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Background Genetic polymorphisms of drug efflux transporters as ATP-binding cassette subfamily B, member 1 (ABCB1) have been suggested to modulate antiepileptic drugs (AEDs) response. We aimed to explore the association of ABCB1 polymorphisms and AEDs resistance among epileptic patients. Methods A total of 86 Jordanian epileptic patients treated with AEDs was included in the study. DNA was extracted from blood samples and genotyping and haplotypes analyses were conducted for Nine single nucleotide polymorphisms (SNPs) on the ABCB1 gene. Results Data revealed that none of the examined SNPs were associated with resistance to AEDs neither on the level of alleles nor genotypes. However, strong association was found between rs2235048 (OR = 10.6; 95%CI = [1.89-59.8], p= 0.01), rs1045642 (OR = 14; 95%CI = [1.3-156.7], p= 0.02), rs2032582 (OR = 9.1; 95%CI = [1.4-57.3], p= 0.04) and rs1128503 (OR = 18.7; 95%CI = [1.6-222.9], p= 0.02), ABCB1 polymorphisms and resistance to AEDs among females but not males. Haplotype analysis revealed statistically significant associations. The strongest significant associations were for haplotypes containing 2677G_1236 T in two-SNPshaplotypes (OR = 4.2; 95%CI = [1.2-14.9], p = 0.024); three-SNPs-haplotypes (OR = 4.2; 95% CI = [1.2-14.9], p = 0.02); four-SNPs-haplotypes (OR = 4.1; 95%CI = [1.2-14.3], p = 0.026). Conclusion Data suggests that there is a gender dependent association between ABCB1 genetic polymorphisms and response to AEDs. Additionally, ABCB1 haplotypes influence the response to AEDs. Further investigation is needed to confirm the results of this study.

BACKGROUND Pharmacogenetics (PGx) science has evolved significantly with a huge number of studies exploring the effect of genetic variants on interindividual variability of drug response. In this study, we assessed the knowledge, attitudes and preparedness of Pharm-D vs. medical students toward PGx. METHOD A paper-based cross-sectional survey was performed. A pilot-tested questionnaire consisting of 21 questions (demographics 5, knowledge 6, attitude 6, and preparedness 4) was administered to 900 healthcare students at different years of study. Descriptive and inferential analyses were used. RESULTS Out of the 900 students approached, 852 (94.7%) completed the questionnaire. The overall students' mean (SD) percentage knowledge score (PKS) was poor [46.7% (18.7)]. The mean (SD) attitude and preparedness scores for all students were 4.68 (1.32), and 1.9 (1.40), respectively, indicating overall positive attitudes, but low preparedness to apply PGx to clinical care. Pharm-D students' overall PKS was significantly higher than medical students (P

High-dose methotrexate (HD- MTX) is the cornerstone of chemotherapy for acute lymphoblastic leukemia (ALL), and one of its target enzymes is Thymidylate Synthase (TYMS). We hypothesized that genetic polymorphisms of TYMS gene would be associated with MTX toxicity in ALL children. 64 children with ALL were included in this study. Genotyping analysis was conducted on three common polymorphisms: tandem repeats in the promoter-enhancer region (VNTR), 6 bp ins/del (1494del6) in the 5′UTR, and rs2790 A > G in the 3′-untranslated region (3′-UTR). The association between genetic polymorphisms and MTX toxicity was studied. Genetic polymorphism of TYMS was associated with hematological toxicities but not with non-hematological adverse events. A significant association between TYMS 1494del6 genotypes and incidence of neutropenia (ANC G genetic polymorphisms and MTX hematologic toxicities. Genetic polymorphism of TYMS1494del6 may modulate susceptibility to MTX toxicity.

Introduction: Megalin is a renal proximal tubular protein that reabsorbs vitamin D from glomerular filtrates. Previous studies found significantly higher levels of urinary megalin in chronic microvascular complications of diabetes with associated metabolic derangements. This study aimed at testing the effect of vitamin D supplements on urinary megalin levels in diabetic nephropathy (DN) patients with vitamin D hypovitaminosis. Methods: Sixty-three participants with vitamin D deficiency and diabetic nephropathy (DN) were enrolled in the pre-post study; urinary megalin levels with various clinical parameters and serum levels of vitamin D3 were measured and compared to the baseline at 3- and 6-month intervals. Results: Interestingly, a supplementation related increase in serum vitamin D3 levels at 3- and 6- month interventions affected a constellation of ameliorations in the DN progression of clinical and metabolic factors. There was a decrease in ACR with a concomitant decrease in urinary megalin and a decrease in blood pressure, fasting plasma glucose (FPG), and low-density lipoprotein – cholesterol (LDL-C) – but an increase in glomerular filtration rate (GFR). Principally, pellet urinary megalin associated positively (p < 0.05) with vitamin D hypovitaminosis and the albumin-to-creatinine ratio (ACR) but negatively (p < 0.05) with Ca2+ and body mass index (BMI). Conclusion: Vitamin D supplementation could elucidate underlying pathophysiological mechanisms and a prognostic significance of urinary megalin association with DN, obesity/MetS-related dyslipidemia, and hyperglycemia modification. Megalin is a putative sensitive and precise predictive marker and an emerging therapeutic target of renal anomalies.

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Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients.Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients.Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 .Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.Takrolimus je široko korišćen imunosupresiv koji sprečava odbacivanje presađenog čvrstog organa. Farmako-kinetika takrolimusa pokazuje značajnu varijabilnost interleukin-10 (IL-10), u imunološkom odgovoru domaćina nakon transplantacije, doprinosi promenljivoj dispoziciji leka zavisne od CIP3A kod takrolimusa. U ovoj studiji, cilj nam je da procenimo uticaj polimorfizama pojedinačnih nukleotida (SNP) u promotorskom regionu IL-10 na zahteve za dozom takrolimusa i koncentraciju prilagođenu dozi (DAC) takrolimusa među primaocima transplantacije bubrega.Nivoi takrolimusa u krvi su mereni korišćenjem imunoeseja mikročestica enzima (MEIA) tokom šest meseci nakon transplantacije. Analiza genotipizacije je izvedena korišćenjem specifične lančane reakcije polimeraze (PCR) praćene metodama sekvenciranja za 98 jordanskih primalaca transplantiranih bubrega.Učestalosti genotipizacije IL-10 (-592) su (CC/CA/AA: 38, 46,7, 15,2%); IL-10 (-819) su (CC/CT/TT: 40,4, 44,1, 15,1%); i IL-10 (-1082) su (AA/AG/GG: 42,6, 44,7, 12,8%). Uticaj IL-10 (-1082) na takrolimus DAC zavisio je od pola. Muškarci koji su nosili najmanje jedan alel A imali su značajno niži DAC od muškaraca koji su nosili genotipizaciju GG samo u prvom mesecu nakon trans plantacije 88,2±32,1 naspram 117,5±22,5 ng/mL po mg/kg/dan, p=0,04 .Naša trenutna studija je pokazala da interakcija između pola i IL-10-1082 utiče na takrolimus DAC kod jordanskih primalaca transplantacije bubrega tokom prvog meseca nakon transplantacije.

