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Biomedical subjects

W S Harris

Publications and source records attributed to W S Harris.

At least 19 recordsLinked to original sources
PubMed2001

Measurement of human chylomicron triglyceride clearance with a labeled commercial lipid emulsion.

Human chylomicron triglyceride (TG) kinetics has been difficult to determine directly owing to technical limitations. This report describes a new method for studying chylomicron metabolism. Healthy volunteers (n = 10) sipped a drink providing 175 mg fat x kg(-1) h(-1) for 7.5 h to produce a steady-state chylomicronemia. A commercial 10% intravenous lipid emulsion was labeled with [3H]triolein, purified by high-performance liquid chromatography, and sterilized. A trace amount of labeled emulsion was injected intravenously 30 min before (i.e., in the fasting state) and 5, 6, and 7 h after sipping began (i.e., triplicate determinations in the fed state). Chylomicron half-lives were calculated from the monoexponential decay curves, and apparent distribution volumes were estimated by back-extrapolation to time zero. Plasma and estimated chylomicron TG concentrations increased from 89+/-13 and 0.8+/-0.3 to 263+/-43 and 91+/-39 mg/dL (mean +/- SEM), respectively, with feeding. Tracer-determined chylomicron TG half-lives were 5.34+/-0.58 and 6.51+/-0.58 min during the fasting and fed states, respectively (P < 0.01). The apparent distribution volume during the fasting state was 24% greater than plasma volume (4515+/-308 vs. 3630+/-78 mL, P < 0.02), consistent with significant margination of lipid emulsion particles to endothelial binding sites. Margination was reduced during the fed state, suggesting that native chylomicrons competed with lipid emulsion particles for endothelial lipoprotein lipase. The results indicate that a radiolabeled commercial lipid emulsion is metabolized in a fashion similar to native chylomicron TG, and thus can be used to study chylomicron TG kinetics.

Adult↗
PubMed2001

Clinical trial evidence for the cardioprotective effects of omega-3 fatty acids.

The notion that marine omega (w)-3 fatty acids might have beneficial cardiovascular effects was first suggested by epidemiologic studies in Greenland Inuits published in the late 1970s. These simple observations spawned hundreds of other studies, the confluence of which strongly suggests a true cardioprotective effect of w-3 fatty acids. The strongest confirmation has come from the publication of three randomized clinical trials, all of which reported benefits to patients with preexisting coronary artery disease. The most convincing of these was the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI)-Prevezione study, in which 5654 patients with coronary artery disease were randomized to either w-3 fatty acids (850 mg/d) or usual care. After 3.5 years, those taking the w-3 fatty acids had experienced a 20% reduction in overall mortality and a 45% decrease in risk for sudden cardiac death. These findings support the view that relatively small intakes of w-3 fatty acids are indeed cardioprotective, and suggest that they may operate by stabilizing the myocardium itself.

Clinical Trials as Topic↗
PubMed2000

Effect of atorvastatin on hemorheologic-hemostatic parameters and serum fibrinogen levels in hyperlipidemic patients.

Plasma fibrinogen and hemorheologic-hemostatic factors contribute to dyslipidemia-induced morbidity. Some of these parameters can be favorably affected when abnormal serum lipoprotein levels are corrected. Thus, we investigated whether treatment with atorvastatin would result in changes in plasma viscosity and other hemorheologic and hemostatic parameters. Twenty-two hyperlipidemic men at a university lipid clinic were treated single-blinded with atorvastatin 80 mg/day for 12 weeks to determine hemostatic-hemorheologic parameters including blood viscosity, fibrinogen levels, whole blood platelet aggregation, tissue plasminogen activator antigen, hematocrit, plasminogen activator inhibitor activity, factor VII activity, red blood cell (RBC) deformity and lipid ratio, sedimentation rate, and fasting serum lipoprotein levels. Atorvastatin treatment provided significant lowering of serum lipoprotein levels: low-density lipoprotein -53% (p = 0.0001), very low density lipoprotein -43% (p = 0.0001), and triglycerides -35% (p < 0.0001). These effects were accompanied by changes in plasma viscosity -10% (p = 0.0007), arachidonic acid-induced whole blood platelet aggregation -11% (p = 0.006), factor VII -8% (p = 0.001), RBC lipid composition +5% (p = 0.0003), and RBC sedimentation -33% (p = 0.0002). Plasma fibrinogen levels were not affected. Thus, atorvastatin 80 mg/day produced marked reductions in serum low-density lipoprotein cholesterol (-53%), very low density lipoprotein cholesterol (-43%), and triglycerides levels (-35%), and significant changes in plasma viscosity as well as other hemorheologic-hemostatic parameters, but no changes in plasma fibrinogen levels.

