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Biomedical subjects

D B Hunninghake

Publications and source records attributed to D B Hunninghake.

At least 73 records · Page 4Linked to original sources
PubMed1994

Hyperlipidemia in long-term survivors of pediatric renal transplantation.

The prevalence of hyperlipidemia in adolescents and young adults who are long-term survivors of pediatric renal transplantation with stable graft function has not previously been examined. We studied 33 renal transplant recipients aged 5 to 23 years, who were an average of 7.4 years (range 3 to 11 years) post-transplant. We found hypercholesterolemia in 17 (total cholesterol (TC) > 5.18 mmol/l). Both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were increased, such that the mean TC/HDL-C and apolipoprotein B/apolipoprotein A1 (Apo B/Apo A1) ratios were below levels associated with increased coronary artery disease risk. Subjects with hypercholesterolemia did not differ from those with normal cholesterol values in current age or age at transplant, serum creatinine, serum albumin, serum triglycerides, HDL-C, TC/HDL-C ratio, Apo B/Apo A1 ratio, prednisone dose, body mass index, gender, use of thiazides or beta blockers, or family history of premature atherosclerosis. Coronary risk factors appear to cluster in these patients, with hypertension in 53% of those with hypercholesterolemia. Lipid profiles were not different in patients treated with prednisone-azathioprine vs. prednisone-azathioprine-cyclosporine A immunosuppression. A significant correlation was found between prednisone dose (mg/m2) and TC, LDL-C and TC/HDL-C. According to National Cholesterol Education Program guidelines, 32% of these long-term survivors of pediatric renal transplantation warrant at least dietary intervention and 10% are candidates for treatment with lipid-lowering drugs. This proportion is likely to increase as the safety of lipid-lowering agents is established in younger children.

Adolescent↗
PubMed1993

Comparative effects of atenolol versus celiprolol on serum lipids and blood pressure in hyperlipidemic and hypertensive subjects.

Antihypertensive drugs may affect serum lipoprotein levels in mixed populations but data in hyperlipidemic patients are scanty. Atenolol versus celiprolol effects on serum lipoproteins were compared in 159 hyperlipoproteinemic hypertensive patients. This was a randomized, double-blind, parallel-group, positive-controlled multicenter trial with centralized lipoprotein laboratory and diet constancy monitoring. Blood pressure reduction and serum lipoprotein and apoprotein levels were monitored for 3 months. Both drugs reduced systolic and diastolic blood pressures. Atenolol had greater effects than celiprolol on diastolic pressure, but effects on systolic blood pressure were not different. Patients receiving atenolol had lower serum high-density lipoprotein cholesterol levels and higher low-density lipoprotein/high-density lipoprotein cholesterol ratios, whereas patients treated with celiprolol showed no contrasting changes. These differences in lipoprotein levels between drug treatment groups were statistically significant at weeks 9 and 12. The difference between drug treatments was also significant if the values of the 9- and 12-week visits were averaged. Patients taking atenolol had statistically significantly higher serum levels of total cholesterol, triglycerides and apoprotein B at 9 weeks. These divergent directional changes were consistent throughout and statistically significantly different between drugs.

Adult↗
PubMed1993

The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia.

