Association of Genetic Variant FVIII Gene and Factor VIII: A Pilot Study Among Hemophilia A Female Relatives in Saudi Arabia.

Hemophilia A (HA) is an X-linked recessive disorder that results from mutations in the factor VIII gene (FVIII). Most affected patients are males due to the inheritance of mutations in the FVIII gene from their mothers. Females are mostly found to be carriers unless they inherited the mutation from both parents. Obligate carriers of HA are mothers whose sons are affected with HA, or daughters who inherit the mutation from their affected fathers. A possible carrier of HA could be any female who has one or more affected relatives with HA in her family. Hemophilia A carriers (HACs) could present with similar symptoms to affected patients, including low factor VIII level, and risk of bleeding especially after surgical procedures or postpartum hemorrhage. OBJECTIVES:  Assessing the phenotype of possible HAC and its association with genetic variants in the FVIII gene for better screening methods for HAC. METHODS: From the period between 25 June and 25 October 2021, the study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. We recruited seven mothers whose sons were affected with HA, and 18 possible HAC who are relatives to sever affected patients with HA. All 25 candidates were assessed for the FVIII level, activated partial thromboplastin time (APTT), and bleeding risk and sequenced a part of Exon14 in their FVIII gene. RESULTS: Twenty-five percent of the participants show a low level of FVIII, however, none of them have prolonged bleeding nor suffer from bleeding tendency. We also identified two missense variants in six of the candidates, but the clinical significance of these variants has not been determined previously. CONCLUSION: This pilot study is the first to explore the phenotype of several HAC in Saudi Arabia. A larger scale study with more HA patients and their female relatives is needed to understand the correlation between phenotype and genotype for better screening for HAC.

Role of human Cytomegalovirus in the etiology of nasopharyngeal carcinoma.

OBJECTIVE: The purpose of this study was to identify human Cytomegalovirus (HCMV) in tissue blocks obtained from patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Formalin-fixed paraffin wax processed NPC tissue were obtained from 150 tissue blocks and retrospectively investigated for the presence of HCMV using polymerase chain reaction. RESULTS: Of the 150 NPC tissue specimens, HCMV was identified in 53/150 (35.3%) of the samples. Out of the 53 samples infected with HCMV, 33/97 (34%) were among males and 20/53 (37.7%) were among females. Of the 53 positive samples, 36/53 (68%) were found to harbor Epstein-Barr virus (EBV). CONCLUSION: The present study has shown a relatively considerable association between HCMV and NPC. The great majority of samples sheltering HCMV were also found to hide EBV, which proposes the potentiality of EBV over HCMV.

Prevalence of intestinal parasite infections among patients in local public hospitals of Hail, Northwestern Saudi Arabia.

OBJECTIVE: To evaluate the prevalence of intestinal parasites among patients in Hail, Northwestern Saudi Arabia. METHODS: Stool samples were collected from 130 patients (69 females and 61 males) in Hail General Hospital. Each sample was examined by direct wet mount microscopic examination using both normal saline and Lugol's iodine preparation and concentration techniques using salt and formol-ether solutions. Permanent stained smears were performed for intestinal coccidian using modified Ziehl-Neelsen technique. RESULTS: The overall prevalence of intestinal parasitic infection was 45.38% (59 cases). Forty-four (33.84%) were found to be infected with one or more intestinal protozoa, 5 (3.84%) were infected with helminthes and 10 (7.69%) had mixed infection with both helminthes and protozoa. The most common intestinal helminth detected was Ancylostoma duodenale (n = 5, 3.84%), followed by Ascaris lumbricoides, Taenia sp. and Trichuris trichiura (n = 2 for each species, 1.5%). For intestinal protozoa, the coccidian Cryptosporidium parvum (n = 25, 19.23%) was the most common followed by Entamoeba histolytica/dispar (n = 21, 16.15%), Giardia lamblia (n = 15, 11.54%), Entamoeba coli (n = 5, 3.85%) and Blastocystis hominis (n = 3, 2.30%). The prevalence of intestinal parasitic infections in females was significantly higher than in males (P < 0.05). CONCLUSIONS: This is the first study highlighting that intestinal parasites are still an important public health problem in Northwestern Saudi Arabia. Therefore, health education would be the best way to prevent from intestinal parasite infections which are mainly food borne diseases.

