| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Eutectic interactions in binary systems containing cholesterol, cholesteryl esters and triacylglycerols Dorset, D. L. (1990), Biochim Biophys Acta 1047(2): 112-20. Abstract: Binary phase behavior of saturated cholesterol esters with trilaurin or cholesterol, and cholesterol with trilaurin, is studied. The existence of specific molecular interactions is detected by comparing the liquidus curve of the eutectic with ideal theory of freezing point depression and correcting the theoretical curve with the Bragg-Williams model when necessary. X-ray data indicate that all eutectic solids are nearly totally fractionated. The phase diagrams are sometimes well-explained by ideal solution theory indicating that polar interactions (e.g., the hydrogen bonding of cholesterol) are much less important than van der Waals interactions between neighboring molecules. However, the hydrogen bonding networks of cholesterol can lead to nonideal solution behavior with other lipids, a phenomenon consistent with previous observations on simpler molecular binaries. An observed nonideal solution behavior of triacylglycerol with cholesterol esters, on the other hand, is unexpected since significant polar interactions are expected to be 'buried' in the predominant nonpolar volume of the molecules involved. |
| Evaluating cholesterol screening. The importance of controlling for regression to the mean Forrow, L., D. R. Calkins, et al. (1995), Arch Intern Med 155(20): 2177-84. Abstract: OBJECTIVES: To determine the overall impact of a voluntary cholesterol screening program and to assess the importance of controlling for regression to the mean when evaluating the impact on higher-risk subgroups. DESIGN: Longitudinal study comparing baseline survey and cholesterol results with those obtained 17 months later, with adjustment for regression to the mean. SETTING: Participants were seen at three sites: an academic teaching hospital, an intermediate-care hospital, and a suburban community center. PARTICIPANTS: One thousand fifty-three participants were enrolled in a voluntary cholesterol screening program. MEASUREMENTS/MAIN RESULTS: Of 1053 study enrollees, 785 (75%) completed a follow-up questionnaire and 656 (62%) returned for follow-up cholesterol tests. Among all participants at high risk, measured cholesterol levels were 0.66 mmol/L (25.5 mg/dL) lower at follow-up, but 58% of this apparent change (0.38 mmol/L 14.7 mg/dL) was attributable to the statistical phenomenon of regression to the mean. Among all participants at increased (both high and moderate) risk, after controlling for regression to the mean, reductions in cholesterol levels were significant for those younger than 60 years (-0.28 mmol/L -10.8 mg/dL; 95% confidence interval, -0.43 to -0.13; n = 390) but not for those 60 years or older (+0.007 mmol/L +0.3 mg/dL; 95% confidence interval, -0.16 to +0.17; n = 266). CONCLUSIONS: For subjects found at high risk in a cholesterol screening program, more than half of the apparent beneficial change in cholesterol level is attributable to regression to the mean. For participants older than 60 years, no clear benefit of cholesterol screening was documented. |
| Evaluating lyophilized human serum preparations for suitability as proficiency testing materials for high-density lipoprotein cholesterol measurement Myers, G. L., J. W. Ross, et al. (1995), Arch Pathol Lab Med 119(8): 686-94. Abstract: OBJECTIVE--To evaluate the suitability of various commercial preparations for use by the College of American Pathologists as survey materials in assessing high-density lipoprotein cholesterol measurement performance. DESIGN--Lyophilized human serum preparations from six vendors (vendors A through F) were evaluated to determine which material(s) best mimicked the commutability of fresh human serum. Two freshly collected unfrozen pools prepared from donor specimens were analyzed concurrently with the vendor materials to identify sources of variation and possible matrix bias. Each material was evaluated using 5 common precipitation reagents (phosphotungstate-magnesium, phosphotungstic acid, dextran sulfate 50K and 500K, and heparin-manganese). To evaluate how each reagent separates lipoproteins in each material, the lipoprotein separation patterns were profiled using high-pressure liquid chromatography and compared with separation