PubMed · 9117697
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T Ito. 1996. [Cholesterol pericarditis].. https://pubmed.ncbi.nlm.nih.gov/9117697/
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The attributable risk (AR) is probably the most useful and commonly used epidemiologic index to measure the importance of a risk factor in public health issues. This paper focuses the discussion on interval estimation of the AR in cross-sectional studies and compares the finite-sample performance of five asymptotic interval estimators of the AR by calculating the coverage probability and the average length in a variety of situations. This paper notes that the coverage probability of the two interval estimators proposed by Leung and Kupper, including the one that combines the interval estimator on the basis of Wald's test statistic, can be substantially less than the desired confidence level when the underlying risk ratio equals 1. As long as the sample size is reasonably large (> or =100) and the probability of exposure is moderate (> or =0.20), the interval estimator suggested by Fleiss can consistently perform well with respect to the coverage probability in a variety of situations considered here. However, using this interval estimator tends to generally lose efficiency. This paper also finds that with respect to the coverage probability, the interval estimator using Fieller's theorem is generally preferable to the interval estimator on the basis of Wald's test statistic when the prevalence rate ratio (RR) between the exposure and the non-exposure groups is > or =2. Finally, this paper notes that if we know that the underlying parameter RR is large (> or =4) and the probability of exposure is not small (> or =0.05), the interval estimator suggested by Leung and Kupper will probably be preferable to all the other estimators considered here.
The three main lipid components of the stratum corneum, namely ceramides, free fatty acids and cholesterol, play a fundamental role in the maintenance of the skin barrier. The current investigation is aimed toward understanding the miscibility and intermolecular interactions of these lipids. Toward this end, Fourier transform infrared spectroscopic studies of the three possible equimolar binary mixtures of cholesterol, a synthetic non-hydroxylated fatty acid N-acyl sphingosine with a C18 chain length (N-stearoylsphingosine, approximating human ceramide 2), and stearic acid were undertaken. The thermotropic responses of the methylene stretching and scissoring vibrations were used to evaluate chain conformation and packing respectively. Selective perdeuteration, of either the stearic acid or the ceramide acid chains, permitted separate and simultaneous evaluation of the conformational order and packing properties of the sphingosine chain, the amide linked fatty acid chains and/or the stearic acid chain. Whereas cholesterol mixed well with ceramide at physiological temperatures, the stearic acid was miscible with the cholesterol only at relatively high temperatures where the fatty acid is disordered. A complex interaction between stearic acid and ceramide was detected. A separate fatty acid-rich phase persisted until at least 50 degrees C, whereas at higher temperatures the components appear to be quite miscible. However, a preferential association of the fatty acid with the ceramide base chain is indicated. None of the binary systems studied exhibit miscibility and interactions resembling those in the ternary mixtures of these substances, which is widely used to model stratum corneum. The role of cholesterol in controlling the miscibility characteristics in the ternary system is evident.
Gel filtration with bile salts at intermixed micellar/vesicular concentrations (IMC) in the eluant has been proposed to isolate vesicles and micelles from supersaturated model biles, but the presence of vesicular aggregates makes this method unreliable. We have now validated a new method for isolation of various phases. First, aggregated vesicles and - if present - cholesterol crystals are pelleted by short ultracentrifugation. Cholesterol contained in crystals and vesicular aggregates can be quantitated from the difference of cholesterol contents in the pellets before and after bile salt-induced solubilization of the vesicular aggregates. Micelles are then isolated by ultrafiltration of the supernatant through a highly selective 300 kDa filter and unilamellar vesicles by dialysis against buffer containing bile salts at IMC values. Lipids contained in unilamellar vesicles are also estimated by subtraction of lipid contents in filtered micelles from lipid contents in (unilamellar vesicle+micelle containing) supernatant ('subtraction method'). 'Ultrafiltration-dialysis' and 'subtraction' methods yielded identical lipid solubilization in unilamellar vesicles and identical vesicular cholesterol/phospholipid ratios. In contrast, gel filtration yielded much more lipids in micelles and less in unilamellar vesicles, with much higher vesicular cholesterol/phospholipid ratios. When vesicles obtained by dialysis were analyzed by gel filtration, vesicular cholesterol/phospholipid ratios increased strongly, despite correct IMC values for bile salts in the eluant. Subsequent extraction of column material showed significant amounts of lipids. In conclusion, gel filtration may underestimate vesicular lipids and overestimate vesicular cholesterol/phospholipid ratios, supposedly because of lipids remaining attached to the column. Combined ultracentrifugation-ultrafiltration-dialysis should be considered state-of-the-art methodology for quantification of cholesterol carriers in model biles.