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Biomedical subjects

J A Cortner

Publications and source records attributed to J A Cortner.

At least 19 recordsLinked to original sources
PubMed1998

Age-related changes in cardiovascular disease risk factors of hypercholesterolemic children.

OBJECTIVE: To describe the age-related changes in cardiovascular disease risk factors in young, hypercholesterolemic (HC) children. METHODS: Hypercholesterolemic (n = 227) and nonhypercholesterolemic (NHC) (n = 80) children between the ages of 4 and 10 years were identified. Height, weight, skin-fold and blood pressure measurements, and total cholesterol levels were measured. The HC group also had insulin levels evaluated. The groups were compared by analysis of variance. Simple Spearman correlations evaluated the associations between factors within each group. RESULTS: The HC and NHC groups had similar mean ages, heights, and weights, both contained 51% girls, and all were white subjects. Percent weight-for-height median, and biceps, triceps, suprailiac and subscapular skin-fold measurements were all larger for the HC group. A significant age interaction demonstrated that the HC group's larger suprailiac and sum of skin-fold measures were expressed in the 8.0- to 9.9-year-old children, but not the 4.0- to 5.9-year-olds. For both groups, systolic blood pressure was associated with the measures of adiposity. For the HC group, insulin levels were also associated with adiposity. CONCLUSIONS: These results suggest that: (1) children with HC have greater body fat, (2) the expression of the hypercholesterolemia precedes the expression of increased body fat, (3) body fat increases with age, and (4) altered insulin and blood pressure levels are expressed in association with the increased body fat in children with HC. Confirmation with longitudinal data is necessary.

Adipose Tissue↗
PubMed1998

One-year follow-up of nutrition education for hypercholesterolemic children.

OBJECTIVES: This study evaluated retention of the effect of a home-based, practitioner-initiated nutrition education model. METHODS: Children with elevated low-density lipoprotein (LDL) cholesterol levels were randomly assigned to one of two nutrition interventions or to an at-risk control group. Intervention effects were evaluated 3, 6, and 12 months postbaseline. RESULTS: The parent-child autotutorial group demonstrated significant increases in knowledge and, along with the counseling group, decreases in total and saturated fat intake. Also, the autotutorial and counseling groups retained a majority of their initial LDL cholesterol decrease. CONCLUSIONS: Knowledge of heart-healthful eating and dietary fat intake as well as dietary change can be affected and retained via home-based, practitioner-initiated nutrition interventions with hypercholesterolemic children, although some form of ongoing intervention may be necessary to produce lasting decreases in LDL cholesterol levels.

Adult↗
PubMed1997

Kinetics of retinyl esters during postprandial lipemia in man: a compartmental model.

Orally ingested vitamin A (retinol) is incorporated into intestinal chylomicrons (CHYLO) in the form of retinyl esters (RE) along with newly absorbed dietary triglycerides (TG). As the intestinal lipoproteins undergo hydrolysis in the circulation, the majority of the RE remain with the secreted intestinal particles and have been used as a marker for intestinally derived lipoproteins during the early phase of the postprandial state. A multicompartmental model was developed for the kinetics of RE during postprandial lipemia in individuals with normal lipid levels (n = 16) and in patients with hyperlipidemia (n = 44). The assumptions used in the development of the model are presented in this report. Some of the key findings include (1) as much as 50% of the newly synthesized RE may be secreted by the intestine as very-low-density lipoprotein (VLDL)-sized particles of S(f) 20 to 400 following consumption of a test meal containing a moderate amount of fat (20 to 30 g); (2) in most individuals, approximately 50% of the RE secreted in S(f) greater than 400 are converted to smaller, less buoyant fractions, and 50% are irreversibly removed directly from the plasma; (3) as much as 5% to 20% of the ingested retinol may be secreted as small intestinal lipoproteins with the buoyance of low-density lipoprotein (LDL) in some individuals; and (4) less than 5% of RE flux through S(f) 20 to 400 is converted to S(f) less than 20, and the primary catabolic pathway for RE in this fraction is direct uptake. Comparable estimates can be obtained for the kinetic parameters when repeat studies are made in the same subjects under comparable conditions.

