A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia.

Fetal hemoglobin (HbF) levels are higher in the Arab-Indian (AI) ß-globin gene haplotype of sickle cell anemia compared with African-origin haplotypes. To study genetic elements that effect HbF expression in the AI haplotype we completed whole genome sequencing in 14 Saudi AI haplotype sickle hemoglobin homozygotes-seven selected for low HbF (8.2% ± 1.3%) and seven selected for high HbF (23.5% ± 2.6%). An intronic single nucleotide polymorphism (SNP) in ANTXR1, an anthrax toxin receptor (chromosome 2p13), was associated with HbF. These results were replicated in two independent Saudi AI haplotype cohorts of 120 and 139 patients, but not in 76 Saudi Benin haplotype, 894 African origin haplotype and 44 AI haplotype patients of Indian origin, suggesting that this association is effective only in the Saudi AI haplotype background. ANTXR1 variants explained 10% of the HbF variability compared with 8% for BCL11A. These two genes had independent, additive effects on HbF and together explained about 15% of HbF variability in Saudi AI sickle cell anemia patients. ANTXR1 was expressed at mRNA and protein levels in erythroid progenitors derived from induced pluripotent stem cells (iPSCs) and CD34+ cells. As CD34+ cells matured and their HbF decreased ANTXR1 expression increased; as iPSCs differentiated and their HbF increased, ANTXR1 expression decreased. Along with elements in cis to the HbF genes, ANTXR1 contributes to the variation in HbF in Saudi AI haplotype sickle cell anemia and is the first gene in trans to HBB that is associated with HbF only in carriers of the Saudi AI haplotype. Am. J. Hematol. 91:1118-1122, 2016. © 2016 Wiley Periodicals, Inc.

BCL11A enhancer haplotypes and fetal hemoglobin in sickle cell anemia.

BACKGROUND: Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia. METHODS AND RESULTS: Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts were approximately 6%. CONCLUSIONS: Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF.

The anticancer gene ORCTL3 targets stearoyl-CoA desaturase-1 for tumour-specific apoptosis.

ORCTL3 is a member of a group of genes, the so-called anticancer genes, that cause tumour-specific cell death. We show that this activity is triggered in isogenic renal cells upon their transformation independently of the cells' proliferation status. For its cell death effect ORCTL3 targets the enzyme stearoyl-CoA desaturase-1 (SCD1) in fatty acid metabolism. This is caused by transmembrane domains 3 and 4, which are more efficacious in vitro than a low molecular weight drug against SCD1, and critically depend on their expression level. SCD1 is found upregulated upon renal cell transformation indicating that its activity, while not impacting proliferation, represents a critical bottleneck for tumourigenesis. An adenovirus expressing ORCTL3 leads to growth inhibition of renal tumours in vivo and to substantial destruction of patients' kidney tumour cells ex vivo. Our results indicate fatty acid metabolism as a target for tumour-specific apoptosis in renal tumours and suggest ORCTL3 as a means to accomplish this.

Haematological, lipid profile and other biochemical parameters in normal and hypertensive subjects among the population of the eastern province of Saudi Arabia.

OBJECTIVE: To determine the lipid profile complete blood count and other biochemical parameters in normotensive and hypertensive individuals. DESIGN: Cross-sectional population-based epidemiological household survey. SETTING: Population sample of the Eastern Province of Saudi Arabia. RESULTS: Hypertensive individuals had significantly higher mean levels of glucose, Tc, LDL-c, HDL-c, triglycerides and HBAIc, compared to normotensive individuals while there were no significant difference in the mean levels of Apo AI and Apo B. Within the same group there were variations in the levels of certain parameters between male and female. While the mean levels of haemoglobin, WBC and platelets were significantly higher in the hypertensive group compared to normotensive, there were no significant differences between these two groups in the levels of RBC, MCV, HCT, MCH and MCHC. However, the mean levels haemoglobin, RBC count and HCT were significantly higher in male compared to female within the same group with no significant difference in levels of WBC, MCV, MCH and MCHC. Furthermore, the mean concentration of platelets was significantly higher in females compared to male within the same group. Hypertensive individuals had significantly higher serum sodium, chloride and calcium levels but a significantly lower potassium level when compared to normotensive with no siginificant differences between male and female within the same group. CONCLUSION: The lipid and electrolyte profile of hypertensive individuals differ from that of normotensive individuals in this population. This study has contributed towards establishing the normal values for a number of parameters involved in the aetiology of cardiovascular diseases in the population of Eastern province.

The association of gastroesophageal reflux with bronchial asthma. Can asthma also trigger reflux?

