to thorough history taking, clinical examination, and laboratory investigation (complete blood count, liver function and renal function tests, and levels of hepatitis B surface antigen, hepatitis C antibody, and initial serum ferritin at the start of the study and final serum ferritin levels after 1 year of chelation).

Results

The mean serum ferritin levels decreased significantly in all groups after 1 year (P<0.001), with more reduction in the combined therapy group. Four (22.2%) patients developed elevated liver transaminases and six (33.3%) developed mild bone pain and arthralgia during treatment with oral DFP. However, none of our patients developed neutropenia/agranulocytosis or significant gastrointestinal tract symptoms. There were no detectable side effects on administering deferasirox, except for some gastrointestinal tract pain that improved with continued treatment.

Conclusion

The three iron-chelating agents are effective in reducing the serum ferritin levels in thalassemic children, with the combined DFO and DFP therapy being more effective.

  1,124 200 -
B-cell clonality and t(14;18) in Egyptian patients with chronic hepatitis C and its relation to antiviral therapy
Walaa Othman, Dalia A. Salem, Sherin M. Abd El-aziz, Mona M. Arafa, Raghda E. Farag, Shahira Eletreby
April 2013, 38(2):90-95
DOI:10.7123/01.EJH.0000428091.03779.b7   
Background

The mechanism of lymphomagenesis of hepatitis C virus (HCV)-related B-cell lymphoma is unknown. Recently, it has been suggested that HCV may induce B-cell clonal proliferation and t(14;18) translocation in patients chronically infected with the virus.

Aim

The aim of this study was to assess the occurrence of immunoglobulin heavy chain (IgH) gene rearrangement and t(14;18) translocation in Egyptian chronic HCV patients and to examine the effect of antiviral treatment on IgH rearrangement and t(14;18) in HCV-infected patients.

Patients and methods

Forty-five Egyptian patients with chronic HCV infection were selected. The level of HCV-RNA in the serum was quantified using the Stratagene Mx3000P Real-Time PCR System at diagnosis and 3, 6, and 12 months from the beginning of the therapy. IgH clonality was detected using multiplex VH-JH (FR2) PCR, whereas t(14;18) was detected using nested PCR before and after antiviral therapy.

Results

After 3 months of antiviral therapy, 24/45 patients (53.3%) showed an early virological response and completed their 12 months of antiviral therapy, after which they showed complete clearance of serum HCV-RNA (responder group). However, 21/45 patients (46.7%) did not show early virological response and hence stopped their therapy (nonresponder group). Clonal IgH rearrangement and t(14;18) were detected in 33.3 and 40% of patients, respectively. The percentage of patients who lose their clonal IgH or t(14;18) varies according to the completion of antiviral therapy. On comparing responder (12 months therapy) versus nonresponder (3 months therapy) groups, the loss of clonal IgH was nonsignificant (100 vs. 66.7%, P=0.134) whereas it was highly significant in terms of regression in t(14;18) (75 vs. 0%, P=0.0006).

Conclusion

In Egyptian patients with chronic HCV infection, the presence of clonal B cell and t(14;18) is a frequent finding. Twelve months of antiviral therapy are efficiently effective for regression of clonal IgH gene rearrangement and t(14;18).

  1,120 77 -
SHP-1 expression in chronic myeloid leukemia ( clinical significance and impact on response to imatinib treatment)
Nihal M Heiba, Shereen A Elshazly
April 2013, 38(2):84-89
DOI:10.7123/01.EJH.0000428064.36941.33   
Background

SH2-containing tyrosine phosphatase (SPH-1) is a negative regulator of protein tyrosine kinases and is also a tumor suppressor that is physically and functionally linked to BCR-ABL, the hallmark for pathogenesis, diagnosis, and targeted therapy in chronic myeloid leukemia (CML).

Aim

This study aimed at investigating the levels of SHP-1 mRNA during chronic phase (CP), accelerated phase (AP), and blast phase (BP) CML and also assessing its impact on the response of CP-CML patients to imatinib mesylate (IM) therapy.

Patients and methods

The study was carried out on 77 newly diagnosed CML patients (56 CP, 13 AP, and eight BP). Ten age-matched and sex-matched volunteers free from any hematological or nonhematological malignancies served as the control group. Patients were diagnosed and classified into appropriate phases according to the WHO criteria by clinical and radiological examination, cytomorphological analysis, neutrophil alkaline phosphatase scoring, conventional cytogenetic analysis, FISH for t(9; 22) and real-time quantitative PCR analysis for BCR-ABL fusion transcripts. CP patients received IM therapy and were followed up for assessment of the response to treatment. SHP-1 mRNA levels were measured at diagnosis using real-time quantitative PCR.

Results

SHP-1 levels were highly significantly increased in CP-CML patients (5.8–538; median 48.1) compared with normal controls (2.6–8.3; 5.2) and patients presenting with AP (2.1–168; 13.8) or BP (1.9–173; 12.3) (P<0.01). The levels were not correlated with the patients’ clinical or laboratory data. Follow-up of CP-CML patients on IM therapy revealed that patients with lower baseline SHP-1 levels were less likely to achieve a major molecular response at 18 months compared with those with higher levels. SHP-1 was highly significantly elevated in optimal responders compared with suboptimal responders and those who failed treatment (12.1–538; 63.2 vs. 5.8–177; 15.1) (P<0.01); these levels not being correlated to the Sokal risk score.