Apolipoproteins B↗
PubMed1997

Effects of family history of heart disease, apolipoprotein E phenotype, and lipoprotein(a) on the response of children's plasma lipids to change in dietary lipids.

We examined the effects of family history of coronary artery disease (CAD), apolipoprotein E (apo E) phenotype, and lipoprotein(a) [Lp(a)] on the response of plasma lipids to change in dietary lipid intake after 3 mo of nutrition education in 125 children aged 4-10 y. The subjects were healthy children with elevated low-density-lipoprotein (LDL)-cholesterol concentrations who participated in the Children's Health Project, a nutrition-education program designed to lower plasma cholesterol by means of dietary modifications in accordance with recommendations of the National Cholesterol Education Program. Dietary and plasma lipids were measured by three 24-h recalls and assessments of two fasting plasma samples collected before and 3 mo after the start of intervention. Family history of CAD was determined by questionnaires administered to parents at baseline. Apo E phenotyping was done with isoelectric focusing followed by immunostaining; Lp(a) was measured with two-site immunoradiometric assays of frozen aliquots of plasma samples collected at baseline and 3 mo. After adjustment for intervention group, age, sex, and body mass index, analysis of covariance showed that baseline plasma lipid concentrations were the strongest independent predictors of change in plasma lipids after 3 mo. Plasma total and LDL-cholesterol concentrations in children with less family history of CAD were significantly more responsive to change in dietary cholesterol than concentrations in children with a stronger family history of CAD. Neither apo E phenotype nor Lp(a) significantly influenced change in plasma lipids independently or interactively with change in dietary lipids.

Apolipoproteins E↗
PubMed1996

The influence of age and relative weight on the presentation of familial combined hyperlipidemia in childhood.

BACKGROUND: Familial combined hyperlipidemia (FCHL) has been described as the leading cause of familial hyperlipidemia. FCHL is dominantly inherited, occurs in at least 1% of the population, and is responsible for about 10% of premature coronary artery disease (CAD). OBJECTIVE: Because FCHL in childhood is not well characterized, we evaluated the interrelationships among age, percentage of ideal body weight (%IBW) and plasma lipoprotein levels in FCHL children (age 2-18 years), exploring the possibility that obesity and age may influence the presentation of FCHL in childhood. METHODS: One hundred and eighty-nine children with FCHL were studied. Significant correlations within this group were further evaluated by examining a subset of 36 FCHL children, each of whom had an unaffected sibling who could serve as a control for comparison. RESULTS: When the full group was divided into those with TG levels > 90% and those with TG levels < 90%, the correlation with %IBW was stronger in the former (r = 0.45, P < 0.005) as compared with the latter (r = 0.25, P = 0.05). Within the subset of 36 FCHL children and their 36 unaffected siblings (controls), age and sex distributions were similar. Percentage IBW (mean +/- S.D.) (117.3 +/- 29.1 for FCHL and 111.2 +/- 19.4 for controls) was similar and in the overweight range. FCHL children had significantly higher levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B) and triglyceride (TG) levels compared with controls (P < 0.0005 for all comparisons). Of several significant correlations observed in the full group (n = 189), only the correlations of %IBW with plasma TG levels (r = 0.45, P = 0.006), and of age with plasma TG levels (r = 0.48, P = 0.003) persisted with a similar degree of magnitude in the subset of 36 FCHL children. No correlation was significant in the controls. By Fisher's Z-test, the correlation between %IBW and TG in the FCHL children was significantly different from controls. CONCLUSIONS: These results suggest that TG levels in FCHL children, but not in their unaffected siblings, and sensitive to the presence of obesity, implying an interaction between obesity and the underlying condition, in addition, the association between age and TG level in FCHL children suggests a gradual expression of the hyperlipidermia (i.e. TG) during childhood.

Adolescent↗
PubMed1995

A 5' splice-region mutation and a dinucleotide deletion in the lysosomal acid lipase gene in two patients with cholesteryl ester storage disease.

