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Biomedical subjects

W Insull

Publications and source records attributed to W Insull.

At least 91 records · Page 5Linked to original sources
PubMed1974

Cholesteryl ester-rich inclusions from human aortic fatty streak and fibrous plaque lesions of atherosclerosis. I. Crystalline properties, size and internal structure.

Cholesteryl esters, the major lipid in the lesions of human atherosclerosis, occurred in fatty streaks and fibrous plaques from 42 adults as spherical inclusions whose diameters averaged 1.99 +/- 0.48 and 2.16 +/- 0.62 mu, respectively, and which with polarizing light microscopy resolved into a mixture of various proportions of anisotropic and isotropic forms. Anisotropic forms had diameters of 1.9 +/- 0.4 mu, uniaxial-like symmetry with a formée cross image, a whitish gray interference color under cross polarizer and analyzer, second order blue and first order yellow interference colors with a tint plate, a birefringence of 0.0412 +/- 0.0054 and a refractive index of 1.559 +/- 0.0014. Their probable structural organization is primarily a lyotropic smectic mesophase (liquid crystal) of cholesteryl esters secondarily organized into multiple concentric lamellae. Isotropic forms had diameters of 2.3 +/- 0.6 mu and were optically inactive irrespective of their orientation. At 23 C, fatty streak inclusions from 21 subjects averaged significantly higher in the proportion of anisotropic forms, 85.5 +/- 9.3%, than did fibrous plaque inclusions from 21 subjects, which had 32.4 +/- 16.3% anisotropic forms (P < 0.01).

Adult↗
PubMed1970

Lipid droplets in atherosclerotic fatty streaks of human aorta.

Preparations of lipid droplets and droplet-free tissue residue (cytoplasm + membranes + nuclei) were obtained by homogenization and centrifugal separation from intimal fatty streak lesions of aortic atherosclerosis of 21 adults who had died suddenly. Neutral lipids and phospholipids were analyzed by quantitative thin-layer chromatography and cholesteryl ester fatty acids by gas-liquid chromatography. Optical properties of droplets were evaluated by differential counting and sizing procedures with the polarizing microscope. The droplets occurred in mixtures of two forms distinguished by their optical properties, anisotropic (i.e. liquid crystals) and isotropic (true liquids). Both forms had average diameters of about 1.8 mu, with a range of 0.5-5mu. The proportions of the two forms varied with temperature as individual droplets changed their form; anisotropic forms averaged 83.7% at degrees C and 37.8% at 37 degrees C, with isotropic forms being 16.3 and 62.2% respectively. The proportions of anisotropic forms at 22 degrees C decreased with age. These forms were not separated for chemical analysis. The droplets contained about half the lipid in the lesions. The composition of the lipids of the droplet mixture was remarkably uniform and strikingly different from that of the droplet-free residue, respectively: cholesteryl esters 94.9% vs. 38.7%, free cholesterol 1.7% vs. 18.6%, total phospholipids 1.0% vs. 38.6%, and triglycerides 2.4% vs. 4.0%. The proportions of individual phospholipids, with the exception of lysolecithin, were also different between the preparations. In the droplets only the proportions of lecithin correlated positively with the proportion of anisotropic forms (at 22 degrees C). Droplet cholesteryl esters were particularly rich in oleic acid and when compared to residue esters had more palmitoleic (+0.7%), oleic (+12.3%), and eicosatrienoic (+2.4%) and less palmitic (-2.2%), linoleic (-12.4%), and arachidonic (-1.6%) acids. The proportions of most individual fatty acids of droplets and residue correlated positively. The lipids of the residue closely resemble those reported for the normal intima.The observations that these droplets are prominent in the morphology of the fatty streak lesions, and that their high content of oleate-rich cholesteryl esters is similar to that reported for analysis of the whole lesions, suggest that the droplets may be involved in the pathogenesis of the fatty streak lesions of artherosclerosis in man.

Adolescent↗
PubMed1969

Studies of arteriosclerosis in Japanese and American men. I. Comparison of fatty acid composition of adipose tissue.

