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1.
Eur Phys J E Soft Matter ; 28(2): 231-42, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19030903

ABSTRACT

By numerical modeling we investigate fluid transport in low-Reynolds-number flow achieved with a special elastic filament or artificIal cilium attached to a planar surface. The filament is made of superparamagnetic particles linked together by DNA double strands. An external magnetic field induces dipolar interactions between the beads of the filament which provides a convenient way of actuating the cilium in a well-controlled manner. The filament has recently been used to successfully construct the first artificial micro-swimmer (R. Dreyfus et al., Nature 437, 862 (2005)). In our numerical study we introduce a measure, which we call pumping performance, to quantify the fluid transport induced by the magnetically actuated cilium and identify an optimum stroke pattern of the filament. It consists of a slow transport stroke and a fast recovery stroke. Our detailed parameter study also reveals that for sufficiently large magnetic fields the artificial cilium is mainly governed by the Mason number that compares frictional to magnetic forces. Initial studies on multi-cilia systems show that the pumping performance is very sensitive to the imposed phase lag between neighboring cilia, i.e., to the details of the initiated metachronal wave.


Subject(s)
Biomimetic Materials/metabolism , Cilia/metabolism , Hydrodynamics , Magnetics , Models, Biological , Biomechanical Phenomena , Flagella/metabolism , Kinetics , Movement , Surface Properties
2.
Am J Cardiol ; 78(4): 420-4, 1996 Aug 15.
Article in English | MEDLINE | ID: mdl-8752186

ABSTRACT

A paucity of substantive data from clinical drug trials is available specifically evaluating the effects of therapy for hypercholesterolemia in African-Americans, even though a substantial number are candidates for medical advice and intervention for high blood cholesterol. The efficacy and safety of lovastatin in 459 African-Americans with hypercholesterolemia were studied in the Expanded Clinical Evaluation of Lovastatin study, a multicenter, double-blind, diet- and placebo-controlled trial. This trial involved 8,245 patients who were randomly assigned, regardless of race, to receive placebo or lovastatin at doses of 20 mg once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for 48 weeks. Among African-Americans, lovastatin produced sustained, dose-related (p <0.001) decreases in low-density lipoprotein cholesterol (20% to 38%), total cholesterol (14% to 28%), and triglycerides (8% to 15%). From 75% to 96% of African-Americans treated with lovastatin achieved the National Cholesterol Education Program goal of low-density lipoprotien cholesterol <160 mg/di, and from 33% to 71% achieved the goal <130 mg/di. The safety profile of lovastotin in African-Americans was generally favorable. A relatively high incidence of creatine kinase levels greater than the upper limit of normal was observed in African-Americans during the study, i.e., 63% in the placebo group and similar levels in lovastatin treatment groups. Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in African-Americans.


Subject(s)
Anticholesteremic Agents/therapeutic use , Black People , Hypercholesterolemia/drug therapy , Lovastatin/therapeutic use , Black or African American , Anticholesteremic Agents/administration & dosage , Anticholesteremic Agents/adverse effects , Cholesterol/blood , Cholesterol, LDL/blood , Creatine Kinase/blood , Dose-Response Relationship, Drug , Double-Blind Method , Drug Tolerance , Female , Humans , Hypercholesterolemia/diet therapy , Incidence , Lovastatin/administration & dosage , Lovastatin/adverse effects , Male , Middle Aged , Placebos , Safety , Triglycerides/blood
3.
Ann Intern Med ; 118(11): 850-5, 1993 Jun 01.
Article in English | MEDLINE | ID: mdl-8480959

