Clinical and genetic characteristics of disorders of sex development in Sudanese patients

Given the scarce data on DSD in Sudan, we aimed to characterize DSD's clinical and genetic profile in Sudanese patients. We studied 60 patients with DSD using clinical data, cytogenetics, and PCR for the SRY gene. The results showed that 65% grew up as females and 35% as males. There was a high percentage of consanguineous parents (85%). Female genital mutilation (FGM) was performed in 75% of females. Patients who presented after pubertal age were 63%, with ambiguous genitalia in 61.7%, followed by primary amenorrhea (PA) in 30%. The SRY gene was positive in 3.3% of patients with 46,XX karyotype and negative in 6.7% of patients with 46,XY karyotype. 5αR2D-DSD was seen in 43.3%, gonadal dysgenesis in 21.7%, Ovotesticular syndrome in 6.7%, Swyer and Turner syndrome in 5% each, and Androgen Insensitivity Syndrome (AIS) in 3.3%. In conclusion, DSD in Sudan has a distinct profile with late presentation, dominated by 5αR2D-DSD due to the increased consanguineous marriage, and FGM represents a significant risk for DSD patients.

Compte tenu du peu de données sur le DSD au Soudan, nous avons cherché à caractériser le profil clinique et génétique du DSD chez les patients soudanais. Nous avons étudié 60 patients atteints de DSD en utilisant des données cliniques, cytogénétiques et PCR pour le gène SRY. Les résultats ont montré que 65 % ont grandi en tant que femmes et 35 % en tant qu'hommes. Il y avait un pourcentage élevé de parents consanguins (85 %). Des mutilations génitales féminines (MGF) ont été pratiquées chez 75 % des femmes. Les patientes qui se sont présentées après l'âge pubertaire étaient 63 %, avec des organes génitaux ambigus dans 61,7 %, suivis d'une aménorrhée primaire (AP) dans 30 %. Le gène SRY était positif chez 3,3 % des patients de caryotype 46,XX et négatif chez 6,7 % des patients de caryotype 46,XY. Le 5αR2D-DSD a été observé dans 43,3 %, la dysgénésie gonadique dans 21,7 %, le syndrome ovotesticulaire dans 6,7 %, le syndrome de Swyer et Turner dans 5 % chacun et le syndrome d'insensibilité aux androgènes (AIS) dans 3,3 %. En conclusion, le DSD au Soudan présente un profil distinct avec une présentation tardive, dominé par le 5αR2D-DSD en raison de l'augmentation des mariages consanguins, et les MGF représentent un risque important pour les patients DSD.

Viral meningitis in Sudanese children: Differentiation, etiology and review of literature.

Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.

Human herpes virus type-6 is associated with central nervous system infections in children in Sudan.

Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan. Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan. Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden. Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9-40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30-44 × 103 copies/PCR run [12 × 103 - 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%. Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.

Clinical Characteristics of Urinary Bladder Cancer in the Sudan; Evidence of Pathoetiology Changes.