patterns observed for the fresh human serum pools. MAIN OUTCOME MEASURES--Similarities in performance characteristics of vendor material(s) were compared with fresh human serum. RESULTS--Two of the six materials gave separation profiles for the lipoproteins similar to the typical patterns observed for human serum. Material from vendor B showed the best commutability across all of the precipitation reagents and had the best combination of low overall variability (10% for level 1 and 9.4% for level 2) and minimal concentration differences among reagents. CONCLUSIONS--Vendor B was selected by the College of American Pathologists to provide materials for use in assessing performance of lipid and lipoprotein testing in the 1994 Comprehensive Chemistry Surveys. This study demonstrates the great variability that different vendor preparations introduce into the measurement of high-density lipoprotein cholesterol. It also emphasizes the effort required to evaluate the suitability of processed materials for use in proficiency testing. |
| Evaluating the efficacy of the National Cholesterol Education Program adult treatment guidelines: cholesterol lowering intervention program Caggiula, A. W., J. E. Watson, et al. (1995), Prev Med 24(5): 485-91. Abstract: BACKGROUND. A cross-sectional analysis was conducted to test the feasibility of the National Cholesterol Education Program Adult Treatment Panel I Guidelines (ATPI) in physician office practices. METHODS. Twenty-two physician practices in communities from western Pennsylvania and West Virginia were recruited. Using a patient tracking system, 9,171 patients were assessed for cholesterol screening and treatment by their physicians according to the ATPI guidelines. RESULTS. Cholesterol screening was ordered for 1,698 patients or 19% of the population visiting the physician offices. The reasons for not screening included the patient was already under therapy (2,371), screened within the past 5 years (1,714), or acutely ill at the time of the visit (1,691). The frequency of patient refusal for screening was low (444). However, the majority of patient diagnoses were based on a single lipid measurement, and only 817 or 56% of patients evaluated had lipoprotein measures obtained prior to treatment. Follow-up measurement was not performed according to the ATPI schedule, and the magnitude of cholesterol response was inversely related to time to first follow-up measurement. CONCLUSIONS. Many patients in these physician practices had initial cholesterol screening. However, repeat measurements as recommended for initial evaluation were not performed routinely, nor were most patients followed within the recommended 3-month time period. This lack of follow-up is detrimental to effective, long-term patient management since the magnitude of the cholesterol response is related to time of the first follow-up measurement. |
| Evaluation and clinical application of a direct low-density lipoprotein cholesterol assay in normolipidemic and hyperlipidemic adults Yu, H. H., G. S. Ginsburg, et al. (1997), Am J Cardiol 80(10): 1295-9. Abstract: This study examines the performance and clinical use of a commercial immunoseparation assay for low-density lipoprotein (LDL) cholesterol in a sample population of normolipidemic and hyperlipidemic adult volunteers. Using paired fasting and nonfasting samples, we compared the direct LDL assay with the beta quantification method and the Friedewald calculation. Overall, the direct LDL assay correctly classified 82% and 60% of fasting and nonfasting subjects, respectively, into National Cholesterol Education Program risk groups. The Friedewald method correctly classified 84% of subjects. The fasting direct LDL assay has comparable positive and negative predictive values to the Friedewald method, except at an LDL cholesterol of 100 mg/dl. The nonfasting direct LDL assay demonstrates unacceptable positive predictive values when LDL cholesterol decreases to the 130 to 159 and > or = 160 mg/dl categories. Overall, direct LDL assay demonstrates limitations in the nonfasting state and at the LDL cholesterol level of 100 mg/dl used for patients with established coronary heart disease. |
| Evaluation and management of atherogenic dyslipidemia: beyond low-density lipoprotein cholesterol Despres, J. P., I. Lemieux, et al. (2001), Cmaj 165(10): 1331-3. |
