Department of Internal Medicine

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    The Diversity of Interferon γ,Interferon γ Receprtor-1 and Toll-like Receptors among Multi Drug Resistance Pulmonary Tuberculosis Patients in Sudan.
    (University of Khartoum, ) Attalla Mohammed Attalla Elhassan ; Ahmed Modawi Musa
    Introduction: The annual incidence of pulmonary tuberculosis reached eight millions leading to 2-3 millions deaths and five percent MDR/TB infection, MDR/TB and XDR/TB are a major threat to global TB control program. There are few studies on impact of host gene regulating the immune response on development of (MDR+XDR) tuberculosis. The objective of this study was to measure TH1 and TH2 cytokine markers and determine the association of (IFNγ,IFNγR1 and TLR4) gene polymorphism with the development of MDR/ TB in Sudan. Material and Methods: This case control study was conducted in Abu Anga Chest Hospital. Sputum samples were collected from every participant for the direct smear using the Z.N stain method to determine the presence of the acid fast bacilli. Ninety one participants were consented and enrolled in the study. Thirty were diagnosed as sensitive pulmonary tuberculosis patients and fifty nine patients were confirmed MDR/TB based on genexpert results. Healthy males attending blood banks and healthy females attending obstetric hospital were enrolled as controls. Venous blood samples were collected in EDTA blood collection tubes and used for DNA extraction and measurement of plasma IFNγ (TH1) and IL-10 (TH2) cytokine markers. The cytokines were measured using captured ELISA. The DNA was analyzed to determine the presence of three polymorphism IFN-γ R1 874 A/T (rs2430561) using arms PCR allele specific primers, PCR-RFLP for screening of IFNγR1 1050T /G (rs1191) and sequencing of TLR4 gene to determine the associations with sensitive TB and MDR/TB. Results: The mean age of the study participants was 36.7 years and the age range was from 18 to 95 years. The highest incidence of the disease was found among the age group (20-30 years). There was no significant difference in IFNγ and IL-10 concentration between MDR/TB and sensitive TB patients and controls. IFN-γ 874 A/T genotype showed significant occurrence among MDR/TB patients compared with controls (P= 0.054). Marked significant difference was noted between cases (TB) patients and controls (p= 0.000) in IFN-γ 874 A/T polymorphism. IFN-γ 874 A/T Genotype showed no significant difference between the patients groups MDR/TB and sensitive TB (P = 0.278). The occurrence of IFNGR1 1050 T/G polymorphism was significantly higher among non MDR patients compared with controls (p=0.015). IFNGR1 1050 T/G polymorphism genotype showed no significant difference between MDR/TB patients and controls (p=0.168). Sequencing of TLR4 5UTR region did not identify any TLR4 SNPs that could be affecting the gene expression or regulation. Conclusion: The developing MDR TB tuberculosis was higher among patients with IFNγ 874 A/T and IFNGR1 1050 T/G polymorphism. المقدمة: يحصي سنويا ثمانية مليون شخصا مصابا بالسل الرئوي مما يؤدي إلي موت حوالي اثنين إلى ثلاثة ملايين سنويا بالسل, وهناك خمسة بالمائة مصاب بالسل المقاوم للأمراض. أصبح السل المقاوم للأدوية و السل المقاوم لمعظم الأدوية عالميا من اكبر العقبات في السيطرة علي مرض السل. هنالك دراسات قليلة تبحث في الجينات الوراثية التي تنظم عمل الاستجابة المناعة لتطور مرض السل الرئوي المقاوم للأدوية . الأهداف هي قياس مستوي و علامات السايتوكينات للخلايا الليمفاوية تي 1 و تي 2 و تحديد دور الطفرات الوراثية انترفيرون (874 ), و مستقبل الانترفيرون الاول) 1050) و تحديد تسلسل مستقبل مثيل التول الرابع في زيادة قابلية الإصابة بمرض السل المقاوم للأدوية في السودان. المواد والطرق: أجريت الدراسة المقارنة بين عينات مرضي السل و العينات القياسية في مستشفي ابو عنجة للأمراض الصدرية .