Genetic polymorphisms of drug efflux transporters as ATP-binding cassette subfamily B, member 1 (ABCB1) have been suggested to modulate antiepileptic drugs (AEDs) response. We aimed to explore the association of ABCB1 polymorphisms and AEDs resistance among epileptic patients.A total of 86 Jordanian epileptic patients treated with AEDs was included in the study. DNA was extracted from blood samples and genotyping and haplotypes analyses were conducted for Nine single nucleotide polymorphisms (SNPs) on the ABCB1 gene.Data revealed that none of the examined SNPs were associated with resistance to AEDs neither on the level of alleles nor genotypes. However, strong association was found between rs2235048 (OR = 10.6; 95%CI = [1.89-59.8],Data suggests that there is a gender dependent association between ABCB1 genetic polymorphisms and response to AEDs. Additionally, ABCB1 haplotypes influence the response to AEDs. Further investigation is needed to confirm the results of this study.

ObjectiveTo evaluate the impact of a 10-week lockdown on children with asthma aged 4–17 years in terms of presentations to the emergency department (ED), frequency of admissions, compliance with medications and changes in pulmonary function testing results.Design and settingA questionnaire-based cross-sectional study using Google Forms to collect parents’ and caregivers’ responses after they consented to participation.ResultsA total of 374 parents/caregivers were contacted and 297 (79%) responded. The majority of the children were male (188 or 63%) and 49.8% were aged 7–12 years. More than half of the participants (194 or 65%) reported improved compliance with medications and spacer use. There was a significant reduction in the number of presentations to the ED from 137 to 80 and admissions to hospital from 56 to 24 during the 10-week lockdown period compared with the same time period in the previous year (p≤0.0001). Around 25% of the participants used telemedicine by phone and social media applications for communication with their treating physician and 59 (80%) described it as easy and smooth.ConclusionThe national lockdown in Jordan due to the COVID-19 pandemic was associated with a fall in emergency presentations and hospital admissions for acute asthma exacerbations. Parental responses indicate that fears focused around COVID-19 were associated with enhanced compliance with use preventer medications during the lockdown.

Acute lymphoblastic leukemia (ALL) is one of the major malignancies affecting children in Jordan. Methotrexate (MTX) is the cornerstone of chemotherapy for ALL, and works by targeting enzymes involved in the folate pathway. We hypothesize that genetic polymorphisms of the folate pathway are associated with MTX toxicity in children with ALL. A total of 64 children with ALL were included in this study; 31 (48.4%) boys and 33 (51.6%) girls aged 2–16 years. The folate pathway genes were genotyped using polymerase chain reaction followed by sequencing and studying the association between genetic polymorphisms and MTX toxicity. The immunophenotype was B-lineage in 55 patients (85.9%) and T-lineage in nine patients (14.1%). All genetic polymorphisms, except for dihydropyrimidine dehydrogenase polymorphisms, were associated with hematological toxicities and did not appear to precipitate any non-hematological adverse events. Patients with ALL carrying dominant alleles of methylene tetrahydrofolate (MTHFR) C677T and dihydrofolate reductase 19 bp deletion were at a higher risk of developing severe leucopenia [OR (95% CI) = 4.5 (1.2–17), p = 0.03; 5.4 (1.6–17.8); p = 0.006] while minor allele carriers of MTHFR A1298C were more likely to develop neutropenia [OR (95% CI) = 6.1 (1.3–29.5); 0.04]. Furthermore, dominant allele carriers of thymidylate synthase 1494 del6 were at a higher risk of developing neutropenia [OR (95% CI) = 6 (1.2–31.1); p = 0.04]. Genetic polymorphisms of the folate pathway may modulate MTX-induced toxicity in childhood ALL.

BackgroundPharmacists have crucial role in providing drug information and medication counseling to patients. This survey aimed to benchmark the current knowledge of the pharmacists concerning food-drug interactions (FDIs) in Jordan.MethodsA cross-sectional study was conducted in Amman, the capital and largest city of Jordan, using a validated questionnaire. It was distributed to pharmacists working in community and hospital pharmacies using a convenience sampling technique. Descriptive and inferential statistics were performed in this study.ResultsA total of 340 questionnaires distributed, 300 (88%) pharmacists responded. Over 50% of pharmacists claimed that they have sufficient knowledge regarding FDI. Virtually, the overall median (interquartile range) knowledge score was 18 (15-21), approximately 60%. The highest knowledge scores were for alcohol-drug interactions section (66.6%) followed by both common food-drug interactions and the timing of drug intake to food consumption sections with a score of (58.3%) for each, reflecting a suboptimal knowledge of FDIs among the pharmacists.ConclusionPharmacists had unsatisfactory knowledge about common FDIs, with no significant difference between hospital and community pharmacists. Therefore, more attention and efforts should be played to improve awareness about potential food-drug interactions.

Colorectal cancer (CRC) is one of the major health issues worldwide. 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for CRC and the major targets of 5-FU are folate-metabolizing enzymes. A total of 103 CRC patients with complete clinical data were included in this prospective cohort study. Genotyping was performed using polymerase chain reaction (PCR) followed by sequencing. Using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between functional polymorphisms in four genes MTHFR (1298A>C and 677C>T), DPYD (496A>G and 85T>C), DHFR 19 bp del, and MTR (2756 A>G) with disease-free survival (DFS). The minor allele frequencies of MTHFR 1298A>C, MTHFR 677C>T, DPYD 496A>G, DPYD 85T>C, DHFR 19 bp del, and MTR 2756 A>G were 0.364, 0.214, 0.116, 0.209, 0.383, and 0.097, respectively. CRC patients carrying the homozygous GG genotype in DPYD 496A>G had 4.36 times shorter DFS than wild-type AA carriers, (DFSGG vs AA: 8.0 ± 4 vs 69.0 ± 10 months; HR 4.36, 95% CI 1.04–18; p = 0.04). Moreover, female carriers of homozygous CC genotype of DPYD 85T>C had shorter DFS compared to either heterozygous or wild-type genotypes, and were 12.7 times shorter than wild-type TT carriers (DFSCC vs TT: 5.0 ± 1.5 vs 42.0 ± 7.6 months; HR 12.7, 95% CI 2.2–71.4; p = 0.004). However, there were no significant associations with the other studied polymorphisms. Genetic polymorphism in DPYD seems to be associated with DFS in CRC patients receiving an adjuvant regimen of 5-FU/capecitabine-based chemotherapy. Further studies are needed to verify these findings.

Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction.64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline.Except for HbA1c, baseline values did not differ significantly between the two groups. The post 3-months relative reductions in BMI (P=0.014) and HbA1c (P=0.037) in metformin combined with TLC intervention were significantly greater than those in TLC alone group. TNFα plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (-22.90±46.76%, P=0.01). Conversely, TLC alone basically worsened proinflammatory status (42.40±40.82 %), P0.001. Metformin with TLC treatment effected a therapeutic decrement of the oxidative stress (-15.44±35.32%, P=0.029 vs. baseline) unlike TLC alone (61.49±122.66%, P=0.01 vs. baseline). Both interventions' effects were sustained in the 6-month follow up periods.In both intervention groups, the relative changes in plasma TNFα were significantly correlated (P0.01) with systolic blood pressure and the relative changes in oxidative stress were markedly correlated (P0.05) with total cholesterol.

Background Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan. Methods In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen. Results No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B. Conclusion The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.

To investigate whether serum carcinoembryonic antigen (CEA) levels are associated with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c).A comparative, cross-sectional, observational study was conducted at Jordan University Hospital, Amman, Jordan, on 282 adult subjects from March 2012 to June 2015. Subjects were classified into 2 groups: T2DM subjects (n = 168) and a healthy comparison group (n = 114). Subjects with any condition known to be associated with elevated CEA levels were excluded. HbA1c and serum CEA levels were measured, and body mass index (BMI) was determined.Subjects with T2DM had significantly higher mean serum CEA than controls (2.4 ± 1.5 vs. 1.5 ± 1.2 ng/mL, P.0001). Sex did not correlate with CEA levels, while age (Spearman's rho [ρ] = 0.18, P = .002) and HbA1c (ρ = 0.56, P.0001) did; however, age no longer correlated after correcting for diabetic status. HbA1c was the only variable shown to correlate with CEA in a stepwise linear regression (r = 0 .37, P.001).We observed a statistically significant association between elevated CEA and T2DM, despite average CEA values for both groups being within the reference range. In addition, serum CEA levels correlated positively with HbA1c values.ADA = American Diabetes Association BMI = body mass index CA 19-9 = carbohydrate antigen 19-9 CEA = carcinoembryonic antigen CRP = C-reactive protein DM = diabetes mellitus HbA1c = glycated hemoglobin JUH = Jordan University Hospital T2DM = type 2 diabetes mellitus ρ = Spearman's correlation coefficient.

Background The prevalence of short stature (SS) and underweight in Jordan on a national level is unknown. This study aimed to investigate, on a national level, the prevalence of short stature (SS), underweight, overweight, and obesity among school aged children in Jordan. Methods This cross-sectional study was conducted from May 2015 to January 2016 and included 2702 subjects aged 6–17 years. Jordan was classified into 3 regions; North, Center (urban), and South (rural). Public and private schools were randomly selected from a random sample of cities from each region. The socioeconomic status of the sampling locations was assessed using several indicators including education, income, healthcare and housing conditions. For each participating subject, anthropometrics were obtained. SS, underweight, overweight and obesity were defined using Center of Disease Control’s (CDC) growth charts. Median Z-scores for each region, age and gender were calculated. Results The Central and Northern regions enjoyed higher socioeconomic status compared to rural Southern regions. The overall prevalence of SS, underweight, overweight, and obesity were 4.9 %, 5.7 %, 17.3 %, and 15.7 %, respectively. SS and underweight were most prevalent in the rural South, while obesity was highest in the Central region. Females were more likely to be overweight, while males were more likely to be obese. Private schools had higher prevalence of obesity and overweight than public ones. Conclusions Variations in height and weight among Jordanian school children might be affected by socioeconomic status.

Study Objectives The aim of this study was to compare the effects of caudal and intravenous (IV) dexmedetomidine (1 μg/kg) on postoperative analgesia after caudal bupivacaine in pediatric patients undergoing lower abdominal and perineal surgeries. Design A randomized controlled double-blind study. Setting University-affiliated teaching hospital. Patients Seventy-five American Society of Anesthesiologists I children, aged 1 to 6 years. Intervention Patients were randomly allocated to 3 groups. All patients received 1 mL/kg caudal 0.25% bupivacaine. In addition, those in group B (n=25) received 10-mL IV saline, those in group B-D cau (n=25) received 1 μg/kg caudal dexmedetomidine and 10-mL IV saline, and those in group B-D IV (n=25) received 1 μg/kg IV dexmedetomidine in 10-mL saline. Measurements Intraoperative mean blood pressure, heart rate, peripheral oxygen saturation, end-tidal sevoflurane, and bispectral index as well as postoperative pain and behavior scores and time to first analgesia were assessed. Main results Group B-D cau had a significantly longer time to first rescue analgesia than groups B-D IV and B, with mean (SD) values of 14.4 (7.5), 9.18 (2.7), and 6.6 (2.5) hours, respectively ( P cau (n=16) required rescue analgesia during the first 24 hours postoperatively compared to group B (n=24) and group B-D IV (n=20) ( P Groups B-D cau and B-D IV had lower pain and behavior scores than Group B. Eight patients Group B had agitation compared to 2 in Group B-D IV and 0 in Group B-D cau . Four patients in Group B-D IV developed bradycardia and hypotension during surgery. Conclusions Compared to IV administration, caudal administration of dexmedetomidine during caudal bupivacaine anesthesia provided prolonged postoperative analgesia and a greater analgesic sparing effect without significant side effects. This suggests a greater role of neuraxial compared to that of peripheral α-2 adrenoceptors in pain processing.

