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Biomedical subjects

W Insull

Publications and source records attributed to W Insull.

At least 37 records · Page 2Linked to original sources
PubMed1994

Plasma lipid effects of three common vegetable oils in reduced-fat diets of free-living adults.

We compared plasma lipid changes due to the polyunsaturated fatty acids (PUFAs) in partially hydrogenated soybean oil, corn oil, and sunflower oil fed in reduced-fat diets (22-26% of total energy). Each oil was the dominant fat in isoenergetic diets of centrally prepared foods consumed by 26 male and 35 female normolipidemic, free-living individuals. Test diets were consumed double-blind, alternating with self-selected diets for 5 wk each. The ranges of proportions of total fat were: 4.7-9.7% polyunsaturated fat, 8.9-14.2% monounsaturated fat and 5.4-7.4% saturated fat. All three diets lowered (P < 0.0001) total cholesterol (11%), LDL cholesterol (13%), and HDL cholesterol (10%), without triglyceride changes. We conclude that PUFAs at approximately 6% of total energy result in clinically relevant plasma cholesterol-lowering and that the proportion of polyunsaturated fat must be an important consideration when planning reduced-fat, reduced-saturated-fat diets.

Adult↗
PubMed1994

A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

The compositions of lesion types that precede and that may initiate the development of advanced atherosclerotic lesions are described and the possible mechanisms of their development are reviewed. While advanced lesions involve disorganization of the intima and deformity of the artery, such changes are absent or minimal in their precursors. Advanced lesions are either overtly clinical or they predispose to the complications that cause ischemic episodes; precursors are silent and do not lead directly to complications. The precursors are arranged in a temporal sequence of three characteristic lesion types. Types I and II are generally the only lesion types found in children, although they may also occur in adults. Type I lesions represent the very initial changes and are recognized as an increase in the number of intimal macrophages and the appearance of macrophages filled with lipid droplets (foam cells). Type II lesions include the fatty streak lesion, the first grossly visible lesion, and are characterized by layers of macrophage foam cells and lipid droplets within intimal smooth muscle cells and minimal coarse-grained particles and heterogeneous droplets of extracellular lipid. Type III (intermediate) lesions are the morphological and chemical bridge between type II and advanced lesions. Type III lesions appear in some adaptive intimal thickenings (progression-prone locations) in young adults and are characterized by pools of extracellular lipid in addition to all the components of type II lesions.

Animals↗
PubMed1994

A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

The compositions of lesion types that precede and that may initiate the development of advanced atherosclerotic lesions are described and the possible mechanisms of their development are reviewed. While advanced lesions involve disorganization of the intima and deformity of the artery, such changes are absent or minimal in their precursors. Advanced lesions are either overtly clinical or they predispose to the complications that cause ischemic episodes; precursors are silent and do not lead directly to complications. The precursors are arranged in a temporal sequence of three characteristic lesion types. Types I and II are generally the only lesion types found in children, although they may also occur in adults. Type I lesions represent the very initial changes and are recognized as an increase in the number of intimal macrophages and the appearance of macrophages filled with lipid droplets (foam cells). Type II lesions include the fatty streak lesion, the first grossly visible lesion, and are characterized by layers of macrophage foam cells and lipid droplets within intimal smooth muscle cells and minimal coarse-grained particles and heterogeneous droplets of extracellular lipid. Type III (intermediate) lesions are the morphological and chemical bridge between type II and advanced lesions. Type III lesions appear in some adaptive intimal thickenings (progression-prone locations) in young adults and are characterized by pools of extracellular lipid in addition to all the components of type II lesions.

Animals↗
PubMed1993

Effect of dietary cholesterol on cholesterol synthesis in breast-fed and formula-fed infants.

The fractional synthesis rate (FSR) of cholesterol was measured in 6 breast-fed and 12 formula-fed infants (ages 4 to 5 months) using the 2H2O method. The breast-fed infants had higher cholesterol intakes (18.2 +/- 4.0 vs. 3.4 +/- 1.8 mg/kg per day, P = 0.001), plasma total cholesterol (183 +/- 47 vs. 112 +/- 22 mg/dl, P = 0.013), and plasma low density lipoprotein (LDL)-cholesterol (83 +/- 26 vs. 48 +/- 16 mg/day, P = 0.023) than the formula-fed infants (6.9 +/- 2.6 vs. 2.1 +/- 0.6%/day, P < 0.001). Among all infants, there was a significant inverse relationship (P = 0.002, r = 0.66) between the FSR of cholesterol and dietary cholesterol intake. Our findings indicate that the greater cholesterol intake of the breast-fed infants was associated with elevated plasma LDL-cholesterol concentrations and that cholesterol synthesis in human infants may be efficiently regulated via HMG-CoA reductase when infants are challenged with high intakes of dietary cholesterol.