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of lovastatin in women with moderate hypercholesterolemia. DESIGN: The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, in which participants were randomly assigned to receive placebo or lovastatin at doses of 20 or 40 mg once daily, or 20 or 40 mg twice daily for 48 weeks. SETTING: Ambulatory patients recruited by 362 participating centers throughout the United States. PATIENTS: Women (n = 3390) from the total cohort of 8245 volunteers. MEASUREMENTS: Plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides; and laboratory and clinical evidence of adverse events monitored periodically throughout the study. RESULTS: Among women, lovastatin (20 to 80 mg/d) produced sustained (12- to 48-week), dose-related changes (P < 0.001): decreases in LDL cholesterol (24% to 40%) and triglycerides (9% to 18%), and increases in HDL cholesterol (6.7% to 8.6%). Depending on the dose, from 82% to 95% of lovastatin-treated women achieved the National Cholesterol Education Program goal of LDL cholesterol levels less than 4.14 mmol/L (160 mg/dL), and 40% to 87% achieved the goal of 3.36 mmol/L (130 mg/dL). Successive transaminase elevations greater than three times the upper limit of normal occurred in 0.1% of women and were dose dependent above the 20-mg dose. Myopathy, defined as muscle symptoms with creatine kinase elevations greater than 10 times the upper limit of normal, was rare and associated with the highest recommended daily dose of lovastatin (80 mg). Estrogen-replacement therapy appeared to have no effect on either the efficacy or safety profile of lovastatin. CONCLUSION: Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in women.


Subject(s)
Hypercholesterolemia/drug therapy , Lovastatin/therapeutic use , Aged , Cholesterol, HDL/drug effects , Cholesterol, LDL/drug effects , Creatine Kinase/drug effects , Double-Blind Method , Estrogen Replacement Therapy , Female , Humans , Lovastatin/adverse effects , Middle Aged , Muscular Diseases/chemically induced , Sex Factors , Transaminases/drug effects
4.
Hypertension ; 19(3): 242-8, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1347757

ABSTRACT

Hypertension and hypercholesterolemia frequently coexist and may require concomitant drug treatments. The efficacy and safety profile of lovastatin given in the presence of antihypertensive medication was evaluated using patient subgroups identified in the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study. The EXCEL study examined 8,245 patients with moderate hypercholesterolemia randomly assigned either to a group treated with lovastatin (20-80 mg daily) or to a group given placebo for 48 weeks. After adjustment for patient characteristics, pairwise comparisons were made between patients taking no antihypertensive agents (n = 3,772) and those taking either calcium antagonists (n = 446), selective beta 1-adrenergic receptor blockers (n = 326), nonselective beta-adrenergic receptor blockers (n = 219), potassium-sparing diuretics (n = 187), thiazide diuretics (n = 126), or angiotensin converting enzyme inhibitors (n = 171). The placebo-corrected dose-dependent effect of lovastatin on the percent change from baseline in low-density lipoprotein cholesterol was not attenuated in any subgroup and was slightly enhanced in the calcium antagonist subgroup (-29% to -44%, p = 0.06) when compared with patients taking no antihypertensive agents (-24% to -40%); this difference, however, was only of borderline significance. Patterns of lovastatin-induced increase in high-density lipoprotein cholesterol and decrease in triglycerides were not consistently different among the subgroups. Examination of mean changes in serum transaminases, mean changes in creatine kinase, and the proportion of patients discontinuing therapy for clinical adverse experiences did not indicate the presence of an interaction.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Antihypertensive Agents/administration & dosage , Calcium Channel Blockers/administration & dosage , Cholesterol, LDL/drug effects , Drug Therapy, Combination , Lovastatin/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Cholesterol, LDL/blood , Diuretics/administration & dosage , Double-Blind Method , Drug Evaluation , Drug Interactions , Female , Humans , Male , Middle Aged , Triglycerides/blood
5.
Am J Med ; 91(1B): 25S-30S, 1991 Jul 31.
Article in English | MEDLINE | ID: mdl-1831006

ABSTRACT

This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step 1 Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase greater than 3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatinine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lovastatin-treated patients (29-35%), and muscle symptoms were reported with similar frequency in all groups (7-9%). The combination of muscle symptoms with marked CK elevations (greater than 10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated.


