Delivery and Biodistribution of Traceable Polymeric Micellar Diclofenac in the Rat

The nonsteroidal anti-inflammatory drugs elevate cardiovascular risk, perhaps, due to their accumulation in the heart and kidneys. We designed nanodelivery systems for cardiotoxic diclofenac to reduce its presence in these organs. Diclofenac ethyl ester (DFEE) was encapsulated in traceable micelles based on poly(ethylene oxide)-b-poly(ε-caprolactone) (DFEE-PCL-TM) or poly(ethylene oxide)-b-poly(α-benzyl carboxylate-ε-caprolactone) (DFEE-PBCL-TM). Diclofenac pharmacokinetics and tissue distribution were studied after intravenous (iv) and intraperitoneal administration of the nanoformulations and compared with those after iv doses of free diclofenac (n = 3-6/group). The average diameters for DFEE-PBCL-TM and DFEE-PCL-TM were 37.2 ± 0.06 and 45.1 ± 0.06 nm, respectively. Drug concentration dropped below the assay sensitivity after free drug administration in 6 h, but persisted for 24 h following DFEE-PBCL-TM (2.3 ± 1.4 μg/mL) and DFEE-PCL-TM (1.9 ± 0.6 μg/mL) iv administration. The diclofenac heart:blood and kidney:blood ratios were 5- to 12-fold lower with the nanoformulations than with free diclofenac. Near-infrared fluorescence measurements in tissues suggested exposure patterns to nanocarriers parallel with those achieved for delivered diclofenac by nanoformulations. Administration of DFEE-PCL-TM by iv or intraperitoneal injection, resulted in comparable pharmacokinetics and 6 h postdose near-infrared fluorescence in the heart, kidneys, liver, and spleen. When compared to each other, DFEE-PBCL-TM showed significantly lower diclofenac levels in the heart compared to DFEE-PCL-TM (0.3 ± 0.03 vs. 0.5 ± 0.1 μg/g). Developed nanoformulations of diclofenac prolonged diclofenac circulation and reduced its presence in the heart and kidneys, strongly suggesting cardiac-safe delivery vehicles for diclofenac.     

Prevalence, predictors, and outcomes of conservative medical management in non-ST-segment elevation acute coronary syndromes in Gulf RACE-2

We assessed the prevalence, predictors, and in-hospital and long-term outcomes of conservative medical management for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) compared with percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG). This prospective study conducted from October 2008 to June 2009 in 65 hospitals from 6 Arabian Gulf countries included 30-day and 1-year mortality follow-up for 3661 patients. Compared with conservative management group (2859 patients; 78.1%), the PCI group (638; 17.4%) had significantly better unadjusted and adjusted in-hospital (odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.17-0.97), 30-day (OR: 0.44, 95% CI: 0.24-0.76) and 1-year (OR: 0.58, 95% CI: 0.40-0.87) mortality rates. Comparison with the CABG group (164; 4.5%) yielded similar results with inclusion of patients scheduled for CABG after hospital discharge. Independent predictors of conservative medical management were mainly country of residence and history of prior CABG.     

Relationship between white blood cell count and in-hospital outcomes in acute coronary syndrome patients from the Middle East

We evaluated the relationship between admission white blood cell (WBC) count and in-hospital outcomes in acute coronary syndrome (ACS) patients from the Middle East. Data were analyzed from 7806 consecutive patients with ACS who were divided into 4 groups (G) according to their WBC count (× 10(9)/L; G1: < 6.00; G2: 6.00-9.99; G3: 10.00-11.99; G4: ≥ 12.00). After significant covariate adjustment, those in G4 were 68% more likely to have cardiogenic shock than those in G1 (95% confidence interval [CI]: 1.05-2.68; P = .030) and G2 (odds ratio [OR], 2.02; 95% CI: 1.51-2.71; P < .001). Those in G4 were 2.02 times (95% CI: 1.11-3.67; P = .021) and 65% (95% CI: 1.17-2.32; P = .004) more likely to die in hospital than those in G1 and G2, respectively. Admission WBC count is an independent risk factor for in-hospital cardiogenic shock and mortality, in Middle Eastern patients with ACS. Novel therapeutic agents targeting WBCs in patients with ACS may improve outcomes.     