Conclusion

SHP-1 mRNA expression is downregulated in patients with more progressive CML. Moreover, determining the SHP-1 levels at diagnosis can provide a biological predictor of the IM response in patients with CP-CML.

  1,054 100 -
Evaluation of platelet dysfunction in viral liver cirrhosis ( relationship to disease severity)
Manal F. Ghozlan, Abeer A. Saad, Deena S. Eissa, Heba M. Abdella
April 2013, 38(2):63-67
DOI:10.7123/01.EJH.0000427964.00166.73   
Background

Hepatitis C virus (HCV) is a major health problem in Egypt, which has the highest HCV prevalence worldwide. Cirrhotic patients are known to have acquired platelet hypofunction; however, HCV-induced inflammatory and immunological phenomena are thought to be responsible for in-vivo platelet activation. This study aimed to evaluate the platelet function in patients with HCV-induced liver cirrhosis and also to study the relationship of platelet function to disease severity and various clinical/laboratory findings in cirrhotic patients.

Materials and methods

Evaluation of platelet function was carried out on 50 patients with HCV-induced liver cirrhosis using the platelet function analyzer-100 (PFA-100), compared with 30 healthy volunteers.

Results

The study demonstrated the presence of platelet hypofunction reflected by the prolonged PFA-100 closure time in patients of Child–Pugh stage B compared with those of stage A and C, in moderate compared with negative/mild and severe ascites, and in grade II esophageal varices compared with other grades. Patients with Child–Pugh stage B and C, severe ascites, and stage III/IV esophageal varices had significantly lower platelet count/spleen size ratios.

Conclusion

Chronic HCV-induced liver cirrhosis is implicated in alterations of primary hemostasis, with platelet hypofunction being more evident during relatively earlier disease stages compared with the later ones. PFA-100 closure time and platelet count/spleen size ratio could be used as noninvasive predictors of the grades of esophageal varices in cirrhotic patients. The simplicity of the PFA-100 could facilitate its use as a convenient primary screening test to detect platelet dysfunction in HCV-induced liver cirrhosis.

  1,000 115 -
Correlation between platelet–monocyte aggregates and prevalence of vascular complications in type II diabetes
Magda A. Zeidan, Ibrahim M. Rageh, Howyda M. Kamal, Asmaa M. Esh
April 2013, 38(2):56-62
DOI:10.7123/01.EJH.0000427963.62047.0a   
Background

Platelet–monocyte aggregates (PMA) play an important role in the development of microvascular disease and atheromatous lesions. Increased numbers of circulating proinflammatory monocytes, activated platelets, and/or leukocyte–platelet aggregates have been observed in patients with chronic inflammatory conditions such as diabetes mellitus (DM).

Objective

The aim of the study was to investigate whether the circulating PMA levels were increased in patients with DM, whether they may be correlated to the vascular damage presently observed in DM, and whether PMA can be used as a simple marker for the early prediction of diabetic microvascular complications.

Patients and methods

We examined PMA in 15 apparently healthy normal individuals who were included as the control group A, in 19 patients with DM without microvascular injuries who constituted control group B, and in 59 patients with DM with microvascular injuries who constituted group C, admitted to Benha University hospitals. All groups were subjected to a full medical history taking, thorough clinical examination and laboratory investigations (complete blood counts and measurement of the levels of cholesterol, triglycerides, serum creatinine, HbA1c), and detection of CD14 (monocyte marker) and CD41 (platelet marker) using flow cytometry.

Results

There was a significant increase in the PMA% in patients with DM compared with the control group A, and it was increased in patients of group C compared with group B. Moreover, the study revealed that there was a significant positive correlation between the PMA% and glycemic state in patients with DM, represented by the HbA1c levels and a significant positive correlation between the PMA% and lipid state of patients (cholesterol and triglycerides).

Conclusion

Determination of levels of circulating PMA using flow cytometry can be used as a simple marker of microvascular injury in patients with DM.

  924 116 -
ADAMTS-13 contents in therapeutic plasma products
Samy B.M. El-Hady, Manal H. Farahat, Eman Almasry
April 2013, 38(2):68-73
DOI:10.7123/01.EJH.0000427965.07789.06   
Background

ADAMTS-13 is a zinc-containing metalloprotease enzyme that cleaves the von Willebrand factor (VWF). In human beings, changes in ADAMTS-13 levels have been observed in a number of diseases. The determination of ADAMTS-13 levels and those of its substrate will help to elucidate therapeutic strategies including ADAMTS-13 supplementation for these diseases. Successful treatment has been reported with both fresh-frozen plasma and cryoprecipitate poor plasma (CPP) as replacement fluids. This study aimed to investigate ADAMTS-13 and some coagulation factors in the different plasma products commonly used to increase ADAMTS-13 levels.

