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Article
Association between HLA-Class II Alleles and T-Cell Proliferation in Response to Enterovirus and Adenovirus

Author: Eman M. Saleh
Journal: Iraqi Academic Scientific Journal المجلة العراقية للاختصاصات الطبية ISSN: 16088360 Year: 2007 Volume: 6 Issue: 2 Pages: 102-108
Publisher: The Iraqi Borad for Medical Specialization المجلس العراقي للاختصاصات الطبية

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Abstract

BACK GROUND:Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus (T1DM), either through direct β-cell infection or as triggers of autoimmunity.OBJECTIVE:To evaluate the T- cell proliferation in response to Enterovirus antigens including Coxsackievirus B and Poliovirus in addition to Adenovirus in an HLA- matched population of children with T1DM and children who were healthy.METHODS:A total of 60 Iraqi T1DM children were included in the presents study. They were new onset of the disease. For the purpose of comparisons, 50 apparently healthy control subjects were selected. HLA typing was measured by microlymphocytotoxicity, while methylthiazoltetrazolium (MTT) assay was used for lymphocyte proliferation by culturing peripheral blood lymphocytes (PBL) with Coxsackievirus B5, Adenovirus 3, 4, and 7, and Poliovaccin.RESULTS & CONCLUSION:No significant differences were shown in the PBL proliferative percentage in response to Con-A mitogen and tested viruses (CVB5 and Adenovirus) between T1DM and healthy controls, but PBL proliferative percentage of patients showed a significant decline in response to Poliovaccine. HLA class II (-DR3, DR4, DQ2 and DQ3) antigens were significantly increased in T1DM patients and they played an important role in the etiology of the disease. Strong T-cell proliferation in response to the tested viral antigens were observed to be related to HLA-DR4 and HLA-DQ3 antigens, whereas the HLA-DR3 and HLA-DQ2 alleles were associated with week responsiveness to the same antigens. However, in children with new- onset diabetes, responses were decreased and this could be caused by trapping of virus- specific T- cells in the pancreas


Article
Genetic characteristics and β-cell Autoimmunity in T1DM Children

Author: Eman M. Saleh
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: 00419419 Year: 2007 Volume: 49 Issue: 4 Pages: 414-424
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: TIDM is known to be polygenic disease that appears from the interaction of mutation in multiple genes including HLA. The autoimmune mediated destruction of pancreatic β-cells is reflected by the presence of autoantibodies against prominent antigens in the pancreatic β-cells. Objective: This study was designed to investigate the role of HLA-class I and class II antigens in the etiology of type 1 diabetes mellitus (T1DM) and also assessment of glutamic acid decarboxylase (GAD65) autoantibodies in the patients at the onset of the disease. Patients & Methods: Sixty T1DM patients who were newly onset of the disease (diagnosed less than five months) were selected. Eighty apparently healthy control subjects, matched with age, sex and ethnic backgrounds underwent the HLA-typing by lymphocytotoxicity assay. Finally 50 healthy individuals were selected randomly to undergo serological assessment of GAD65 autoantibodies using IRMA method. Results & Conclusion: At HLA-class I region, T1DM patients showed a significant increased frequency of antigen A9 (40.0 vs.18.75%) and B8 (28.33 vs.8.75%) as compared to control subject. At HLA-class II region, DR3 and DR4 were significantly increased in patients (53.33 vs.26.25% and 50.0 vs. 12.5% respectively) as compared to controls. In addition to that, T1DM was significantly associated with DQ2 (33.33 vs.15%) and DQ3 (40.0 vs. 20%) antigens as compared to controls, suggesting that these haplotypes had a role in disease susceptibility, while the frequency of DR2 and DQ1 antigens were significantly lowered in patients compared to controls (6.66 vs. 25% and 6.66 vs. 22.5% respectively). These molecules might had protective effect. Anti-GAD65 autoantibodies were present in 50% of T1DM children especially in older ages and in females more than males. High proportion of GADA was found in the patients carrying HLA-DR3/DR4 heterozygous. In conclusion, susceptibility to T1DM is genetically controlled.


