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Biomedical subjects

D B Hunninghake

Publications and source records attributed to D B Hunninghake.

At least 91 records · Page 5Linked to original sources
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

Cholesterol-lowering effects of soluble-fiber cereals as part of a prudent diet for patients with mild to moderate hypercholesterolemia.

Soluble-fiber breakfast cereals were examined for their cholesterol-lowering ability in 58 male patients with mild to moderate hypercholesterolemia in a randomized, double-blind, placebo-controlled study. Patients followed a step 1 diet for a minimum of 6 wk, then were randomly assigned to groups incorporating either corn flakes or one of two soluble-fiber cereals (pectin enriched or psyllium enriched) in the diet for an additional 6 wk. During the diet-only phase, total cholesterol dropped 3.8%. During the cereal-plus-diet phase, total and LDL cholesterol values of the pectin-enriched cereal group dropped an additional 2.1% (P = 0.243) and 3.9% (P = 0.16), respectively, and they dropped 5.9% (P = 0.005) and 5.7% (P = 0.034), respectively, in the psyllium-enriched cereal group. During the cereal-plus-diet phase, no significant effects on HDL cholesterol, triglyceride, or body weight were found within or between any cereal groups. These results support use of soluble-fiber cereals as an effective and well-tolerated part of a prudent diet in the treatment of mild to moderate hypercholesterolemia.

Adult↗
PubMed1990

Drug treatment of dyslipoproteinemia.

The bile-acid sequestrants, nicotinic acid and lovastatin, are the most effective drugs for lowering LDL-cholesterol. Nicotinic acid and gemfibrozil are more effective for lowering triglycerides and increasing HDL. Important considerations for proper selection of drugs in the treatment of the various dyslipoproteinemias are presented. Currently available drugs now permit effective control of blood lipid and lipoprotein levels.

Bile Acids and Salts↗
PubMed1989

Cholesterol-lowering effects of psyllium hydrophilic mucilloid. Adjunct therapy to a prudent diet for patients with mild to moderate hypercholesterolemia.

Psyllium hydrophilic mucilloid was examined for its ability to lower serum cholesterol levels in hypercholesterolemic patients. Seventy-five patients with mild to moderate hypercholesterolemia were evaluated in this randomized, double-blind, placebo-controlled parallel study. Patients were treated with a Step I diet for 12 weeks before receiving placebo or 3.4 g of psyllium (equivalent to 1 teaspoon) three times per day for 8 weeks. Compared with placebo, psyllium achieved an additional 4.8% reduction in total cholesterol level, 8.2% reduction in low-density lipoprotein cholesterol level, and 8.8% reduction in apolipoprotein B level. Psyllium did not significantly affect blood pressure or levels of high-density cholesterol, triglycerides, serum glucose, or iron. Reported adherence to diet and treatment was excellent, and no significant adverse side effects were noted. These results indicate psyllium hydrophilic mucilloid is an effective and well-tolerated adjunct to diet in the management of mild to moderate hypercholesterolemia.

Adult↗
PubMed1989

Comparative effects of prazosin and propranolol on blood lipid profiles in hypertensive, hypercholesterolemic patients. Preliminary results.

Preliminary results are presented for the first 13 patients to complete an ongoing crossover study comparing the effects of prazosin and propranolol on blood pressure control, in which blood lipid profiles were monitored. The study population consisted predominantly of white men (mean age, 67.5 years) with mild-to-moderate hypertension and coexisting hypercholesterolemia (mean plasma cholesterol level, 244 mg/dl). Both agents resulted in statistically significant reductions in diastolic blood pressure. It is recognized that with prazosin use, there are generally no adverse changes noted between pre- and post-treatment lipid levels. The results of this study demonstrated a 243.5 mg/dl total cholesterol level at baseline and 229.5 mg/dl maintenance levels following prazosin treatment. In contrast, the results following propranolol treatment showed a tendency to increase plasma levels of triglycerides and very low-density lipoprotein cholesterol, and to reduce levels of high-density lipoprotein cholesterol and high-density lipoprotein2 cholesterol. Because of a great deal of variability in lipid responsiveness to the study drug, none of the above changes attained statistical significance. Additional data from this ongoing study are required to confirm these preliminary observations.

Adult↗
PubMed1989

Fenofibrate for the treatment of type IV and V hyperlipoproteinemias: a double-blind, placebo-controlled multicenter US study.