Progesterone ameliorates diabetic nephropathy in streptozotocin-induced diabetic Rats.

BACKGROUND: Previous studies reported that 17ß-estradiol may influence the progression of diabetic renal disease in females. The present study was intended to provide an insight into the specific effects of progesterone, the other female sex hormone, in the diabetic renal complications. METHODS: Adult female wistar rats were divided into four groups (n = 6/group): intact control (non-diabetic, ND), intact diabetic (D), ovariectomized diabetic (D-OVX) and ovariectomized diabetic which were treated with progesterone (D-OVX + P; 10 mg/kg, s.c, every second day) for 10 weeks. Diabetes was induced by a single dose injection of 55 mg/kg streptozotocin. Expressions of transforming growth factor-ß (TGF-ß), fibronectin, vascular endothelial growth factor-A (VEGF-A), angiotensin II type 1 receptor (ATR1) and podocyte markers (nephrin and podocin) were assessed by immunohistochemistry and real-time PCR. RESULTS: The treatment of D-OVX rats with progesterone attenuated diabetic-associated increases in the urinary albumin to creatinine ratio, glomerulosclerosi and the expression of profibrotic and angiogenic factors (TGF-ß, Fibronectin and VEGF-A). Furthermore, progesterone supplementation prevented diabetes-induced downregulation of nephrin and podocin while the overexpression of ATR1 in the diabetic rats was inhibited by the progesterone supplementation. CONCLUSION: These results provided evidence, for the first time, that the replacement of progesterone can ameliorate the renal damage in the experimental models of diabetic nephropathy through improving the renal function; the inhibition of renal fibrosis and abnormal angiogenesis; along with the amelioration of podocyte injury. Additionally, the blocking of renin-angiotensin system through the down-regulation of ATR1 expression may also account for the reno-protective effect of progesterone.

Frequency of Human Papilloma Virus (HPV) subtypes 31,33,35,39 and 45 among Yemeni women with cervical cancer.

BACKGROUND: Identification of different HPV subtypes in unidentified communities provides sufficient information for screening and monitoring potential impact of a vaccination program. Therefore, the aim of this study was to screen for the presence of HPVs subtypes 31,33,35,39 and 45 among Yemeni women with Cervical Cancer. METHODOLOGY: A total of 200 (150 malignant and 50 benign) tissue samples were obtained from Yemeni women with cervical cancer, were investigated for the presence of HPV subtypes 31,33,35,39 and 45 by Polymerase Chain Reaction (PCR). RESULTS: Of the 150 cervical cancer tissue specimens, HPV 31, HPV 33, HPV35, HPV 39 and HPV45 were identified in 10/150 (6.7 %), 6/150 (4 %), 6/150 (4 %), 5/150 (3.3 %) and 10/150 (6.7 %), respectively. The frequency of these HPV subtypes among Yemeni women with cervical cancer was 24 %. CONCLUSION: HPV 31, HPV 33, HPV35, HPV 39 and HPV45 were prevalent among Yemeni women with cervical cancer.

Prevalence of obesity in Hail region, KSA: in a comprehensive survey.

BACKGROUND: Obesity contributes significantly to morbidity and mortality rates worldwide. We, therefore, aimed to provide epidemiological data on the prevalence of obesity in Hail, Kingdom of Saudi Arabia (KSA). METHODOLOGY: Data were collected during cross-sectional survey which included 5000 Saudi selected from 30 primary health care centers (PHCs) in Hail Region. RESULTS: The overall prevalence of obesity in Hail was 63.6%. Moreover, the prevalence of males was 56.2% and the prevalence of females was 71%. CONCLUSION: Obesity is prevalent in the Hail Region which necessitates urgent interventions including health education.

Incidence of Epstein-Barr virus in pediatric leukemia in the Sudan.