Article
Investigation of Circulating anti- Coxsackie B, anti- Polio and anti- Adeno IgG in newly diagnosed T1DM Children

Author: Eman M. Saleh
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: 00419419 Year: 2007 Volume: 49 Issue: 4 Pages: 477-481
Publisher: Baghdad University جامعة بغداد

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Abstract

Back ground: Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus (T1DM), either through direct β-cell infection or as triggers of autoimmunity. Objective: To investigate the presence of specific anti- viral IgG antibodies for Coxsackie virus type B (CVB5), Poliovirus, and Adenovirus which proposed to be involved in the etiology of T1DM. Subjects & methods: A total of 60 Iraqi T1DM children were included in the presents study. They were new onset of the disease (diagnosis was from one week up to five months). For the purpose of comparisons, 50 apparently healthy control subjects were selected. Serum IgG against Coxsackie virus type B5, Adenovirus type 3, 4, and 7, and Poliovaccin Trivalent were detected quantitatively with an indirect ELISA. Results: High proportion of anti-CVB5 IgG (20%)(p<0.05) and anti- Polio IgG (31.67%) were found in T1DM children compared to controls (8%, 26% respectively), while anti- Adeno IgG were detected in diabetic patients only (6.67%)(p<1.0001).


Article
Serum levels of cytokines (TNF-&#945;, IFN-&#947;& IL-10) in Type-2 diabetic patients with HCV infection

Authors: Zena T. Mall-Allah --- Eman M. Saleh --- May Y. Saour
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: 00419419 Year: 2011 Volume: 53 Issue: 2 Pages: 198-200
Publisher: Baghdad University جامعة بغداد

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Abstract

Back ground: Type 2 Diabetes mellitus (T2D) is a common complication of all liver diseases. However clinical and experimental data suggest a direct role of HCV in the perturbation of glucose metabolism. The aim of this study is to investigate the role of HCV infection as a risk factor to develop type 2 diabetes mellitus, and to study the immunopathogenicity of HCV in diabetes mellitus patients, through the assessment of IFN-γ, TNF- α and IL-10 serum levels.
Objectives: Is to investigate the role of HCV infection as a risk factor to develop type 2 diabetes mellitus, and to study the immunopathogenecity of HCV in diabetes mellitus patients, through the assessment of IFN-γ, TNF- α and IL-10 serum levels.
Patients and Methods: Thirty six known T2D patients attending the endocrine and diabetes center in Baghdad for check-up were enrolled in this study. Their age ranged from 15- 70 year. Twenty one patients have T2D only while the other Fifteen were have diabetes with HCV infection. Thirteen healthy individuals without any signs or symptoms of disease were also included in this study as healthy controls. Serum levels of cytokines including IFN- γ, TNF-α and IL-10 were analyzed by ELISA immunoassay.
Results: Higher serum levels of IFN-γ and TNF-α were observed in the investigated HCV patients with diabetes (43.87pg/ml, 68.1pg/ml respectively) compared to T2D patients (19.75 and 55.10 pg/ml respectively) and controls (8.08 and 31.4 pg/ml respectively). The statistical analysis revealed a significant difference between these three groups (P= 0.01). The mean serum levels of IL-10 were significantly elevated in T2D group as compared to HCV patients with T2D and control groups (28.7, 10.32, 15.78 pg/ml respectively, p=0.05).
Conclusion: The over production of proinflammatory cytokines (IFN-γ, TNF- α) and the low IL-10 level could play a crucial role in pathogenesis of HCV that leads to T2D via increasing the insulin resistance.

