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.

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.

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.

The future of academic medical centers in saudi arabia: difficulties encountered in a teaching hospital.

OBJECTIVE: The objective of this study was to define and analyze the major difficulties experienced and documented in a university teaching hospital. METHODOLOGY: The academic medical center (AMC) reviewed was the King Fahd Hospital of the University (KFHU), Al-Khobar, Eastern Saudi Arabia. Data sources included student registration figures, budget allocation and the hospital annual reports. The retrospective analysis was restricted to difficulties encountered. RESULTS: While numbers of medical students increased, staff positions remained static. There was remarkable budgetary deficiency over 9 years; especially for pharmacy, equipment's and supplies. The number of patients' visit markedly increased. The difficulties encountered were 237 in 70 sections of KFHU. Other problems included recruitment difficulties and the triple role for the faculty; teaching, researching and service. CONCLUSION: The role of leadership is emphasized to provide answers for the problems; to manage AMC's more efficiently; to find ways of providing medical care more cost-effectively and to generate more funds.

Breast cancer in the eastern province of Saudi Arabia.

In the Kingdom of Saudi Arabia (KSA), hospital and population based statistics have shown that breast cancer has the highest crude frequency rate among Saudi women. The scarcity of reports about the disease in the KSA has been the impetus to this analysis about breast cancer in the eastern province of KSA. Data on female patients with invasive breast carcinoma seen at King Fahd Hospital of the University in the eastern province of KSA, were retrospectively reviewed. The analysis intended to examine the pattern of the disease and the outcome for patients. Between 1985 and 1995, 292 patients were identified. Their median age +/- SD (standard deviation) was 42 +/- 10.5 years. Most patients were younger than 50 years (78%) and were predominantly premenopausals (79%). Only 25 (9%) of patients had stage I cancer, whilst 130 (44%), 90 (30%), and 47 (16%) had stage II, III, and IV, respectively. Among patients with known axillary nodal status (242 patients), only 37% were node-negative whilst 32% and 31% had 1-3, and > or = 4 positive nodes, respectively. Adjuvant chemotherapy and tamoxifen were commonly offered; nonetheless, other adjuvant modalities were rarely utilised. The median follow-up +/- SD of all patients was 62.3 +/- 8.9 months: 152 patients (52%) were alive with no evidence of disease, 25 (9%) were alive with evidence of disease, and 115 (39%) were dead from breast cancer or its related complications. The median survival of the entire group was not obtained, but the 10-year projected survival was 55%. For stage I and II patients, 118 (76%) were alive with a projected 10-year actuarial survival of 64%. On the other hand, only 51 (57%) of patients with stage III disease were alive with a median survival of 41.5 months (95% Confidence interval (CI), 18.9 to 51.3). Patients with stage IV disease demonstrated a poor outcome with a median survival of 23.5 (95%, CI 12.2 to 31.4). Multivariate analyses were performed to explore the influence of independent variables on overall survival (OS) for patients with non-metastatic disease. Besides the expected adverse effect of disease progression, the favourable influence of adjuvant chemotherapy and tamoxifen prevailed. The amount of benefit gained from tamoxifen, however, was small. Similar analyses were undertaken to determine the influence of independent variables on progression-free survival (PFS). These analyses ascertained the adverse effects of advanced stage and the favourable impact of adjuvant chemotherapy. Breast cancer in the KSA has features that are distinctive from those of industrialised countries. Survival data, however, were comparable. The favourable influence of adjuvant chemotherapy was evident on both OS and PFS. Adjuvant tamoxifen, however, had little effect. Due to its infrequent use, the role of other adjuvant modalities could not be asserted.

Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy-induced oral mucositis in non-neutropenic cancer patients.