Breast Feeding↗
PubMed1992

Adjuvant dietary fat intake reduction in postmenopausal breast cancer patient management. The Women's Intervention Nutrition Study (WINS).

Management of localized breast cancer now commonly involves a breast-sparing approach combined with systemic adjuvant therapy resulting in improved cosmetic results and patient survival. Reducing dietary fat intake represents a conceptually new approach to further improve outcome of patients with resected breast cancer. The rationale supporting evaluation of dietary fat reduction in the management of patients with localized breast cancer is based on: (1) epidemiologic observations (along with biochemical and hormonal correlates) of major differences in stage-by-stage survival of patients with localized breast cancer comparing outcome in countries with low fat (Japan) versus high fat (U.S.A.) dietary intakes; (2) relationships between dietary fat intake and factors prognostic of clinical outcome in patients with established breast cancer; (3) effects of weight gain (especially that associated with adjuvant chemotherapy) on breast cancer clinical outcome; (4) in vivo animal studies demonstrating adverse influence of increased dietary fat intake (especially linoleic acid) on growth and metastatic spread of mammary cancer; (5) direct adverse effects of increased linoleic acid on human breast cancer growth in vitro; (6) plausible mechanisms which could mediate the effects of dietary fat intake reduction on breast cancer growth and metastatic spread; (7) demonstration of adherence to dietary fat reduction regimens in ongoing clinical feasibility studies including those involving postmenopausal patients with resected breast cancer; and (8) favorable sample size requirements for definitive assessment of dietary fat intake reduction influence on breast cancer growth and metastases (using as endpoints relapse-free survival and overall survival) in postmenopausal breast cancer patients with localized disease.

Animals↗
PubMed1992

Neonatal genetically lean and obese pigs respond differently to dietary cholesterol.

The impact of cholesterol exposure in early life on later cholesterol metabolism is not clearly understood. Sixteen newborn genetically lean and obese pigs were fed 0 or 5.0 g cholesterol/kg diet (0 or 0.5%) (liquid diets for 12 d, dry diets thereafter) for 33 d, after which they were all fed 10.0 g cholesterol/kg diet (1.0%) for 23 d. All animals were killed on d 56 and whole-body protein, fat and water were determined on the ground carcass. Dietary cholesterol had no consistent effect on growth rates or body composition. Mean fat content of lean pigs was 15.1% compared with 22.7% for obese pigs; corresponding values were 14.8 and 14.4% for protein and 65.5 and 58.3% for water. Concentrations of plasma total cholesterol, HDL cholesterol and apolipoproteins B and A-1 were increased by 0.5% dietary cholesterol in obese but not in lean piglets, although dietary cholesterol caused HDL and LDL size distribution profiles to shift toward larger-sized components in both strains. Plasma total cholesterol and apolipoprotein B concentrations rose two- to eightfold in all groups after the 1% cholesterol diet was consumed; these changes were accompanied by shifts in LDL and HDL size distribution profiles towards larger-sized components. With 1.0% cholesterol in the diet of all groups, HDL cholesterol concentration increased by approximately 50% in both groups of lean pigs and in obese pigs previously fed cholesterol, but did not increase further in obese pigs previously fed 0.5% cholesterol. The magnitude of the hypercholesterolemic response in lean pigs was blunted by previous exposure to 0.5% dietary cholesterol, but the response was accentuated in obese animals that had been previously exposed to 0.5% dietary cholesterol. These data provide evidence that genetic differences between obese and lean pigs affect their serum lipoprotein responses to high cholesterol intake.

Animals↗
PubMed1992

Effect of dietary fat and cholesterol level on growing pigs selected for three generations for high or low serum cholesterol at age 56 days.