The results of a randomized, double-blind, placebo-controlled multicenter trial of fenofibrate in the treatment of type IV/V hyperlipoproteinemia are reported. Ten study centers in the United States recruited 147 adults with a history of type IV or V hyperlipoproteinemia. After a six- to 12-week dietary stabilization period and a four-week placebo period, patients whose 12-hour fasting total plasma triglyceride levels ranged from 350 to 1,500 mg/dl were continued in the study; 55 patients with levels of 350 to 499 mg/dl were placed in group A and 92 with levels of 500 to 1,500 mg/dl in group B. Patients in each group were randomly assigned to receive 100 mg of fenofibrate or placebo three times daily for eight weeks. In both groups A and B fenofibrate-treated patients showed statistically significant reductions in levels of total cholesterol, very-low-density lipoprotein cholesterol, total triglycerides, and very-low-density lipoprotein triglycerides, and significant increases in high-density lipoprotein cholesterol; patients in group B also showed a significant increase in low-density lipoprotein cholesterol levels. Sixteen of the 75 fenofibrate-treated patients and 11 of the 72 placebo patients reported adverse events that were potentially drug related; most of these were gastrointestinal and a few reported musculoskeletal and skin reactions. It is concluded that fenofibrate is an effective and safe agent in the treatment of type IV/V hyperlipoproteinemia.

Adolescent↗
PubMed1989

Safety of long-term large doses of aspartame.

Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a randomized, double-blind, placebo-controlled, parallel-group design in 108 male and female volunteers aged 18 to 62 years. Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks. No persistent changes over time were noted in either group in vital signs; body weight; results of standard laboratory tests; fasting blood levels of aspartame's constituent amino acids (aspartic acid and phenylalanine), other amino acids, and methanol; or blood formate levels and 24-hour urinary excretion of formate. There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject. These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day.

Adolescent↗
PubMed1988

Altered platelet deformability in patients with type IIa and type IV hyperlipoproteinemia.

Platelets from subjects with hyperlipoproteinemia (HLP) differ from normal platelets in lipid composition and function depending upon the phenotypic classification of the HLP. The present study has evaluated the deformability of platelets from human subjects with type IIa and type IV HLP. Platelets suspended in autologous plasma diluted 30-fold with buffer were aspirated into micropipettes 0.7-0.8 microns in diameter by step-wise increment in tension, and the resulting extension lengths were recorded. Platelets from type IIa subjects could not be aspirated as far into the micropipettes as normal platelets. However, less tension was required to reach maximum cell extension than with normal platelets, and the initial extension lengths and slopes of the stress responses were the same as the control. In contrast, platelets from subjects with type IV HLP showed a generalized increase in deformability. The initial cell extensions aspirated from type IV platelets were longer than normal, and larger maximum cell extensions were achieved at lower tensions than control platelets. The type IV platelets were also mechanically fragile and fragmented at lower tensions than control or type IIa platelets. The variance in platelet deformability between subjects of the same phenotype was not directly correlated to plasma lipid or lipoprotein concentrations. This study confirms alterations in the structural organization of platelets from subjects with type IIa and type IV HLP.

Blood Platelets↗
PubMed1988

Intestinal HMG-CoA reductase activity is low in hypercholesterolemic patients and is further decreased with lovastatin therapy.

Significant cholesterol synthesis occurs in gut mucosa of animals and humans. However, the role of gut synthesis in hypercholesterolemia and the effect of drugs on this function have not been defined. We obtained jejunal biopsies and bile samples from 21 Type II hypercholesterolemic subjects (mean serum cholesterol = 331 mg/dl) on a low fat diet after an over-night fast. Whole gut mucosal homogenate was assayed for activity of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, the rate-determining enzyme of cholesterol synthesis. Mean reductase activity (pmol/mg per min) was 5.5 +/- 1.0 (n = 21) in hypercholesterolemic subjects versus 11.3 +/- 1.0 in 52 normal subjects (P less than 0.01). This is consistent with the hypothesis that the primary defect in these patients is not excessive cholesterol synthesis but decreased low density lipoprotein (LDL) clearance. It implies that high LDL levels down-regulate gut reductase activity. After treatment of 7 patients with lovastatin (40-80 mg/day for at least 6-13 weeks), gut reductase activity decreased from 7.7 +/- 2.6 to 3.6 +/- 0.5 (P less than 0.05), in biopsies obtained 12 hr after the last drug dose. Inhibition of reductase activity by this drug was detected 12 hr after a dose, and the enzyme was not measurably induced during 6-13 weeks of therapy. In keeping with the decrease in serum cholesterol (332----239 mg/dl) and mucosal reductase activity during lovastatin therapy, mean gallbladder bile cholesterol saturation index also decreased (1.045 +/- 0.112 vs. 0.883 +/- 0.109, n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1987

Effect of fibric acid derivatives on blood lipid and lipoprotein levels.