Cholesteryl ester storage disease (CESD) results from inherited deficiencies of the lysosomal hydrolase, acid lipase (LAL; E.C. 3.1.1.13). To establish the molecular defects in LAL deficiency, two unrelated probands with severely reduced LAL activity were examined. DNA amplification by reverse-transcription polymerase chain reaction and subsequent sequence analysis of LAL cDNA identified two mutant alleles. Patient 1, presenting with hepatosplenomegaly, mildly elevated liver function tests, and hyperlipidemia, was homozygous for a deletion of nucleotides 823 to 894 of the LAL cDNA. This 72-bp deletion maintained the reading frame and resulted in a loss of 24 amino acids from the LAL protein. Analysis of genomic DNA revealed that the 72 bp corresponded to an exon of the LAL gene. A single G to A point mutation at the last exon position was observed in the genomic DNA of patient 1, indicating a splicing defect with consecutive exon skipping underlying the 72-bp deletion. Patient 2 was a compound heterozygote for the 72-bp deletion and a dinucleotide deletion at positions 967 and 968. This deletion resulted in a shifted reading frame carboxyterminal of codon 296, and 43 random amino acids followed the frame shift. A premature stop at codon 339 truncated the mutant LAL protein by 34 amino acids. Allele-specific hybridization confirmed that patient 1 was homozygous for the 72-bp deletion mutation, and that patient 2 was a compound heterozygote for the 72-bp deletion and the 2-bp deletion.

Adult↗
PubMed1994

Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management.

The first evidence that elevation of plasma levels of cholesterol is a risk factor for the development of atherosclerosis in children came from the Bogalusa Heart Study in 1986, which reported an association between aortic fatty streaks in 3- to 26-year-old subjects and increased plasma levels of low-density lipoprotein cholesterol (LDL-C). The most compelling evidence of a cause-and-effect relationship has come from the multicenter cooperative study called the Pathobiological Determinants of Atherosclerosis in Youth. When the investigators examined the abdominal aorta and the right coronary artery of adolescents and young adults who had died of trauma, they found a significant relationship between the sum of the very low density lipoprotein (VLDL) plus LDL-C level and both fatty streaks and raised atherosclerotic lesions. They also found an inverse relationship between those lesions and increased high-density lipoprotein cholesterol (HDL-C) levels. In addition, their studies showed that smoking (as assessed by the serum thiocyanate level) promotes atherogenesis in children as young as age 15 years. Thus many pediatricians have now accepted the importance of identifying children with significant hypercholesterolemia so that appropriate dietary and life-style modifications can be recommended. This is especially important because there is often a major genetic component to the hyperlipidemia seen in children.

Adolescent↗
PubMed1994

Reduction of elevated LDL-cholesterol levels of 4- to 10-year-old children through home-based dietary education.

OBJECTIVE: To assess the effects of a home-based, parent-child autotutorial (PCAT) dietary education program on the dietary knowledge, lipid consumption, and plasma low density lipoprotein-cholesterol (LDL-C) of 4- to 10-year-old children with elevated plasma LDL-C. METHODS: "At-risk" children (screening total cholesterol, (TC), exceeded 4.55 mmol/L and average LDL-C from two fasting samples was between 2.77 and 4.24 mmol/L for boys or 2.90 and 4.24 mmol/L for girls) were randomized to the PCAT program (N = 88), for dietary counseling with a registered dietitian (N = 86), or to an at-risk control group (N = 87). Dietary knowledge, diet, and LDL-C of these groups were assessed at baseline and after the educational period (3-month follow-up). The knowledge and diet of a not-at-risk (TC below 4.22 and 4.34 mmol/L for boys and girls, respectively) control group (N = 81) was also assessed and compared with that of the at-risk control group. RESULTS: At the 3-month follow-up, the PCAT children's knowledge scores had increased three times more than those of the counseling and at-risk control groups (P < .001). Mean grams of total and saturated fat consumed by PCAT and counseling groups declined while that of the at-risk control group increased slightly; these differences were significant (P < .05). The mean LDL-C decline of the PCAT group was significantly different (P < .05) from the decline of the at-risk control group (0.26 vs 0.09 mmol/L), and approached significance (P = .07) when compared with that of the counseling group (0.26 vs 0.11 mmol/L). The at-risk control group's knowledge and diet did not differ from that of the not-at-risk group. CONCLUSION: The PCAT program offers a mechanism for providing effective dietary education to children with elevated cholesterol and to their families.

