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Biomedical subjects

W V Brown

Publications and source records attributed to W V Brown.

At least 37 records · Page 2Linked to original sources
PubMed1997

Rationale, design, and baseline characteristics of a trial comparing aggressive lipid lowering with Atorvastatin Versus Revascularization Treatments (AVERT).

This study describes the design, methodologic features, and baseline characteristics of an open-label randomized trial to determine whether aggressive lipid-lowering therapy with atorvastatin is an alternative to angioplasty or other catheter-based revascularization procedures in patients with significant coronary artery disease. Three-hundred forty-one patients with low-density lipoprotein (LDL) cholesterol > or = 115 mg/dl and > or = 1 defined narrowing of a major coronary artery were randomized to atorvastatin or the indicated catheter-based revascularization and conventional care (including lipid-lowering therapy if prescribed). Ischemic events are tracked for 18 months. The primary efficacy parameter is the incidence of an ischemic event, defined as 1 of the following: cardiovascular death, cardiac arrest, nonfatal myocardial infarction, the need for coronary bypass grafting or angioplasty, cerebrovascular accident, and worsening angina verified by objective evidence requiring hospitalization (including unstable angina).

Angioplasty, Balloon, Coronary↗
PubMed1997

Hypercholesterolemia in the United States: how far have we come?

In a series of clinical trials and epidemiologic studies over the past 30 years, clear associations have been established between saturated fat in the diet, elevated serum cholesterol levels, and the risk of coronary heart disease (CHD). This understanding has been applied in intervention trials using diet, exercise, and drugs to lower cholesterol. The National Cholesterol Education Program was established in 1985 to coordinate efforts to make U.S. citizens aware of the risks of elevated cholesterol and to provide guidelines for lowering it. Trials over the last several years have demonstrated benefit of cholesterol lowering in secondary prevention and producing regression of coronary lesions. While much progress has been made, we are still far from the goal of eliminating hypercholesterolemia in the United States. Improved educational efforts and new strategies for cholesterol management are needed.

Clinical Trials as Topic↗
PubMed1997

Basic demographic and professional characteristics of US women physicians.

Women physicians are a rapidly growing percentage of the physician population in the United States; yet, their fundamental characteristics and largely unknown. The Women Physicians' Health Study is the first large, national study of US women physicians, comprising a random sample (n = 4,501 respondents) of women physicians aged 30 to 70. Data from the Women Physicians' Health Study showed that African-American and Latina or Hispanic physicians were underrepresented, and Asian-American and foreign-born physicians were overrepresented in proportion to their prevalence in the US female population. Women physicians were more likely to be married and less likely to have never married and less likely to have never married or to be divorced or widowed than other US women. Younger physicians were more likely to be residency trained and board-certified and to work more hours per week than older physicians. Younger physicians were also less likely to be in solo practice, government work, or inactive; they tended to be concentrated in group or hospital-based practices. We found that although US women physicians have some common characteristics that differentiate them from other US women, their practice and other characteristics vary substantially by age and specialty in ways that have not previously been reported.

Adult↗
PubMed1997

Protocol for the preparation of a segmental linear polyacrylamide gradient gel: simultaneous determination of Lp[a], LDL, and HDL particle sizes.

We describe in this report a protocol for the preparation of a polyacrylamide gel system (S-GGE 2.8/8.30) that consists of two linear gradients designed for the simultaneous determination of the diameters of LDL and HDL from whole plasma. The lower gel consists of an 8-30% linear gradient which is optimum for the resolution of HDL subfractions and the upper gel consists of a 2-8% linear gradient to allow for the resolution of LDL and larger lipoprotein fractions such as Lp[a] and small VLDL. In contrast to other non-denaturing gradient gel systems which are based on protein staining, the present system uses lipid stain to specifically identify lipoproteins. This approach also allows the plasma to be pre-stained with immediate visualization of the lipid bands being possible at the completion of the electrophoretic run. Using commercially available gel casting equipment, the present gradient gel system can accommodate up to 21 lanes per gel. The inter-run and intra-run coefficients of variation for LDL particle size are 0.47 and 0.16%, respectively. The inter- and intra-run CVs for Lp[a] particle size are 0.92% and 0.89%, respectively. The inter-run and intra-run coefficients of variation for HDL2 and HDL3 particle size are 1.36% and 3.23%, respectively.

Calibration↗
PubMed1996

Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia.