جمعت عينة تفاف من كل مشترك في هذه الدراسة وتم عمل مسحة تفاف مباشرة و صبغت بطريقة زيل و نيلسون من اجل تحديد الإصابة بعصيات السل, واحد و تسعون مشتركا أجريت عليهم الدراسة منهم عدد تسعة و خمسون مصابا بالسُلِّ الرئوي المقاوم للأدوية تأكدت إصابتهم عن طريق نتائج اختبار( مورث/ اكسبرت) و اثنان وثلاثون مصابا بالسل المعالج بالادوية,كما تم اختيار ذكور أصحاء ممن جاءوا من اجل التبرع العائلي بالدم في بنك الدم و سيدات ممن يتابعن في قسم النساء و الولادة من اجل متابعة دورية و كانوا هم المختارين كعينات قياسية.جمعت عينات من الدم الوريدي من المشاركين في وعاء اديتا لجمع الدم و تم استخلاص الحمض النووي باستخدام محاليل انترون لاستخلاص الحمض النووي ,وتم قياس مستوي تركيز السايتوكينات في البلازما للانترفيرون غاما(الخلايا اليمفاوية تي1) و انترليوكين- 10(الخلايا الليمفاوية تي2) عن طريق الاختبار الانزيمي القياسي المقترن (اليزا) ,تم القياس بطريقة اليزا باللاجسام المضادة القابضة .تم تحليل الحمض النووي للمشاركين بالدراسة من اجل تحديد ثلاثة طفرات وراثية انترفيرون غاما (874 ) عن طريق تحديد الاليلات للتفاعل المتسلسل البلمري, مستقبل الانترفيرون الاول ( 1050) عن طريق الإنزيمات القاطعة للحمض النووي و تسلسل مستقبل مثيل التول الرابع لمحاولة ايجاد العلاقة بين بعض الجينات وقابلية الإصابة بالسل الرئوي المقاوم للأدوية. النتائج: أوجدت النتائج أن متوسط اعمار المشاركين في الدراسة 36 سنة.وكانت اعمار المشاركين تتراوح ما بين 18 سنة و 95 سنة ,نسبة الذكور تساوي 61% و نسبة السيدات 39%,الفئة الأكثر إصابة بالمرض في العمر ما بين 20-30 سنة, لا يوجد اختلاف ذا دلالة إحصائية في مستوي تركيز الانترفيرون غاما و الانترليوكين- 10 بين مرضي السل و مرضي السل المقاوم وبين مجموعة الاصحاء القياسية ,تبين من النتائج في هذه الدراسة بان طفرة انترفيرون 874 اظهرت ان هنالك اختلاف ذا دلالة إحصائية بين مجموعة المصابون بالسل المقاوم للادوية و مجموعة الاصحاء بقيمة بي تساوي 0.054 , هنالك اختلاف كبير ذا دلالة إحصائية بين مجموعة مصابى السل المعالج مع مجموعة الاصحاء بقيمة بي تساوي 0.000 .بيد انه لا يوجد اختلاف في توزيع الطفرة انترفيرون 874 بين المصابين بالسل المقاوم للادوية والسل المعالج بقيمة بي تساوي 0.278 .أوضحت الدراسة انه ليس هناك اختلاف ذا دلالة إحصائية في توزيعِ طفرة مستقبل الانترفيرون الأول 1050 بين مجموعة السل ومجموعة الأصحاء, قيمة بي تساوي 0.015 وكما أوضحت انه ليس هناك اختلاف في توزيعِ طفرة مستقبل الانترفيرون الأول بين مجموعة السل المقاوم ومجموعة الأصحاء, قيمة بي تساوي 1.68 ,كما أوضحت انه ليس ثمة اختلاف في تتبع سلسلة مستقبل مثيل التل الرابع ومرضي السل المقاوم للأدوية او السل المعالج. الخلاصة: التطور في الإصابة بمرض السل المقاوم للأدوية تحدث بصورة كبيرة في المرضي الذين توجد لديهم الطفرتين الوراثيين انترفيرون (874 ) و مستقبل الانترفيرون الأول( 1050 )
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    Detection of HPV,EBV,P53 arg /pro polymorphisim and Methylation Patterns in Esophageal Cancer in Sudan
    (University of Khartoum, ) Dalia Mursi Abdelhalim Nasr ; Muntaser Eltyeb Ibrahim
    Introduction: Esophageal carcinoma is a common malignancy and its mortality rate is among the highest for cancer overall.An association between viral infection and the development of esophageal carcinoma has been reported, particularly the human papilloma virus (HPV) and Esptein-Bar virus (EBV). P53 codon 72 polymorphism a single-nucleotide substitution at codon 72 that results in the presence of either proline (p53pro) or arginine (p53arg) in the amino-acid sequence. It was reported that the p53 codon 72 polymorphism (C/G) is a high- risk factor for the development HPV- associated cervical carcinoma, although is still considered controversial in several studies of cervical and esophageal carcinoma. Hypermethylation of CpG islands, an epigenetic event, is coming more and more into focus in carcinogenesis of the esophagus. Recent studies have proved that promoter hypermethylation of tumor suppressor genes are frequently observed in esophageal carcinoma and seem to play an important role in the pathogenesis of this tumor type. In this study, we aimed to detect HPV and EBV infection by polymerase chain reaction, and to elucidate their association with carcinogenesis of the esophagus, also to characterize the p53 codon 72 polymorphism in Sudanese esophageal cancer patients. The study also aims to investigate the methylation pattern of P16, P14 and Hmlh1 genes among these patients. Method: Pairs of primary esophageal cancer tissue and corresponding