Child↗
PubMed1993

A quality assurance program for the measurement of capillary blood cholesterol levels in private pediatric practices. The Children's Health Project.

OBJECTIVE: To develop an easy to use quality assurance program for the measurement of capillary blood cholesterol levels in private pediatric practices. The program needed to comply with the guidelines laid down by the National Cholesterol Education Program. DESIGN: Intervention study. SETTING: Nine private pediatric practices in and around northern Philadelphia, Pa. PARTICIPANTS: The analysts included clinic staff members with laboratory expertise ranging from none to some previous experience. None of the participants had previous experience with a quality assurance program. INTERVENTIONS: Progress was reported monthly to the Lipid Research Laboratory, Philadelphia, and action was taken to correct inaccuracies in bias or variance. MAIN OUTCOME MEASURE: Compliance with the analytical guidelines laid down by the National Cholesterol Education Program in that the coefficient of variation was no greater than 5% and the bias was no greater than +/- 5% in the first year of the study. RESULTS: Within the first year of the study, there were 152 monthly quality assurance returns for each of two lyophilized control materials. On four occasions the coefficient of variation was greater than 5% while the overall bias was within the desired +/- 5% on 143 (94%) of 152 occasions. After the first 3 months of the study, as user confidence increased, intervention by the Lipid Research Laboratory became minimal. The internal quality assurance was further evaluated by a successful performance in a quarterly external quality assurance program. CONCLUSIONS: It is possible to devise an easy to use quality assurance program for extra laboratory measurement of cholesterol levels in children, and, with minimal assistance, maintain acceptable standards of cholesterol analysis. The quality assurance improved following the first 3 months of training and education. Subsequent continuous quality improvement was maintained with minimal involvement of the specialist center. Should the controversial issue of private office measurement of blood cholesterol levels become universally acceptable, the implication from our study is that standards acceptable to the National Cholesterol Education Program and the Clinical Laboratory Improvement Amendments of 1988 are possible using a suitable quality assurance program.

Bias↗
PubMed1993

Genotype at a major locus with large effects on apolipoprotein B levels predicts familial combined hyperlipidemia.

A sample enriched for familial combined hyperlipidemia (FCHL) was examined for evidence of an association between genotype at an apolipoprotein B (apoB) elevating locus defined by complex segregation analysis and FCHL. Complex segregation analysis detected a locus with a large effect on plasma apoB levels and was used to compute the most probable genotype of family members. None of the 35 normolipidemic adults carried a copy of the allele associated with elevated apoB levels, yet 58% of the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 28 (7%) normal children had 1 copy of this allele and none had 2 copies, while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copies. Further, 41 of 48 (85%) individuals classified as having hyperapobetalipoproteinemia did not carry a copy of this "elevated apoB" allele. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot be explained solely by the presence of elevated apoB levels in FCHL, suggesting that the locus controlling apoB levels may play an etiologic role in FCHL.

Adolescent↗
PubMed1993

The effect of lovastatin on very low-density lipoprotein apolipoprotein B production by the liver in familial combined hyperlipidaemia.

Overproduction of very low-density lipoprotein apolipoprotein B by the liver is a metabolic marker for familial combined hyperlipidaemia, a common inherited disorder of lipoprotein metabolism. Four subjects with familial combined hyperlipidaemia had rates of apolipoprotein B production which were 2-7 times normal, using a protocol in which [15N]glycine was used to label newly synthesized hepatic proteins. Following 4-6 months of therapy with lovastatin, very low-density lipoprotein apolipoprotein B production in all four subjects had returned to the normal range. This demonstrates that lovastatin, an inhibitor of cholesterol biosynthesis, acts also to reduce the apparent production rate of apolipoprotein B by the liver.

Adult↗
PubMed1993

Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management.