Adult↗
PubMed2000

Lipid risk factor correlates of ischemic heart disease as diagnosed by myocardial perfusion scintigraphy.

Patients with known coronary artery disease frequently change their lifestyles (e.g., diet, exercise, and smoking habit) after the diagnosis is made. Such changes can alter lipid risk factor levels and obscure etiologic risk factor associations with the presence of coronary artery disease. It is therefore preferable to determine the contribution of potential risk factors before the diagnosis of coronary artery disease has been established. In this trial, we used stress nuclear myocardial perfusion imaging to diagnose coronary artery disease in patients presenting for evaluation of chest pain. Two groups of age- and sex-matched patients were identified: a normal group (patients with no evidence of coronary artery disease), and an abnormal group (patients whose scans indicated the presence of significant coronary artery disease due to either fixed or reversible perfusion defects). Blood samples were drawn before scanning and analyzed for lipid risk factors. Compared to the normal group, the abnormal group had higher levels of triglycerides (189±91 vs. 135±51 mg/dL, p=0.003), lower levels of high-density lipoprotein cholesterol (39±9 vs. 45±14 mg/dL, p=0.037), and higher levels of small, dense low-density lipoprotein (LDL(3)) (42±18 vs. 32±13 mg/dL, p=0.007). Total cholesterol, low-density lipoprotein, and lipoprotein(a) levels were similar between groups. These findings suggest that ischemic heart disease, as assessed by myocardial perfusion scintigraphy, is more closely associated with the low high-density lipoprotein/high triglyceride syndrome than with increased low-density lipoprotein or total cholesterol levels. (c) 2000 by CHF, Inc.

Journal Article↗
PubMed2000

A new method for the study of chylomicron kinetics in vivo.

Our understanding of the metabolism of chylomicrons, the lipoprotein that transports dietary fat from the intestine to peripheral tissues, is incomplete. The present studies were conducted to determine whether a labeled intravenous lipid emulsion could be used to estimate chylomicron triglyceride (TG) rate of appearance (R(a)) and thereby quantify the rate of intestinal fat absorption. After an overnight fast, healthy volunteers (n = 6) sipped a (3)H-labeled drink over 6.5 h at a rate of 175 mg fat. kg(-1). h(-1). Beginning at hour 5, an HPLC-purified, (14)C-labeled lipid emulsion was infused intravenously for 90 min. During the study, plasma total and chylomicron TG concentrations increased from 100 +/- 21 to 237 +/- 40 mg/dl and from undetectable to steady-state levels of 35 +/- 13 mg/dl, respectively. After a minor correction for VLDL contamination, tracer-determined chylomicron TG R(a) was 175 +/- 30 mg. kg(-1). h(-1), equal to the presumed ingestion rate. In summary, a radiolabeled intravenous lipid emulsion is able to accurately estimate chylomicron TG R(a) and therefore can be used to measure in vivo fat absorption rates.

Adult↗
PubMed2000

From Inuit to implementation: omega-3 fatty acids come of age.