Keywords

T2D --- HCV --- IFN-γ --- TNF-α --- IL-10


Article
Cytokines Profile in Newly Diagnosed Children with Type 1 Diabetes Mellitus

Author: Eman M. Saleh * BSc, PhD د. ايمان مهدي صالح
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: 00419419 Year: 2009 Volume: 51 Issue: 3 Pages: 295-299
Publisher: Baghdad University جامعة بغداد

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Abstract

Summary :Background: Cytokines have long been implicated in the pathogenesis of autoimmune diabetes in a number of studies, and playing a role in the initiation of β-cell damaging process. The objective of this study is to gain more understanding about the role of cytokines in initiation of T1DM, through assessment of IFN-γ, IL-10 and IL-6 in diabetic patients.Patients and methods: A total of 60 patients who were newly diagnosed as having T1DM (diagnosed less than five months) were included in the present study. Fifty apparently healthy control subjects were underwent the measurement of serum IFN-γ, IL-10 and IL-6 by ELISA. Results: Higher serum levels of IFN-γ, IL-10, and Il-6 were observed in the investigated patients ≤10 years (75.60, 104.92, 147.6 pg/ml respectively) compared to controls (42.66, 57.01, 80.4 pg/ml respectively). The statistical analysis revealed a significant difference between patients and controls (P1= 0.005, 0.003, 0.036 respectively). The mean levels of serum IFN-γ, IL-10, and Il-6 were also significantly elevated in >10 years old patients (70.78, 84.22, 171.8 pg/ml respectively) than controls (40.39, 59.50, 81.6 pg/ml respectively), (P1= 0.006, 0.037, 0.04 respectively). A statistically difference of mean IL-10 concentration appears between patients in both age groups (P2= 0.04). No significant differences appear in the mean serum concentrations of IFN-γ, and IL-6 between the two age groups (P2=0.73, 0.07 respectively).Conclusions: In children with diabetes, a significant elevation of serum levels of IFN-γ, IL-10 and IL-6 were observed.Key Words: T1DM, IFN-γ, IL-10 and IL-6

Keywords

: T1DM --- IFN-γ --- IL-10 and IL-6


Article
Detection of GAD¬65 Antibodies in Newly Onset Type 1 Diabetic Children
الأجسام المضادة الذاتية ل (GAD) في الأطفال المصابين بداء السكري من النوع الأول

Authors: Eman M. Saleh ايمان مهدي صالح --- Nidhal abdul Mohymen
Journal: IRAQI JOURNALOF COMMUNITY MEDICINE المجلة العراقية لطب المجتمع ISSN: 16845382 Year: 2008 Volume: 21 Issue: 1 Pages: 75-78
Publisher: Al-Mustansyriah University الجامعة المستنصرية

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Abstract

Summary:Back ground: Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in type 1 diabetes mellitus (T1DM).Aim of the study: Assessment of GAD¬65 autoantibodies in the serum of T1DM children at onset of the disease.Patients & Methods: Serum GAD¬65 autoantibodies has been estimated in 60 sera samples of newly diagnosed T1DM children (diagnosed less than 5 months) in comparison with 50 healthy control children using IRMA method.Results & conclusion: A higher significant proportion of the patients were positive to GAD65 autoantibodies (50%) in comparisons with healthy controls (4.76%) in age group ≤10 years old and (6.90%) in > 10years old (p<0.0001), whereas a significant proportion of girls tested positive for GADA were in age group >10years old (p<0.05). We concluded that GADA are an excellent diagnostic marker for T1DM.Key wards: GAD autoantibodies, T1DM.

المخلص:تم تصميم هذه الدراسة لتحديد المستوى المصلي للأجسام المضادة الذاتية (GAD) في المرضى عند حدوث المرض.شملت الدراسة ستون (60) مريضاً حديثي الإصابة بمرض السكري النوع الأول (مشخصين بالإصابة خلال فترة أقل من خمسة أشهر)، حيث تم قياس المستويات المصلية للأجسام المضادة الذاتية(GAD) بطريقة التالق المناعي(IRMA) ومقارنتها مع عينة السيطرة المؤلفة من(50) شخص.اظهرت النتائج ان هناك ارتفاعا معنويا في نسبة المرضى الموجبين للاجسام المناعية الذاتية (50%) مقارنة مع مجموعة السيطرة(4.76%) في الاعمار اقل من 10 سنوات و (6.9%) في الاعمار اكثر من 10 سنوات (P<0.0001).بالاضافة الى ذلك فان النسبة الاكبر من المرضى الاناث الموجبة لفحص الاجسام المناعية من الاعمار الكبيرة,(P<0.05). وبالتالي فان ان هذا الفحص يعتبر من الفحوص التشخيصية المهمة لمرض السكر من النوع الاول.