| Evaluation and optimization of DNA delivery into gliosarcoma 9L cells by a cholesterol-based cationic liposome Lesage, D., A. Cao, et al. (2002), Biochim Biophys Acta 1564(2): 393-402. Abstract: This paper reports results concerning the transfection of gliosarcoma cells 9L using an original cholesterol-based cationic liposome as carrier. This cationic liposome was prepared from triethyl aminopropane carbamoyl cholesterol (TEAPC-Chol) and a helper lipid, dioleoyl phosphatidyl ethanolamine (DOPE). The used concentration of liposome was not cytotoxic as revealed by the MTT test. TEAPC-Chol/DOPE liposomes allowed the plasmids encoding reporter genes to enter the nucleus as observed both by electron microscopy and functionality tests using fluorescence detection of green fluorescent protein (GFP) and luminometric measurements of luciferase activity. By changing the cationic lipid/DNA molar charge ratio, optimal conditions were determined. Further, improvement of the transfection level has been obtained by either precondensing plasmid DNA with poly-L-lysine or by adding polyethylene glycol (PEG) in the transfection medium. The optimal conditions determined are different depending on whether the transfection is made with cells in culture or with tumors induced by subcutaneous (s.c.) injection of cells in Nude mice. For in vivo assays, a simple method to overcome the interference of haemoglobin with the chemiluminescence intensity of luciferase has been used. These results would be useful for gaining knowledge about the potential for the cationic liposome TEAPC-Chol/DOPE to transfect brain tumors efficiently. |
| Evaluation in vivo of the differential uptake and processing of high-density lipoprotein unesterified cholesterol and cholesteryl ester in the rat Bravo, E., K. M. Botham, et al. (1994), Biochim Biophys Acta 1215(1-2): 93-102. Abstract: The uptake and processing of high-density lipoprotein (HDL) unesterified and esterified cholesterol were compared in vivo in the rat. HDL labelled with 3H in either unesterified cholesterol or cholesteryl ester was administered intravenously, and the clearance of radioactivity from the blood, its distribution in plasma lipoprotein density fractions, uptake by tissues, and appearance in bile were studied at intervals up to 180 min. 3H in HDL unesterified cholesterol was cleared more rapidly from the blood than that in HDL cholesteryl ester, and this difference was mainly due to rapid sequestration of 3Hunesterified cholesterol by the liver, with 58.2% of the administered dose found in this tissue after 10 min, compared to 6.8% of the 3Hcholesteryl ester dose. Non-hepatic tissues took up only a small proportion of the administered label from both HDL unesterified and esterified cholesterol, but on a per gram wet weight basis, the specific uptake of HDL cholesteryl ester in the adrenal glands and the spleen was higher than in the liver, particularly in the first 60 min. The distribution of radioactivity in the plasma lipoprotein density fractions remained constant between 10 and 180 min when 3Hunesterified cholesterol was used, but the proportion of plasma radioactivity from HDL labelled in esterified cholesterol in the very-low-density lipoprotein (VLDL) fraction increased from 0% to 26%, while in HDL there was a shift in the distribution of radioactivity from the most (d 1.125-1.250 g/ml) to the least (d 1.050-1.085 g/ml) dense sub-fractions. A greater percentage of the administered label from HDL unesterified cholesterol (8.8%) than from HDL cholesteryl ester (3.3%) was secreted into bile during 180 min, but the proportions secreted in bile acids and unesterified cholesterol were similar with both labels. These findings indicate that there are significant differences in the uptake and processing of HDL unesterified as compared to esterified cholesterol in the rat in vivo. |