Materials and methods

A total of 180 U of whole blood (WB) were collected from healthy young male blood donors, their ages ranging from 20 to 32 years. Sixty donors were of blood type O+, 50 were A+, 50 were B+, and 20 were AB+. All blood donors included in this study underwent tests for assessment of their liver and kidney functions, and they were declared free from any disease. Plasma from the blood samples was extracted either on the day of collection (the platelet-rich plasma method) or after an overnight hold of WB (the Buffy coat method). Factor VIII (FVIII) activity was measured and levels of fibrinogen, VWF, and human ADAMTS-13 in plasma were quantitatively determined.

Results

There was no difference in the mean concentrations of ADAMTS-13 in plasma products obtained using the two different methods. Blood group O showed a higher concentration compared with other ABO blood groups. The concentration of ADAMTS-13 was higher in cryoprecipitate than in plasma and CPP. The mean values of FVIII activity were lower in many plasma and cryoprecipitate units prepared by overnight holding of WB for close to 24 h. In addition, the mean values of FVIII activities and VWF levels were lower in plasma and cryoprecipitate units prepared from blood group O compared with those prepared from other ABO blood groups. No differences were detected in the mean values of fibrinogen and VWF in the plasma products when different methods were used for preparation.

Conclusion

The observation that the concentration of ADAMTS-13 is higher in cryoprecipitate than in plasma and CPP suggests that cryoprecipitate may be a reasonable source of ADAMTS-13 in clinical settings when volume is an issue. In addition, in our study, the use of cryoprecipitate from blood group O in clinical settings yielded higher concentrations of ADAMTS-13 with less VWF. Although the use of cryoprecipitate instead of plasma or CPP could potentially double the amount of ADAMTS-13 infused, further studies from multiple centers are needed to validate the results.

  875 120 -
Smac/DIABLO gene expression in acute myeloid leukemia patients
Ghada A. Suliman, Maaly M. Mabrouk, Enaam S. Rabee, Amr Gawaly
April 2013, 38(2):80-83
DOI:10.7123/01.EJH.0000428063.29317.e1   
Background

Smac/DIABLO enhances apoptosis by antagonizing the inhibitors of apoptotic proteins. The expression of Smac/DIABLO in different cancers has been reported. The study aimed to evaluate Smac/DIABLO gene expression in patients with acute myeloid leukemia (AML) and also to determine its relation to the clinical outcome and survival of these patients.

Materials and methods

Smac/DIABLO gene expression was studied using real-time PCR in bone marrow samples from 70 newly diagnosed AML patients.

Results

The Smac/DIABLO gene was expressed in 88.5% of AML patients. A total of 32 patients (51.6%) with positive Smac/DIABLO expression responded to treatment, and the remaining 30 patients (48.4%) were treatment resistant. Smac/DIABLO expression was associated with decreased lactate dehydrogenase levels and increased disease-free survival (P=0.01 and P<0.001, respectively). The expression was associated with an increase in the survival rate (P<0.05).

Conclusion

There was an increase of Smac/DIABLO expression in AML patients, and this was associated with the treatment response, increased disease-free survival, and better overall survival.

  733 87 -
Prognostic value of chemokine CCL3 cellular mRNA expression and serum CCL3 level in lymphoma patients
Maaly M. Mabrouk, Amal Ezzat, Ghada A. Suliman, Dareen A. Aziz, Omnia Abd Elfattah
April 2013, 38(2):74-79
DOI:10.7123/01.EJH.0000428062.52188.cc   
Background

Chemokines are responsible for metastatic dissemination of cancers, including lymphomas. CCL3, a monocyte inflammatory protein-1 α, has been shown to be active as an inhibitor of primitive hematopoietic cell proliferation in vitro and in vivo. A dysfunction in this inhibitory process has been postulated to contribute to lymphomagenesis. The aim of this study was to measure the serum level of CCL3 and CCL3 mRNA in lymphoma patients compared with its expression during reactive lymphadenopathy; we also studied their effect on treatment response and survival of lymphoma patients.

Materials and methods

The study included 53 lymphoma patients and 20 reactive lymphadenopathy patients. The serum level of CCL3 was assessed using the enzyme-linked immunosorbent assay technique, and CCL3 gene expression was measured using real time PCR.

Results

There was a significant increase in the serum level of CCL3 in lymphoma patients (mean, 72.5±24.3 pg/ml) compared with reactive lymphadenopathy patients (mean, 31.5±12.6 pg/ml). Receiver–operator characteristic curve analysis showed a cutoff value of more than 55 pg/ml. There were positive and negative correlations with the lactate dehydrogenase level and time of follow-up (months), respectively. CCL3 expression was higher in lymphoma patients (90.5%) than in reactive lymphadenopathy patients (35%). Increased serum levels and expression of CCL3 were associated with treatment resistance. As regards survival, increased CCL3 expression was associated with decreased survival rate in lymphoma patients.

Conclusion

CCL3 serum levels or gene expression could be a valuable prognostic marker and may provide insight into creating a new therapeutic modality.

  743 70 -