The proportions of fatty acids in lipids of subcutaneous adipose tissue was compared in closely age-matched, urban men from two populations with a great difference in mortality from arteriosclerosis, namely in 50 Americans and 56 Japanese aged 15-65 yr who had died suddenly and unexpectedly. Specimens from both groups were analyzed side by side for fatty acids by gas-liquid chromatography. Compared with Japanese, Americans had significantly (P<0.01) higher proportions of lauric (+ 0.2%), myristic (+ 0.4%), palmitic (+ 1.4%), stearic (+ 2.2%), and oleic (+ 5.3%) and lesser of palmitoleic (- 1.8%), linoleic (-6.3%), and linolenic (-0.4%) acids. Japanese had higher proportions of longer chain polyunsaturated fatty acids. The distributions of fatty acids for the groups at ages 35-44 yr had significant differences. With age, Americans showed significant increases of palmitic and oleic acids and decreases of lauric, myristic, stearic, and linoleic acids; Japanese showed no correlations of proportions of fatty acids with age. The significant correlations between per cent standard body weight and fatty acids in Americans were positive for palmitic and negative for lauric and stearic acids, and in Japanese, negative for myristic acid. The patterns of interacid correlations were dissimilar for the groups. These patterns may be stable characteristics of these groups providing further insight into their fatty acid metabolism. The relationships with the fatty acid compositions of the American and Japanese diets are discussed.

Adipose Tissue↗
PubMed1969

Correlation between percentage of palmitic acid in adipose tissue and serum cholesterol level in patients with multiple sclerosis.

To investigate mechanisms controlling the concentration of serum cholesterol we studied its relationship to the proportions of fatty acids in the lipids of adipose tissue of patients with multiple sclerosis. In 26 men the serum cholesterol concentration had a significant multiple linear regression on the proportion of palmitic, palmitoleic, and grouped longer-chain acids in adipose tissues. In 29 women the serum cholesterol had a significant regression on the proportion of palmitic acid and age. Whether these observations would hold for normal people must be determined in future studies.

Adipose Tissue↗
PubMedDate not supplied

Efficacy and safety of cerivastatin 0.8 mg in patients with hypercholesterolaemia: the pivotal placebo-controlled clinical trial. Cerivastatin Study Group.

This pivotal, multicentre, double-blind, parallel-group study evaluated the efficacy and safety of cerivastatin 0.8 mg. Patients with primary hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on an American Heart Association (AHA) Step I diet, to treatment with cerivastatin 0.8 mg (n = 776), cerivastatin 0.4 mg (n = 195) or placebo (n = 199) once daily for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (-35.6%, P < 0.0001) or placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by 23.9 -58.4% (6th - 95th percentile). Overall attainment of the National Cholesterol Education Program (NCEP) goal was achieved by 84% of patients receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease (CHD). In the sub-population meeting the NCEP criteria for pharmacological therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD, reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by 22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 were elevated 8.7% (P < 0.0001) and 4.5% (P < 0.0001), respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in HDL-C were dependent upon triglyceride baseline levels; in patients having baseline triglyceride levels 250 - 400 mg/dl, cerivastatin 0.8 mg reduced median triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well tolerated. The most commonly reported adverse events included headache, pharyngitis and rhinitis (4 - 6%). Symptomatic creatine kinase elevations > 10 times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin 0.8 mg is an effective and safe treatment for patients with primary hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP-recommended levels.

Adolescent↗
PubMedDate not supplied

Maintenance of a low-fat diet: follow-up of the Women's Health Trial.

This report examines the maintenance of a low-fat diet 1 year on average after the completion of intervention sessions among participants in the Women's Health Trial (WHT). The WHT was a randomized controlled trial of the feasibility of adoption of a low-fat diet among women of moderate or increased risk of breast cancer, conduced in Seattle, Houston, and Cincinnati in 1985-1988. The women randomized to the low-fat diet attended an intensive dietary intervention program for 5-37 months. Intervention women were highly successful in reducing their dietary fat intake from 40.0% of energy intake at baseline to 26.3% by the end of the trial, based on a food frequency questionnaire (or an estimated 24% adjusted for the inaccuracies of a food frequency questionnaire versus a 4-day diet record). During 1989, 1 year on average after the WHT ended, 448 intervention women and 457 control women (87% of eligibles) completed a follow-up survey to determine the degree of maintenance of the diet. The intervention women maintained the low-fat diet with an increase of only 1.4 percentage points of energy from fat, despite the fact that they had attended no further intervention sessions and had made no commitment to maintain the diet beyond the end of the WHT. Furthermore, the degree of maintenance of the low-fat diet was not dependent on the length of time in the intervention, which suggests that intervention led to a sustained change in eating habits after as little as 5-9 months (8-13 classes).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