Keywords

GAD autoantibodies --- T1DM.


Article
Abnormal Lymphocyte Subsets in Children with Type 1 Diabetes Mellitus

Authors: Majed Al-Jelawy ماجد الجيلاوي --- Nidhal Abdul Mohymen نضال عبد المهيمن --- Eman M. Saleh
Journal: Mustansiriya Medical Journal مجلة المستنصرية الطبية ISSN: 20701128 22274081 Year: 2008 Volume: 7 Issue: 1 Pages: 9-14
Publisher: Al-Mustansyriah University الجامعة المستنصرية

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Abstract

This study was designed to investigate the cellular changes of peripheral blood lymphocytes (PBL) in children with type 1 diabetes mellitus (T1DM) by determining the surface antigens (CD markers). Sixty T1DM patients who were newly diagnosed as type1diabetetics (duration of their illness is less than five months) were selected from the National Diabetes Center at Al-Mustansiriya University during the period May 2004 to October 2005. All the patients were treated with daily replacement doses of insulin. Their age ranged from (3-17) years. Fifty apparently healthy control subjects, matched with age (4-17) years and sex underwent the PBL phenotyping. Phenotyping of lymphocyte surface antigens was done by direct Immunoflurocent (IF) technique using mouse antihuman CD3, CD4, CD8, CD19 and CD56.T1DM patients showed a remarkable lowering in CD3+, CD8+, and CD56+ cells but the decrease in CD4+ cells percentage was not significant in patients in comparison to healthy controls. In contrast, a significant elevation of CD19+ cell percentage and CD4+: CD8+ ratio were observed in the patients.

Keywords

T1DM --- CD markers --- Immunophenotyping


Article
HLA-CLASS II RISK ALLELES CONTROL T-LYMPHOCYTE PROLIFERATION IN RESPONSE TO ENTEROVIRUS AND ADENOVIRUS ANTIGENS AND IgG ANTIBODY PREVALENCE IN NEWLY DIAGNOSED T1DM CHILDREN
دور اليلات الخطورة لنظام مستضدات خلايا الدم البيض البشرية- الصنف الثانى فى استجابة الخلايا اللمفية ضد مستضدات الحمات المعوية والغدية وتفشى اضداد IgG هذه المستضدات في الأطفال المشخصين حديثاًبمرض السكر من النوع الأول

Authors: Nidhal abdul Mohymen نضال عبد المهيمن --- Eman M. Saleh إيمان مهدي صالح
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2007 Volume: 5 Issue: 3 Pages: 47-56
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background: Viral infections are implicated in the pathogenesis of type 1 diabetes mellitus (T1DM) in a number of studies, and playing a role in the initiation of beta-cell damaging process.Objective: To evaluate the T- cell proliferation in response to enterovirus antigens including coxsackievirus B and poliovirus in addition to adenovirus in an HLA- matched population of children with T1DM and children who were healthy, in addition to screening for specific anti-viral IgG antibodies.Subjects and methods: A total of 60 Iraqi T1DM children were included in the presents study. They were newly diagnosed diabetics. For the purpose of comparisons, 50 apparently healthy children were selected. HLA typing was measured by microlymphocytotoxicity, while MTT assay was used for lymphocyte proliferation by culturing peripheral blood lymphocytes (PBLs) with Con-A, Coxsackievirus B5 (CVB5), Adenovirus 3, 4, and 7 serotypes, and Poliovaccine. Serum IgG against these viruses were detected quantitatively with an indirect ELISA.Results & conclusion: No significant differences were shown in the PBL proliferative percentage in response to Con-A mitogen and tested viruses (CVB5 and adenovirus) between T1DM and healthy controls, but PBL proliferative percentage of patients showed a significant decline in response to poliovaccine. Strong T-cell proliferation in response to the tested viral antigens were observed and was related to HLA-DR4 and HLA-DQ3 antigens, whereas the HLA-DR3 and HLA-DQ2 alleles were associated with week responsiveness to the same antigens. High significant mean proliferative percentage for all tested viruses were detected in those patients who were sero-positive IgG as compared to the sero-negative IgG diabetic children.Conclusion: In children with new- onset diabetes, responses were generally decreased, but higher in children who carried risk HLA- class II alleles and who were sero positive to anti- viral IgG antibodies.Key Words: T1DM, HLA class II alleles, Lymphocyte proliferation, Anti- CVB5 IgG, Anti- polio IgG, Anti-adeno IgG.