Familial combined hyperlipidemia (FCHL) is a dominantly inherited hyperlipidemia that occurs in at least 1% of the adult population and is responsible for 10% of premature coronary artery disease. In families referred for evaluation because of primary hyperlipidemia in a child, FCHL is expressed three times more commonly than familial hypercholesterolemia and half of the siblings are affected. Several metabolic defects apparently are associated with the FCHL phenotype. Most commonly, excess production of very low density lipoprotein apolipoprotein B can be demonstrated. In other families, reduced lipoprotein lipase activity is associated. One allele at a locus influencing apolipoprotein B levels predicts FCHL in a large proportion of families ascertained through affected children. Whether this allele is responsible for the excess of very low density lipoprotein apolipoprotein B detected in metabolic studies has not been elucidated. Management of FCHL in children begins with dietary modification. A bile acid sequestrant may be considered as well if diet cannot reduce the plasma low-density lipoprotein cholesterol level to less than 4.13 mmol/L (160 mg/dl) after the age of 10 years. Although the hydroxymethylglutaryl-coenzyme A reductase inhibitors are not currently recommended for children younger than 19 years of age, we speculate that they will be increasingly utilized for the management of FCHL in teenage boys who continue to have low density lipoprotein cholesterol levels greater than 4.13 mmol/L (160 mg/dl) after dietary modification.

Adolescent↗
PubMed1993

Use of cholestyramine in the treatment of children with familial combined hyperlipidemia.

We studied the effectiveness of and compliance with the use of cholestyramine in children with heterozygous familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL). During a 10-year period, 673 children (aged 10.5 +/- 4.0 years) were referred for evaluation of hyperlipidemia, of whom 87 (36 with FH; 51 with FCHL) were treated with cholestyramine (8 to 24 gm/day). In both groups, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B levels were significantly reduced after cholestyramine use. In those with FH, plasma LDL-cholesterol levels decreased from 258 +/- 35 mg/dl (6.67 +/- 0.90 mmol/L) to 190 +/- 31 mg/dl (4.91 +/- 0.80 mmol/L); in those with FCHL, LDL-cholesterol levels dropped from 207 +/- 40 mg/dl (5.35 +/- 1.03 mmol/L) to 141 +/- 35 mg/dl (3.64 +/- 0.90 mmol/L). High-density lipoprotein-cholesterol levels were not significantly changed after cholestyramine use in either group. In the FCHL group, plasma triglyceride levels increased significantly from 81 +/- 35 mg/dl (0.92 +/- 0.40 mmol/L) to 134 +/- 42 mg/dl (1.52 +/- 0.48 mmol/L). Seven patients were lost to follow-up; 18 discontinued the medication within 1 month. Of the remaining 62 children, 59 had a good response to the drug. Of the 62 patients, 52 discontinued the medication after 21.9 +/- 10 months. Adverse effects included foul taste (73%), nausea with bloating (18%), and constipation. Cholestyramine is effective in reducing LDL-cholesterol levels in children with inherited hyperlipidemia, but the majority of children will not comply with its long-term use.

Adolescent↗
PubMed1992

Determinants of fasting plasma triglyceride levels: metabolism of hepatic and intestinal lipoproteins.

The contribution of the kinetics of exogeneous and endogenous lipoproteins in determining the level of triglyceride in fasting plasma was assessed in a group of 19 normolipidaemic and hypertriglyceridaemic subjects. From data derived during a 9-h infusion of [15N]-glycine, we have assessed very low density lipoprotein apolipoprotein B production, and from data analysed by kinetic modelling obtained following ingestion of retinol and triolein, we have assessed chylomicron and chylomicron remnant clearance in a group of 19 normolipidaemic and hypertriglyceridaemic subjects. A strong positive correlation was observed between the fasting plasma triglyceride level and the reciprocal of the apolipoprotein B fractional synthetic rate (r = 0.83, P less than 0.01). A positive correlation was also found with the rate of clearance of chylomicron remnants (Sf 20-400; r = 0.87, P less than 0.01) and of chylomicrons (Sf greater than 400; r = 0.69, P less than 0.01). No correlation was found between the fasting plasma triglyceride level and either of the plasma post-heparin lipolytic activities. Multivariate analysis revealed that 95% of the variance in triglyceride levels could be explained by the apolipoprotein B fractional synthetic rate and the chylomicron remnant clearance rate. The strong correlation between chylomicron remnant clearance, a measure of exogenous lipid metabolism, and fasting (hence, endogenous) plasma triglyceride levels suggests that remnants of chylomicrons and very low density lipoproteins share some common components of the removal process.