Subject(s)
Hypercholesterolemia/drug therapy , Lovastatin/adverse effects , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Combined Modality Therapy , Creatine Kinase/blood , Dietary Fats/administration & dosage , Double-Blind Method , Drug Eruptions/epidemiology , Drug Eruptions/etiology , Female , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/epidemiology , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/diet therapy , Incidence , Lovastatin/administration & dosage , Lovastatin/therapeutic use , Male , Middle Aged , Muscular Diseases/blood , Muscular Diseases/chemically induced , Muscular Diseases/epidemiology , Nervous System Diseases/chemically induced , Nervous System Diseases/epidemiology
6.
Arch Intern Med ; 151(1): 43-9, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1985608

ABSTRACT

In the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, we evaluated the efficacy and safety of lovastatin in 8245 patients with moderate hypercholesterolemia. Patients were randomly assigned to receive placebo or lovastatin at a dosage of 20 mg once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for 48 weeks. Lovastatin produced sustained, dose-related (P less than .001) changes as follows (for dosages of 20 to 80 mg/d): decreased low-density lipoprotein-cholesterol level (24% to 40%), increased high-density lipoprotein-cholesterol level (6.6% to 9.5%), decreased total cholesterol level (17% to 29%), and decreased triglyceride level (10% to 19%). The National Cholesterol Education Program's low-density lipoprotein-cholesterol level goal of less than 4.14 mmol/L (160 mg/dL) was achieved by 80% to 96% of patients, while the less than 3.36 mmol/L (130 mg/dL) goal was achieved by 38% to 83% of patients. The difference between lovastatin and placebo in the incidence of clinical adverse experiences requiring discontinuation was small, ranging from 1.2% at 20 mg twice daily to 1.9% at 80 mg/d. Successive transaminase level elevations greater than three times the upper limit of normal were observed in 0.1% of patients receiving placebo and 20 mg/d of lovastatin, increasing to 0.9% in those receiving 40 mg/d and 1.5% in those receiving 80 mg/d of lovastatin (P less than .001 for trend). Myopathy, defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal, was found in only one patient (0.1%) receiving 40 mg once daily and four patients (0.2%) receiving 80 mg/d of lovastatin. Thus, lovastatin, when added after an adequate trial of a prudent diet, is a highly effective and generally well-tolerated treatment for patients with moderate hypercholesterolemia.


Subject(s)
Hypercholesterolemia/drug therapy , Lipoproteins/blood , Lovastatin/therapeutic use , Adult , Aged , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Creatine Kinase/metabolism , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Hypercholesterolemia/blood , Liver Function Tests , Lovastatin/adverse effects , Male , Middle Aged , Muscular Diseases/chemically induced , Patient Compliance , Triglycerides/blood
7.
J Behav Med ; 12(5): 425-33, 1989 Oct.
Article in English | MEDLINE | ID: mdl-2614820

ABSTRACT

Social and psychological variables are used to explain why young people become cigarette smokers, whereas biological factors have been virtually ignored as possible determinants of that behavior. In this study, salivary testosterone was positively associated with cigarette smoking among 201 subjects 12-14 years of age. This finding suggests that testosterone should be included in future considerations of adolescent cigarette smoking.


Subject(s)
Saliva/metabolism , Smoking/metabolism , Testosterone/metabolism , Adolescent , Humans , Male , Regression Analysis
8.
Am J Epidemiol ; 130(2): 327-37, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2665477

ABSTRACT

This study assessed the validity of self-reports of smokeless tobacco use by adolescents and the validity of cotinine as a measure of adolescent cigarette smoking. For a sample of 1,854 persons aged 12-14 years living in the southeastern United States in 1985, a combination of three biochemical measures (salivary cotinine, salivary thiocyanate, and alveolar carbon monoxide) and self-reports of cigarette smoking were used to identify subjects who used only smokeless tobacco and subjects who did not use smokeless tobacco. The sensitivity and specificity of self-reports of smokeless tobacco use were 40.8% and 97.9%, respectively. It was determined that of the 175 subjects who ordinarily would be considered smokers because they had salivary cotinine levels greater than or equal to 10 ng/ml, 43.4% used only smokeless tobacco.


Subject(s)
Adolescent Behavior , Cotinine/analysis , Nicotiana , Plants, Toxic , Predictive Value of Tests , Pyrrolidinones/analysis , Smoking/epidemiology , Tobacco, Smokeless , Adolescent , Carbon Monoxide/pharmacokinetics , Cotinine/pharmacokinetics , Humans , Male , Saliva/analysis , Sensitivity and Specificity , Sex Factors , Surveys and Questionnaires , Thiocyanates/pharmacokinetics , United States
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