Background Early relapse in colorectal cancer (CRC) after curative resection is mainly attributed to the key determinants such as tumor histology, stage, lymphovascular invasion, and the response to chemotherapy. Case presentation Interindividual variability in the efficacy of adjuvant chemotherapy between patients receiving the same treatment may be ascribed to the patients’ genetic profile. In this report, we highlight a clinical case of a patient with stage II CRC who relapsed within a short period after starting adjuvant chemotherapy and was later found to have multiple genetic polymorphisms in the DPYD, TYMS, MTHFR, and DHFR genes. Conclusions Based on the clinical data of the patient and the key role of these genes in 5-fluorouracil pathway, we hypothesize that these variants may contribute to the drug response and early relapse in CRC.

BACKGROUND Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. MATERIALS AND METHODS An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. RESULTS Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR 57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin's coefficient [D']) (LC: D' =0.03, r2: 0. 001, p= 0.8; CONTROLS D' =0.29, r2: 0.08, p=0.02). Carriers of the "3 tandem repeats_insertion" haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. CONCLUSIONS Genetic polymorphism of TS at 3` UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 `UTR is more informative than TSER polymorphism in predicting increased risk.

Background: Breast cancer is a major cause of morbidity and mortality in Jordan and worldwide. Abnormality of DNA methylation is a possible mechanism for the development of cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation. Our aim was to study the association between genetic polymorphisms of MTHFR at two sites (C677T and A1298C) and their haplotypes and the risk of breast cancer among Jordanian females. Materials and Methods: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique and sequencing were conducted to determine the genotypes. Results: There was a significant difference in genotype frequency of C677T in the 41-60 year age category [cases: CC (37.4%), CT (49.5%) and TT (13.2%); controls: CC (56.3%), CT (35.6%) and TT (8%), p= 0.04; OR TT vs. CC : 2.5, 95% CI: (0.9-6.9); OR at least on T : 2.1, 95%CI: (1.2-3.9)]. There was no significant difference in genotype frequency of A1298C between cases and controls [cases: AA (46.6%), AC (41.8%) and CC (11.6%); controls: AA (43%), AC (47.4%) and CC (9.6%); p= 0.6]. There was a significant difference of MTHFR genetic polymorphism haplotypes among breast cancer cases and controls [cases/control: CA: 38.3/45.4%; CC: 28.9/25.2%; TA: 29.2/21; TC: 3.6/8.3; p value= 0.01; OR TA vs. CA = 1.6; 95% CI (1.1-2.5); p= 0.02]. Conclusions: Genetic polymorphism of MTHFR C677T may modulate the risk of breast cancer especially in the 41-60 year age group. Additionally, TA haplotype amends the risk of breast cancer. Future studies with a larger sample size are needed to validate the role of MTHFR genetic polymorphisms in breast cancer.

Background/Aims: Cyclooxygenase-2 (COX2) is a crucial enzyme involved in the metabolism of Prostaglandins and it has been implicated in several processes. This study was done to investigate the associations of polymorphisms in COX2 gene with the risk of colorectal cancer or polyps development among Jordanian population and to correlate with other ethnicities. Materials and Methods: One hundred and thirty five cases (135) of colorectal carcinoma were studied for COX2 −A1195G polymorphisms employing PCR-RFLP technique, in addition to 104 cases of adenomatous polyps and 115 matched controls taken from the general population. Results: Sixty eight colorectal cancer patients were males and 67 of patients were females with a median age of (58.0±13.9 year). Sixty six (66) of polyp cases were males and 38 were females with a median age of (58.1±14.16). The A-1195G AA carriers were 3.1 times less likely to develop CRC (95% CI: 1.8-5.3, p

Objectives: Aim of this study was to determine the pattern of toilet training (TT) in Jordan, the factors that are related to the initiation age, duration and the methods of training used among different sociocultural groups. Methods: Mothers of 1257 children attending pediatric clinics at Jordan University Hospital were directly interviewed. Results: Mean initiation and completion ages were 22.5 ± 6.50 and 26.48 ± 9.37 months respectively. Families living in urban settlement, first child in family, child-oriented approach, working mothers and mothers with higher level of education started training later. The duration of toilet training was 5.80 ± 8.06 weeks and it was shorter in families who used the child-oriented approach. Intensive method was used in 59.4%, child-oriented in 40.6%. Young mothers used more frequently the intensive method. Constipation and stool toilet refusal developed in 15.4% and 15.1% respectively and there was a significant association between constipation and older age of starting toilet training. Conclusions: Intensive method of training is more popular in our country and the initiation and completion age are earlier than in other countries. The age of initiation may be increased as parents are better educated and a child-oriented approach becomes more popular than the intensive approach.

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA synthesis and repair. We here aimed to investigate two common polymorphisms, C677T and A1298C, with genotype and haplotype frequencies in colorectal cancer (CRC) cases among Jordanian. Materials and Methods: 131 CRC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 117 controls taken from the general population, employing the PCR-RFLP technique. Results: We found the frequency of the three different genotypes of MTHFR C677T among Jordanians to be CC: 61.7%, CT: 35.2%, and TT 3.1% among CRC cases and 50.9%, 38.8% and 10.3% among controls. Carriers of the TT genotype were less likely to have CRC (OR=0.25; 95%CI: 0.076-0.811; p=0.021) as compared to those with the CC genotype. Genotype analysis of MTHFR A12987C revealed AA: 38.9%, AC: 45%, and CC 16% among CRC cases and 37.4%, 50.4% and 12.2% among controls. There was no significant association between genetic polymorphism at this site and CRC. Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the TA haplotype (677T-1298A) between cases and controls. The TA haplotype was associated with a decreased risk for colorectal cancer (OR=0.6; 95% CI: 0.4-0.9, p=0.03). Conclusions: The genetic polymorphism of MTHFR at 677 and the TA haplotype may modulate the risk for CRC development among the Jordanian population. Our findings may reflect an importance of genes involved in folate metabolism in cancer risk.