Primary Melanoma of the Adrenal Gland,a Continuous Dilemma: Report of a Case

The adrenal gland can frequently be the site of metastatic deposits, including malignant melanocytic tumors; however, primary melanoma of the adrenal gland is exceptional. We reviewed 18 cases reported in the English literature to date, and here add another case which occurred in a 78-year-old man. The patient underwent right suprarenalectomy and the pathology report showed a malignant melanoma of the adrenal gland. Immunohistochemical staining revealed a positive antibody-specific cytoplasmic reactivity to S-100 and HMB-45 proteins with a negative reaction for cytokeratin (AE1, AE3), synaptophysin, chromogranin and neuron-specific enolase. There are diagnostic criteria for accepting an adrenal melanoma as primary; however, an autopsy is the final step to confirm this infrequent pathology.     

Prevalence of the metabolic syndrome among Omani adults

OBJECTIVE: To estimate the prevalence of the metabolic syndrome by age and sex in the Omani population as defined by the third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) of North America. RESEARCH DESIGN AND METHODS: We analyzed data from a cross-sectional survey conducted in 2001 containing a probability random sample of 1,419 Omani adults aged > or =20 years living in the city of Nizwa. The metabolic syndrome, defined by the ATP III, was defined as having three or more of the following abnormalities: waist circumference >102 cm in men and >88 cm in women, serum triglycerides > or =150 mg/dl (1.69 mmol/l), HDL cholesterol <40 mg/dl (1.04 mmol/l) in men and <50 mg/dl (1.29 mmol/l) in women, systolic blood pressure > or =130 mmHg and/or diastolic > or =85 mmHg or on treatment for hypertension, and fasting serum glucose > or =110 mg/dl (6.1 mmol/l) or on treatment for diabetes. RESULTS: The age-adjusted prevalence of the metabolic syndrome was 21.0%. The crude prevalence was slightly lower (17.0%). The age-adjusted prevalence was 19.5% among men and 23.0% among women (P = 0.236). Low HDL cholesterol was the most common component (75.4%) of the metabolic syndrome among the study population followed by abdominal obesity (24.6%). Abdominal obesity was markedly higher in women (44.3%) than in men (4.7%). CONCLUSIONS: The prevalence of the metabolic syndrome in Oman is similar to that in developed countries. Future prevention and control strategies should not overlook the importance of noncommunicable disease risk factors in rapidly developing countries.     

Attitude of the Omani population toward organ transplantation

Transplantation from deceased donors is still scarce in Oman, mainly due to family refusal. We conducted a survey to learn the attitudes of the Omani population regarding transplantation. SUBJECTS AND METHODS: Among 500 individuals who were distributed, a questionnaire 304 responded including 247 (81%) Omani and 57 (19%) foreign residents. There were 213 (70%) male respondents of the 304 subjects, 256 individuals (84%) were between 18 and 50 years of age, and 270 (89%) had at least a high school education. RESULTS: Thirty-eight percent and 32% of Omani individuals had a family member or a friend with kidney disease or a renal transplantation, respectively. Only 42% of respondents knew that renal transplantation is performed in Oman. It was encouraging to note that 65% of Omanis knew that commercial transplantations are against Islamic and international standards. Sixty-four percent of the respondents stated that they would donate a kidney to a relative with renal failure. Nevertheless, only 49% knew that donation after death is permitted by Islam; 42% respondents would accept a kidney from a deceased person. Only 35% would donate a kidney or an organ after death. We concluded that the awareness of the Omani people toward donation after death is low, with a great need for public education and awareness programs, particularly for high school and university students.     

