Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome.

Warfarin is the most widely prescribed anticoagulant drugs. Cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase-oxidaxe complex subunit 1 (VKORC1) contribute significantly to the variability of warfarin dose requirements among patients. We investigated the impact of CYP2C9 and VKORC1 polymorphisms on the variability of warfarin dosage requirements in Egyptian patients with acute coronary syndrome and their association with other nongenetic factors. Eighty participants with acute coronary syndrome were enrolled in this cross-sectional study. Associations between CYP2C9 and VKORC1 gene variants together with daily warfarin dose, demographic data, clinical status of patients and time to target international normalized ratio were assessed. Mean warfarin dose among patients with wild-type CYP2C91/1 genotype was significantly higher than heterozygous CYP2C91/2 and CYP2C91/3 variants (P ≤ 0.001). Patients with wild VKORC1 (G/G) genotype were treated with significantly higher daily warfarin dosages than homozygous (A/A) and heterozygous (G/A) genotypes. Patients carrying VKORC1 (G/G) genotype in combination with the CYP2C91/1 type alleles had the highest daily warfarin dosage, whereas the lowest daily warfarin dosage to achieve the required clinical effect was found among patients having CYP2C91/2 and CYP2C91/3 genotypes combined with VKORC1 (A/A) genotype (P ≤ 0.001). Regression analysis revealed that age, height, CYP2C9 and VKORC1 genotypes were significantly associated with warfarin dose. Genetic polymorphisms in VKORC1, CYP2C9 along with age and height are determinants of warfarin dose requirements in Egyptian population acute coronary syndrome. Higher warfarin loading dose is required for both wild CYP2C9 and VKORC1 gene variants which may contribute to warfarin-resistant cases.

ADAMTS13 Levels in Young Patients With ß-Thalassemia Major: Relation to Hepatitis C Virus Infection, Liver Cirrhosis, and Iron Overload.

UNLABELLED: We measured levels of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in 50 children and adolescents with ß-thalassemia major (25 without hepatitis C virus [HCV] infection and 25 with HCV infection) compared to 25 healthy controls and assessed their relation to iron overload, HCV infection, and liver cirrhosis. Hematological and coagulation profiles, serum ferritin, and von Willebrand factor antigen were assessed. Levels of ADAMTS13 were significantly lower in ß-thalassemia major with and without HCV infection compared to healthy controls, with a more significant reduction in levels among patients with HCV (P < .001). HCV-positive patients with thalassemia having liver cirrhosis had the lowest ADAMTS13 levels than those without cirrhosis (P = .012) or HCV-negative patients with thalassemia (P < .001). Levels of ADAMTS13 were positively correlated with platelet count while inversely correlated with partial thromboplastin time, serum ferritin, and VWF: Ag (P < .05). CONCLUSION: Patients with ß-thalassemia major infected with HCV have low ADAMTS13 levels, and a marked reduction was observed among patients with liver cirrhosis and, therefore, may be liable to thromboembolic manifestations.

Antibiogram testing of pediatric skin infections in the era of methicillin-resistant Staphylococci aureus: an Egyptian University Hospital-based study.

BACKGROUND: Community-associated methicillin-resistant Staphylococci aureus (CA-MRSA) pediatric skin infections have been reported worldwide. However, little is known about pathogens' implications in Egyptian children, and beta-lactams are still the empiric antimicrobials prescribed. This warrants Egyptian studies on antibiogram testing of pediatric skin infections. OBJECTIVES: To determine antibiotic susceptibility patterns of bacterial isolates from Egyptian pediatric skin infections to find out if we need reconsideration of the empiric beta-lactam antimicrobial therapy. MATERIALS AND METHODS: Throughout an eight-month cross-sectional study, antibiogram testing was conducted on bacterial isolates from pediatric skin infections. Determination of inducible resistance to clindamycin using D-test was performed for isolates susceptible to clindamycin and resistant to erythromycin. RESULTS: One-hundred and 21 children (mean age 6.9 years ± 3 SD) presented with pyogenic skin infections. Methicillin-sensitive Staphylococci aureus (MSSA) were isolated from 114 children, associated with group A Streptococci (GAS) in four of them, while GAS were the only isolates in three patients. A diagnosis of CA-MRSA was fulfilled in four children. Antibiotic susceptibilities differed between isolated organisms but with no statistically significant differences between susceptibility patterns of isolates from primary skin infections and those from secondary infection of skin diseases. Positive D-test was detected in five MSSA isolates. CONCLUSIONS: CA-MRSA skin infections are not common among Egyptian children and, therefore, beta-lactams are still effective empiric antimicrobial therapy for most infections. Antibiogram testing from suppurative skin lesions are, however, better to be recommended to guide individual therapy. Clindamycin should not be considered for susceptible isolates unless they are erythromycin susceptible or D-test negative.

Androgenetic alopecia and insulin resistance: are they truly associated?

BACKGROUND: Controversies exist regarding the association of androgenetic alopecia (AGA) with insulin resistance. Are they truly associated, or is insulin resistance just related to aging, obesity, or to the presence of metabolic syndrome? OBJECTIVE: To assess insulin resistance in young nonobese patients with AGA with and without metabolic syndrome. METHODS: The study included four equally distributed groups of age-, sex-, and body mass index-matched young, nonobese subjects: 30 patients with AGA and metabolic syndrome (group 1); 30 patients with AGA and no metabolic syndrome (group 2); 30 patients with metabolic syndrome and no AGA (group 3); and 30 healthy controls (group 4). Insulin resistance based on fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) was assessed in all groups. RESULTS: Twenty-three patients in group 1, four patients in group 2, 25 patients in group 3, and three healthy controls had insulin resistance with statistically significant differences in fasting insulin and HOMA-IR levels between all groups, between groups 1 and 2, groups 1 and 4, groups 2 and 3, and groups 3 and 4. No significant differences existed between groups 2 and 4 or groups 1 and 3. Correlations between insulin resistance parameters, age of patients, disease duration, and stages of AGA in males and females revealed nonsignificant differences. CONCLUSIONS: Patients with metabolic syndrome, with or without AGA, were significantly more insulin resistant compared with patients with AGA with no metabolic syndrome and with healthy subjects and, therefore, no true association exists between AGA and insulin resistance.