During the past 25 years, the cardiovascular effects of marine omega-3 (omega-3) fatty acids have been the subject of increasing investigation. In the late 1970s, epidemiological studies revealed that Greenland Inuits had substantially reduced rates of acute myocardial infarction compared with Western control subjects. These observations generated more than 4,500 studies to explore this and other effects of omega-3 fatty acids on human metabolism and health. From epidemiology to cell culture and animal studies to randomized controlled trials, the cardioprotective effects of omega-3 fatty acids are becoming recognized. These fatty acids, when incorporated into the diet at levels of about 1 g/d, seem to be able to stabilize myocardial membranes electrically, resulting in reduced susceptibility to ventricular dysrhythmias, thereby reducing the risk of sudden death. The recent GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)-Prevention study of 11,324 patients showed a 45% decrease in risk of sudden cardiac death and a 20% reduction in all-cause mortality in the group taking 850 mg/d of omega-3 fatty acids. These fatty acids have potent anti-inflammatory effects and may also be antiatherogenic. Higher doses of omega-3 fatty acids can lower elevated serum triglyceride levels; 3 to 5 g/ d can reduce triglyceride levels by 30% to 50%, minimizing the risk of both coronary heart disease and acute pancreatitis. This review summarizes the emerging evidence of the use of omega-3 fatty acids in the prevention of coronary heart disease.

Cardiovascular Agents↗
PubMed1999

A randomized, controlled trial of the effects of remote, intercessory prayer on outcomes in patients admitted to the coronary care unit.

CONTEXT: Intercessory prayer (praying for others) has been a common response to sickness for millennia, but it has received little scientific attention. The positive findings of a previous controlled trial of intercessory prayer have yet to be replicated. OBJECTIVE: To determine whether remote, intercessory prayer for hospitalized, cardiac patients will reduce overall adverse events and length of stay. DESIGN: Randomized, controlled, double-blind, prospective, parallel-group trial. SETTING: Private, university-associated hospital. PATIENTS: Nine hundred ninety consecutive patients who were newly admitted to the coronary care unit (CCU). INTERVENTION: At the time of admission, patients were randomized to receive remote, intercessory prayer (prayer group) or not (usual care group). The first names of patients in the prayer group were given to a team of outside intercessors who prayed for them daily for 4 weeks. Patients were unaware that they were being prayed for, and the intercessors did not know and never met the patients. MAIN OUTCOME MEASURES: The medical course from CCU admission to hospital discharge was summarized in a CCU course score derived from blinded, retrospective chart review. RESULTS: Compared with the usual care group (n = 524), the prayer group (n = 466) had lower mean +/- SEM weighted (6.35 +/- 0.26 vs 7.13 +/- 0.27; P=.04) and unweighted (2.7 +/- 0.1 vs 3.0 +/- 0.1; P=.04) CCU course scores. Lengths of CCU and hospital stays were not different. CONCLUSIONS: Remote, intercessory prayer was associated with lower CCU course scores. This result suggests that prayer may be an effective adjunct to standard medical care.

Aged↗
PubMed1999

Nonpharmacologic treatment of hypertriglyceridemia: focus on fish oils.

Early studies in Greenland Eskimos stimulated interest in evaluating the effect of Omega-3 fatty acids on coronary artery disease. Subsequent studies showed a significant decrease in triglyceride levels in patients receiving high doses of fish oil containing DHA and EPA. Slight increases in LDL were also observed in patients receiving fish oil supplements. These studies have also shown a dose-response effect which persists as long as supplementation continues. Later trials, specifically the Diet and Reinfarction Trial and the Indian Experiment of Infarct Survival, have demonstrated a reduction in cardiac death rates and in the incidence of cardiac symptoms in patients receiving fish oil.

Controlled Clinical Trials as Topic↗
PubMed1999

Omega-3 fatty acids alter lipoprotein subfraction distributions and the in vitro conversion of very low density lipoproteins to low density lipoproteins.