Aim: Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel-IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM® to describe the time course of clopidogrel-IM in plasma and to design a sparse-sampling strategy to predict clopidogrel-IM exposures for use in characterizing anti-platelet activity.Methods: Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel-IM using reverse phase high performance liquid chromatography. A two-compartment (2-CMT) PK model with first-order absorption and elimination plus an absorption lag-time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3–12 post-dose samples.Results: A two-compartment model with EHC provided the best fit and reduced bias in Cmax (median prediction error (PE%) of 9.58% versus 12.2%) relative to the basic two-compartment model, AUC0-24 was similar for both models (median PE% = 1.39%). The OSS for fitting the two-compartment model with EHC required the collection of seven samples (0.25, 1, 2, 4, 5, 6 and 12 h). Reasonably unbiased and precise exposures were obtained when re-fitting this model to a reduced dataset considering only these sampling times.Conclusions: A two-compartment model considering EHC best characterized the time course of clopidogrel-IM in plasma. Use of the suggested OSS will allow for the collection of fewer PK samples when assessing clopidogrel-IM exposures. Copyright © 2013 John Wiley & Sons, Ltd.

Clopidogrel is an oral antiplatelet drug. Loading dose of 600 mg clopidogrel was shown to improve clinical outcome in patients following percutaneous coronary intervention (PCI). Wide inter-individual variation has been detected in clopidogrel response that can be related to variation in Clopidogrel serum concentration. The aim of this study was to assess the pharmacokinetics parameters of 600 mg loading dose clopidogrel among Jordanian patients undergoing PCI. Additionally, the development of a simple and a validated High-performance liquid chromatography (HPLC) method for the quantification of clopidogrel carboxylate was described. 80 patients who received a loading of 600 mg Clopidogrel were included in our study, several blood samples were collected at different time points. Validated reverse phase HPLC method was used to determine Clopidogrel carboxylic acid metabolite. Non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC). The pharmacokinetic-parameters were characterized by considerable inter-individual differences [Cmax=24.49±11.64 µg/ml, Tmax=2.02±1.52 h, AUC0→∞= 123.17± 54.6 mg/ml.h, and t1 ⁄ 2e=4.29±2.92 h]. 15% of the patients who had less than one third of the Cmax 8.09±2.34 µg/ml had delayed Tmax of 4.17±1.76 h, which was not explained by standard in vitro dissolution test. Pharmacokinetic parameters of 600 mg Clopidogrel showed marked inter-individual differences. The low plasma concentrations in some of the patients and the high inter-individual variability may contribute to reported cases of resistance to Clopidogrel therapy. Further studies are needed to explain low Cmax and delayed Tmax values in some patients. Key words: Clopidogrel carboxylic acid, loading dose, percutaneous coronary intervention, reverse phase High-performance liquid chromatography (HPLC), pharmacokinetics.

BACKGROUND CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. PURPOSE The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. MATERIALS AND METHODS Blood samples were collected from 112 breast cancer female patients and 115 age-matched controls who underwent breast cancer screening with imaging and showed negative results (BI- RADS I or BI-RADS II). Genotyping was performed using the PCR-RFLP technique. RESULTS No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p-value = 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p-value= 0.95; OR= 0.95; 95% CI= 0.51- 1.88). Analysis of subgroups defined by menopausal status or smoking history also revealed no association with these polymorphisms. Furthermore, the four identified haplotypes (AC; AA; GC and GA) were equally distributed among cases and controls, and haplotype analysis showed a strong linkage disequilibrium of both studied loci in either cases or controls (D'=1). CONCLUSIONS Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females.

BACKGROUND Breast cancer is the leading cause of cancer death among women and the second in humans worldwide. Many published studies have suggested an association between MDR1 polymorphisms and breast cancer risk. Our aim was to study the association between genetic polymorphism of MDR1 at three sites (C3435T, G2677A/T, and C1236T) and their haplotype and the risk of breast cancer in Jordanian females. MATERIALS AND METHODS A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. The polymerase chain reaction/restriction fragment length polymorphism (PCR- RFLP) technique and sequencing were performed to analyse genotypes. RESULTS The distribution of MDR1 C3435T genotypes differed between cases and controls [cases, CC 45.3%, CT 41.3%, and TT 13.3%; controls, CC 13.4%, CT 43.3%, and TT 30.2%, p < 0.001]. Similarly, the distribution of G2677A/T significantly differed [cases, GG 43.1 %, GT+GA 50.9% and AA+TT 6%; controls, GG 29.6 %, GT+GA 50.9%, and AA+TT 19.4%, p = 0.004]. On the other hand, genotype and allelotype distribution of C1236T was not statistically different between cases and controls (p=0.56 and 0.26, respectively). The CGC haplotype increased the risk to breast cancer by 2.5-fold compared to others, while TGC and TTC haplotypes carried 2.5- and 5-fold lower risk of breast cancer, respectively. CONCLUSIONS Genetic polymorphisms of MDR1 C3435T and G2677A/T, but not C1236T, are associated with increased risk of breast cancer. In addition, CGC, TGC and TTC haplotypes have different impacts on the risk of breast cancer. Future, larger studies are needed to validate these findings.

Drug metabolizing enzymes participate in the neutralizing of xenobiotics and biotransformation of drugs. Human cytochrome P450, particularly CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, play an important role in drug metabolism. The genes encoding the CYP enzymes are polymorphic, and extensive data have shown that certain alleles confer reduced enzymatic function. The goal of this study was to determine the frequencies of important allelic variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 in the Jordanian population and compare them with the frequency in other ethnic groups. Genotyping of CYP1A1(m1 and m2), CYP2C9 (*2 and *3), CYP2C19 (*2 and *3), CYP3A4*5, CYP3A5 (*3 and *6), was carried out on Jordanian subjects. Different variants allele were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). CYP1A1 allele frequencies in 290 subjects were 0.764 for CYP1A1*1, 0.165 for CYP1A1*2A and 0.071 for CYP1A1*2C. CYP2C9 allele frequencies in 263 subjects were 0.797 for CYP2C9*1, 0.135 for CYP2C9*2 and 0.068 for CYP2C9*3. For CYP2C19, the frequencies of the wild type (CYP2C19*1) and the nonfunctional (*2 and *3) alleles were 0.877, 0.123 and 0, respectively. Five subjects (3.16 %) were homozygous for *2/*2. Regarding CYP3A4*1B, only 12 subjects out of 173 subjects (6.9 %) were heterozygote with none were mutant for this polymorphism. With respect to CYP3A5, 229 were analyzed, frequencies of CYP3A5*1,*3 and *6 were 0.071, 0.925 and 0.0022, respectively. Comparing our data with that obtained in several Caucasian, African-American and Asian populations, Jordanians are most similar to Caucasians with regard to allelic frequencies of the tested variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.