The literature for the last seven years was reviewed in terms of the effect of the various fibric acid derivatives on blood lipid and lipoprotein levels. The criteria for review resulted in a greater focus on three of the newer fibric acid derivatives: bezafibrate, ciprofibrate, fenofibrate. In type II A hyperlipoproteinemia, all fibric acid derivatives produce modest reductions in total plasma cholesterol and low-density lipoprotein cholesterol. The evidence suggests that bezafibrate, ciprofibrate, and fenofibrate may produce greater reductions in low-density lipoprotein cholesterol than those usually observed with clofibrate and gemfibrozil. All fibric acid derivatives produce modest reductions in triglycerides and modest increases in high-density lipoprotein cholesterol in type II A hyperlipoproteinemia. In type II B hyperlipoproteinemia, the low-density lipoprotein cholesterol lowering effect of fibric acid derivatives is generally less than that observed in type II A hyperlipoproteinemia. In type II B hyperlipoproteinemia, there is a mean decrease in low-density lipoprotein cholesterol for all patients studied. However, there is a considerable interpatient variation ranging from significant decreases to significant increases in low-density lipoprotein cholesterol. Further studies are required to assess whether the low-density lipoprotein cholesterol lowering effect is greater with the newer fibric acid derivatives. All fibric acid derivatives produce clinically significant decreases in triglyceride levels in type II B. There is also an associated increase in high-density lipoprotein cholesterol. In type IV hyperlipoproteinemia, all fibric acid derivatives produce clinically significant reductions in triglyceride. There is also an associated increase in high-density lipoprotein cholesterol and generally also an increase in low-density lipoprotein cholesterol levels. The available data do not suggest a clinically significant difference in the hypotriglyceridemic effect of the various fibric acid derivatives in type IV hyperlipoproteinemia. The lipid-altering effects of the various fibric acid derivatives were usually less in those studies that contained placebo and dietary controls. Additional controlled clinical trials are needed to accurately discriminate the relative lipid-and lipoprotein-altering effects of the various fibric acid derivatives.

Anticholesteremic Agents↗
PubMed1987

Recruitment experience in clinical trials: literature summary and annotated bibliography.

A literature review was conducted to determine what problems exist in accruing adequate numbers of patients for clinical trials. Accrual rates are often not clearly reported, and most studies report that the time period for accrual was extended. Delays in recruitment have an impact on costs and workload throughout the trial. Other problems with the recruitment outcomes include miscalculations in the number of eligible participants in the total population, variations in yield from different types of recruitment sources, and level of community awareness. Planning for recruitment should be part of the overall trial design. Ideally, recruitment planning should be conducted in harmony between the national and local levels. Local community members should be involved. Data-based management of recruitment is necessary and should include a comprehensive data monitoring system with strong administrative support at both central and local levels. Recruitment goals and provisions for corrective action if recruitment lags should be included. Socioeconomic characteristics and attitudes of patients and physicians should be considered in recruitment efforts because they can affect patient participation during all phases of the study.

Bibliographies as Topic↗
PubMed1987

Recruitment in NHLBI population-based studies and randomized clinical trials: data analysis and survey results.

Data on screening and recruitment from current and previous NHLBI population-based studies (PBSs) and randomized clinical trials (RCTs) were examined. In only two of the studies examined was the projected recruitment completed within the planned recruitment period. The shape of the graph of the relation between enrollment of participants and time varies by study. A single summary statistic for measuring the efficiency of recruitment in RCTs and PBSs is proposed and applied to the examined studies. In addition to providing summary data on recruitment for several studies, this article reports the survey results of a questionnaire sent to the coordinating centers of currently and previously funded National Heart, Lung, and Blood Institute and Veteran's Administration studies. The purpose was to ascertain the desirability of recommending that a generic core of information be collected on recruitment and screening in future studies. Most respondents believed that comparing data collected uniformly and prospectively might be helpful in designing further studies. The variables most respondents believed to be potentially useful are described.

Clinical Trials as Topic↗
PubMed1987

Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia. A multicenter study.

STUDY OBJECTIVE: To evaluate the efficacy and tolerability of lovastatin under controlled conditions in heterozygous familial hypercholesterolemia. DESIGN: Randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Five lipid clinics with a central laboratory and coordinating center. PATIENTS: 101 adult patients with heterozygous familial hypercholesterolemia. INTERVENTIONS: Patients were on a lipid-lowering diet throughout the study. After a 4-week placebo baseline period, patients were randomized to five equal treatment groups. Each group received a different sequence of placebo or lovastatin 5 to 40 mg twice daily or 20 to 40 mg once daily in the evening, during three consecutive 6-week periods. MEASUREMENTS AND MAIN RESULTS: The mean reductions in total plasma cholesterol and low-density lipoprotein cholesterol across the dosage ranges were 14% to 34% and 17% to 39%, respectively (p compared with zero and placebo less than 0.01). High-density lipoprotein cholesterol and apolipoproteins AI and AII rose slightly. Apolipoprotein B fell substantially at the higher dosage levels (-23% at 40 mg twice daily, p less than 0.01), indicating a reduction in the concentration of circulating low-density lipoprotein particles. Maximum response was achieved in 4 to 6 weeks. Twice-daily dosing was slightly more efficient than once-daily dosing. Of those patients receiving 40 mg twice a day, 89% had a fall in low-density lipoprotein cholesterol of at least 20%, and 61% had a fall of at least 40%. Adverse effects attributable to lovastatin were minimal, and no patient was withdrawn from the study. CONCLUSION: Lovastatin was well tolerated and effective in the treatment of familial hypercholesterolemia.

Adult↗