The purpose of this study was to determine the effects of a fish oil concentrate (FOC) on the in vitro conversion of very low density lipoproteins (VLDL) to intermediate (IDL) and low density lipoproteins (LDL). Six hypertriglyceridemic patients were randomly allocated to receive either placebo (olive oil) or FOC (1 g/14 kg body weight/day) for 4 weeks in a crossover study with a 4-week washout period. The FOC provided 3 g of eicosapentaenoic + docosahexaenoic acid per 70 kg of body weight, and it lowered plasma triglyceride and VLDL cholesterol levels by 35% and 42%, respectively. Decreases in the largest particles (VLDL(1)) were primarily responsible, with no effect noted in smaller VLDL particles (VLDL(2) and VLDL(3)). The FOC increased LDL cholesterol levels by 25% (P < 0.06) but did not affect LDL particle size. VLDL(1) and VLDL(3) were incubated in vitro with human postheparin lipases. Although triglycerides from both types of VLDL were hydrolyzed to the same extent with both treatments, particles isolated during the FOC phase were more readily converted into IDL and LDL than were control particles. These data suggest that the marine omega3 fatty acids may enhance the propensity of VLDL to be converted to LDL, partly explaining the decreased VLDL and increased LDL levels in FOC-treated patients.

Clinical Trial↗
PubMed1997

Inhibition of cholesterol absorption with CP-148,623 lowers serum cholesterol in humans.

OBJECTIVE: To determine the effects of the reduction of intestinal cholesterol absorption with CP-148,623 on serum cholesterol levels in men with mild hyperlipidemia. METHODS: In an outpatient study in a university medical center, healthy male volunteers (n = 25) with borderline-high serum cholesterol levels participated in a double-blind, placebo-controlled parallel-group study. A 3-week dietary run-in period was followed by 2 weeks of treatment with either CP-148,623 (300 mg twice a day; n = 12) or placebo (n = 13). RESULTS: Fractional cholesterol absorption (by the dual-isotope, continuous-feeding technique), fecal neutral sterol excretion, and serum lipids were measured after the diet run-in and after the treatment periods. CP-148,623 caused a marked inhibition (by 38%) of fractional cholesterol absorption (50% +/- 2% [baseline] to 31% +/- 1%) and a 71% increase in fecal neutral sterol excretion (481 +/- 39 mg/day [baseline] to 804 +/- 55 mg/day), compared with negligible changes in the placebo group (p < 0.0001 for both). Mean percent reductions from baseline in serum low-density lipoprotein (LDL) cholesterol levels were 11.6% with CP-148,623 (119 +/- 17 mg/dl to 104 +/- 13 mg/dl) versus a nonsignificant 1.8% reduction with placebo (change with CP-148,623 versus placebo, p < 0.0002). CONCLUSIONS: In healthy male volunteers with mild hypercholesterolemia, treatment for 2 weeks with 600 mg/day CP-148,623 inhibited fractional cholesterol absorption by 35% to 40%, increased fecal neutral sterol excretion by 60% to 70%, and reduced serum LDL cholesterol by 10% to 12%.

Adult↗
PubMed1997

Influence of fitness status on very-low-density lipoprotein subfractions and lipoprotein(a) in men and women.

The purpose of this study was to examine the influence of the physical activity level of men and women on the very-low-density lipoprotein (VLDL) subfractions and lipoprotein(a) [Lp(a)]. Fifty-four men (n = 30) and women (n = 24) aged 30 to 53 years were recruited based on their level of activity over the past 2 years, and formed three groups: sedentary (S), no routine activity; recreational exercise (R), routine moderate exercise three to five times per week; and trained (T), competition-based, high-volume aerobic training five to seven times per week. Each subject underwent a maximal oxygen consumption (VO2max) test and was measured for body composition (skinfolds) and waist to hip ratio (WHR). Following a prescribed 24-hour diet and abstinence from activity, a blood sample was obtained from each subject and the plasma was analyzed for cholesterol and triglycerides (TGs) in VLDL1, VLDL2, and VLDL3 subfractions. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Lp(a) also were analyzed. Total VLDL-C was higher in men than in women, but no gender differences were observed in VLDL subfractions. VLDL1-TG and VLDL2-TG were elevated in the S group compared with groups R and T, even though total VLDL-TG, LDL-C, and HDL-C values were not different among the groups. Values for Lp(a) were not significantly different between men and women or among the groups. The two exercising groups were not different on any lipoprotein variable or WHR. VLDL1-TG was inversely correlated with VO2max and HDL-C. These results suggest that life-style activity is associated with a favorable VLDL subfraction pattern and WHR, but not Lp(a). In addition, long-term recreational activity is associated with a lipoprotein profile and WHR similar to those obtained with higher-volume exercise training.