Adult↗
PubMed1991

Familial combined hyperlipidaemia: use of stable isotopes to demonstrate overproduction of very low-density lipoprotein apolipoprotein B by the liver.

We have assessed very low-density lipoprotein apolipoprotein B production, using [15N]glycine as an endogenous marker in a 9-hour primed constant infusion protocol, in four adult male subjects with familial combined hyperlipidaemia and in four normolipidaemic adult male controls. The mean very low-density lipoprotein apolipoprotein B absolute synthetic rate was significantly greater in the familial combined hyperlipidaemic subjects than in control subjects (26.31 +/- 8.37 vs 9.36 +/- 4.07 mg/kg per 24 h, p less than 0.05). These results confirm findings using exogenous radioisotope labelling techniques that very low-density lipoprotein apolipoprotein B production is significantly increased in most patients with familial combined hyperlipidaemia. A modified 9-hour protocol can be safely done repeatedly and in children and pregnant women.

Adult↗
PubMed1990

Measurement of (C13)arginine incorporation into apolipoprotein B-100 in very low density lipoproteins and low density lipoproteins in normal subjects using (13C)sodium bicarbonate infusion and isotope ratio mass spectrometry.

We describe a new stable isotope technique for the in vivo study of hepatic plasma protein synthesis in humans. The method involves the infusion of (13C)sodium bicarbonate for 1 h and the measurement of the isotopic enrichment of (13C)arginine in newly synthesized apolipoprotein B of very low density lipoproteins (VLDL-apoB) and low density lipoproteins (LDL-apoB) in blood samples taken over a 5-6 h period from the commencement of the infusion. Isotope ratio mass spectrometry was utilized to measure 13CO2 enrichment following hydrolysis of these proteins and conversion of the guanidinium carbon of arginine in the hydrolysate to carbon dioxide by sequential incubation with arginase and urease. The method is capable of measuring isotopic enrichment as low as 0.001 at.% excess (APE) with a precision of 1.2%. In both subjects studied, the (13C)arginine of VLDL-apoB reached enrichments of 0.2 APE and that of the arginine of LDL-apoB, 0.03 APE. Incorporation of labeled arginine into LDL-apoB was demonstrable at 60-90 min. The new technique is safe and is applicable to the study of the hepatic biosynthesis of a wide range of plasma proteins.

Adult↗
PubMed1990

Prevalence and expression of familial combined hyperlipidemia in childhood.

The objectives of this study were (1) to determine the incidence of dominantly inherited hyperlipoproteinemia in children referred to our medical center because of hyperlipidemia associated with a family history of premature coronary artery disease and (2) to assess the degree of expression in childhood of the most common inherited hyperlipoproteinemia, familial combined hyperlipidemia. Among 129 families referred to us by area pediatricians, we identified a dominantly inherited hyperlipoproteinemia in 97 of them. Twenty had familial hypercholesterolemia, 65 familial combined hyperlipidemia, 11 hyperapobetalipoproteinemia, and one familial hypertriglyceridemia. As expected, almost half (9/20) of the siblings of probands with familial hypercholesterolemia were affected. Although we expected incomplete gene penetrance in the siblings of the probands with familial combined hyperlipidemia, we found 43 affected and 40 unaffected among the 83 siblings of the 65 probands. Our findings suggest that hyperlipidemia in children, caused by familial combined hyperlipidemia, occurs more than three times as frequently as familial hypercholesterolemia and that in families identified by a child proband, the penetrance is complete. Pediatricians should identify this primary hyperlipidemia in childhood and attempt to prevent the associated risk of premature coronary artery disease by prescribing appropriate diet and life-style modifications.

Adult↗