Background Hypertension affects 70–90 % of all kidney transplant recipients. It is associated with poor graft survival and is a contributing factor to the increased cardiovascular mortality. The reasons for the insufficient blood pressure control in transplanted patients have not been thoroughly investigated. Objective To evaluate the extent of blood pressure control in Jordanian hypertensive renal transplant recipients and to assess factors associated with such control. Setting Three outpatient renal transplant clinics in Amman. Method A cross-sectional observational study including 181 patients. We have considered blood pressure

Glucuronidation is one of the most important phase II metabolic pathways. It is catalyzed by a family of UDP-glucuronosyltransferase enzymes (UGTs). One of the subfamilies is UGT1A. Allele frequencies in UGT1A4 differ among ethnic groups. The aim of this study was to determine the allelic frequency of two most common defective alleles: UGT1A4*2 and UGT1A4*3 in a Jordanian population. A total of 216 healthy Jordanian Volunteers (165 males and 51 females) were included in this study. Genotyping for UGT1A4*1, UGT1A4*2 and UGT1A4*3 was done using a well established polymerase chain reaction-restriction fragment length polymorphism test. Among 216 random individuals studied for UGT1A4*2 mutation there were 26 individuals who were heterozygous, giving a prevalence of 12% and an allele frequency of 6.5%. Only one individual was homozygous for UGT1A4*2. The UGT1A4*3 mutation was detected as heterozygous in 9 of 216 individuals indicating a prevalence of 4.2% and allele frequency of 3.5%. Three individuals were homozygous for the UGT1A4*3 indicating a prevalence of 1.4%. The prevalence of UGT1A4*2 is similar to the Caucasians but different from other populations whilst the UGT1A4*3 prevalence in the Jordanian population is distinct from other populations. Our results provide useful information for the Jordanian population and for future genotyping of Arab populations in general.

Objectives The aim of this study was to identify the prevalence and characteristics of treatment related problems (TRPs) in hospitalized internal medicine patients in Jordan as well as to identify diseases and drugs associated with each specific TRP. We have also aimed at investigating physicians’ acceptance of recommendations made by clinical pharmacist and to identify the outcomes of pharmacist interventions. Setting Internal medicine department of a general hospital in Jordan. Methods We have utilized a systematic, prospective, bedside, comprehensive clinical assessment approach that allowed us to effectively identify, communicate and follow up TRPs. Main outcome measures: prevalence and nature of identified TRPs, clinical significance of TRPs, associated diseases and drugs and clinical outcomes of clinical pharmacist interventions. Results 402 patients were included in the study. The average number of the identified TRPs was 9.35. Fifty-three percent of identified TRPs were classified as major and 28% were classified as moderate. Ninety-one percent of the recommendations were accepted by physicians. Efficacy related problems were the most common TRP category followed by safety related problems and indication related problems. Sixty-four percent of the TRPs were resolved or prevented through the clinical pharmacist intervention. Conclusions We have found that prevalence of TRPs is substantially high among patients hospitalized at the internal medicine department. TRPs related to Dosage regimens, untreated conditions, patient monitoring, drug interactions, and drug choices were the most common. Most of TRPs identified by pharmacists were clinically significant. Pharmacists’ interventions contributed substantially to the resolving of many of the identified TRPs. Patients suffering from higher number of medical conditions and receiving higher number of medications should be given the priority for clinical pharmacy service in hospitalized internal medicine patients.

To analyze the influence ofhyperleptinemia on fasting lipid and hematological parameters in healthy Arab male youth in Jordan, this cross-sectional study was carried out in April 2009 on a sample of 120 students aged 18-24 years. Subjects were stratified by fasting leptin into two groups (control

Thymidylate synthase (TS) is a well-validated cancer target that undergoes conformational switching between active and inactive states. Two mutant human TS (hTS) proteins are predicted from crystal structures to be stabilized in an inactive conformation to differing extents, with M190K populating the inactive conformation to a greater extent than A191K. Studies of intrinsic fluorescence and circular dichroism revealed that the structures of the mutants differ from those of hTS. Inclusion of the substrate dUMP was without effect on M190K but induced structural changes in A191K that are unique, relative to hTS. The effect of strong stabilization in an inactive conformation on protein phosphorylation by casein kinase 2 (CK2) was investigated. M190K was highly phosphorylated by CK2 relative to an active-stabilized mutant, R163K hTS. dUMP had no detectable effect on phosphorylation of M190K; however, dUMP inhibited phosphorylation of hTS and R163K. Studies of temperature dependence of catalysis revealed that the Eact and temperature optimum are higher for A191K than hTS. The potency of the active-site inhibitor, raltitrexed, was lower for A191K than hTS. The response of A191K to the allosteric inhibitor, propylene diphosphonate (PDPA) was concentration dependent. Mixed inhibition was observed at low concentrations; at higher concentrations, A191K exhibited nonhyperbolic behavior with respect to dUMP and inhibition of catalysis was reversed by substrate saturation. In summary, inactive-stabilized mutants differ from hTS in thermal stability and response to substrates and PDPA. Importantly, phosphorylation of hTS by CK2 is selective for the inactive conformation, providing the first indication of physiological relevance for conformational switching.

The aim of this study was to investigate abuse/misuse of prescription and nonprescription drugs in community pharmacies in Jordan by random distribution of a structured questionnaire to 405 pharmacies (November 2005-January 2006). Data were analyzed using SPSS for windows (version 14.0). Most respondents (94.1%) suspected that some level of abuse/misuse occurred in their pharmacy, which was highest for decongestants, cough/cold preparations, benzodiazepines, and antibiotics. Abuse/misuse of prescription and nonprescription drugs is present in Jordan, but current methods for controlling the problem are ineffective, and better methods should be developed. The study's limitations are noted..