INTRODUCTION: Bladder cancer (BC) is highly heterogeneous with regard to clinical course, etiology, histology, and geographic distribution. Recent clinical observations suggest changes in the pattern of BC in the Sudan perhaps due to lifestyle change following the massive displacement from rural to urban areas. The present study aimed to characterize the clinical profile of the BC among Sudanese patients and compare it with what has been previous reported. MATERIAL AND METHODS: Demographic, habitual, clinical, and histopathology information of 1610 patients with BC were obtained from the hospital record of Ibn Sina specialized hospital, Soba University hospital, Khartoum North hospital and Khartoum teaching hospital during the period 2007-2019. The data was analyzed using SPSS program version 23. RESULTS: Of the 1610 cases of BC, 1480 cases (91.9%) were males and 130 cases (8.1%) were females. The most affected patients (39.3%) were those with age group ranging between 61-75 year-old. The vast majority of the patients (73%) were from urban and/or metropolitan areas of the capital Khartoum, whereas the remaining (27%) were farmers coming from rural areas. Although, smoking habits information were missed in 410 patients, 44% of the patients were smokers. History of hematuria was present in almost all cases (99.4%), whereas history of urinary bilharziasis was mentioned in 40.9% of the patients' records. The TCC histology type was seen in 77.4% of the cases, SCC in 21.1%, and adenocarcinoma in only 1.5% of all cases. The vast majority of the tumors were poorly differentiated tumors (700/52.6%), followed by moderately differentiated tumors (430/32.3%) and well differentiated ones (200/15.1%). Of the total tumors, 346/26% were Ta-T1, 456/34% were T2, and 528/40% were T3-T4a,b. Most of tumors were solid ones, accounting for 74% compared with the papillary ones (26%) with most (54.9%) of the tumor located in the lateral wall of the bladder. Although in 620 (38.5%) patients, the follow up information were missing from the records, still the recurrence of the tumors were recorded in 890 (55.3%) of the patients 6 month after the initial therapy. DISCUSSION: The results showed that poorly differentiated, muscle invasive, and high recurrent TCCs tumors dominate BC profile of Sudanese patients. It revealed also that the most affected population are those between 61-75 yearold. These findings are in clear contrast with BC profile, previously, reported in which solitary muscle invasive Bilharzia-associated SCCs tumors affecting younger population was the dominated patterns as reported by Daoud el al (1968), Malik et al., (1975) and later by Sharfi et al., (1992). Thus clear change in BC profile in Sudan is evident, perhaps due to increased urbanization and style of life that led to change in the causative etiology, and eventually the histology type. KEY WORDS: Bladder cancer, Squamous cell carcinoma, Transitional Cell Carcinoma, Post-bilharzial carcinoma.

Are Pathogenic Leptospira a Possible Cause of Aseptic Meningitis in Suspected Children in Sudan?

INTRODUCTION: Clinical presentations of leptospirosis are diverse, with meningitis easily confused with other microbial causes. We aimed to investigate the involvement of pathogenic leptospira in the cerebrospinal fluid (CSF) of meningitis-suspected children in Sudan. METHODS: A total of 153 CSF specimens were collected over 5 months from patients attending a reference pediatric hospital in Omdurman, Sudan. All patients had provisionally been diagnosed with meningitis on admission. Demographic, clinical, and conventional laboratory findings were obtained. DNA was extracted using a QIAamp mini kit, and the secY gene investigated using real-time PCR. RESULTS: Nine of 153 (6%) CSF specimens were positive for pathogenic leptospiral DNA. All these patients were male (seven infants and two toddlers aged ˂4 years). Typical conventional laboratory findings for aseptic meningitis (ie, CSF turbidity/pleocytosis, normal or reduced CSF glucose, normal or elevated proteins) were seen in five (56%). All patients presented with fever and seizures, 56% vomiting and stiff neck, and 29% bulging fontanel. Most (67%) patients presented in summer (March to May). Polymicrobial infections were identified in three patients (33%). CONCLUSION: We conclude that pathogenic leptospira are probably a common cause of meningitis in children in Sudan; therefore, we recommend including leptospirosis in the differential diagnosis of CNS infections and other undifferentiated febrile illnesses in this country.

Blood markers (lymphocyte percentages, neutrophils, CRP and ESR) can help in prioritizing rRT-PCR test for suspected COVID-19 patients in countries with limited health resources.