BACKGROUND/AIMS: The frequency of gastroesophageal reflux (GER) among asthmatic patients was found to range from 34% to 89% at different locations. The aims of this study have been to determine the frequency of GER in patients with asthma in the Saudi environment, to ascertain the main mechanism whereby GER triggers asthma, and to seek any evidence whether asthma can also trigger GER. METHODOLOGY: Fifty asthmatic patients were consecutively recruited as they reported to King Fahd Hospital of the University (KFHU), Al-Khobar, Saudi Arabia, in the period from February 2000 to February 2001; their mean age +/- SD was 38.0 +/- 9.8 years. Twenty-two subjects without asthma or GER served as controls; their mean age +/- SD was 29.4 +/- 8.6. Both groups were subjected to a questionnaire, esophageal manometry, dual probe ambulatory 24-hour pH monitoring, and pulmonary function tests. RESULTS: Among the asthmatic group 22 patients (44%) had GER. Accordingly, the asthmatic patients were divided into two groups: asthmatic with GER (n=22), and asthmatic without GER (n=28). Hoarseness of voice and nocturnal symptoms were found to be significant predictors for the presence of GER in asthmatics. Manometry revealed that asthmatic patients with GER had higher gastric pressure (11.4 +/- 4.0 mmHg vs. 8.4 +/- 2.8 mmHg; p=0.006) and lower resting pressure at the lower esophageal sphincter (LES) (21.2 +/- 8.7 mmHg vs. 28.2 +/- 9.3 mmHg; p=0.013) when compared with controls, both factors favoring the occurrence of reflux. With regard to pH data, acid reflux occurred both at the distal and proximal esophagus but the percent total acid exposure time was about 7 times longer at the distal than at the proximal esophagus (5.80 vs. 0.9). In addition, gastric pressure was positively and significantly correlated with distal esophageal acid exposure time and the DeMeester score, negatively correlated with spirometric parameters in asthmatic patients, as well as found to be a significant predictor of the severity of asthma (p=0.006). CONCLUSIONS: Forty-four percent of the sample of asthmatic patients reporting to KFHU had GER. Since distal esophageal total acid exposure time was nearly 7 times longer than at the proximal esophagus, the main mechanism for GER triggering asthma is the vagally mediated reflex initiated by acid in the distal esophagus. In addition, the positive correlation of increased gastric pressure with the distal esophageal acid exposure time and the DeMeester score, its negative correlation with spirometric parameters and being a significant predictor of asthma severity suggest that severe asthma may trigger or aggravate GER.

Physicians' knowledge, attitude and practice towards erectile dysfunction in Saudi Arabia.

We aimed to test the knowledge, attitude and practice (KAP) of physicians towards erectile dysfunction in the Eastern province of Saudi Arabia. At a scientific meeting about erectile dysfunction, 159 physicians from both government and private sectors answered a 34-item questionnaire in private. The mean total KAP score for the group was below the expected standard of 60%. Male physicians scored significantly higher than females. Urologists scored the highest, followed by andrologists. Surprisingly, physicians with higher qualifications scored lower than those with intermediate qualifications and even less than general practitioners. Those who had practised for > or = 10 years scored better than those with < 10 years practice. The role of cardiologists in the diagnosis and management of erectile dysfunction is discussed.

Physicians' knowledge, attitude and practice towards erectile dysfunction in Saudi Arabia

We aimed to test the knowledge, attitude and practice [KAP] of physicians towards erectile dysfunction in the Eastern province of Saudi Arabia. At a scientific meeting about erectile dysfunction, 159 physicians from both government and private sectors answered a 34-item questionnaire in private. The mean total KAP score for the group was below the expected st and ard of 60%. Male physicians scored significantly higher than females. Urologists scored the highest, followed by and rologists. Surprisingly, physicians with higher qualifications scored lower than those with intermediate qualifications and even less than general practitioners. Those who had practised for >/= 10 years scored better than those with < 10 years practice. The role of cardiologists in the diagnosis and management of erectile dysfunction is discussed

Drug resistance pulmonary tuberculosis in the Eastern Province of Saudi Arabia.

OBJECTIVE: To evaluate the prevalence and pattern of antituberculous drug resistance and patients with pulmonary tuberculosis in the Eastern Province and its impact on the tuberculosis control program. METHODS: Patients with pulmonary tuberculosis, proven by culture, admitted to Dammam Chest Hospital from November 1993 through May 1996 were reviewed. Patients who had at least one documented isolate of mycobacterium tuberculosis resistant to at least one standard anti-tuberculosis drug were identified. Medical records were reviewed and information was retrieved regarding age, sex, nationality, history of previous tuberculosis, human immune deficiency status, and results of direct smear and chest radiograph abnormalities. RESULTS: A total of 411 cases of culture positive pulmonary tuberculosis with drug susceptibility testing, were identified during the period mentioned, of these 123 (30%) were Saudi nationals and 228 (70%) were non-Saudis. Drug resistance to at least one drug was observed in 43 (10.5%) patients, resistance to isoniazid alone was observed in 25 (6%) patients, whereas resistance to rifampicin was noted in only one (0.2%) patient, and to streptomycin in 3 (1%) patients, multidrug resistance was observed in 11 (3%) patients. CONCLUSION: The study has shown that the overall drug resistance rate of 10.5% in the Eastern Province of Saudi Arabia is the lowest reported in the Kingdom, compared with Riyadh (13%), Taif (23%) and Gizan (44%). However, it appears to be similar to that reported in neighboring countries. In light of the study findings, and as per the recommendation of the World Health Organization, we suggest that a 4-drug regimen, as an initial treatment for pulmonary tuberculosis should be maintained, as resistance to isoniazid is still higher than the cut off value of 4%, and susceptibility testing for first line antituberculosis drugs should be carried out whenever possible. We also recommend applying stricter medical criteria for tuberculosis screening in newcomers, and for Saudi nationals, application of directly observed therapy should be a priority.