Adult↗
PubMed1997

n-3 fatty acids and urinary excretion of nitric oxide metabolites in humans.

Fish oils rich in n-3 fatty acids have been shown to augment endothelium-dependent vasodilation in human peripheral and coronary arteries. This suggests that n-3 fatty acids may enhance arterial nitric oxide production. To explore this hypothesis we measured total urinary nitrate output in healthy volunteers supplemented with a fish oil concentrate (FOC; n = 15) or purified eicosapentaenoic acid (EPA; n = 14) in a placebo-controlled, parallel-group study. The FOC contained 41% EPA and 23% docosahexaenoic acid (DHA) ethyl esters, whereas EPA was 91% pure; the placebo contained olive oil ethyl esters. Doses were 5 g placebo, 5 g FOC, and 3 g EPA to keep the total n-3 fatty acid content equal in the latter two groups. The placebo period was 2 wk long and was followed by a 3-wk n-3 fatty acid phase. At the end of each period, 24-h urine collections and fasting blood samples were obtained. Serum and urinary nitrate concentrations were measured in a blinded fashion. The FOC produced a 43% increase in daily, creatinine-adjusted, nitrate excretion rates (P < 0.029). Because serum nitrate concentrations were not different, these findings suggest that FOC supplementation may stimulate systemic nitric oxide synthesis. The lack of effect with EPA supplementation suggests that this component of the FOC is not likely to be an active component. If confirmed, these observations suggest another mechanism whereby n-3 fatty acids may be antiatherogenic.

Adult↗
PubMed1997

n-3 fatty acids and serum lipoproteins: animal studies.

This review examines the effects of n-3 fatty acids on serum lipid and lipoprotein concentrations in seven species of experimental animals. n-3 Fatty acids consistently lower serum triacylglycerol concentrations in humans but not in most animals. In addition, a common effect of n-3 fatty acids in animals is a marked reduction in high-density-lipoprotein-cholesterol concentrations, a response virtually never seen with fish-oil supplementation in humans. These differences between animals and humans arise not only from underlying species differences in lipoprotein metabolism but also from differences in experimental designs, the most notable of which is the tendency to feed animals much larger amounts of n-3 fatty acids than supplements provide for humans. Thus, great care must be taken not only to use appropriate animal models when studying lipoprotein metabolism but also to feed the animals comparable amounts of n-3 fatty acids. Failure to properly address these issues will make it difficult to uncover the biochemical basis for the hypolipidemic effect of fish oils in humans through use of experimental animals.

Animals↗
PubMed1997

n-3 fatty acids and serum lipoproteins: human studies.

The effects of n-3 fatty acids from fish oils (eicosapentaenoic acid and docosahexaenoic acid) and plant oils (alpha-linolenic acid) on human serum lipids and lipoproteins are reviewed. Studies were included in this review if they were placebo-controlled, crossover, or parallel design studies providing < 7 g n-3 fatty acids/d and with treatment periods of > or = 2 wk duration. Only three studies were available for evaluation of the effects of alpha-linolenic acid on serum lipid concentrations. From these studies it appeared that alpha-linolenic acid (18:3n-3) was equivalent to n-6-rich oils vis-vis lipid and lipoprotein effects. Only when very large amounts of flaxseed oil were fed did the hallmark effect of marine n-3 fatty acids-reduced triacylglycerol concentrations-appear. Thus, in terms of effects on lipoprotein metabolism, the plant-derived n-3 fatty acid is not equivalent to the marine-based acids. More studies using the marine-based acids were examined and summarized. Both crossover (n = 36) and parallel (n = 29) design studies reached the same conclusions: total cholesterol is not materially affected by n-3 fatty acid consumption, low-density-lipoprotein cholesterol concentrations tend to rise by 5-10% and high-density-lipoprotein cholesterol by 1-3%, and serum triacylglycerol concentrations decrease by 25-30%. These effects of marine n-3 fatty acids are now well-established; what remains is to determine the mechanisms behind these effects and, more importantly, their health consequences.

Cholesterol↗