normal mucosa were obtained from 30 patients (60 samples in all), undergoing surgical treatment, after taken written consent. Polymerase chain reaction was used to amplify and detect the HPV type 16,18 and EBNA-1, LMP-1 genes for EBV. Detection of DNA methylation was carried out by specific restriction enzymes flowed by PCR for p14, p16 and Hmlh1 genes. Results: EBV genome was detected in only 3 out of 30 tumor tissue samples, while HPV type 18 DNA were detected in 18 of 30 (60%) samples. For the p53 polymorphism the heterozygous frequency with arg/pro 40 %, arg/arg 30 %, and pro/pro 30 %. The Methylation frequencies of selected genes in 20 esophageal cancer specimens were found to be as follows 75%, 80%, and 75% for p14, p16 and Hmlh1 respectively. Conclusions: The results of this study indicated that HPV-18 is generally associated with esophageal carcinogenesis but no specific association of EBV genome with esophageal SCCs. For the p53 polymorphism in esophageal cancer the difference seems to be insignificant and was not supported statistically. The results suggest that p16, together with p14, and Hmlh1 genes are among the hypermethylation hotspot in human esophageal cancer. More epidemiological studies of esophageal cancer with larger sample size in different parts of Sudan are required. It will be important in future studies to investigate the germline polymorphism of other related genes, for example, the genes in the p53 pathway.Methylation changes should be detected by using more developed methods and a genome wide approach (methylome).
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    Age At Menarche and Sexual Maturation in Khartoum School Girls
    (University of Khartoum, 2016-02-25) Elfaki, Amna Mohammed Salih ; Mohammed Ibrahim Ali Omer
    Age At Menarche and Sexual Maturation in Khartoum School Girls
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    Anaemia And Micronutrients Deficiency Among Pregnant Women And Adolsecent Girls In Eastern Sudan
    (University of Khartoum, 2015-04-14) Ishraga Izzeldin Abdelrahim ; Mustafa Idris Elbashir ; Medical Biochemistry
    Background: Anaemia has been reported to be associated with poor maternal and perinatal outcomes. In Sudan, no data exist about the type of anaemia, and its maternal and perinatal effect. Objectives: We conducted this study in eastern Sudan to investigate the prevalence and types of anaemia among pregnant women and adolescent schoolgirls of eastern Sudan. Methodology and Results: We determined the levels of haemoglobin (Hb), ferritin, folate and vitamin B12 and some minerals (zinc and copper) in sera of pregnant women and compared them with nonpregnant women as well as adolescent schoolgirls. Among two hundred and seventy nine pregnant Sudanese women were enrolled in the study, anaemia (Hb < 11 g/dl) and iron deficiency (ferritin< 15 μg/1) were prevalent in 80.3% and 14.3% of the study sample, respectively. Of the total sample, 11.1% had iron-deficiency anaemia. Serum folate (< 6.6 ng/ ml) and vitamin B12 (< 150 pg/ ml) deficiency was reported in 57.7% and 1%, respectively, and none of the women had both folate and vitamin B12 deficiencies. Regression analysis showed that ferritin, serum folate and vitamin B12 levels were not significantly associated with anaemia. In addition, a cross-sectional study was conducted among adolescent schoolgirls where one hundred eighty one (96.8%) out of 187 were shown to have anaemia (Hb <12 gm/dl); 21% had mild anaemia (Hb: 11.0-11.9 gm/dl), 66.8% had moderate anaemia (Hb: 8.0-10.9 gm/dl), and 12.1 % had severe anaemia (Hb < 8gm/dl), respectively. Iron deficiency (serum ferritin < 12μg/l), iron deficiency anaemia (Hb <12gm/dl and serum ferritin < 12μg/l) and folate deficiency (serum folate < 3 ng/ml) were prevalent in 17.6%, 16.5% and 69% of these girls, respectively. Eight percent and 7% of these girls had zinc (< 70 μg/dl) and copper deficiency (< 80 μg/dl), respectively. 