INTRODUCTION: the outbreak of coronavirus disease 2019 (COVID-19) started in China in December 2019 and spread causing more than 14 million cases all over the world on July 19th, 2020. Although, real-time reverse transcription polymerase chain reaction (rRT-PCR) test is the gold standard test, it needs a long time and requires specialized laboratories and highly trained personnel. All these difficulties forced many countries with reduced health resources to limit rRT-PCR tests to individuals with severe symptoms. Thus, routine blood marker that may help physicians to suspect COVID-19 and hence, prioritize patients for molecular diagnosis is badly needed. METHODS: fifty-six Sudanese COVID-19 patients admitted to Jabra hospital were included in this study. For all the patients we analyzed complete blood count (CBC), CBC, plasma levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), liver function tests (LFT) and renal function tests (RFT). Statistical analysis was done using SPSS program with a significance level of p≤0.05 and confidence limits (CLs) 95%. The difference between groups was tested using Mann-Whitney test was for quantitative variables while qualitative variables was tested using chi-square (Fisher exact) test. RESULTS: the result shows that, 35 out of the 56 patients (62.5%) were male and 21 (37.5%) were females with a median age of 60-year-old for both sexes. Lymphocytes % showed decrease to 9.2 (P-value=0.000) and significant increase in neutrophils to 83.05 (P-value=0.005), ESR to 65.54 (P-value=0.000) and CRP to 91.07 (P-value=0.000). The receiver operating characteristic curve (ROC)/area under the curve (AUC) ensured the expellant result of lymphocytes % as a predictor with 92% area under the curve, neutrophils were 90% and ESR 95.8%. The percent of detecting COVID-19 positive RT-PCR (98%) for suspected individuals using ROC showed best cutoff of ≤21.8 for lymphocytes %, ≥67.7 for neutrophils, ≥37.5 for ESR, ≥6.2 for CRP and ≥7.15 for WBCs. CONCLUSION: the results also showed that, lymphocyte percentages, neutrophils, CRP and ESR may be used as markers for COVID-19 helping prioritizing individuals for rRT-PCR test.

Bacterial meningitis in Sudanese children; critical evaluation of the clinical decision using clinical prediction rules.

BACKGROUND: Sudan falls in the meningitis belt where most global cases of bacterial meningitis are reported. Highly accurate decision support tools have been developed by international specialized societies to guide the diagnosis and limit unnecessary hospital admissions and prolonged antibiotic use that have been frequently reported from countries around the world. The goals of this study are to critically evaluate the clinical decision of bacterial meningitis in children in Sudan using clinical prediction rules and to identify the current bacterial aetiology. METHODS: This cross-sectional hospital-based study was conducted in October to July of 2010 in a major referral pediatric hospital in Khartoum, Sudan. Febrile children age 1 day to 15 years who were provisionally diagnosed as having meningitis on admission were included (n = 503). Cerebrospinal fluid (CSF) specimens were obtained from all patients while clinical and demographic data were available for only 404. Conventional laboratory investigations were performed. The clinical decision was evaluated by the International Classification of Diseases-Clinical Modification code 320.9 and the Bacterial Meningitis Score. Ethical clearance and permissions were obtained. RESULTS: Out of 503 provisionally diagnosed bacterial meningitis patients, the final clinical confirmation was assigned to 55.9%. When codes were applied; 5.7% (23/404) with CSF pleocytosis were re-classified as High Risk for bacterial meningitis and 1.5% (6/404) with confirmed bacterial aetiology as Proven Bacterial Meningitis. Neisseria meningitidis was identified in 0.7% (3/404) and Streptococcus pneumoniae in another 0.7%. Typical laboratory findings (i.e. CSF pleocytosis and/or low glucose and high protein concentrations, Gram positive or Gram negative diplococcic, positive bacterial culture) were seen in 5 (83%). Clinically, patients showed fever, seizures, chills, headache, vomiting, stiff neck and bulging fontanelle. All confirmed cases were less than 5 years old and were admitted in summer. All patients were prescribed with antibiotics; they were all recovered and discharged. CONCLUSIONS: Bacterial meningitis is over-diagnosed in hospitals in Khartoum therefore clinical prediction rules must be adopted and applied to guide the clinical decision. The sole bacterial aetiology in this selected group of Sudanese children remain N. meningitidis and S. pneumoniae, but with significant decrease in prevalence. Some cases showed atypical clinical and laboratory findings.

Acacia Senegal (Gum Arabic) Supplementation Modulate Lipid Profile and Ameliorated Dyslipidemia among Sickle Cell Anemia Patients.