| Evaluation of a commercial enzyme-based serum cholesterol test kit for analysis of phytosterol and phytostanol products Moreau, R. A., M. J. Powell, et al. (2003), J Agric Food Chem 51(23): 6663-7. Abstract: Plant sterols (phytosterols) have been shown to possess serum cholesterol-lowering properties. In recent years, several phytosterol-enriched functional food products have been developed and marketed. Some phytosterol products contain common unsaturated sterols and some contain a subset of phytosterols called phytostanols (saturated sterols, also called plant stanols). Current methods for the quantitative analysis of plant sterols are labor intensive and require sophisticated gas or liquid chromatographs. In this study, a popular commercial spectrophotometric serum cholesterol test kit was evaluated for the analysis of plant sterols. The results indicate that the method could be modified to analyze phytosterols and phytostanols by increasing the incubation time. Both free phytosterols and fatty acyl phytosteryl esters were quantitatively analyzed, but ferulate phytosteryl esters, such as those that are found in corn and other cereals, were not hydrolyzed by the enzymes in the test kit and therefore were not detected. |
| Evaluation of a homogeneous assay for high-density lipoprotein cholesterol: limitations in patients with cardiovascular, renal, and hepatic disorders Simo, J. M., I. Castellano, et al. (1998), Clin Chem 44(6 Pt 1): 1233-41. Abstract: We evaluated the performance of a homogeneous assay for the automated measurement of high-density lipoprotein cholesterol (HDL-C) and compared it with a conventional precipitation technique in the following groups of people: control subjects (group A), clinically-healthy elderly (group B), myocardial infarction patients (group C), nephrotic syndrome patients (group D), and liver cirrhosis patients (group E). The performance of the technique was acceptable with respect to precision, accuracy, linearity, and detection limit. Triglycerides up to 40 mmol/L and bilirubin up to 150 micromol/L did not cause interferences. Hemoglobin decreased HDL-C measurements. Samples were stable at -20 degrees C for up to four months. Bland-Altman plots showed a good agreement between both techniques in the control group but with a progressive divergence in the patient groups B to E. Results indicate limitations of the technique in certain clinical conditions and, coincidentally, the need for reliable calibration materials. |
| Evaluation of a homogeneous direct LDL-cholesterol assay in diabetic patients: effect of glycemic control Ragland, B. D., R. J. Konrad, et al. (2000), Clin Chem 46(11): 1848-51. |
| Evaluation of a new assay for the direct determination of HDL-cholesterol Larrose, C., J. C. Piton, et al. (1998), Ann Biol Clin (Paris) 56(1): 108-11. |
| Evaluation of a rapid homogeneous method for direct measurement of high-density lipoprotein cholesterol Hubbard, R. S., S. V. Hirany, et al. (1998), Am J Clin Pathol 110(4): 495-502. Abstract: We evaluated the performance of a direct Liquid N-geneous HDL-C assay (N-HDL; Genzyme Diagnostics, Cambridge, Mass) and compared it with a Centers for Disease Control and Prevention (CDC) modified reference procedure (M-REF) and phosphotungstic acid (PTA) precipitation method in patients with normotriglyceridemia (triglyceride level, <400 mg/dL) and hypertriglyceridemia (triglyceride level, > or =400 mg/dL). Excellent intra-assay and interassay coefficients of variation were obtained (<2.0%) using the N-HDL assay. The N-HDL and PTA assays correlated well with M-REF in normotriglyceridemic samples. In hypertriglyceridemic samples, however, the N-HDL method exhibited better correlation with M-REF than the PTA assay. In addition, compared with M-REF, the mean absolute percentage bias of N-HDL was lower than the PTA assay in normotriglyceridemic (4.9% vs 5.8%) and hypertriglyceridemic (5.4% vs 12.9%) samples. Hemolysis, ascorbic acid, and bilirubin did not interfere with the N-HDL assay. On the basis of these findings, the N-HDL assay compares favorably with the modified CDC reference method and seems superior to the PTA assay. It also has the advantage of being suited for complete automation and, thus, would prove useful in large clinical laboratories. |
| Evaluation of alternative calculation methods for determining low-density lipoprotein cholesterol in hemodialysis patients Bairaktari, E. T., C. Tzallas, et al. (2004), Clin Biochem 37(10): 937-40. Abstract: OBJECTIVES: To evaluate alternative equations for the estimation of low-density lipoprotein cholesterol (LDL-C) than the Friedewald equation in hemodialysis patients. DESIGN AND METHODS: The equations LDL-C = 0.41TC - 0.14TG + 0.66ApoB - 10.43 and LDL-C = 0.94TC - 0.94HDL-C - 0.19TG were evaluated in 86 patients and compared with the Friedewald equation and the ultracentrifugation procedure. RESULTS: The alternative equations yield significantly lower bias than the Friedewald equation and are less affected by increased triglycerides (TG) levels. CONCLUSION: The alternative equations for LDL-C yield slightly better results than the Friedewald equation especially in hypertriglyceridemia. |