Diabetes risk score in Oman: a tool to identify prevalent type 2 diabetes among Arabs of the Middle East

We used Oman's 1991 National Diabetes Survey data (n=4881) to develop a simple diabetes risk score for identification of individuals at high risk of having diabetes mellitus. The logistic regression model used included age, waist circumference, body mass index, family history of diabetes and hypertension status at the time of the survey for individuals aged > or =20 years. The validity of the model was assessed in another cohort (2001 Nizwa study n=1432). On applying this model to both cohorts, the area under the receiver-operating characteristic curve was 0.83 (95% confidence interval (CI) 0.82-0.84) for the 1991 cohort and 0.76 (95%CI 0.74-0.79) for the 2001 cohort. The Risk Score of >10 was depicted as the optimal cut-point to predict diabetes diagnosed by serum glucose > or =11.1 mmol/L 2-h post 75 g oral glucose load. This score had a sensitivity of 78.6 and 62.8% and specificity of 73.4 and 78.2% in the two cohorts, respectively. Test of the Thai, Dutch, Finnish and Danish diabetes risk scores showed poor performance of these models among Omani Arabs. In comparison, the self-administered diabetes risk score of Oman could identify most individuals at high risk of having type 2 diabetes in community-based settings in Oman.     

Fasting cut-points in determining prevalence of diabetes in an Arab population of the Middle East

We used two cross-sectional surveys involving 6356 Omanis aged >or= 20 years to estimate the effect of the 1997 American Diabetes Association (ADA) criteria on the prevalence of diabetes mellitus in Oman and develop a validated optimal fasting plasma glucose (FPG) cut-point which best predicts diabetes diagnosed 2-h post oral glucose tolerance test. Applying the 1997 ADA criteria to Oman would underestimate diabetes by 18%. The sensitivity of the ADA criteria was 68.3% (95% CI 64.0-72.4%) and specificity was 98.6% (95% CI 98.2-98.9%). Receiver-operating characteristic (ROC) curve depicted FPG>5.9 mmol/l to best predict 2-h post-load glucose >or=11.1 mmol/l. The area under the ROC curve was 0.95 (95% CI 0.94-0.95%) with no significant difference between obese and non-obese individuals. This cut-point had a sensitivity of 87.5% (95% CI 84.3-90.3%), specificity of 90.8% (95% CI 89.9-91.7%) and likelihood ratio of 9.5. On validation in an independent population, the sensitivity and specificity of the depicted cut-point remained high 84.2% (95% CI 77.0-89.8%) and 80.2% (95% CI 78.0-82.4%) compared to the ADA values 60.4% and 96.6%, respectively. Our study identified a lower cut-point to diagnose diabetes than that suggested by the 1997 ADA criteria.     

Increasing prevalence of diabetes mellitus in Oman.

AIMS: To determine the prevalence of diabetes mellitus and impaired fasting glucose by age, gender, and by region and compare results with the 1991 survey; and estimate previously undiagnosed diabetes mellitus in the Omani population. METHODS: Cross-sectional survey containing a probability random sample of 5838 Omani adults aged >or= 20 years. Diabetes and impaired fasting glucose (IFG) were assessed by fasting venous plasma glucose using 1999 World Health Organization's diagnostic criteria (normoglycaemia < 6.1 mmol/l, IFG >or= 6.1 but < 7 mmol/l,and diabetes >or= 7 mmol/l). The 1991 survey was reanalysed using the same diagnostic criteria, and results were compared. RESULTS: In 2000, the age-adjusted prevalence of diabetes among Omanis aged 30-64 years reached 16.1% (95% confidence interval (CI) 14.7-17.4) compared with 12.2% (95% CI11.0-13.4) in 1991. IFG was found among 7.1% (95% CI6.2-8.1) of males and 5.1% (95% CI 4.4-6.0) of females. Generally, diabetes was more common in urban then rural regions. Only one-third of diabetic subjects knew that they had diabetes. Nearly half of the study population had a body mass index > 25 kg/m2. CONCLUSIONS: The prevalence of diabetes is high in Oman and has increased over the past decade. The high rate of abnormal fasting glucose together with high rates of overweight and obesity in the population make it likely that diabetes will continue to be a major health problem in Oman. Primary prevention programmes are urgently needed to counteract major risk factors that promote the development of diabetes.