26 (14%) girls had ≥ two micronutrients deficiencies. Serum ferritin and zinc were significantly lower in patients with severe anaemia. Hb levels were significantly positively correlated with zinc levels (r=0.161, P= 0.03) and with copper levels (r=0.151, P= 0.03). Furthermore, a case-control study (38-40 parturient women in each arm of the study) was conducted to investigate levels of maternal serum folate and ferritin in relation to short interpregnancy interval (short IPI) (< 18 months), preterm delivery (< 37 weeks) and low birth weight (LBW) (< 2500gm). There were no significant differences in levels of serum folate and ferritin in parturient women with; short IPI, preterm delivery, LBW and controls. There were significantly lower levels of folate and ferritin in women who had short IPI and preterm delivery than in the controls. In univariate analyses, there was no significant association between serum folate, ferritin, preterm delivery and LBW. Univariate and multivariate analyses showed significant association between low serum folate level (<2.5 ng/ ml) and short IPI and preterm delivery (OR = 3.5; 95% CI =1.1- 10.6; P = 0.02) and significant association between low serum folate levels and short IPI (OR = 1.9; 95% CI =1.0-3.6; P = 0.03). We also compared serum folate, zinc and copper levels among well matched two groups of pregnant Sudanese women (41 in each arm); with short IPI (< 18 months) and control group with referral IPI (18-30 months) at the mean (SD) gestational age of 10.1 (2.0) weeks. The mean (SD) serum zinc concentration was significantly lower, 86.8 (35.3) versus 90.7(22.5) μg/dl; P = 0.02, serum copper was significantly higher, 251.2 (81.0) versus 216.0 (71.7) μg/dl, P= 0.04 in women with short IPI. There was no significant difference in the levels of serum folate between the two study groups. There was significant positive correlation between haemoglobin and folate levels (r= 0.218, P= 0.04). There was no correlation between haemoglobin, IPI, serum zinc and copper levels. Conclusion: The main findings of this study were; high prevalence of anaemia and folate deficiency, and relatively low prevalence of iron deficiency anaemia and very low prevalence of Vitamin B12 deficiency
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    Description of Total Hip Replacement Case Series in Military Corp (Feb 2004- Feb 2006)
    (University of Khartoum, 2015-04-12) Motaz Ahmed Abdallah M. Khier ; Mohammed Said Omer ; Orthopedics and Trauma
    The aims of total hip replacement include alleviation of pain and restoration of movement. This procedure is being carried for decades out side Sudan. This case series unicentric descriptive study, presents the description of the protocol in the military corp. hospital and description of early results of this experience .The questionnaire based study was undertaken to document the pre-op findings, intra-op protocol and post-op complications. Thirty four THR (Thirty two patients) were done over a period of 24 months, 25 Males and 9 females. Radigraphically, 10 were trauma, 14 AVN, 15 OA, 2 loose THR, and 3 were protrusi acetabuli. All patients with trauma had pre-op shortening .All patients received LMW heparin (Tinazaparin) as prophylaxis, none of them developed DVT . Two patients had dislocations, one was revision THR and the other one was done by junior surgeon. None of the patients developed post-op infection. One hip showed evidence of loosing. It was revision of THR. Sub group of 10 hips had post op shortening. All of them were having shortening secondarily to trauma. 4 Hips had lengthening post operatively. One patient died immediately post-op, the surgery was revision of hip and was the only patient who received general anesthesia on top of spinal anesthesia due to long procedure. The study concluded that, with such limited experience over twenty four months of treating thirty four hips the results of THR is quite promising with the conditions and staff we have, providing that more and more surgeons enrolled in arthroplasty training scheme.