Thirty-six female pigs selected for three generations for high (HS, n = 18) and low (LS, n = 18) serum cholesterol at 56 d of age were used to test the hypothesis that the two populations would respond differently to a high-fat, high-cholesterol diet (HD) and a low-fat, low-cholesterol diet (LD). The animals were four-way crosses (Chester White x Landrace x Large White x Yorkshire). All pigs were fed a standard corn-soybean meal starter diet from weaning (at 4 wk) to 8 wk of age and a grower diet from 8 to 12 wk of age. Initial serum total cholesterol concentration at 12 wk of age was higher (P less than .05) in HS than in LS pigs (94.6 vs 76.9 mg/dL, respectively). The effect of genetic background persisted throughout the 13-wk experiment (25 wk of age); there was no interaction between diet and genetic background in serum total cholesterol (final concentrations were 114.3 mg/dL in HS-HD; 107.0 mg/dL in HS-LD; 105.9 mg/dL in LS-HD; and 89.7 mg/dL LS-LD). Trends over time revealed significant effects of diet (P less than .01) and genetic background (P less than .01) on serum total cholesterol. There was no effect of genetic background on high-density lipoprotein-cholesterol concentration; high-density lipoprotein-cholesterol as a percentage of serum total cholesterol was similar for all groups: 43% for HS-HD, 48% for HS-LD, 42% for LS-HD, and 45% for LS-LD.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Comparison of the efficacy of Questran Light, a new formulation of cholestyramine powder, to regular Questran in maintaining lowered plasma cholesterol levels.

Sixty-one men with known hypercholesterolemia (plasma cholesterol greater than 265 mg/dl), most of whom were previous participants in the Coronary Primary Prevention Trial of the U.S. Lipid Research Clinic Program, were chosen to take part in this study to test the effectiveness of a new low-calorie (Questran Light) cholestyramine formulation against the proven effectiveness of the currently marketed formulation Questran in maintaining lowered plasma cholesterol levels. The study recorded changes in fasting plasma lipids, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and calculated low-density lipoprotein cholesterol. After establishing baseline lipid/lipoprotein levels in a 3-week period during which all participants received the currently marketed formulation, the men were randomized into 2 groups, 1 group (n = 31) taking the new Questran Light formulation of 4 g of cholestyramine in 5 g of powder per pack, while the other group (n = 30) continued to take the marketed Questran formulation of 4 g of cholestyramine in 9 g of powder per pack. Each group consumed a total of 24 g/day of cholestyramine in 2 divided doses. At the end of the maintenance phase of the study there were no statistically significant mean changes in percentage from baseline to end-point lipid/lipoprotein levels within either group, nor were there any significant differences between the Questran Light group or the currently marketed Questran formulation group. The new low-calorie cholestyramine formulation appears to be equally as effective in maintaining lowered plasma cholesterol levels as the currently marketed formulation.

Adult↗
PubMed1990

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. II. Once-daily versus twice-daily dosing.

This 8-week multicenter, placebo-controlled trial compared the efficacy and safety of the HMG-CoA reductase inhibitor, pravastatin, when administered either as single doses of 40 mg in the morning (AM) or evening (PM) or 20 mg twice daily (bid) in 196 diet-stabilized outpatients with primary type II hypercholesterolemia. Mean reductions in total and low-density lipoprotein (LDL) cholesterol concentrations were observed in all pravastatin groups after 1 week and were sustained throughout the study (P less than or equal to 0.001 versus baseline and placebo). At week 8, mean reductions from baseline in the pravastatin treatment groups were 23-27% for total cholesterol and 30-34% for LDL cholesterol. LDL cholesterol was reduced greater than or equal to 15% by pravastatin in all patients in the group treated with 40 mg PM and in 88 and 96% in those receiving 20 mg bid and 40 mg AM, respectively. High density lipoprotein cholesterol was elevated (up to 8%) and triglycerides were reduced (up to 25%) by all pravastatin regimens (P less than or equal to 0.05). Pravastatin was well tolerated and was associated with a low incidence of adverse events. No patient withdrew from the study due to a pravastatin-related adverse event. Once-daily pravastatin is a safe and effective treatment for patients with primary hypercholesterolemia and has a favorable safety profile.

Adult↗
PubMed1990

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study.

This multicenter, double-blind, placebo-controlled, dose-response study was conducted in patients with primary hypercholesterolemia to examine the effects of pravastatin, a selective inhibitor of HMG-CoA reductase, on plasma lipids and lipoproteins. A total of 306 patients on cholesterol-lowering diets received twice daily doses of 5 mg, 10 mg, 20 mg pravastatin, or placebo for 12 weeks. Marked reductions in low density lipoprotein (LDL) cholesterol and total cholesterol were observed after 1 week of treatment; maximum lipid-lowering effects occurred at 4 weeks and were sustained for the duration of the trial. At week 12, pravastatin treatment resulted in dose-dependent mean reductions from baseline in LDL cholesterol of 17.5%, 22.9%, and 30.8% for the 3 doses tested (P less than or equal to 0001 compared with baseline and placebo). The reduction in LDL cholesterol was log-linear with respect to dose; each doubling of dose reduced LDL cholesterol an additional 6.5%. Dose-dependent reductions in total cholesterol from 12.9% to 23.3% also occurred (P less than or equal to 0.001). Triglycerides decreased by as 15.4% (P less than or equal to 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P less than or equal to 0.01), but these effects were not dose-dependent. No patient receiving pravastatin was discontinued during the 12-week trial. Transient episodes of rash and headache occurred. Slight increases in mean serum levels of ASAT and ALAT occurred, and 2% of both placebo- and pravastatin-treated patients reported myalgia although there was no clinically significant elevation of creatine kinase. These data indicate that pravastatin favorably affects all lipid parameters and is well tolerated.