OBJECTIVE: To assess the lipid-lowering effect of atorvastatin (a new 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitor) on levels of serum triglycerides and other lipoprotein fractions in patients with primary hypertriglyceridemia, determine if atorvastatin causes a redistribution of triglycerides in various lipoprotein fractions, and assess its safety by reporting adverse events and clinical laboratory measurements. DESIGN: Randomized double-blind, placebo-controlled, parallel-group, multicenter trial. SETTING: Community- and university-based research centers. PATIENTS: A total of 56 patients (aged 26 to 74 years) with a mean baseline triglyceride level of 6.80 mmol/L (603.3 mg/dL) and a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 3.07 mmol/L (118.7 mg/dL). INTERVENTIONS: Cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step I Diet) and either 5 mg, 20 mg, or 80 mg of atorvastatin, or placebo. MAIN OUTCOME MEASURES: Percent change from baseline in total triglycerides for three dose levels of atorvastatin compared with placebo. RESULTS: Mean reductions in total triglycerides between 5 mg, 20 mg, and 80 mg of atorvastatin and placebo after 4 weeks of treatment were -26.5%, -32.4%, -45.8%, and -8.9%, respectively. Mean reductions in LDL-C were -16.7%, -33.2%, -41.4%, and -1.4%, respectively, and very low-density lipoprotein cholesterol (VLDL-C) were -34.3%, -45.9%, -57.7%, and -5.5%, respectively. Similar mean changes in total apolipoprotein B (apo B) (-16.9%, -32.8%, -41.7%, and +1.0%), apo B in LDL (-14.8%, -29.8%, -42.0%, and -3.1%), and apo B in VLDL (-23.8%, -35.8%, -34.4%, and +11.7%) were observed. In addition, comparable mean changes in LDL triglycerides (-22.5%, -30.7%, -39.9%, and +3.9%) and VLDL triglycerides (-28.1%, -34.0%, -47.3%, and -10.8%) were seen. CONCLUSIONS: In atorvastatin treatment groups, total serum triglyceride levels decreased in a dose-dependent manner, reductions in the 20-mg and 80-mg groups were statistically significant (P < .05) compared with placebo. Atorvastatin did not cause a redistribution of triglycerides but consistently lowered triglycerides in all lipoprotein fractions. Atorvastatin was well tolerated.

Adult↗
PubMed1995

Niacin for lipid disorders. Indications, effectiveness, and safety.

Niacin can be very effective and safe in lowering low-density lipoprotein cholesterol and triglyceride levels and also in increasing high-density lipoprotein cholesterol levels. In combination with other lipid-lowering drugs (eg, bile acid sequestrants), it has reduced the incidence of cardiovascular events and stopped the progression of coronary artery lesions. It may be the most cost-effective lipid-lowering agent currently available. At lower doses, sustained-release forms of niacin may also improve patient compliance.

Contraindications↗
PubMed1994

Lipoprotein disorders in diabetes mellitus.

In IDDM or NIDDM, the total plasma cholesterol and triglycerides are usually within normal limits when the blood glucose is controlled. Marked hypertriglyceridemia can develop with loss of glycemic control and is often due to superimposed genetic abnormalities in lipoprotein metabolism. Tight control in IDDM usually reduces LDL and VLDL to normal levels and may raise HDL above the normal range. Low HDL cholesterol and mild to moderate elevations of VLDL triglyceride are common in NIDDM if obesity or proteinuria is also present. Both HDL and LDL may be smaller and more dense and may be enriched with triglyceride as compared with cholesterol. These abnormalities may require weight loss for control. The increased incidence of cardiovascular disease in diabetes is unexplained but is amplified by the well-defined cardiovascular risk factors. The new American Diabetes Association guidelines call for treatment of high triglycerides and LDL cholesterol to be aggressively reduced. Triglycerides should be under 200 mg/dL, are considered borderline high between 200 and 400 mg/dL, and high when above 400 mg/dL. Low HDL is defined as less than 35 mg/dL. Control of obesity with diet and exercise and reduced intake of saturated fat and cholesterol are important first steps. If needed, drug therapy is appropriate to reduce LDL to levels below 130 mg/dL in all adult diabetics and below 100 mg/dL in those with cardiovascular disease.

Arteriosclerosis↗
PubMed1992

When do we treat hypercholesterolemia?

Although the relationships between elevated total and low-density lipoprotein (LDL) cholesterol and coronary heart disease (CHD) are relatively well established and published treatment guidelines are available, clinicians face a number of complex issues when deciding whom to treat. Specific patient characteristics and potential risk factors, of which less is known, may influence treatment decisions. In this presentation, the current guidelines for treating patients with hypercholesterolemia are reviewed and therapeutic issues that must be considered when selecting patients for treatment are identified.

Adult↗
PubMed1992

When do we treat hypercholesterolemia?