OBJECTIVE: The study was designed to assess prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of chemotherapy-induced oral mucositis in non-neutropenic cancer patients. MATERIAL AND METHODS: In a prospective open study, adult cancer patients with chemotherapy-induced, neutropenia-independent oral mucositis were treated with GM-CSF (Schering Plough Corporation, Kenilworth, NJ) prepared as mouthwash solution (5 to 10 µgm /ml). GM-CSF was administered within 24 hours of occurrence of oral mucositis at a frequency of 4 to 6 times daily. Systemic GM-CSF was not permissible. Oral mucositis was graded according to the modified Radiation Therapy Oncology Group criteria. RESULTS: Forty-nine patients were recruited but nine were subsequently excluded as they experienced neutropenia during GM-CSF therapy. The remaining 40 patients were all evaluable. Most patients had either Grade 3 or 4 gross (71%) or functional (70%) mucositis. The mean ± SEM gross oral mucositis scores for all 40 patients combined decreased from 3.3 ± 0.11 at baseline to 2.1 ± 0.12 (p<0.0001) after 2 days, 0.95 ± 0.11 (p<0.0001) after 5 days and 0.23 ± 0.07 (p <0.0001) after 10 days of therapy. Likewise, the mean ± SEM functional oral mucositis scores decreased from 3.03 ± 0.13 at baseline to 1.58 ± 0.13 (p<0.0001) after 2 days, 0.68 ± 0.11 (p<0.0001) after 5 days, and 0.15 ± 0.06 (p<0.0001) after 10 days of therapy. The duration of severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis grading score) was evident in 12 (30%), 29 (73%), and 40 (100%) patients by the 2(nd), 5(th) and 10(th) day of therapy, respectively. Similarly, Grade 0 or 1 (functional mucositis grading score) reported in 19 (48%), 31 (78%), and 40 (100%) patients by the 2(nd), 5(th) and 10(th) day of therapy, respectively. The use of GM-CSF mouthwash was not associated with any apparent ill effect. CONCLUSION: GM-CSF mouthwash as used in this study has a significant recuperative efficacy on the severity, morbidity, and duration of chemotherapy-induced oral mucositis. A large randomized, placebo-controlled study is warranted to ascertain that benefit and determine the optimal dosage and schedule.

Hepatitis C virus infection among hemodialysis patients in the eastern region of saudi arabia.

The prevalence of anti-HCV antibodies among hemodialysis patients in the Eastern region of Saudi Arabia was 42.8%. This is comparable to the observations from the Central region of the country. Repeated blood transfusions of non-screened HCV blood seems to be the major factor responsible for this high prevalence. Clinical liver disease was infrequent in the early phase of the infection.

Autosomal dominant polycystic kidney disease: observations from a university hospital in saudi arabia.

Thirty cases of autosomal dominant polycystic kidney disease (ADPKD) seen at King Fahd Hospital of the University, Al-Khobar over a period of eight years, were analysed with respect to clinical features, laboratory investigations, radiological findings, complications and outcome. There were 13 males and 17 females with a mean age of 45 yrs + 10.1 (range 16-65 years). There was positive family history of renal disease in 17 cases. At the time of presentation, 27 cases had abdominal pain. The other features noted were hematuria (20 cases), polyuria (10 cases), urinary tract infection (22 cases), headache (9 cases), uremia (7 cases) and nephrolithiasis (5 cases). Bilaterally palpable kidneys were present in all cases. Hypertension (17 cases) was the next common clinical finding. Other clinical features noted were hepatomegaly (5 cases) and mitral valve prolapse (5 cases). Twenty-one patients had cysts in liver and five had cysts in spleen. Varying degrees of renal failure were seen in 15 cases. Six (20%) patients progressed to end stage renal disease during the period of observation.

Pattern of pleural effusion in Eastern Province of Saudi Arabia: a prospective study.

In order to establish the clinical pattern and aetiology of pleural effusion in adults in the eastern province of Saudi Arabia, all patients aged 18 years and above presenting with clinical and radiological evidence of pleural effusion, between 1st December 1987 and 30th November 1991, at three participating hospitals, were prospectively studied. Of the 201 (145 male, and 56 female) patients recruited, 102 (51%) were Saudis; their mean age was 43.4 +/- 17.8 years. Pleural effusion was more common on the right side (56%) than the left (32%). In rank order, the most common diagnoses were tuberculosis (37%), neoplasm (18%), parapneumonia (14%), and congestive cardiac failure (14%). There were a variety of other causes. The aetiology was indeterminate in only 3 (1.5%) patients. Patients with tuberculosis (75 patients) were relatively young (mean age 33.4 years) and 50 (67%) of them were expatriates, mainly from the Indian subcontinent and Yemen. Of the diagnostic procedures, the most useful were histological examination and culture of pleural biopsy. The contribution of culture and cytology of pleural fluid to diagnosis was rather small. It is concluded that the clinical pattern and aetiology of pleural effusion observed in this study are similar to those of the developing countries, although they seem to have been influenced by the large migrant labour force in the country.

Tuberculous pleural effusion in the eastern province of Saudi Arabia.