BACKGROUND: A diet low in saturated fat and cholesterol is the standard initial treatment for hypercholesterolemia. However, little quantitative information is available about the efficacy of dietary therapy in clinical practice or about the combined effects of diet and drug therapy. METHODS: One hundred eleven outpatients with moderate hypercholesterolemia were treated at five lipid clinics with the National Cholesterol Education Program Step 2 diet (which is low in fat and cholesterol) and lovastatin (20 mg once daily), both alone and together. A diet high in fat and cholesterol and a placebo identical in appearance to the lovastatin were used as the respective controls. Each of the 97 patients completing the study (58 men and 39 women) underwent four consecutive nine-week periods of treatment according to a randomized, balanced design: a high-fat diet-placebo period, a low-fat diet-placebo period, a high-fat diet-lovastatin period, and a low-fat diet-lovastatin period. RESULTS: The level of low-density lipoprotein (LDL) cholesterol was a mean of 5 percent (95 percent confidence interval, 3 to 7 percent) lower during the low-fat diet than during the high-fat diet (P < 0.001). With lovastatin therapy as compared with placebo, the reduction was 27 percent. Together, the low-fat diet and lovastatin led to a mean reduction of 32 percent in the level of LDL cholesterol. The level of high-density lipoprotein (HDL) cholesterol fell by 6 percent (95 percent confidence interval, 4 to 8 percent) during the low-fat diet (P < 0.001) and rose by 4 percent during treatment with lovastatin (P < 0.001). The ratio of LDL to HDL cholesterol and the level of total triglycerides were reduced by lovastatin (P < 0.001), but not by the low-fat diet. CONCLUSIONS: The effects of the low-fat-low-cholesterol diet and lovastatin on lipoprotein levels were independent and additive. However, the reduction in LDL cholesterol produced by the diet was small, and its benefit was possibly offset by the accompanying reduction in the level of HDL cholesterol.

Apolipoproteins↗
PubMed1993

Finasteride, a steroid 5 alpha-reductase inhibitor, does not affect the oxidative metabolism of antipyrine.

A single-blind study was conducted to investigate the effect of multiple doses of finasteride, a 5 alpha-reductase inhibitor for the treatment of benign prostatic hyperplasia, on the single-dose pharmacokinetics of antipyrine. Twelve patients with benign prostatic hyperplasia received a total of four single oral doses of 18 mg/kg antipyrine before, during, and after treatment with 10 mg/day of finasteride for 28 days. Finasteride had no effect on antipyrine concentration profiles. There were also no changes in urinary excretion of three principal antipyrine metabolites. A slight increase in renal clearance of antipyrine was observed; however, this is not considered relevant because excretion of unchanged antipyrine represents a minor fraction of total elimination and is not directly related to oxidative metabolism. These results imply that significant interactions between finasteride and drugs metabolized by these cytochrome P-450 enzymes are unlikely.

Administration, Oral↗
PubMed1993

Effects of one year of treatment with pravastatin, an HMG-CoA reductase inhibitor, on lipoprotein a.

Lipoprotein a [Lp(a)] has emerged as a critical factor in the assessment of cardiovascular risk. In the study reported here, Lp(a) concentrations were monitored in patients taking pravastatin, a new hydrophilic, HMG-CoA reductase inhibitor. A cohort of patients with frozen plasma aliquots at baseline, week 12 of the double-blind therapy, and week 48 of open-label therapy (1 years' treatment) was selected from 306 participants in a phase 2 dose-ranging study of pravastatin. The 125 men and women in the cohort had mean low-density lipoprotein cholesterol (LDL-C) concentrations of at least 150 mg/dL (3.88 mmol/L), and mean plasma triglyceride concentrations less than 250 mg/dL (2.82 mmol/L) during the baseline diet phase. During the double-blind phase, 46 patients received placebo, and 79 received pravastatin 10, 20, or 40 mg daily. Only the 79 pravastatin-treated patients in the cohort continued in the 48-week open-label study of pravastatin. During the double-blind phase, Lp(a) decreased 4.6% in patients taking placebo, and 0.4% in patients taking pravastatin. Net change was not significant. At week 48, in the patients taking pravastatin, Lp(a) had increased 2.4%, a difference that again was not statistically significant. Low-density lipoprotein cholesterol (-33.6%), total cholesterol (-25.6%), triglycerides (-19.9%), high-density lipoprotein cholesterol (HDL-C) (+7.0%), apolipoprotein A-I (+13.3%), and apolipoprotein B (-33.0%) changed significantly (P < .01). Among 19 patients with baseline Lp(a) levels greater than 30 mg/dL, Lp(a) decreased insignificantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Factors influencing the development of hypercholesterolemia after cardiac transplantation.