Anticholesteremic Agents↗
PubMed1990

High-density lipoprotein response to 5-alpha-dihydrotestosterone and testosterone in Macaca fascicularis: a hormone-responsive primate model for the study of atherosclerosis.

A decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease, occurs during puberty in males. Previous studies have shown this decrease with testosterone (T) therapy for adolescent males, but the mechanism of this effect is unknown and has not been studied in a non-human primate. Two adult male monkeys (Macaca fascicularis) were studied to determine simultaneous changes in plasma androgens and HDL-C during the phases precastration (Ci); postcastration (Cx); Cx and T therapy; Cx and dihydrotestosterone (DHT) therapy; and T and 5-alpha-reductase inhibitor therapy (4-MA). After castration, the HDL-C concentrations increased significantly in both animals (monkey A, 57.0 +/- 1.8 mg/dL SE to 66.6 +/- 2.2, P less than .005; monkey B, 62.9 +/- 1.6 to 80.2 +/- 1.7, P less than .001). T-propionate treatment produced a significant decrease in HDL-C (monkey A, 48.0 +/- 5.0, P less than .01; monkey B, 43.5 +/- 0.5, P less than .001), which was similar to HDL-C reductions seen when treated with a nonaromatizeable androgen, DHT-propionate (monkey A, 47.5 +/- 1.5, P less than .005; monkey B, 44.5 +/- 3.5, P less than .001). T and the 5-alpha-reductase inhibitor therapy did not increase HDL-C from the levels with T therapy alone (monkey A, 55.7 +/- 1.9, NS; monkey B, 57.3 +/- 0.3, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1990

Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study.

The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention.

Aged↗
PubMed1990

Analysis of the costs of a large prevention trial.

Total direct costs of the Women's Health Trial (WHT), a large multicenter prevention trial, were reduced by more than 50% by means of research cost analysis conducted during the trial design phase. The unit costs of specific trial activities were estimated so that total direct costs of the trial could be predicted from design parameters. The relative costs of screening, treatment, and follow-up, and the fixed costs associated with each clinical center in a multicenter prevention trial were taken into account. Direct costs of the WHT were reduced from +195 million to +95 million by refinement of the trial protocol, selection of an efficient design, and consideration of trial logistics. The analyses suggest several ways to reduce costs in a prevention trial. Use of the case-cohort approach can reduce costs substantially when the protocol includes collection of specimens or data that are costly to process. When establishing and maintaining a clinical center represents a significant proportion of a clinical center's costs, use of a smaller number of larger clinical centers offers important cost savings. Because restrictive eligibility requirements reduce the recruitment potential of each clinical center, use of high-risk participants may not improve the efficiency of a prevention trial; its favorable impact on sample size may fail to compensate for its cost in terms of additional clinical centers and higher recruitment costs.

Aged↗
PubMed1990

Changes in food patterns during a low-fat dietary intervention in women.

The Women's Health Trial was initiated by the National Cancer Institute to study the effects of a low-fat diet on the incidence of breast cancer in women at elevated risk for the disease. The purpose of this article is to examine the specific dietary changes that 173 women made while participating in a feasibility intervention program to reduce their fat intake to approximately 20% of total calories over a 12-month period. The intervention program used group sessions to teach nutrition information and behavioral skills necessary to make a life-style dietary change. Four-day food records were collected from participants at the beginning of the study and again at 12 months. Women in the intervention group reduced their total fat intake from a mean of 76 gm (39% of total energy) to 31 gm (22% of total energy), mainly by decreasing their fat intake from milk products, red meats, and fats/oils. These women used cheddar cheese, American cheese, whole milk, butter, mayonnaise, salad dressing, bacon, and hamburgers less frequently, and used diet American cheese, low-fat cottage cheese, and skim milk more frequently. They consumed less fat in their vegetable dishes, and their total caloric intake from fruit increased slightly. In addition, the overall quality of the diets improved, since there was a 20% to 50% increase in the energy-adjusted intake of vitamins and minerals from food sources.

Aged↗