The incidence and clinical pattern of tuberculous pleural effusion (TPE) and the contribution of individual laboratory procedures in the diagnosis of TPE were assessed in a five year prospective study. Two hundred and fifty-three patients presenting in three participating hospitals with pleural effusion (PE) were assessed clinically and had various laboratory investigations. Eighty-nine (35.2%) of them, including 73 (82%) men and 31 (34.8%) Saudis had TPE. Their mean age +/- SD was 33.4 +/- 11.2 years. Main symptoms in rank order were cough (80%), fever (75%), shortness of breath (64%), chest pain (61%), anorexia and weight loss (47%). PPD was positive in 82 (92%) patients. Positive culture or histological evidence of tuberculosis (TB) was observed in pleural biopsy (68.5%), pleural fluid (10%) and sputum (2%). Pleural fluid microscopy was positive in only one patient, chest radiological features of TB in 3 (3.4%). Six months anti-TB therapy resulted in complete recovery in 86 patients. It is concluded that in this community TPE constitutes over a third of all the causes of PE. The relatively young age of patients reflects the age structure of the indigenous population as well as immigrant workers. PPD, histology and culture of pleural biopsy were the most useful diagnostic tools while pleural fluid and sputum microscopy were unhelpful. The 6-months anti-TB therapy was excellent.

Postmenopausal osteoporosis in Saudi women: A pilot screening.

One hundred and ten radiographs of calcaneum were reviewed for postmenopausal osteoporosis in Saudi women. These patients had presented to the emergency room with unrelated complaints. The mean (+/- SD) age of this group was 58 (+/-8.9) years with a range of 45 to 80 years. Of these eighty-six (76%) patients had osteoporosis; of these, 42 had mild osteoporosis, 31 had frank osteoporosis, and 11 were diagnosed to have sever osteoporosis. Women with severe osteoporosis were significantly older than those with mild (P=0.0417) as those who were normal (P=0.002). This study indicates a high prevalence of postmenopausal osteoporosis in Saudi women and multicenter, large scale screening should be instituted to determine the incidence of postmenopausal osteoporosis among Saudi women.

Public knowledge, misperceptions, and attitudes about cancer in Saudi Arabia.

We interviewed six hundred adults to assess their awareness, attitude and misperceptions about cancer. The mean age (+/- SD) was 31.2 (+/- 8.7) years. Fifty-six percent of the participants were males and 75% were Saudis. Nationality and having a relative who had cancer were found to be insignificant predictors of attained knowledge. Despite a minor difference between males' and females' performance, gender did not influence knowledge. Education was the most significant factor that influenced individuals' knowledge and misperceptions. The most significant difference was noted between those who had university or higher education (level III, 41%) and those who were illiterate or only had primary schooling (level I, 16%). The difference between level I and level II (secondary and high school, 43%) was less obvious. The analysis also showed that individuals who were > 30 years of age generally showed more knowledge and fewer misconceptions about cancer than younger participants. Age, however, together with education deviated only 5% in the variability of the total score. A high level of misperception was observed among all respondents specifically relating to questions regarding side effects of conventional therapy and statements about unproven treatment. This analysis demonstrated that knowledge about cancer was disappointingly poor and the level of misperceptions significantly high. Possessing higher academic credentials alone, is not sufficient to acquire an optimal standard of health knowledge. The data also suggest that there should be comprehensive cancer health education and primary and secondary cancer prevention programs in Saudi Arabia. To achieve this goal, primary care physicians and community cancer centers should work jointly. Brief guidelines are proposed.

Percutaneous subclavian vein catheterization for hemodialysis: a report of 57 insertions.

The authors report an analysis of 57 subclavian vein catheterizations for hemodialysis. A total of 51 patients (34 men, 17 women) kept the Cobe single- and double-lumen catheters for 1,726 days. The youngest patient was eighteen and the oldest seventy-two years of age. There were no catheter-related deaths. Complications were encountered in 9 patients. The only life-threatening complication was cardiac arrest, which occurred during flushing of the catheter. The patient was successfully revived. The other complications were pneumothorax and hydrothorax in 1 patient, catheter site infection in 5 patients, and arrhythmias in 2 patients, which stopped after readjustment of the catheter tips. Their experience indicates that percutaneous subclavian vein catheterization is safe and provides quick access for hemodialysis with no morbidity and mortality if done correctly, patiently, and meticulously. The authors believe that this should be the first choice in patients with reversible renal failure and in patients with chronic renal failure, who are usually elderly and medically compromised, till a permanent vascular access is ready for use.