Although hypercholesterolemia is a frequent complication in cardiac transplant recipients, the exact mechanisms contributing to its development are not known. Cholesterol levels in 151 thoracic transplant patients treated with cyclosporine, azathioprine and prednisone were retrospectively examined to evaluate the factors influencing the heterogeneity of changes after the first year after transplantation in patients on a standard 3-drug immunosuppression regimen. Three groups were compared including ischemic heart transplant (n = 72), nonischemic heart transplant (n = 64) and heart-lung/lung transplant (n = 15) recipients. After the first year, 64 patients (43%) developed consistent hypercholesterolemia (greater than 240 mg/dl) for which pharmacologic treatment was initiated. Forty-eight patients (67%) in the ischemic heart transplant group required treatment, significantly (p less than 0.001) greater than both the nonischemic (n = 14; 22%) and heart-lung/lung transplant (n = 2; 13%) group. Univariate and forward stepwise multivariate regression analysis identified 4 factors that were all significantly and independently correlated with follow-up cholesterol including prednisone dose (p less than 0.001), baseline cholesterol (p less than 0.001), glucose (p less than 0.001) and weight gain (p less than 0.01). Changes in triglycerides in the 3 groups of patients were similar to changes in cholesterol. Furthermore, the increase in cholesterol in patients requiring treatment was primarily due to an increase in low-density lipoprotein cholesterol. These data demonstrate that hypercholesterolemia is common in heart transplant recipients treated with standard 3-drug immunosuppression and generally develops within the first 2 years after transplantation. However, this complication is not uniform and appears to be most strongly related to previous coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of gemfibrozil on composition of lipoproteins and distribution of LDL subspecies.

We studied the effect of gemfibrozil on the compositions of VLDL, LDL and distribution of LDL subspecies in type II hyperlipidemic patients. Gemfibrozil significantly lowered serum triglyceride levels in this group of patients who had normal to moderately elevated triglyceride prior to therapy. Gemfibrozil also changed the composition of VLDL by lowering its free cholesterol, cholesterol ester and raising the protein content. In contrast, no measurable changes in LDL chemical composition were found following gemfibrozil therapy. Changes in LDL, however, can be detected using ultracentrifugal and electrophoretic methods. Peak densities of LDL were lowered and LDL subspecies shifted to larger, slower-moving bands on gradient gel electrophoresis in patients receiving gemfibrozil treatment. These results suggest that gemfibrozil treatment resulted in qualitative changes in both VLDL and LDL even in patients with moderately elevated baseline serum triglyceride levels.

Adult↗
PubMed1992

Evaluation of implementation of a cholesterol management program in physicians' offices.

This article describes an evaluation of the implementation of a cholesterol management program in family physicians' offices as part of the Physician-Based Nutrition Program to Lower Coronary Heart Disease Risk (PBNP). The evaluation, conducted through a partnership evaluation model, used multiple case study methodology and combined the use of quantitative and qualitative methods. Data sources included office staff reports and interviews, records of contacts with study personnel, patient care data, and patient telephone interviews. Data from these sources revealed gradual program implementation and considerable variation in practitioner and clinic involvement in cholesterol management. Clinic staff reported that the support provided by PBNP in the form of training, operations materials, patient education materials and ongoing assistance was very useful. This formative evaluation has implications for refinement of the PBNP and for other prevention programs in primary care settings. It demonstrates the feasibility and acceptability of a systems approach to physicians, cholesterol/nutrition educators and clinic support staff. It also suggests ways in which researchers and clinicians can implement and evaluate health care innovations.

Adult↗
PubMed1992

Appropriate days for measuring intake of dietary fat and cholesterol.