Emergence of methicillin-resistant Staphylococcus aureus as a community pathogen.

Methicillin-Resistant Staphylococcus aureus (MRSA) infection is an established nosocomial pathogen, with hospital-based outbreaks occurring worldwide. An increase in MRSA infections without risk factors has been recently documented in several reports. A prospective study was conducted over a 36-month period to determine the prevalence and risk factors for community-acquired MRSA infection at King Fahad Hospital of the University Al-Khobar, Saudi Arabia. Patients hospitalized within the previous 12 months or transfers from hospitals or nursing homes were excluded. The number of patients with community-acquired MRSA disease increased from a single patient in 1998 to fifteen patients in the year 2000 and the percentage of community-acquired MRSA/total number of MRSA increased from 5% to 33%. Fifteen (75%) of 20 patients with community-acquired MRSA infection had no discernible characteristics of MRSA infections. Skin and soft tissue infections were the predominant presentation. Most MRSA isolates (95%) were susceptible to multiple antibiotics. Our data suggest that MRSA is an emerging community pathogen. Hospital infection control strategies will have to be redefined and community approaches developed to reduce transmission.

Disease profile, complications and outcome in patients on maintenance haemodialysis at King Faisal University Hospital, Saudi Arabia.

OBJECTIVE: To determine the primary renal disease, acute complications and long term outcome of patients with end stage renal disease(ESRD) undergoing maintenance haemodialysis (MHD). DESIGN: A prospective descriptive study. SETTING: King Faisal Hospital of the University, Al-Khobar, Saudi Arabia. PATIENTS: Patients who had chronic renal failure with end stage renal disease (ESRD) and had been on regular dialysis for more than three months between September 1983 and September 1996 were included in the study. They were classified into three age groups, namely, group I comprising those aged below 29 years (48 patients); group II 30-59 years (147 patients), and group III, those aged 60 years and above (38 patients). Data were collected on disease characteristics, laboratory and radiological investigations, intra-dialytic complications and long-term outcome. The nature of renal disease was ascertained by review of medical data, clinical examination and laboratory investigations. RESULTS: Two hundred and thirty-three patients with ESRD on MHD were studied. The major causes of ESRD were chronic glomerulonephritis (42.9%) and diabetic nephropathy (27.9%). Hypotension, the most frequent acute complication was seen in 27% of dialytic treatments. Long-term complications resulted mainly from the vascular access and included thrombosis (60 cases), infection (50 cases), haemorrhage from access sites (20 cases) and aneurysmal dilatation (13 cases). These were more frequent in diabetics. Survival in groups I, II and III were 95%, 84% and 27% respectively at the end of the study. The 53 (22.7%) deaths that occurred in the whole study population were mostly due to cerebrovascular accidents (24.5%), cardiovascular events (15.1%), pulmonary oedema and sepsis, each contributed 13.2% of the deaths. CONCLUSION: In our patients with chronic renal failure on MHD, younger patients had better survival than the elderly. The main causes of death were cardiovascular and cerebrovascular diseases. Hypotension was the most frequent acute complication. Long-term complications were frequent, especially in diabetics.

Osteoarthritis of the knee among Saudi Arabian security forces personnel.

The prevalence and pattern of osteoarthritis of the knee and its association with obesity among security forces personnel was investigated. A single survey with a control group was done at the Mobile Hospital, Ministry of Interior, Makkah Al Mukarramah. One hundred twenty-five patients presenting to the orthopedic clinic with painful knees of at least 12 months duration gave detailed histories and were treated with bi-planar conventional radiography; they were matched with a similar number from the clinics of internal medicine without painful knees. One hundred three patients (82.4%) with 126 painful knees had various degrees of osteoarthritis. The mean age was 41 and 41.76 years for the patient and control group, respectively. The medial tibio-femoral and patello-femoral compartment were involved in 116 cases (92%). Fifty-nine knees (46.8%) had mild, 46 (36.5%) had moderate, and 21 (16.6%) had severe osteoarthritis changes. There were statistically significant differences between the two groups for weight and Quetelet index of body mass (p < 0.047 and < 0.0001). In the study group, the mean Quetelet body index was 31.6638 kg/m2, and in the control group it was 28.5633 kg/m2. The prevalence of osteoarthritis among the security forces personnel was 1.19%. The medial and patello-femoral compartment was affected in the majority of cases, and obesity was confirmed as one of the important causes of osteoarthritis in the Saudi Arabian population.