BACKGROUND: Sickle cell disease (SCD) is an inherited haemolytic anemia with a variable course and severity. Knowledge of prognostic biomarkers may help in the establishment of therapeutic intervention, management, and follow-up of patients. There have been scattered reports of low high-density lipoprotein cholesterol (HDL-C) and increased triglyceride (TG) in SCD patients. In addition, TG levels have been suggested to be elevated in patients with increased endothelial activation. An increased TG level has been associated with haemolysis, vascular dysfunction, and increased prevalence of pulmonary hypertension. Gum Arabic (GA) is an edible, dried, gummy exudate from the acacia Senegal tree. Several studies on GA ingestion have shown reduced plasma cholesterol and low-density lipoprotein (LDL) concentrations in both animals and humans. We investigated GA's therapeutic potential to modulate serum lipids in patients with sickle cell anemia. METHODS: This study recruited and documented secondary outcomes in 47 patients (aged 5-42 years) carrying hemoglobin SS. The patients received 30 g/day of GA for 12 weeks. Total cholesterol, TG, LDL, and HDL were measured before and after GA intake. Cobas C311 (Roche, Germany) automated chemistry analyser was used for direct determination of the values of the lipid profile. RESULTS: GA significantly decreased total cholesterol (TC), TG, and LDL (p = 0.006, 0.04, and 0.02, resp.). GA showed no effect on HDL level. Baseline serum TG and LDL correlated significantly with the hydrogen peroxide (H2O2) level, which is known as an oxidative stress marker (p = 0.003 and 0.04, resp.). None of the lipid profile elements correlated with age. CONCLUSION: Our results revealed that dyslipidemia in sickle cell patients is associated with oxidative stress but not associated with age. The findings showed that GA significantly decreased TC, LDL, and TG levels, revealing a novel effect of GA, which is considered a natural dietary fibre that can modulate lipid profile in patients with sickle cell anemia. TRIAL REGISTRATION: This retrospective trial is registered with ClinicalTrials.gov Identifier: NCT02467257 on 3 June, 2015.

Gum Arabic as novel anti-oxidant agent in sickle cell anemia, phase II trial.

BACKGROUND: Sickle cell anemia patients suffer from oxidative stress due to chronic inflammation and self-oxidation of sickle hemoglobin (Hb S). Chronic oxidative stress contributes to endothelial dysfunction, inflammation and multiple organ damage in sickle cell disease (SCD). Thus, antioxidant medication may favorably influence the disease. Gum Arabic (GA), edible, dried, gummy exudates from Acacia Senegal tree, has been claimed to act as an anti-oxidant and cytoprotective agent, protecting against experimental hepatic, renal and cardiac toxicities in rats. We hypothesized that regular intake of GA increases anti-oxidant capacity and reduce oxidative stress. METHODS: Forty-seven patients (5-42 years) carrying hemoglobin SS were recruited. Patients received 30 g/day GA for 12 weeks. Total anti-oxidant capacity (TAC), malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels were measured by spectrophotometric methods before and after GA intake. Complete blood count was measured by sysmex. RESULTS: Gum Arabic significantly increased TAC level P < 0.001and decreased the oxidative markers MDA (P < 0.05) and H2O2 (P < 0.005). CONCLUSIONS: GA has potent anti- oxidative properties in sickle cell anemia. The anti-oxidant effect of GA may thus favorably influence the clinical condition of this and further diseases characterized by oxidative stress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02467257. Registered 3rd June 2015. Retrospective registration.

Sexually transmitted infections other than HIV/AIDS among women of low socio-economic class attending antenatal clinics in Khartoum, Sudan.