Although the relationships between elevated total and low-density lipoprotein (LDL) cholesterol and coronary heart disease (CHD) are relatively well established and published treatment guidelines are available, clinicians face a number of complex issues when deciding whom to treat. Specific patient characteristics and potential risk factors, of which less is known, may influence treatment decisions. In this presentation, the current guidelines for treating patients with hypercholesterolemia are reviewed and therapeutic issues that must be considered when selecting patients for treatment are identified.

Age Factors↗
PubMed1992

A missense (Asp250----Asn) mutation in the lipoprotein lipase gene in two unrelated families with familial lipoprotein lipase deficiency.

We have identified the molecular basis for familial lipoprotein lipase (LPL) deficiency in two unrelated families with the syndrome of familial hyperchylomicronemia. All 10 exons of the LPL gene were amplified from the two probands' genomic DNA by polymerase chain reaction. In family 1 of French descent, direct sequencing of the amplification products revealed that the patient was heterozygous for two missense mutations, Gly188----Glu (in exon 5) and Asp250----Asn (in exon 6). In family 2 of Italian descent, sequencing of multiple amplification products cloned in plasmids indicated that the patient was a compound heterozygote harboring two mutations, Arg243----His and Asp250----Asn, both in exon 6. Studies using polymerase chain reaction, restriction enzyme digestion (the Gly188----Glu mutation disrupts an Ava II site, the Arg243----His mutation, a Hha I site, and the Asp250----Asn mutation, a Taq I site), and allele-specific oligonucleotide hybridization confirmed that the patients were indeed compound heterozygous for the respective mutations. LPL constructs carrying the three mutations were expressed individually in Cos cells. All three mutant LPLs were synthesized and secreted efficiently; one (Asp250----Asn) had minimal (approximately 5%) catalytic activity and the other two were totally inactive. The three mutations occurred in highly conserved regions of the LPL gene. The fact that the newly identified Asp250----Asn mutation produced an almost totally inactive LPL and the location of this residue with respect to the three-dimensional structure of the highly homologous human pancreatic lipase suggest that Asp250 may be involved in a charge interaction with an alpha-helix in the amino terminal region of LPL. The occurrence of this mutation in two unrelated families of different ancestries (French and Italian) indicates either two independent mutational events affecting unrelated individuals or a common shared ancestral allele. Screening for the Asp250----Asn mutation should be included in future genetic epidemiology studies on LPL deficiency and familial combined hyperlipidemia.

Amino Acid Sequence↗
PubMed1991

Molecular cloning of mouse hepatic triacylglycerol lipase: gene expression in combined lipase-deficient (cld/cld) mice.

cDNA clones coding for mouse hepatic triacylglycerol lipase (HL) were isolated from a mouse liver cDNA library with a human HL cDNA as a probe. The cloned HL cDNA of 1652 nucleotides predicts a mature protein of 488 amino acids preceded by a signal peptide of 22 amino acids. Two potential sites for N-glycosylation are identified, which are both conserved in rat and human HL. Combined lipase deficiency (cld) is a recessive mutation in mice, which causes the functional deficiency of HL and lipoprotein lipase, the isolated cDNA was used to study the expression of HL gene in cld/cld mice. Northern blot analysis of total cellular RNA from livers of cld/cld and normal mice showed that there are two mRNA species for HL with the sizes of 1.8 and 1.9 kilobases in both groups. However, the mRNA for HL was more abundant in cld/cld than in normal mice. RNase A protection assay of HL mRNA suggested that the multiple mRNA species for HL in cld/cld and normal mice are generated by differential utilization of polyadenylation signals and that there is no mutation in the structural gene for HL in cld/cld mice. The present study supports our hypothesis that the defect of HL activity in cld/cld mice is caused by abnormal post translational modification or processing of the lipase.

Amino Acid Sequence↗
PubMed1991

Effect of acute intravenous alcohol on plasma lipoproteins in man.

The effect of acute administration of ethanol was determined on plasma lipoproteins and post-heparin lipolytic activities in six normal subjects. Ethanol was administered intravenously (IV) in a dose of 0.6 g/kg body weight over 1 hour and blood samples were obtained for 4 hours thereafter. In four subjects, the determinations were repeated after the infusion of an isovolumetric amount of saline. Ethanol resulted in a rapid increase in plasma triglycerides, which persisted throughout the study. Ethanol did not result in changes in high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, or apolipoprotein administration of heparin. The increase in triglycerides without changes in HDL-cholesterol after acute ethanol administration may contribute to an increased severity of cardiovascular disease in binge drinkers.

Adult↗