Background and objectives: Clopidogrel is an important antiplatelet drug that is effective in preventing thrombotic events, especially for patients undergoing percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has been limited by documented inter-individual heterogeneity in platelet inhibition, which may be attributable to known clopidogrel pharmacokinetic variability. The objective of this study was to assess the influence of smoking cigarettes and abnormal body weight on the pharmacokinetics of clopidogrel. Methods: Seventy-six healthy adult male volunteers were selected randomly. Each subject received a single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel carboxylate plasma levels were measured and non-compartmental analysis was used to determine peak plasma concentration (C max ), time to peak plasma concentration (T max ), elimination half-life (t 1/2e ), and area under the curve (AUC 0 → ∞ ). Results: One-third of volunteers were smokers (n = 27) and one-half had abnormal body weight (n = 39). Smokers had lower AUC 0 → ∞ (smokers: 6-24 ± 2-32 μg/h/mL vs. non-smokers: 8.93 ± 3-80 μg/h/mL, P < 0-001) and shorter half-life (smokers: 5-46 ± 2-99 vs. non-smokers: 8.43 ± 4·26, P = 0-001). Smoking behaviour had no influence on C max (P = 0·3) and T max (P = 0·7). There was no statistically significant difference in C max, AUC 0 → ∞ , T max and t 1/2e between volunteers with abnormal body weight and normal body weight. However the difference in body weight of the two groups was relatively narrow (mean ± SE; 26-93 ± 0-16 vs. 23·11 ± 0·27). In general, the pharmacokinetic parameters were characterized by considerable inter-individual differences (C max = 3·09 ± 0·99 μg/mL, CV = 32%), (T max = 0·76 ± 0-24 h, CV = 31-6%), (AUC 0 → ∞ = 7·98 ± 3-58 μg/h/mL, CV = 44·8%), and (t 1/2e = 7·38 ± 4-10 h, CV = 55·6%). Conclusion: Smoking is a significant factor affecting the pharmacokinetics of clopidogrel, following administration of a single 75 mg dose in healthy young volunteers. The study supports smoking-cessation recommendations. Further studies are required to evaluate the influence of smoking and body weight on the pharmacokinetics of the active metabolite of clopidogrel and on the clinical effects of any differences observed.

This study aimed to evaluate the effects of single nucleotide polymorphisms CYP3A4*1B and CYP3A5*3 on tacrolimus dose requirement among kidney transplant recipients.Blood levels of tacrolimus were measured using microparticle enzyme immunoassay. Genotyping analysis utilized specific polymerase chain reaction-restriction fragment length polymorphism methods for 137 kidney transplant recipients.The median tacrolimus dose was significantly lower in the CYP3A4*1/*1 carriers (0.06 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d) as compared to the CYP3A4*1B/*1B carriers (0.1 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d; P = .001). Patients with at least 1 CYP3A5*1 wild-type allele required higher median doses of tacrolimus (median, 0.08 mg/kg/d; range, 0.03 mg/kg/d to 0.22 mg/kg/d) as compared to the CYP3A5*3 carriers (median, 0.05 mg/kg/d; range, 0.007 mg/kg/d to 0.17 mg/kg/d; P = .002).This study showed that tacrolimus dose requirement is lower in Jordanian kidney transplant recipients compared to other populations. Moreover, we found a correlation between genetic variations in CYP3A4 and CYP3A5 enzymes and tacrolimus blood levels among our kidney transplant recipients.

This study is the first of its type to evaluate sources, patterns and appropriateness of antibacterial drug consumption within the Jordanian population. It uses a structured random interview to customers arriving at community pharmacy stores seeking antibacterial medication for systemic infections. Dispensed antibacterial drugs belonged to eight different main classes of systemically used antibacterial drugs in accordance with the Anatomical Therapeutic Chemical (ATC) classification system. Just less than one-half of all dispensed antibacterial drugs were without a prescription (46%), either via self-medication (23.2%) or pharmacist recommendation (23.1%). Inappropriateness in use was seen in 29.9% and 34% of the prescribed and non-prescribed (over-the-counter) antibacterial drugs, respectively. No uniformity in the treatment profile of the different treated complaints was seen. Our study shows great misuse and abuse of antibacterial drugs and hence there is a need to force regulations to control community use of antibacterial drugs and to increase awareness of the consequences of their inappropriate and uncontrolled use.

SummaryObjective The prevalence of isolated growth hormone deficiency (IGHD) among short-statured children in Jordan, where consanguineous marriage (CM) is common, is unknown. No studies have investigated the relationship between degrees of consanguinity and IGHD. This study aimed to determine the prevalence of IGHD among short-statured children referred to a university hospital in Jordan and its relationship with different degrees of consanguinity. Design We conducted a 24-month cross-sectional observational trial at an outpatient tertiary care center in Amman, Jordan. Patients We obtained detailed family histories, medical evaluations and laboratory tests for 94 short-statured children (50 boys and 44 girls aged 6–16 years). Measurements Complete and partial GHD were defined as peak GH responses of 5 and 7 μg/l (15 and 21 mIU/l) [IRMA/DiaSorin®], respectively, in both exercise and insulin tolerance tests. Results GHD was diagnosed in 69·1% of the short children, including 86% (43/50) of the children of consanguineous parents (83·3%, 93·8% and 81·8% of children of first cousins, first cousins once removed and second cousins, respectively) and 50% (20/44) of the children of nonconsanguineous parents (P = 0·039, 0·002 and 0·013, respectively). However, there was no statistically significant difference in the prevalence of small pituitary MRI between GH-deficient children of consanguineous parents and those of nonconsanguineous parents (28·6% vs 13·6%, P = 0·3). Conclusions The prevalence of IGHD among referred short children in Jordan was exceptionally high and significantly higher in the children of CM. In countries where CM is common, preconception counselling and rigorous surveillance for GHD in short children may be indicated.

Purpose: To assess modifiable clusters of cardiovascular risk factors and patterns of antihypertensive drugs use as well as identify clinical characteristics associated with blood pressure control in Jordanians.Methods: A cross-sectional observational study was conducted in cardiology outpatient clinics at two hospitals in Amman, Jordan. Outcomes studied were prevalence of cardiovascular risk factors, patterns of antihypertensive medication use, rate of blood pressure control and factors associated with such control.Results: The number of concomitant medical conditions was high: diabetes mellitus (51 %), dyslipidemia (82 %), coronary artery disease (71 %), history of acute coronary syndrome (37 %) or coronary revascularization (64 %). Hypertension was controlled in 44 % of patients. Average number of antihypertensive medications was 2.38 ± 1.21. The most commonly prescribed monotherapy medications were beta-blockers (48 %), followed by angiotensin-converting enzyme inhibitors (ACEIs) with 28 % and angiotensin II receptor blockers (ARBs) with 23 %. Among all patients, beta-blockers (67 %) were also the most prescribed, followed by ACEIs (47 %) and ARBs (41%). Multivariate logistic regression analysis revealed inverse association between BP control and the presence of diabetes mellitus.Conclusion: There is inadequate cardiovascular risk assessment and control of blood pressure in hypertensive patients in Jordan. Several practical measures need to be taken urgently to mitigate these deficiencies.Keywords: Hypertension management, Blood pressure control, Cardiology clinic, Cardiovascular risk factors, Antihypertensive medications.

