High-density lipoprotein cholesterol and the risk of obstructive coronary artery disease beyond low-density lipoprotein cholesterol in non-diabetic individuals.

AIMS: The relationship between high-density lipoprotein cholesterol and the severity of coronary artery disease beyond low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy, remains uncertain. We evaluated the association between high-density lipoprotein cholesterol and obstructive coronary artery disease using parameters of any obstructive plaque, obstructive plaque in the left main coronary artery or proximal left anterior descending artery, and obstructive plaque in multi-vessels, according to low-density lipoprotein cholesterol levels. METHODS AND RESULTS: We analyzed 5130 asymptomatic non-diabetics who underwent coronary computed tomography angiography for general health examination. Obstructive plaque was defined as a plaque with ≥50% luminal diameter stenosis. The participants were divided into three groups based on low-density lipoprotein cholesterol levels of ≤129, 130-159, and ≥160 mg/dl. The prevalence of any obstructive plaque (5.9% vs 6.4% vs 10.6%) and obstructive plaque in the left main coronary artery or proximal left anterior descending artery (2.1% vs 2.1% vs 4.3%) significantly increased with low-density lipoprotein cholesterol category (all p < 0.05). Compared with subjects with high-density lipoprotein cholesterol level ≥40 mg/dl, those with high-density lipoprotein cholesterol level <40 mg/dl had a significantly higher prevalence of any obstructive plaque (10.4% vs 5.1%), obstructive plaque in the left main coronary artery or proximal left anterior descending artery (3.6% vs 1.8%), and obstructive plaque in multi-vessels (4.3% vs 1.1%), only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). Multiple regression analysis showed that increased high-density lipoprotein cholesterol levels were associated with a reduced risk of all obstructive coronary artery disease parameters only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). CONCLUSION: Increased high-density lipoprotein cholesterol levels were independently associated with a lower risk of obstructive coronary artery disease in asymptomatic non-diabetics with low low-density lipoprotein cholesterol levels.

Enzyme and Transporter Kinetics for CPT-11 (Irinotecan) and SN-38: An Insight on Tumor Tissue Compartment Pharmacokinetics Using PBPK.

BACKGROUND: Computational tools are becoming more and more powerful and comprehensive as compared to past decades in facilitating pharmaceutical, pharmacological and clinical practice. Anticancer agents are used either as monotherapy or in combination therapy to treat malignant conditions of the body. A single antineoplastic agent may be used in different types of malignancies at different doses according to the stage of the disease. OBJECTIVE: To study the behavior of CPT-11 (Irinotecan) and its metabolite SN-38 in tumor tissue compartment through the Whole Body-Physiologically Pharmacokinetics (WB-PBPK) and to determine the activity of metabolic enzymes and transporters participating in the disposition of CPT-11 and SN-38 working in their physiological environment inside the human body. METHODS: Whole body PBPK approach is used to determine the activity of different metabolic enzymes and transporters involved in the disposition of CPT-11 and its active metabolite, SN-38. The concentrations and pharmacokinetic parameters of the parent compound and its metabolite administered at clinically applicable dose via the intravenous route in the tumor tissue are predicted using this approach. RESULTS: The activity rate constants of metabolic enzymes and transporters of CPT-11 are derived at their natural anatomic locations. Concentration-time curves of CPT-11 and SN-38 with their 5th to 95th percentage range are achieved at the tumor tissue level. Mean tumor tissue pharmacokinetics of both compounds are determined in a population of 100 individuals. CONCLUSION: Tumor tissue concentration-time curves of CPT-11 and SN-38 can be determined via PBPK modeling. Rate constants of enzymes and transporters can be shown for healthy and tumor bearing individuals. The results will throw light on the effective concentration of active compound at its target tissue at the clinically applied IV dose.

Clinical characteristics of defecation and micturition syncope compared with common vasovagal syncope.

BACKGROUND: Little is known about the clinical characteristics of patients with situational syncope such as defecation syncope (DS) or micturition syncope (MS) compared with those with common vasovagal syncope (VVS). METHODS: Among 680 consecutive patients, who underwent a head-up tilt test between January 2006 and November 2010, 282 patients (40.4±16.7 years; 48.6% men) diagnosed as DS (n = 38), MS (n = 38), or common VVS (n = 208) were included. RESULTS: Ages at diagnosis (38.7±17.3 vs 48.3±14.1 vs 42.0±13.8, P = 0.004) and the first syncope (33.7±18.4 vs 44.5±15.3 vs 37.5±14.6, P = 0.002) were significantly less in patients with common VVS than those with DS or MS, respectively. The patients with MS were more likely to be men (73.7%, P = 0.036), whereas patients with DS were more commonly women (73.7%). No sexual preference was observed in patients with common VVS. Body mass index was significantly lower (P = 0.047) and syncopal episodes were more recurrent (P = 0.049) in patients with common VVS than those with DS or MS. The frequency of drinking alcoholbefore syncope was significantly higher in patients with MS (39.5%, P < 0.001). CONCLUSIONS: DS tended to occur in older women, whereas MS tended to occur in middle-aged men and drinking alcohol was an important precipitating factor for MS. However, common VVS was observed more in a thin and young population, which was more recurrent compared with those situational syncopes.

Reliability and validity of the Korean version of Kidney Disease Quality of Life instrument (KDQOL-SF).

Although the Kidney Disease Quality of Life instrument (KDQOL-SF), which was designed to measure the comprehensive quality of life in patients with end stage renal disease, has been tested and widely administered in many other counties, it has not yet been translated, validated and reported for Korea. The primary purpose of this study was to validate a Korean version of KDQOL-SF and to evaluate its psychometric properties. The study subjects were 164 patients with hemodialysis or continuous ambulatory peritoneal dialysis in university dialysis centers in Korea. In order to investigate the reliability, test-retest reliability and internal consistency reliability were assessed. Both test-retest reliability and internal consistency reliability were found to be high. In order to investigate the construct validation, all the items of the SF-36 scales, an established generic QOL measures, were compared with an overall health rating scale in kidney disease-targeted scale. They found to be highly correlated with each other. Moreover, overall health rating scale was significantly correlated with symptoms/problems, effects of kidney disease, burden of kidney disease, cognitive function (p < 0.001), and quality of social interaction (p < 0.05). These results suggest that the Korean version of KDQOL-SF satisfies its reliability and validity in Korean patients with hemodialysis or continuous ambulatory peritoneal dialysis. This questionnaire provides important and clinically valuable information for understanding the health related quality of life in the Korean patients with dialysis.