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Biomedical subjects

F A Franklin

Publications and source records attributed to F A Franklin.

At least 37 records · Page 2Linked to original sources
PubMed1992

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. Effect of patient characteristics on lovastatin-induced changes in plasma concentrations of lipids and lipoproteins.

BACKGROUND: Lovastatin produces consistent dose-related reductions in plasma levels of low density lipoprotein (LDL) cholesterol along with variable decreases in triglycerides and increases in high density lipoprotein (HDL) cholesterol. Patient characteristics from the Expanded Clinical Evaluation of Lovastatin (EXCEL) study were examined to determine their association with the magnitude of lovastatin-induced changes in these lipids and lipoproteins. METHODS AND RESULTS: After a baseline period consisting of dietary therapy, 8,245 patients with moderate hypercholesterolemia were randomized to five groups that received 48 weeks of treatment with either placebo or daily doses of lovastatin ranging from 20 to 80 mg. By use of linear statistical models, 20 different patient characteristics were examined for modification of the dose-dependent responses observed. For LDL cholesterol, the following were associated with enhanced lowering (p less than 0.05; percent changes are placebo-corrected, adjusted mean changes from baseline for the 80-mg/day lovastatin group): full drug compliance (-41.9%) versus 80% compliance (-20.3%); an age of 65 (-43.4%) versus 45 years (-38.1%) for women; white race (-40.9%) versus black race (-38.0%); and 4.5-kg weight gain (-42.6%) versus 4.5-kg weight loss (-37.9%). Similar relations for enhanced triglyceride lowering were found with older age and weight gain. Patients with initially low HDL cholesterol (less than 0.91 mmol/l) and high triglycerides (greater than 2.26 mmol/l) had enhanced responses for these parameters: placebo-corrected percent changes at 80 mg/day were -27.4% for triglycerides and +12.3% for HDL cholesterol. CONCLUSIONS: Overall, patient characteristics had very little impact of clinical importance on the dose-dependent LDL cholesterol lowering found with lovastatin. In patients with initially high levels of triglycerides and low levels of HDL cholesterol, the elevation of HDL cholesterol produced by lovastatin appears to be enhanced.

Cholesterol, HDL↗
PubMed1991

Expanded clinical evaluation of lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia.

In the multicenter, double-blind EXCEL (Expanded Clinical Evaluation of Lovastatin) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated. Patients were randomly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day, or 20 or 40 mg twice a day. At all of these dosages, lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein (LDL)-cholesterol levels, averaging 24% (20 mg/day) to 40% (80 mg/day). The magnitude of the effect of this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program (NCEP) goals. In the absence of coronary artery disease (CAD) or two other CAD risk factors, the LDL-cholesterol goal of 4.14 mmol/L (160 mg/dL) was attained by 22% of patients in the placebo group and between 81% (20 mg/day) and 96% (80 mg/day) of those treated with lovastatin. For those with CAD or at least two other CAD risk factors, the LDL-cholesterol goal of 3.36 mmol/L (130 mg/dL) was attained by 4% of placebo patients and between 38% (20 mg/day) and 83% (80 mg/day) of those treated with lovastatin. Lovastatin also increased high-density-lipoprotein cholesterol (7-10%) and decreased triglycerides (10-19%) in a dose-dependent manner. Thus, when used as an adjunct to a prudent diet, lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia.

Cholesterol, HDL↗
PubMed1991

Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin.

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.

Alanine Transaminase↗
PubMed1991

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia.

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.

Adult↗
PubMed1991

Psychosocial changes during the first year of medical school.

The goal of this study was to assess psychosocial changes during the first year, on measures thought related to the long-term adjustment of medical students. Measures of self-esteem, health locus of control, hassles, uplifts, mood, and symptoms of stress were administered at the beginning and end of first year to 128 of 181 students. Self-esteem, powerful other locus of control, and uplifts decreased while hassles increased during the year. Positive mood decreased (joy, contentment, vigour, and affection) while negative mood increased (depression and hostility). Hassles at the beginning of the year were positively associated with health outcome at the beginning and end of the year. End-of-the-year first-year students appear to be worse off psychosocially than when they entered. With greater emphasis on health promotion and disease prevention and the adoption of other reforms in medical education, as suggested in the GPEP Report, medical students may learn to cope more effectively with stress as they pursue their medical education.

Affect↗
PubMed1990

Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia.

The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol (greater than or equal to 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The 5 treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume greater than 1 alcoholic beverage daily and 67% reporting no strenous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy.

Adult↗
PubMed1990

Screening, diagnosis, and management of dyslipoproteinemia in children.

The authors provide an extensive and comprehensive review of dyslipoproteinemia in children. An effective program for CVD reduction in this population will include an accessible screening program to identify high-risk children, high-quality measurements of TC and LP-C, careful follow-up of screening results with multiple measurement to classify risk status and diagnose primary dyslipidemia, a key role for family and education, and consistent and long-term follow-up for diet and drug adherence, efficacy, and safety.

Adolescent↗
PubMed1988

A dynamic family approach for the prevention of cardiovascular disease.

