A prospective, randomized comparison of promus everolimus-eluting and TAXUS Liberte paclitaxel-eluting stent systems in patients with coronary artery disease eligible for percutaneous coronary intervention: the PROMISE study.

We aimed comparing two-year clinical outcomes of the Everolimus-Eluting Promus and Paclitaxel-Eluting TAXUS Liberte stents used in routine clinical practice. Patients with objective evidence of ischemia and coronary artery disease eligible for PCI were prospectively randomized to everolimus-eluting stent (EES) or paclitaxel-eluting stent (PES) groups. The primary end-point was ischemia-driven target vessel revascularization (TVR) at 2 yr after intervention, and the secondary end-point was a major adverse cardiac event (MACE), such as death, myocardial infarction (MI), target lesion revascularization (TLR), TVR or stent thrombosis. A total of 850 patients with 1,039 lesions was randomized to the EES (n=425) and PES (n=425) groups. Ischemic-driven TVR at 2 yr was 3.8% in the PES and 1.2% in the EES group (P for non-inferiority=0.021). MACE rates were significantly different; 5.6% in PES and 2.5% in EES (P = 0.027). Rates of MI (0.8% in PES vs 0.2% in EES, P = 0.308), all deaths (1.5% in PES vs 1.2% in EES, P = 0.739) and stent thrombosis (0.3% in PES vs 0.7% in EES, P = 0.325) were similar. The clinical outcomes of EES are superior to PES, mainly due to a reduction in the rate of ischemia-driven TVR.

Safety evaluation and risk assessment of d-Limonene.

d-Limonene, a major constituent of citrus oils, is a monoterpene widely used as a flavor/fragrance additive in cosmetics, foods, and industrial solvents as it possesses a pleasant lemon-like odor. d-Limonene has been designated as a chemical with low toxicity based upon lethal dose (LD50) and repeated-dose toxicity studies when administered orally to animals. However, skin irritation or sensitizing potential was reported following widespread use of this agent in various consumer products. In experimental animals and humans, oxidation products or metabolites of d-limonene were shown to act as skin irritants. Carcinogenic effects have also been observed in male rats, but the mode of action (MOA) is considered irrelevant for humans as the protein α(2u)-globulin responsible for this effect in rodents is absent in humans. Thus, the liver was identified as a critical target organ following oral administration of d-limonene. Other than the adverse dermal effects noted in humans, other notable toxic effects of d-limonene have not been reported. The reference dose (RfD), the no-observed-adverse-effect level (NOAEL), and the systemic exposure dose (SED) were determined and found to be 2.5 mg/kg/d, 250 mg/kg//d, and 1.48 mg/kg/d, respectively. Consequently, the margin of exposure (MOE = NOAEL/SED) of 169 was derived based upon the data, and the hazard index (HI = SED/RfD) for d-limonene is 0.592. Taking into consideration conservative estimation, d-limonene appears to exert no serious risk for human exposure. Based on adverse effects and risk assessments, d-limonene may be regarded as a safe ingredient. However, the potential occurrence of skin irritation necessitates regulation of this chemical as an ingredient in cosmetics. In conclusion, the use of d-limonene in cosmetics is safe under the current regulatory guidelines for cosmetics.

The epidemiological and clinical characteristics of patients admitted for coronary angiography to evaluate ischemic heart disease.

BACKGROUND: Most of the known risk factors associated with ischemic heart disease are based on studies from Western countries; there is only limited information on Korean populations. This study was designed to analyze age related differences in epidemiologic and clinical characteristics in patients who were admitted for coronary angiography for the evaluation of ischemic heart disease. METHODS: As part of the multicenter KCAR (Korean Coronary Artery disease Registry) Study, the clinical data of 6,549 patients, who were evaluated at the cardiac catheterization laboratory by coronary angiography, at seven university hospitals in Korea from March 1999 to December 2005, were registered into the KCAR database and analyzed. All patients were divided into three groups according to age: age < or = 40, age 41-70 and age > or = 71. All demographic and coronary angiographic features were analyzed for the different groups. RESULTS: The demographic data showed that compared to the older patients young patients < or = 40 had a higher prevalence of males and smokers, but a lower prevalence of hypertension, diabetes and prior history of stroke and myocardial infarction. For the lipid profiles, the younger patients had much higher levels of total cholesterol, triglycerides and LDL-cholesterol than the older groups; however, there was no difference in the HDL-cholesterol levels among the three age groups. The most common component of the metabolic syndrome was obesity (79%) in the younger patients and hypertension (92%) in the older patients. The most common reason for presentation was ST-segment elevated myocardial infarction in the younger patients and unstable angina in the older patients. CONCLUSIONS: Ischemic heart disease in younger adults < or = 40 had different demographic characteristics and clinical presentation than older patients.

Suppression of proliferative cholangitis in a rat model by local delivery of paclitaxel.

BACKGROUND: Proliferative cholangitis (PC) leads to biliary stricture, which is the main cause of hepatolithiasis, recurrent cholangitis, and biliary cirrhosis. The aim of this study was to determine whether local delivery of paclitaxel, which inhibits cell proliferation by overstabilization of microtubules, prevents PC in a rat model. METHODS: PC was induced by introducing a fine nylon thread into the bile duct in a rat. Paclitaxel (100 microl of 10, 100, and 1000 micromol/l) or solvent vehicle was administered into the bile duct for 15 min. One week after treatment, histopathologic examination and 5-bromodeoxyuridine (BrdU) labeling of the bile duct were performed. RESULTS: In comparison with the control, the mean thickness of the bile duct was reduced by 29% in the 1000 micromol/l paclitaxel-treated group (2.61 +/- 0.31 microm vs 3.67 +/- 0.25 micro m, P << 0.05). The luminal area increased ( P << 0.0001) and the grade of epithelial-glandular proliferation was decreased ( P << 0.01) as the dose of paclitaxel increased. Ductal fibrosis and inflammatory cell infiltration were similar in both groups. The BrdU labeling index was significantly lower in the paclitaxel-treated group ( P << 0.05). CONCLUSIONS: Local delivery of paclitaxel suppressed PC in a rat model by the inhibition of epithelial-glandular proliferation and may offer an effective therapeutic option for biliary stricture.