Sexually transmitted infections (STIs) are major health threats affecting people globally; however, the burden of STIs is greatest in low-income countries. Since they are physiologically more vulnerable, women are mostly affected. The risk is increased dramatically during pregnancy leading to serious health complications that may affect the newborn. Underprivileged pregnant women attending antenatal clinics for routine checkups in displaced camps, a women's prison and several peripheral health centres were clinically and laboratory screened for trichomoniasis, chlamydial infections, gonorrhea and syphilis. A total of 426 women with an age range of 14-45 years were included. Clinical data, blood, cervical and vaginal swabs were collected. Conventional bacteriological and serological methods were applied. All attendees were HIV1/2-negative. The prevalence of Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae and Treponema pallidum infections was found to be 7.8%, 4.9%, 0% and 5%, respectively. Although vaginal discharge, among other symptoms, is known to be the most significant indicator for STIs, our identified positive predictive value was only 14.1%. We conclude that use of syndromic approach for diagnosing and treating attendees of antenatal settings is of low clinical value and many easily curable STIs will be overlooked. Consequently, trichomoniasis, chlamydial infection and syphilis prevailed widely among this population.

Extra virgin olive oil potentiates the effects of aromatase inhibitors via glutathione depletion in estrogen receptor-positive human breast cancer (MCF-7) cells.

There have been numerous evidences supporting the relationship between olive oil and cancer, with most of the attention being directed toward its fat and phenolic content. The aims of this study were to investigate whether EVOO and OA could enhance the effects of aromatase inhibitors (letrozole and anastrozole) in ER-positive MCF-7 cells, as well as to investigate its influence on cytochrome c release and GSH levels. It was observed that upon combination treatment, anti-proliferation effects and apoptosis induction were augmented. Apoptosis was triggered via the intrinsic pathway in accordance with cytochrome c release into the cytosol based on IF-IC and ELISA observations. Intracellular GSH levels were also reduced upon EVOO/OA treatment in combination with aromatase inhibitors, and were found to be inversely correlated to cytosolic cytochrome c levels. Additionally, the estrogenic suppressive effects of letrozole and anastrozole were amplified when used in combination with EVOO/OA. Therefore, the employment of aromatase inhibitors in combination with EVOO/OA could orchestrate a reduction in intracellular estrone biosynthesis which feeds ER-positive cells, while simultaneously depleting GSH levels and increasing ROS generation, thus releasing cytochrome c and subsequent induction of apoptosis in MCF-7 cells.

Frequency of BCR-ABL fusion transcripts in Sudanese patients with chronic myeloid leukemia using real-time reverse transcription-polymerase chain reaction.

OBJECTIVE: To report the frequencies of BCR-ABL transcript variants studied in Sudanese patients with chronic myeloid leukemia (CML). METHODS: This is a descriptive cross-sectional study carried out in 112 CML patients who attended at different clinics of Khartoum state, Sudan from February 2007 to December 2010. Transcript analysis was successful in 109 venous blood and bone marrow samples using quantitative real-time-polymerase chain reaction (RT-PCR). RESULTS: The transcripts analysis of 109 patients showed that 32.1% (35/109) expressed one or both of the P210 BCR/ABL rearrangements (b2a2 and b3a2). Of those 35 (32.1%), 21 patients expressed b2a2, 6 expressed b3a2, and 8 expressed both transcripts b2a2/b3a2. The remaining 74 patients revealed transcripts combination of P190 BCR/ABL and P210 BCR/ABL (e1a2/b2a2/b3a2), of which 19 patients had all the transcripts (e1a2/b2a2/b3a2), 33 revealed 2 transcripts (e1a2/b2a2), and the remaining 22 patients had (e1a2/b3a2). CONCLUSION: The frequencies of BCR-ABL rearrangements in the Sudanese population demonstrated distinct profiles in contrast with the frequencies reported in similar studies conducted in other geographical regions.This might be due to the distinct ethnic group involved in this study which has been supported further by reported distinct genetic profiles in Sudanese patients with bladder and breast cancer.

Significance of serum total prostate specific antigen and digital rectal examination in the diagnosis of prostate cancer.