Seven consecutive day food records were assessed in 224 free-living adult volunteers to (1) identify the smallest number of days, and which days of the week, would provide most of the information about dietary fat and cholesterol intake (assessed by B score) and (2) whether a complex mathematical formula for weighting certain days was required to achieve reasonable validity. A factor analytic approach was used to identify 3- and 4-day sets. The correlations with the 7-day average B score ranged from 0.95 for the best 4-day (Saturday through Tuesday) average B score to 0.91 for the best 3-day (Sunday through Tuesday) average B score. Simple averaging (no weighting) was found to be adequate to achieve this level of validity.

Adult↗
PubMed1992

Intense dietary counseling lowers LDL cholesterol in the recruitment phase of a clinical trial of men who had coronary artery bypass grafts.

Intense dietary counseling lowered low-density-lipoprotein (LDL) cholesterol levels during the recruitment phase of a 5-year clinical trial of men who had undergone coronary artery bypass grafts. At visit 1, a 24-hour dietary recall was obtained and analyzed for intakes of total energy; total, saturated, monounsaturated, and polyunsaturated fat; and dietary cholesterol. Participants were then instructed to follow the National Cholesterol Education Program (NCEP) Step I diet. Additional dietary counseling was provided at 1-month intervals during visits 2 and 3. At visit 3, another 24-hour dietary recall was obtained and analyzed similarly. Of 59 men with an LDL cholesterol level greater than 4.5 mmol/L at visit 1, 52 decreased their level to 4.5 mmol/L or less to qualify for the 5-year study. Between visits 1 and 3, mean LDL cholesterol levels decreased significantly from 4.86 +/- 0.04 mmol/L to 4.27 +/- 0.05 mmol/L, which coincided with significant mean decreases in dietary intake of total fat from 33.4 +/- 1.3% to 25.2 +/- 1.4%, saturated fat from 11.1 +/- 0.6% to 7.0 +/- 0.4%, and dietary cholesterol from 122 +/- 6.1 to 90 +/- 6.3 mg/1,000 kcal. Overall, the dietary intake improved to more closely follow the NCEP Step II diet and resulted in a 10.7% decrease in total cholesterol level and a 12.4% decrease in LDL cholesterol level.

Adult↗
PubMed1992

Effects of long-term cholestyramine administration on vitamin D and parathormone levels in middle-aged men with hypercholesterolemia.

The objective of this study was to evaluate possible adverse effects of long-term bile acid-binding resin (cholestyramine) treatment on vitamin D, parathyroid hormone, and calcium levels in middle-aged men. A double-blind randomized clinical trial was carried out over a period of 7 to 10 years at the University of Minnesota's Lipid Research Clinic as part of the Lipid Research Clinic's Coronary Primary Prevention Trial. Two hundred and sixty-eight men aged 42 to 68 years who had been previously randomized in the CPPT to cholestyramine or placebo and who had taken at least 75% of the prescribed study medication (6 packets or 24 gm/day) as determined by packet counts for the duration of the Coronary Primary Prevention Trial including the last 4 months of the trial were studied: one group (n = 124) received cholestyramine and the other group (n = 144) received a corresponding dose of placebo. Serum samples were obtained at the time of the final study visit in cholestyramine and placebo groups. (Results are reported as mean +/- SD in SI units). There were no differences in plasma levels of calcium (2.3 +/- 0.1 mmol/L vs 2.3 +/- 0.1 mmol/L), phosphorus (0.99 +/- 0.14 mmol/L vs 0.98 +/- 0.12 mmol/L), albumin (45 +/- 3 gm/L vs 46 +/- 0.6 gm/L), calcifediol (62.6 +/- 29.2 nmol/L vs 63.4 +/- 28.4), 25(OH)D2 (14 +/- 11 nmol/L vs 12 +/- 10 nmol/L) or calcitriol (99 +/- 190 pmol/L vs 91 +/- 56 pmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1991

Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition on human gut mucosa.