خلفية الدراسة: أثبتت العديد من الدراسات أن للفايروسات دورا تؤديه في إحداث أمراضية مرض السكر من النوع الأول وقد يكون لها دوراً في بدء عملية تحطيم خلايا بيتا في البنكرياس.هدف الدراسة: الهدف من الدراسة هو لتقييم الفعالية الوظيفية للخلايا اللمفية بعد تحفيزها بمستضدات الحمات المعوية والتي تشمل فايروس الكوكساكي نوعB- (CVB) وفايروس شلل الأطفال فضلاً عن ألحمة الغدية (Adenovirus) في مجموعة من الأطفال المصابين بمرض السكري من النوع الأول ومجموع من الأطفال الأصحاء المطابقين لمستضدات التطابق النسيجي (HLA) من الصنف الثاني فضلاً عن التقصي عن وجود الكلوبيولينات المناعية نوعIgG ضد هذه الفايروسات.طريقة العمل: شملت الدراسة ستون مريضاً حديثي الإصابة بمرض السكري النوع الأول (مشخصين بالإصابة خلال فترة أقل من خمسة أشهر).والذين تم اختيارهم من المركز الوطني للسكري / الجامعة المستنصرية للفترة من مايس 2004 ولغاية تشرين الأول 2005. ولغرض المقارنة تم اختيار مجموعة من الأطفال (50) طفلاً الاصحاء ظاهريا لغرض التحري عن وجود اليلات الخطورة لمستضدات التطابق النسيجي – الصنف الثاني ثم قياس الفعالية الوظيفية للخلايا اللمفية بعد حضنها مع الفايروسات المذكورة سابقاً باستخدام طريقة MTT فضلاً عن قياس المستويات المصلية للكلوبيولين المناعي IgG ضد الفايروسات الثلاثة باستخدام طريقة ELISA الغير مباشرة .النتائج: أظهرت الدراسة الحالية انخفاضاً غير معنوياً في الفعالية الوظيفية للخلايا اللمفية كاستجابة للمشطر Con-A وكذلك باستخدام فايروس CVB النوع المصلي (5) وفايروس الـ Adenoللانواع المصلية 3 ، 4 و 7 في الأطفال المرضى مقارنة بالأصحاء. ولكن هذا الانخفاض كان معنوياً فقط عند استخدام فايروس شلل الأطفال (P < 0.05). وكانت الزيادة في الفعالية الوظيفية للخلايا اللمفاوية معنوياً (P < 0.05) عند المرضى الحاملين للاليلات الخطورة من الصنف الثاني HLA-DR3 ; - DR4 ; - DQ2 ; - DQ3 مقارنة بالمرضى الحاملين للاليلات الأخرى وكذلك عند المرضى الموجبين للكلوبيولينات المناعية نوع IgG مقارنة بالمرض السالبين .الاستنتاج: انخفضت الاستجابة المناعية عموماً في الأطفال المصابين ولكنها ازدادت في الأطفال الحاملين للاليلات الخطورة HLA من الصنف الثاني و الموجبين للكلوبيولينات المناعية نوع IgG المضادة للفايروسات.مفاتيح الكلمات: مرض السكر من النوع الأول ، مستضدات التطابق النسيجي - الصنف الثاني ، الفعالية الوظيفية للخلايا اللمفية ، الكلوبيولينات المناعية نوع IgG ضد فايروس الكوكساكي B النوع المصلي 5 وشلل الأطفال والحمى الغدية.