| Evaluation of an automated method for measuring low-density lipoprotein cholesterol Desideri-Vaillant, C., S. Bouvier, et al. (2004), Ann Biol Clin (Paris) 62(6): 691-4. Abstract: We evaluated an automated method for measuring low-density lipoprotein cholesterol (LDL-cholesterol) with Integra 800 (Roche Diagnostics). This method uses detergents which show selectivity for the different lipoproteins. Our evaluation has shown a within run imprecision of 2% and a between-assay imprecision of 1.2%. This method was not perturbed by haemoglobin, bilirubin or lipids. However, the reagents remain expensive: we will use it when calculation or interpretation of lipid results are not possible. |
| Evaluation of an immunoseparation method for quantitative measurement of remnant-like particle-cholesterol in serum and plasma Leary, E. T., T. Wang, et al. (1998), Clin Chem 44(12): 2490-8. Abstract: Substantial evidence indicates that triglyceride-rich lipoprotein remnants are atherogenic. Additional research has, however, been limited by available methods for separation and quantification of remnants. We have evaluated an immunoseparation assay developed to measure cholesterol in remnant-like particles (RLP-C). This method uses monoclonal antibodies to human apolipoproteins B-100 and A-I to remove most of the apolipoprotein B-100-containing lipoproteins (namely LDL and nascent VLDL) and apolipoprotein A-I-containing lipoproteins (namely chylomicrons and HDL), leaving behind a fraction of triglyceride-rich lipoproteins, including chylomicron and VLDL remnants, both of which are enriched in apolipoprotein E. Cholesterol in the unbound fraction is measured with a sensitive enzymatic assay. The RLP-C concentration was highly correlated with total triglyceride-rich lipoproteins (sum of VLDL-cholesterol and IDL-cholesterol) separated by ultracentrifugation and by polyacrylamide gel electrophoresis (r = 0.86 and 0.76, respectively). The within-run and run-to-run imprecision (CV) of the assay was approximately 6% and 10%, respectively. The assay was not affected by hemoglobin up to 5000 mg/L (500 mg/dL), bilirubin up to 342 mmol/L (20 mg/dL), glucose up to 67 mmol/L (1200 mg/dL), or ascorbic acid up to 170 mmol/L (3.0 mg/dL). In 726 subjects (men, n = 364; women, n = 362) in the US, the 75th percentiles of RLP-C concentration were 0.17 mmol/L (6.6 mg/dL) and 0.23 mmol/L (8.8 mg/dL) in sera obtained after overnight fasting or randomly, respectively. A group of 151 patients from nine US centers and one Canadian center with coronary artery atherosclerosis established by angiography had higher median RLP-C concentrations than 302 gender- and age-matched controls (P <0.05). We conclude that the RLP-C assay compares favorably to ultracentrifugation and electrophoresis and provides a convenient and economical approach to measure triglyceride-rich lipoprotein remnants in routine clinical laboratories. |
| Evaluation of cholesterol absorption in rats using markers labeled with stable isotopes. Effect of complete bile diversion Decker, P., J. F. Brinkmann, et al. (1998), Hepatogastroenterology 45(24): 2033-7. Abstract: BACKGROUND/AIMS: An easily performed method to measure cholesterol absorption with isotope labeled cholesterol and beta-sitostanol in humans is described. The first aim of the study was to show whether this method can also be used in rats. Secondly, to see whether complete bile diversion results in a complete loss of cholesterol absorption. METHODOLOGY: Cholesterol absorption was evaluated in rats by the constant isotope feeding method using 2H6cholesterol and 2H4sitostanol as markers. Fecal samples were analyzed by gas-chromatography/mass spectrometry. RESULTS: In 8 rats with intact enterohepatic circulation of bile acids, cholesterol absorption averaged 61 (3% (SD) (range: 54-69%)). Complete bile diversion was followed by an almost total loss of cholesterol absorption (5.5+/-0.6%, range: 2.4-6.9%, n=7). CONCLUSIONS: The results indicate that deuterated cholesterol and deuterated sitostanol are reliable markers for measurement of cholesterol absorption in rats and that bile acids are essential for cholesterol absorption. |
