Prevention of restenosis after coronary angioplasty

PURPOSE OF REVIEW: Despite numerous advances in coronary interventional techniques, the frequent occurrence of restenosis continues to plague interventional cardiology. With the widespread use of drug-eluting stents, there is a need to reexamine critically the roles of the various interventional techniques currently available. RECENT FINDINGS: Drug-eluting stents have dramatically reduced the rates of restenosis and target vessel revascularization in a wide spectrum of patients with varying lesion morphologies. However, when restenosis does occur, it still tends to be dependent on the same factors that predict restenosis with bare metal stenting. The routine use of drug-eluting stents entails high initial costs to the health care system. Debulking as a means to improve outcomes after angioplasty has not lived up to expectations. Gene therapy is rapidly evolving into a viable means to reduce neointimal proliferation after angioplasty. SUMMARY: Careful patient selection and attention to the procedure of stent deployment optimize the results of angioplasty with drug-eluting stents. Because of cost considerations, drug-eluting stents should be used in patients who are expected to have the greatest absolute benefit. In this context, when judiciously used, conventional balloon angioplasty and bare metal stenting still have a definite role in the management of patients with obstructive coronary artery disease.     

Influence of SLCO1B3 haplotype-tag SNPs on docetaxel disposition in Chinese nasopharyngeal cancer patients

AIMS

To completely screen the SLCO1B3 gene in three distinct healthy Asian populations (Chinese, Malay and Indian, n = 168) and investigate the influence of haplotype-tag SNPs (htSNPs) on docetaxel disposition in 50 nasopharyngeal carcinoma patients.

METHODS

Genomic DNA of individuals was screened for SLCO1B3 polymorphisms by direct sequencing. htSNPs were derived based on the sequence clustering algorithm and profiled in the patients. Population based genetic association analysis was performed using Haplostats package implemented in R and PLINK.

RESULTS

A strong linkage disequilibrium pattern was detected across a total of 88 polymorphisms and 15-htSNPs were identified. The SLCO1B3 haplotypic region comprising seven htSNPs was found to be significantly associated with docetaxel clearance (P = 0.003). Conditional haplotype analyses revealed that the haplotypic constructs comprising the IVS4+76G>A, 699G>A(Met233Ile), IVS12-5676A>G, and *347_*348insA polymorphisms were critical determinants of variability in docetaxel disposition [clearance and area under the plasma concentration−time curve (AUC(0,∞)): r² = 29% and 22%, respectively]. Patients harbouring the GAG*347insA haplotype were significantly associated with a 30% decrease in clearance and a 40% increase in AUC(0,∞) of docetaxel compared with patients harbouring the reference haplotype, GGA*347wt (P = 0.025 and 0.018, respectively). In contrast, a 50% higher clearance was observed in patients carrying the GAG*347wt haplotype compared with those with the reference haplotype (P = 0.002). The functional SLCO1B3 haplotypic constructs included the widely studied Met233Ile variant and *347_*348insA located in the putative miR-890 binding site in the 3′-untranslated region which may influence the transport characteristics of SLCO1B3.

CONCLUSIONS

This study highlights the importance of SLCO1B3 polymorphic variations in influencing docetaxel disposition in nasopharyngeal carcinoma patients.     

The effects of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of docetaxel in nasopharyngeal carcinoma patients

Purpose  

This exploratory study aimed to explain the interindividual variabilities of docetaxel pharmacokinetics and pharmacodynamics in Asian nasopharyngeal carcinoma patients (n = 54) through the genotyping of CYP3A4, CYP3A5, ABCB1, ABCC2, ABCG2 and SLCO1B3 genes.     

An Alternative Technique for the Atrial Switch Operation for Transposition of the Great Arteries in an Unoperated Adult Patient

Abstract We report a 26‐year‐old patient with d‐transposition of great arteries, intact ventricular septum, and an atrial septal defect. The relevant literature on late natural survivors with this condition is reviewed and the technical aspects of an alternative technique for accomplishing a successful atrial switch in this situation are discussed . (J Card Surg 2010;25:406‐409)     

Influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian patients

Warfarin exhibits wide interpatient variability in dosing requirements. Recent studies have shown a novel polymorphism (rs2108622, V433M) in the CYP4F2 gene to be associated with variability in warfarin requirements in Caucasians. The purpose of this study was to evaluate the impact of rs2108622 on warfarin dose requirements in the Asian population. The mean warfarin dose was found to be significantly lower in patients carrying homozygous wild-type allele CC when compared with patients carrying variant alleles CT and TT (CC vs CT+TT: 3.0 mg/day vs 3.75 mg/day, p = 0.033). In patients harboring VKORC1 diplotypes associated with low warfarin requirements, a linear regression model which included age, weight, CYP2C9 and CYP4F2 variants accounted for 38% of the variability in warfarin dose. Approximately 11% of the dose variation was explained by CYP4F2 rs2108622 (p = 0.004). The influence of rs2108622 in patients harboring VKORC1 diplotypes associated with high warfarin requirements was not significant. This study suggests that CYP4F2 rs2108622 may significantly affect warfarin dose requirements in carriers of VKORC1 low-dose-associated diplotypes.