Article
CD38 EXPRESSION ON PERIPHERAL T AND B LYMPHOCYTES IN NEWLY DIAGNOSED T1DM CHILDREN
الواسم السطحى (CD38) على سطوح الخلایا اللمفیة التائیة والبائیة في الاطفال حدیثي الاصابة بالسكري من النوع الاول

Authors: Nidhal Abdul Mohymen نضال عبد المهيمن محمد --- Eman M. Saleh ایمان مھدي صالح
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2008 Volume: 6 Issue: 3 Pages: 42-46
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background: In Type 1 Diabetes Mellitus (T1DM), numerous changes in the cellular as well humoral immune response have been identified. However, it is not known whether both the CD4+ and CD8+ subpopulation or onlyone of these or CD19+ contains increased numbers of activated cells.Objective: The aim was investigate the expression of CD38 as activated marker on the peripheral blood lymphocytes of T1DM children at the onset of the disease.Patients and methods: A total of 60 T1DM patients who were newly onset of the disease (diagnosed less than five months) were included in the present study, all the patients were treated with daily replacement doses of insulin. Fifty apparently healthy control subjects underwent the peripheral blood lymphocytes (PBL)phenotyping. Phenotyping of surface antigens was done by direct Immunoflurocent (IF)technique using mouse antihuman CD38.Results: Increased percentage of activation marker CD38+ cells were observed in T1DM patients (24.72%, 23.83%) as compared with the control group (16.86%, 15.97%) in the age group ≤10 years and >10 years old respectively. These differences were highly significant (P1=0.0001)between the patients and healthy individuals, but failed to reach a significant level (P2= 0.44)between the patients in both age groups.Conclusion: A significant elevated percentage of CD38+ activation marker cells were detected in the patients.

خلفية الدراسة: فى مرض السكرى من النوع الاول تحدث تغييرات فى كثير من الاستجابات الخلوية بالاضافة الى الدموية. ولا يعرف بالتحديد هل ان هذه التغييرات تحدث فى الخلايا الحاملة للواسم CD4 او الواسم CD8 او كلاهما او الحاملة للواسم CD19. هدف الدراسه: تهدف الدراسة الى التقصى عن تعبير الواسم CD38 على سطوح الخلايا اللمفية الفعالة فى الدم المحيطى للاطفال حديثى الاصابة بالسكرى من النوع الاول. المرضى وطريقة العمل: اجريتالدراسة على ستين (60) مريضاً حديثي الإصابة بمرض السكري النوع الأول (مشخصين بالإصابة خلال فترة أقل من خمسة أشهر)، تم اختيارهم من المركز الوطني للسكر / الجامعة المستنصرية. جميع المرضى هم تحت المعالجة اليومية بجرعات الانسولين وتمت المقارنة مع (50) شخص يبدون اصحاء كمجموعة سيطرة لغرض اجراء التشخيص المظهرى للواسمات السطحية للخلايا اللمفية بطريقة التالق المناعي المباشر وباستخدام الواسم السطحي CD38. النتائج: أظهر مرضى السكر من النوع الأول ارتفاعاً معنوياً ملحوظاً (p=0.0001)في عدد الخلايا اللمفية الموجبة للواسم الفعال CD38 (24.72% و 23.83) مقارنة بمجموعة السيطرة (16.86% و15.97) فى مجموعة الاعمار اقل من 10 سنوات واكثر من 10 سنوات بالتعاقب. ولكن هذه الزيادة لم تكن معنويةً للخلايا الموجبة للواسمة عند المقارنة بين مجاميع المرضى (p=0.4).الاستتاجات: هنك زيادة ملحوظة في نسبة الخلايا اللمفية المحيطية الحاملة للواسم الفعال CD38 في مرضى السكر من النوع الاول.مفاتيح الكلمات: مرض السكري من النوع الاول, الواسمة السطحية CD38, التشخيص المظهري المناعي.


Article
Analysis of Data Obtained From Chromosomal StudiesPerformed During the Period from 2000-2007A Retrospective Study

Authors: Eman M. Saleh ايمان مهدي صالح --- nidhal abdul mohymen نضال عبد المهيمن
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: 00419419 Year: 2008 Volume: 50 Issue: 1 Pages: 56-62
Publisher: Baghdad University جامعة بغداد

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