| Evaluation of deuterated cholesterol and deuterated sitostanol for measurement of cholesterol absorption in humans Lutjohann, D., C. O. Meese, et al. (1993), J Lipid Res 34(6): 1039-46. Abstract: The continuous isotope feeding method of Crouse and Grundy (1978. J. Lipid Res. 19: 967-971) for measurement of dietary cholesterol absorption has been modified by using markers labeled with stable isotopes (2,2,4,4,6-2H5cholesterol or 25,26,26,26,27,27,27-2H4cholesterol or 26,26,26,27,27,27-2H6 cholesterol and 5,6,22,23-2H4sitostanol) quantified by gas-liquid chromatography-selected ion monitoring. Tracing of the isotope distribution of the authentic markers and after their intestinal passage, including the microbiological products (coprostanol and coprostanone) revealed stability of the labels. The new method was evaluated in six monkeys on two occasions by comparison with the original method using radioactively labeled cholesterol and sitosterol. The results obtained by the two different methods were in excellent agreement, and absorption ranged from 49% to 73% (mean 60%) for the stable isotope method and from 51% to 69% (mean 62%) for the radioactive method. The coefficient of variation of cholesterol absorption in animals ranged from 3.9% to 15.1% (mean 7.1%) for stable isotopes and 1.9% to 13.6% (mean 5.7%) for radioactive isotopes. In twelve subjects cholesterol absorption was measured by the new method from total fecal samples frozen immediately and compared to results obtained from small fecal aliquots (approximately 1 g) sent by ordinary mail to the laboratory. A significant correlation of cholesterol absorption between the two different sample handlings was obtained (r = 0.981, P < 0.001). In addition, measurement of cholesterol absorption twice in seven volunteers 2 weeks apart revealed identical results. Thus, the new method is extremely safe and reproducible without radioactive exposure to the subjects and labortory staff and can be used on women of child-bearing age. |
| Evaluation of drug delivery characteristics of microspheres of PMMA-PCL-cholesterol obtained by supercritical-CO2 impregnation and by dissolution-evaporation techniques Elvira, C., A. Fanovich, et al. (2004), J Control Release 99(2): 231-40. Abstract: Poly(methyl methacrylate), PMMA, and of PMMA/Poly(epsilon-caprolactone), PCL, microspheres were loaded with different amounts of cholesterol by using a supercritical carbon dioxide (SC-CO2) impregnation process in order to use a clean technique with the absence of organic solvents, and to provide information for the infusion of additives into nonporous polymeric substrates. A conventional dissolution-evaporation method was also used to obtain PMMA and PMMA-PCL microparticles loaded with cholesterol. The obtained microspheres were characterized by environmental scanning electronic microscope, ESEM, nuclear magnetic resonance spectroscopy, NMR, and differential scanning calorimetry, DSC, thermal analysis. A comparison of drug release from particles obtained using both methods, the supercritical and the conventional, is presented. |
| Evaluation of five different high-density lipoprotein cholesterol assays: the most precise are not the most accurate de Keijzer, M. H., D. Elbers, et al. (1999), Ann Clin Biochem 36 (Pt 2): 168-75. Abstract: We evaluated the accuracy and performance of four different test kits for the direct determination of high-density lipoprotein (HDL)-cholesterol and compared them with the phosphotungstic acid/MgCl2 assay. All four homogeneous assays were precise (within-run CV of < 2.0% and between-run CV of < 6.4%); both assays based on immuno-inhibition had the lowest CVs (within-run 1.3% and 0.9%; between-run 2.3% and 2.2%). Interference from haemolysis was negligible, but triglyceride concentrations gave a negative interference. The effects of conjugated and unconjugated bilirubin were opposite; conjugated bilirubin showed a negative interference of up to 40%; unconjugated bilirubin interfered positively up to 50%. Using the recently validated indirect phosphotungstic acid/MgCl2 method as a comparison, all four homogeneous assays did not fulfil the National Cholesterol Education Program total error standard, mainly due to the positive biases of 12 to 42%, apparently associated with improper calibrators. Both assays involving immuno-inhibition showed a concentration-dependent bias. |