Mevalonic acid is an important biochemical intermediate in cholesterol synthesis and other processes involved in cell replication. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the enzyme which catalyzes mevalonic acid synthesis. To determine whether a potent competitive inhibitor of this enzyme, the drug simvastatin, may have an adverse effect on enterocyte cell replication and cholesterol metabolism, small intestinal biopsies from nine hypercholesterolemic subjects were obtained before and during treatment with simvastatin as a lipid-lowering agent. Histologic review of biopsies in a blinded manner detected no change in ratio of villous length to crypt length or in mitotic index which might indicate altered cell replication. Similarly, no significant change in measured activity of HMG-CoA reductase activity was observed. In spite of the high exposure of jejunal mucosal cells to this potent competitive inhibitor of a key enzyme, no adverse effect on growth could be detected.

Anticholesteremic Agents↗
PubMed1991

Effects of celiprolol and other antihypertensive agents on serum lipids and lipoproteins.

The expected reduction in coronary heart disease morbidity and mortality has not been observed in intervention trials with antihypertensive agents, and attention has focused on the lipid and lipoprotein effects of antihypertensive agents. Diuretics, especially thiazides, chlorthalidone, and the loop diuretics, increase total and low-density lipoprotein cholesterol and triglyceride levels with generally no significant change in high-density lipoprotein cholesterol. Selective and nonselective beta-blockers decrease high-density lipoprotein cholesterol and increase triglyceride levels, whereas those with intrinsic sympathomimetic activity do not significantly alter lipid and lipoprotein levels. Celiprolol, a beta-blocker with vasodilatory effects, appears to favorably affect lipid and lipoprotein levels as do the alpha 1-adrenergic blockers. The other commonly used antihypertensive agents do not produce significant effects.

Adrenergic beta-Antagonists↗
PubMed1991

The effects of cardioselective vasodilating beta-blockers on lipids.

Ideally, an antihypertensive agent should have a neutral effect or, preferably, produce a favorable shift in the serum lipid and lipoprotein profile, which is associated with a decrease in coronary heart disease risk. The thiazides and loop diuretics increase total lipid levels, low-density lipoprotein (LDL) cholesterol, and triglycerides. beta-Blockers without beta 2-agonist properties increase triglycerides and decrease high-density lipoprotein (HDL) cholesterol levels. Calcium antagonists, angiotensin converting enzyme inhibitors, and combined alpha/beta-blockers are generally thought to have little effect on the lipid profile, although some studies have indicated a modest beneficial effect. alpha-Adrenoceptor antagonists are known to reduce LDL cholesterol levels modestly and to increase HDL cholesterol levels. The overall results of the currently available studies with celiprolol, a selective beta 1-antagonist with ancillary beta 2-agonist and vasodilating properties, indicate a favorable effect of the drug on serum lipid and lipoprotein profiles.

Adrenergic beta-Antagonists↗
PubMed1991

Effects of fluvastatin (XU 62-320), an HMG-CoA reductase inhibitor, on the distribution and composition of low density lipoprotein subspecies in humans.

We studied the effect of fluvastatin (XU 62-320), a new HMG-CoA reductase inhibitor, on the distribution of low density lipoprotein (LDL) subspecies and composition in humans. As expected, fluvastatin significantly lowered serum LDL levels (25% after 6 weeks of therapy). In addition, treatment with fluvastatin changed the LDL subspecies. In the group treated with fluvastatin, 38.5% of the individuals showed changes in the shape of LDL absorbance profile obtained from density gradient ultracentrifugation and 54% of the group showed changes in the electrophoretic mobility of the LDL bands. Of those showing changes in electrophoretic mobility, the majority (78%) shifted to slightly larger, less dense LDL after drug therapy. However, the LDL-cholesterol/apo B ratio changes were relatively small in all fluvastatin-treated individuals including the group with changes in electrophoretic mobility, confirming that HMG-CoA reductase inhibitor causes relatively small and subtle changes in the distribution of LDL subspecies.

Apolipoproteins B↗