Social and behavioral learning methods, combined with nutrition counseling and innovative education modules, provide a well-rounded approach to eating behavior intervention. Dietitians can apply this multifaceted approach in various settings to maximize eating behavior change.

Adolescent↗
PubMed1987

Implementation of "Heart Smart:" a cardiovascular school health promotion program.

The Bogalusa Heart Study, an investigation of 8,000 children, has compiled a large data bank on cardiovascular (CV) risk factors in children during the past 12 years. Precursors of heart disease begin at a young age, with many children already possessing one or more known clinical risk factors--hypertension, obesity, and adverse lipoprotein changes. Having obtained data examining the determinants, distributions, interrelationships and trends over time for CV risk factors, a foundation was provided to address additional questions directed toward intervention strategies. "Heart Smart" is a comprehensive, research-based CV health promotion program testing differential effects of a population (public health) strategy versus a high-risk approach within four elementary schools. The major goal of "Heart Smart" is to reduce CV risk factors in children with an intervention to facilitate the adoption of healthful lifestyles. Objectives, intervention modalities, and design and evaluation procedures for children and adults in a total school environment (K-6) are described.

Cardiovascular Diseases↗
PubMed1987

Cardiovascular risk in parents of children with elevated blood pressure. "Heart Smart"--family health promotion.

The Heart Smart Family Health Promotion identified elementary-school-age children with elevated blood pressure (BP), based on sex-, race-, height-specific 90th percentiles, and ponderal index (wt/ht3), based on sex-, race-, and age-specific 90th percentiles (norms developed in the Bogalusa Heart Study). These children and their parents were recruited into a behavioral program aimed at reducing cardiovascular (CV) risk factors for both children and parents and preventing "tracking" of children's elevated risk factors into adulthood. Cardiovascular screening consisted of BP, anthropometric evaluation, serum lipids, and 24-hour urinalysis. Self-reported assessments were personal and family medical history, eating, exercise, smoking, and alcohol behaviors. Both child and parent subjects were predominantly black and female. Data were stable over two baseline measurements and indicated CV risk factor abnormalities in one or both of the parents selected: 67% of the black parents and 25% of the white parents were hypertensive; 91% had positive familial CV history; 41% had total cholesterol greater than or equal to 220 mg/dl; 50% had LDL-C levels greater than or equal to 140 mg/dl; 74% were overweight; 44% were smokers; and 91% were completely sedentary. Using percentile grids to identify children with elevated BP also identifies families with hypertension and associated risk factors.

Adolescent↗
PubMed1986

The relation of apolipoproteins A-I and B in children to parental myocardial infarction.

Clinical studies suggest that serum levels of apolipoproteins A-I and B may be more strongly related to coronary artery disease than are their respective lipoprotein-cholesterol fractions. Therefore, we assessed the association between levels of apolipoprotein B, apolipoprotein A-I, lipids, and lipoprotein cholesterols in children and the reported histories of myocardial infarction in their parents in a survey of 2416 black and white school-age children. As compared with children whose fathers did not report a myocardial infarction, those whose fathers reported having had an infarction (n = 139) had a lower mean level of apolipoprotein A-I (137 vs. 141 mg per deciliter; P = 0.04) and a lower ratio of low-density lipoprotein cholesterol to apolipoprotein B (1.08 vs. 1.11; P = 0.007), along with a higher ratio of apolipoprotein B to apolipoprotein A-I (0.64 vs. 0.61; P = 0.04). These associations existed independently of the children's race, sex, age, and history of obesity, smoking, alcohol intake, and use of oral contraceptives. Children whose mothers reported having had a myocardial infarction (n = 56) had no decrease in the ratio of low-density lipoprotein cholesterol to apolipoprotein B, but they tended to have an elevated ratio of apolipoprotein B to apolipoprotein A-I. In contrast, serum lipoprotein-cholesterol fractions in children were not related to myocardial infarctions in either parent. These results provide further evidence that apolipoproteins are more strongly related to the risk of cardiovascular disease than are lipoprotein-cholesterol fractions.

Adolescent↗
PubMed1985

The effects of total parenteral nutrition on gastrointestinal growth and development.

Total parenteral nutrition (TPN) is vital for the nutritional support of infants with disorders of the gastrointestinal tract that prevent adequate enteral intake. Studies in adult rodents maintained on TPN have demonstrated intestinal atrophy and decreased activity of the brush border enzymes of the small bowel mucosa. We studied the effects of TPN during the phase of rapid intestinal growth and development in piglets. Matched groups of three 6-week-old weaned piglet littermates received a glucose (45 g/kg/d), amino acid (8 g/kg/d), and fat (2.5 g/kg/d) solution intravenously (IV) or by gastrostomy (GF), or were given hog chow (Chow) at an equivalent caloric value for three weeks. No differences were noted in the mean weight gain (13-15 g/kg/d), total serum protein (4.5-4.8 g/dL), BUN (9-12 mg/dL), or Hct (25% to 30%). The IV and GF animals, compared to the Chow animals, had decreased growth of the stomach, small bowel, and pancreas with decreased small bowel mucosal disaccharidase activity. The IV group, compared to Day 0 animal measurements, had decreased small bowel length and weight and pancreatic weight. Histology of the proximal small bowel mucosa in the IV animals showed decreased mucosal depth, villus height, crypt depth, and epithelial cell number from the crypt base to the midvillus. These findings suggest that stomach, small bowel, and pancreatic growth are dependent on the route of administration and/or the composition of the diet, the small bowel mucosa and the pancreas atrophies in young piglets maintained on TPN, the activity of some intestinal brush border disaccharidases are decreased in the small bowel in piglets maintained on either an intravenous or an intragastric infusion of a TPN solution.