Bcr‑abl fusion transcripts, resulting from translocation t(9;22), are hallmarks of Philadelphia chromosome positive (Ph+) leukemias. This translocation is detected in >90% of patients with chronic myelogenous leukemia and ~20% of acute lymphoblastic leukemia patients, which predominantly express the p210 and p190 proteins, respectively. Although the occurrence of t(9;22) in healthy individuals has been previously demonstrated, the number of studies is limited and the results are inconsistent. The present study screened for the presence of bcr‑abl transcripts in the blood of a group of healthy individuals using a sensitive‑nested reverse transcription polymerase chain reaction (RT‑PCR) assay. Samples were collected from 189 healthy volunteers (145 adults and 44 children). RNA was reverse transcribed and amplified by two rounds of PCR, amplifying the two common variants of bcr‑abl transcripts, p190 and p210. While the bcr‑abl p190 transcript was not detected, the p210 transcript was detected in ~10% of samples. Notably, the incidence of p210 translocation was higher in males (12.2%) compared with females (7.7%) and males were 2.4 times more likely to have the translocation. A significant incidence was also observed in adults compared with children, where adults were 6 times more likely to have the translocation. The presence of bcr‑abl transcripts in the blood of a significant proportion of healthy individuals should be considered in long‑term investigations to establish its exact association with the risk of developing leukemia. Furthermore, the current assays should be revised to consider the proportion of normal samples carrying the p210 transcripts when making a differential diagnosis.

Background: There is a high prevalence of arterial thrombosis in schizophrenia. Several studies investigated the cause of this high risk among schizophrenic patients and variable finding reported. The aim of this study was to investigate whether second generation antipsychotics (risperidone, olanzapine and ziprasidone) exert antiplatelet action in the presence of different platelet agonists. Methods: We performed an in vitro study of different antipsychotics (risperidone, olanzapine and ziprasidone) effect on platelet aggregation induced by different platelet agonists (ADP, collagen, serotonin and epinephrine) when added to blood of healthy volunteers using Multiplate® analyzer. Results: Risperidone and ziprasidone but not olanzapine showed clinically significant inhibition of platelet aggregation induced by by serotonin, while only ziprasidone showed statistically significant inhibition on serotonin aggregation. All tested antipsychotics showed clinically (but not statistically) significant inhibition on platelet aggregation induced by epinephrine. On the other hand, no remarkable effect of antipsychotics on platelet aggregation induced by ADP or collagen was observed. Marked amplification reaction between serotonin and epinephrine was observed (AUC 66 U). When antipsychotics were added to serotonin-epinephrine combination, all of them produced AUC inhibition in a dose-dependent manner with highest potency for risperidone (IC50= 14.86 nM) and the lowest potency for olanzapine (IC50= 27.56 nM). Conclusion: All tested antipsychotics showed clinically (but not statistically) significant inhibition effect on platelet aggregation induced by either serotonin or epinephrine. All antipsychotics studied inhibited platelet aggregation induced by a combination of serotonin and epinephrine in a dose-dependent manner.

Thrombosis is a major cause of morbidity and mortality worldwide. Genetic factors are one component of thrombosis. We studied the prevalence of two mutations that are known risk factors in the pathogenesis of arterial and venous thrombosis in the genetically isolated Circassian population in Jordan. Factor II G20210A and Factor V Leiden single nucleotide polymorphisms were analysed by polymerase chain reaction and restriction fragment length polymorphism method in 104 random unrelated subjects from the Circassian population in Jordan. The prevalence rates among the Circassian population in Jordan for Factor II G20210A was 12.2 % and for Factor V Leiden was 7.7 %. We have shown that the population is in Hardy–Weinberg equilibrium and that the prevalences of both mutations are within the range of other ethnic groups. This is the first study to describe Circassian health related genetic characteristics in Jordan. Such population-based studies will contribute to understanding the interaction between genetic and environmental risk factors. It will remain to be seen whether carriers of Factor II G20210A and Factor V Leiden are more likely to develop thrombosis. This issue should be studied in the future to determine the need for screening of these mutations particularly in thrombophilia patients.

Fructose-1,6-bisphosphatase – hereafter abbreviated as FBPase has been recently implicated in diabetes prompting several attempts to discover and optimize new FBPase inhibitors. Toward this end we explored the pharmacophoric space of 136 FBPase inhibitors using three diverse sets of inhibitors. This identified 520 pharmacophores that were subsequently clustered into 104 groups. Cluster centers were evaluated by receiver operating characteristic (ROC) curves analysis and correlation with bioactivities of collected compounds. Pharmacophore model Hypo1/7 illustrated the best combination of classification power (ROC-AUC) and correlation with bioactivity. Two other pharmacophores (Hypo2/1 and Hypo2/6) were found to be mergeable and their combined model (Hypo2-1/2-6) illustrated excellent ROC performance. We employed Hypo1/7 and Hypo2-1/2-6 models to screen the National Cancer Institute (NCI) list of compounds. In silico mining identified 18 FBPase inhibitors out of which six were of sub-micromolar IC 50 values.

Irrational antibiotics use is a major reason for the spread of antibiotic resistance. Earlier studies from Jordan indicated irrational antibiotic use among the public. Our aim is to evaluate the current knowledge, attitude and behaviour regarding antibiotic use and reasons for resistance development among university students in Jordan. A cross-sectional, questionnaire-based survey involving medical and non-medical students at the University of Jordan was conducted. Response rate was 85% and the majority of the sample was non-medical female students. Scoring level analysis revealed inadequate knowledge, high consumption rates and self-medication among students regardless of their specialty. Forty four percent of non-medical and 28.1% medical students agreed that antibiotics cure common colds and viral infections. Almost 61% of students did not complete their last course of antibiotic, 31.2% requested antibiotic prescriptions from clinicians and 37.5% were prescribed antibiotics over the phone. In conclusion, gaps in terms of knowledge, attitude and practice regarding antibiotics use among students were observed. National education programs should target these gaps aiming at increasing awareness on proper antibiotics use and its association with drug resistance. Enforcing antibiotic regulations at a national level is paramount targeting over the counter sale hence, reducing self-medication and high rates of consumption. Key words: Antimicrobial resistance, prescribing practice, health education.