BACKGROUND: Results of several studies have suggested a probable etiologic association between Epstein-Barr virus (EBV) and leukemias; therefore, the aim of this study was to investigate the association of EBV in childhood leukemia. METHODS: A direct isothermal amplification method was developed for detection of the latent membrane protein 1 (LMP1) of EBV in the peripheral blood of 80 patients with leukemia (54 had lymphoid leukemia and 26 had myeloid leukemia) and of 20 hematologically healthy control subjects. RESULTS: EBV LMP1 gene transcripts were found in 29 (36.3%) of the 80 patients with leukemia but in none of the healthy controls (P < .0001). Of the 29 EBV(+) cases, 23 (79.3%), 5 (17.3%), and 1 (3.4%) were acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, respectively. CONCLUSION: EBV LMP1 gene transcriptional activity was observed in a significant proportion of patients with acute lymphoblastic leukemia. EBV infection in patients with lymphoid leukemia may be a factor involved in the high incidence of pediatric leukemia in the Sudan.

Association between AgNORs and Immunohistochemical Expression of ER, PR, HER2/neu, and p53 in Breast Carcinoma.

Settings. Despite the limited diagnostic utility of AgNORs (argyrophilic nucleolar organiser region-associated proteins) for individual breast lesions, AgNOR analysis bears a significant potential for characterizing cell proliferative activity of breast lesions. Methodology. The present study investigated the relationship between mean AgNORs count and immunohistochemical expression of ER, PR, HER2/neu, and p53 in breast carcinoma in serial paraffin sections from 137 breast carcinomas. Twenty control cases of benign breast lesions were included. Results. Mean AgNOR counts correlated significantly inversely with hormone estrogen receptors (ER), Progesterone receptors (PR), and p53 immunohistochemical expression, denoting P values of 0.05, 0.01, and 0.001, respectively. No significant correlation was found between mean AgNOR counts and HER2/neu, P = 0.9. Mean AgNOR count was significantly higher in grade II tumor cells. We conclude that mean AgNOR counts correlate with ER, PR, and P53 tumor markers in breast carcinomas. Conclusion. We recommend the use of mean AgNOR count for accurate reporting of breast carcinomas, as well as prediction of ER, PR, and P53 in routine paraffin sections.

Evaluation of 2 real-time PCR assays for the investigation of mecA gene in clinical isolates of MRSA in Western Saudi Arabia.

OBJECTIVE: In diagnostic microbiology laboratories, Methicillin resistant Staphylococcus aureus (MRSA) is identified by positive coagulase test and positive deoxyribonuclease (DNase) activity followed by demonstration of oxacillin resistance on susceptibility testing on agar plate. This usually takes an approximately 48-72 hours. The purpose of this study is to evaluate 2 real-time polymerase chain reaction (PCR) assays for the presence of mecA gene in a population of MRSA strains circulating in Jeddah, Western Saudi Arabia, in order to determine their usefulness in the speedy diagnosis of MRSA in our clinical setting and their contribution to optimal patient management. METHODS: Ninety MRSA isolates obtained from clinical samples were identified by using conventional methods. They were collected between February 2004 and August 2004, from 2 major hospitals in Jeddah; King Abdul-Aziz University Hospital, Jeddah (50 strains) and King Khalid National Guard Hospital, Jeddah (40 strains). All isolates were confirmed as MRSA using Gram stain, catalase and coagulase activity, confirmatory DNAse activity and Kirby Bauer disc diffusion method with resistance to oxacillin by the agar disc method. The DNA extract was tested by 2 assays. The first was the commercial IVD Roche kit, which detects the mecA gene using the Light Cycler system. The other method employs multiplex PCR which detects As442 fragment and mecA optimized for the Smart Cycler system (Cephied). The length of time taken to perform the assays was recorded. RESULTS: All isolates were positive for Sa442 fragment and the coa gene specific for Staphylococcus aureus (S. aureus). However, 88/90 isolates (97.7%) tested were positive for mecA gene with both systems. The amplification, detection and melting curve analysis took 59.2 minutes for 32 samples on the Light Cycler and 46.7 minutes for 16 samples on the Smart Cycler. CONCLUSION: The 2 methods studied were equally specific and sensitive for the detection of mecA gene in confirmed S. aureus isolates and capable of identifying MRSA much earlier than conventional methods. The detection of 2 targets in the multiplex PCR assay reduces the 2-hour time required for DNase testing and may be used as a primary screening test for the detection of MRSA in clinical samples, such as blood cultures and sterile body fluids.