OBJECTIVE: To assess the significance of serum total prostate specific antigen (tPSA) and digital rectal examination (DRE) in the diagnosis of prostate cancer (PC). METHODS: One hundred and eighteen patients with serum tPSA ranging between 2.5 and 10 ng/ml with lower urinary tract symptoms presented at the Urology Clinic of Soba University Hospital, Khartoum, Sudan from August 2008 and January 2010 were included in the study. Serum tPSA was measured using enzyme immunoassay method, and accordingly, the patients were classified into 2 groups: patients that had tPSA between 2.5-4.0 ng/ml; and patients that had tPSA between 4.1-10 ng/ml. The DRE was performed on all patients by a qualified urologist, and were recorded as a group with suspicion of PC, and a group with no suspicion of PC. All patients underwent transrectal sextant prostate biopsy. RESULTS: The DRE alone showed 63.8% sensitivity and 68% specificity with 46.9% positive predictive value (PPV) for the diagnosis of PC. The tPSA test revealed 91.6% sensitivity and 24% specificity with PPV of 34%. However, when combining DRE and tPSA, the sensitivity reached 100% and the specificity increased to 92% with PPV of 49%. CONCLUSION: Combining DRE and tPSA test increases the sensitivity, specificity, and PPV of PC detection.

Age-specific reference range for serum prostate-specific antigen in Sudanese men.

OBJECTIVE: To determine age-specific prostate-specific antigen (PSA) reference values in a community-based sample of Sudanese men, aged 40-90 years. METHODS: This study was conducted in the Central Laboratory Services, Soba University Hospital, Khartoum, Sudan from January 2008 to May 2010. Total serum PSA in 3475 Sudanese men with no clinical evidence of lower urinary tract symptoms were measured using immunoenzometric assay. Out of the 3475, only 1051 men met the inclusion criteria. Those with total PSA<10 ng/ml and no recent urinary tract infection were included in this study. The data were analyzed using SPSS for Windows to define age-specific reference ranges of PSA. RESULTS: The geometric mean of total serum PSA in the study group of Sudanese men was 1.48 ng/ml. The 95th percentile total serum PSA ranges in the age groups was 0-3 ng/ml for 40-49 years, 0-3.02 ng/ml for 50-59 years, 0-3.8 ng/ml for 60-69 years and 0-8.7 ng/ml for 70-90 years. CONCLUSION: The currently adopted age-specific total PSA reference ranges are not appropriate for Sudanese men. Accordingly, our study indicates that the reference ranges of this study may be more suitable.

Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and susceptibility to anti-tuberculosis drugs.

BACKGROUND: Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. METHODS: In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status--new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). RESULTS: Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. CONCLUSIONS: We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem.

A case of Cornelia de Lange syndrome from Sudan.

BACKGROUND: Brachmann de Lange syndrome (BDLS) is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. CASE PRESENTATION: Here we present for the first time a case of BDLS from Sudan, a 7-month-old female infant, who was referred as a case of malnutrition. The patient was from a Sudanese western tribe. Clinical investigation showed that the child was a classical case of BDLS, but with some additional clinical findings not previously reported including crowded ribs and tied tongue. CONCLUSION: Reporting BDLS cases of different ethnic backgrounds could add nuances to the phenotypic description of the syndrome and be helpful in diagnosis.

Chromosomal changes in uroepithelial carcinomas.