Animals↗
PubMed1985

Effect of dietary treatment on the plasma levels of lipids, lipoprotein cholesterol and LDL B protein in children with type II hyperlipoproteinemia.

These data confirm the effectiveness of therapeutic diets in children with type II hyperlipoproteinemia in conventional terms. However, the decrease in LDL cholesterol was not accompanied by a significant decrease in LDL B (suggesting only a small change in the number of LDL particles in plasma), and a fall in HDL cholesterol occurred, with no significant improvement in the LDL to HDL cholesterol ratio. These findings indicate that further research is needed to develop diets with more optimal effects. Finally, our hypothesis that such diets may produce an LDL particle of altered composition, needs to be confirmed using additional physical-chemical measurements of the size, composition and molecular weight distribution of LDL in plasma before and after dietary intervention.

Adolescent↗
PubMed1982

High-affinity uptake and degradation of apolipoprotein E free high-density lipoprotein and low-density lipoprotein in cultured porcine hepatocytes.

Isolated pig liver membranes contain a specific "lipoprotein binding site" that recognizes low-density lipoproteins (LDL) and apolipoprotein E (apoE) free high-density lipoprotein (HDL) [Bachorik, P. S., Kwiterovich, P. O., & Cooke, J. (1978) Biochemistry 17, 5287-5299]. We report here that a similar site exists in cultured porcine hepatocytes and that it mediates the uptake and degradation of apoE-free HDL. The binding of 125I-labeled HDL and 125I-labeled LDL (125I-HDL and 125I-LDL, respectively) at 4 degrees C and the uptake and degradation of the lipoproteins at 37 degrees C were time dependent and saturable and were not inhibited by unrelated proteins. Chloroquine (6 x 10(-5)M) inhibited the degradation of 125I-HDL by 76% and of 125I-LDL by greater than 99%; leupeptin inhibited the degradation of both lipoproteins by about 25%. 125I-HDL binding (4 degrees C), uptake, and degradation (37 degrees C) were inhibited by LDL, methyl-LDL, and methyl-HDL about as well as by unlabeled HDL but were unaltered in Pronase-treated cells or in cells that were cultured for 24 h in either lipoprotein-free medium containing HDL or LDL (200 micrograms/mL). In contrast, these conditions affected the uptake and degradation of 125I-LDL disproportionately. HDL and methyl-LDL inhibited 125I-LDL uptake by 50% or more but had little effect on degradation. 125I-LDL binding was reduced by 12% and degradation by 57% in Pronase-treated cells. Preincubation of the cells with LDL (200 micrograms/mL) reduced uptake by 35% and degradation by 68%. Similar preincubation with HDL (200 micrograms/mL) increased 125I-LDL degradation by 60% but did not affect 125I-LDL uptake. The findings indicated the presence in porcine hepatocytes of at least two distinct sites for lipoproteins. One site resembled the LDL receptor and mediated 125I-LDL degradation. A second, Pronase-insensitive site recognized both HDL and LDL. This site mediated almost all of the degradation of 125I-HDL but little if any degradation of 125I-LDL.

Animals↗
PubMed1982

Association of hyperapobetalipoproteinemia with endogenous hypertriglyceridemia and atherosclerosis.

Researchers disagree on whether plasma triglyceride levels are an independent risk factor for atherosclerotic coronary artery disease. We hypothesized that patients with endogenous hypertriglyceridemia would differ: Some would have normal values of plasma low-density lipoprotein (LDL) B protein; others, despite their normal level of LDL cholesterol, would have increased levels of LDL B protein. We believe the latter patients--those with hyperapobetalipoproteinemia--would be the ones at risk for atherosclerosis. We studied two populations. Group 1, consisting of 162 patients with type IV lipoprotein patterns, was divided into two groups. One subgroup (A), which included 38 patients with elevated plasma LDL B atherosclerotic disease than the other subgroup (B) of 36 patients with normal levels of plasma LDL B protein (10 patients versus two, p less than 0.02). Group 2 consisted of 100 patients who had had myocardial infarction. Eighty-one percent of the 47 hypertriglyceridemic and 70% of the 53 normotriglyceridemic patients had elevated plasma LDL B protein levels (129 mg/dL or greater)--a proportion significantly higher than that in Group 1 (p less than 0.001). Thus, an elevated plasma level of LDL B protein not only identifies subgroups of patients with type IV lipoprotein patterns, but also may be an important marker for atherosclerotic disease.

Adult↗