This article reviews and summarizes chromosomal changes responsible for the initiation and progression of uroepithelial carcinomas. Characterization of these alterations may lead to a better understanding of the genetic mechanisms and open the door for molecular markers that can be used for better diagnosis and prognosis of the disease. Such information might even help in designing new therapeutic strategies geared towards prevention of tumor recurrences and more aggressive approach in progression-prone cases. The revision of 205 cases of uroepithelial carcinomas reported with abnormal karyotypes showed karyotypic profile characterized by nonrandom chromosomal aberrations varying from one or few changes in low-grade and early stage tumors to massively rearranged karyotypes in muscle invasive ones. In general, the karyotypic profile was dominated by losses of chromosomal material seen as loss of entire chromosome and/or deletions of genetic materials. Rearrangements of chromosome 9 resulting in loss of material from 9p, 9q, or of the entire chromosome were the most frequent cytogenetic alterations, seen in 45% of the cases. Whereas loss of material from chromosome arms 1p, 8p, and 11p, and gains of chromosome 7, and chromosome arm 1q, and 8q seem to be an early, but secondary, changes appearing in superficial and well differentiated tumors, the formation of an isochromosome for 5p and loss of material from 17p are associated with more aggressive tumor phenotypes. Upper urinary tract TCCs have identical karyotypic profile to that of bladder TCCs, indicating the same pathogenetic mechanisms are at work in both locales. Intratumor cytogenetic heterogeneity was not seen except in a few post-radiation uroepithelial carcinomas in which distinct karyotypic and clonal pattern were characterized by massive intratumor heterogeneity (cytogenetic polyclonality) with near-diploid clones and simple balanced and/or unbalanced translocations. In the vast majority of cases strong correlation between the tumors grade/stage and karyotypic complexity was seen, indicating that progressive accumulation of acquired genetic alterations is the driving force behind multistep bladder TCC carcinogenesis. Although most of these cytogenetic alterations have been identified for many years, the molecular consequences and relevant cancer genes of these alterations have not yet been identified. However, loss of TSG(s) from chromosome 9 seems to be the primary and important event(s) in uroepithelial carcinogenesis.

Chromosomal abnormalities in inflammatory pseudotumor of the urinary bladder.

Inflammatory pseudotumors of the urinary bladder are rare, benign, nonepithelial tumors. Fewer than 30 have been reported, and no data are available on their karyotypic characteristics and/or the molecular mechanisms of pathogenesis. We performed short-term culturing and cytogenetic analysis of an inflammatory pseudotumor of the bladder, finding a der(20)t(12;20)(q13 approximately q15;q13) as the only cytogenetic aberration. The detection of a 12q13 approximately q15 rearrangement in the inflammatory pseudotumor indicates that this lesion is pathogenetically related to other benign mesenchymal tumors displaying, for example, lipogenic or leiomyomatous differentiation, something that is in sharp contrast to the karyotypic profile of epithelial tumors of the urinary bladder mucosa.

Chromosomal aberrations in benign and malignant bilharzia-associated bladder lesions analyzed by comparative genomic hybridization.

BACKGROUND: Bilharzia-associated bladder cancer (BAC) is a major health problem in countries where urinary schistosomiasis is endemic. Characterization of the genetic alterations in this cancer might enhance our understanding of the pathogenic mechanisms of the disease but, in contrast to nonbilharzia bladder cancer, BAC has rarely been the object of such scrutiny. In the present study, we aimed to characterize chromosomal imbalances in benign and malignant post-bilharzial lesions, and to determine whether their unique etiology yields a distinct cytogenetic profile as compared to chemically induced bladder tumors. METHODS: DNAs from 20 archival paraffin-embedded post-bilharzial bladder lesions (6 benign and 14 malignant) obtained from Sudanese patients (12 males and 8 females) with a history of urinary bilharziasis were investigated for chromosomal imbalances using comparative genomic hybridization (CGH). Subsequent FISH analysis with pericentromeric probes was performed on paraffin sections of the same cases to confirm the CGH results. RESULTS: Seven of the 20 lesions (6 carcinomas and one granuloma) showed chromosomal imbalances varying from 1 to 6 changes. The most common chromosomal imbalances detected were losses of 1p21-31, 8p21-pter, and 9p and gain of 19p material, seen in three cases each, including the benign lesion. CONCLUSION: Most of the detected imbalances have been repeatedly reported in non-bilharzial bladder carcinomas, suggesting that the cytogenetic profiles of chemical- and bilharzia-induced carcinomas are largely similar. However, loss of 9p seems to be more ubiquitous in BAC than in bladder cancer in industrialized countries.