Peter M. Laskarzewski

Lipids, Lipoproteins, and Sexual Maturation During Adolescence: The Princeton Maturation Study

Abstract This study encompassed a cross-sectional and longitudinal examination of schoolchildren as they entered into and passed through puberty, examining interrelationships between lipids, lipoproteins, and sexual maturation. In the first year of the study (1976), 529 schoolchildren in grades 5–12 participated; 203 were restudied in 1977, and 141 in 1978. At each yearly visit, the childrens stage of sexual maturation was assessed using the Tanner scale. Plasma cholesterol and triglyceride were quantitated each year; high, low, and very low density lipoprotein cholesterol (C-HDL, C-LDL, C-VLDL) levels were measured in the second and third years of the study. In males, cross-sectional decrements in plasma cholesterol were observed with increasing sexual maturation (Tanner stages 1–4), with an increment at Tanner 5 (sexual maturity); plasma triglyceride levels rose at all stages save Tanner 4. The mid-Tanner fall in plasma cholesterol appears (longitudinally) to be accounted for by reduction in C-HDL, while the rise in plasma cholesterol at Tanner 5 may be produced by an increase in C-LDL. Changes in age and Quetelet indices did not appear to relate closely to changes in C-VLDL in 12- and 13-yr-old males, but increasing age and Quetelet indices in 14–15-yr old males accompanied increasing C-VLDL. Cross-sectional studies in females revealed that plasma cholesterol fell at Tanner stages 3 and 4 and rose at stage 5; plasma triglyceride rose during all stages except Tanner 4. Longitudinal studies suggested that the decrements in plasma cholesterol in females may be partially accounted for by reductions in C-HDL; the increase in plasma cholesterol in late sexual development may be accounted for by an increase in C-LDL. In male children, we speculate that the fall in C-HDL and late rise in C-LDL as sexual maturation progresses is associated with increased testosterone production.

Use of an emollient as a steroid-sparing agent in the treatment of mild to moderate atopic dermatitis in children

Abstract: The effectiveness of an emollient as an adjunct to topical corticosteroid therapy for the treatment of mild to moderate atopic dermatitis was studied for 3 weeks in 25 children 3 to 15 years of age in comparison with corticosteroid therapy alone. The adjunctive regimen of a once‐daily application each of hydrocortisone 2.5% cream and of a water‐in‐oil cream was equivalent in efficacy to the comparative regimen of twice‐daily applications of hydrocortisone 2.5% cream. Both treatment regimens elicited significant improvement in skin condition by day 7 (p < 0.005) and further significant improvement by day 14 (p < 0.005). No significant differences between the two treatment regimens were observed in the rates of improvement (p > 0.545) or in the reductions in mean lesion size (p > 0.9B). No differences were observed in parental evaluations, except for ease of application where a slight preference was expressed for the hydrocortisone 2.5% cream preparation (p < 0.038). We conclude that emollient adjunct i ve therapy offers a steroid‐sparing alternative to topical corticosteroids alone in the treatment of mild to moderate atopic dermatitis.

Severe Depression of High-Density Lipoprotein Cholesterol Levels in Weight Lifters and Body Builders by Self-Administered Exogenous Testosterone and Anabolic-Androgenic Steroids

The effects of nonphysician prescribed, self-obtained, self-administered exogenous anabolic-androgenic steroids and testosterone on plasma total, high- and low-density lipoprotein cholesterol (HDLC, LDLC), and triglycerides were evaluated in 14 adult white men, 11 body builders and 3 power weight lifters. Lipids and lipoprotein cholesterols were quantified during active physical conditioning, both on (for at least 1 month, mean +/- SD 1.8 months) and off (for at least 4 months, 7.3 +/- 2.7 months) self-administered exogenous androgenic steroids. The subjects took 50 to 100 mg methandrostenolone daily plus weekly injections of testosterone 100 to 200 mg and nandrolone decanoate 100 to 200 mg per week. Mean (SD) HDLC on exogenous androgenic steroids, 29 +/- 8 mg/dL, was severely depressed, and was less than 50% of the consistently elevated mean HDLC when exogenous steroids were not used (61 +/- 14 mg/dL, P less than .01 for paired differences). During anabolic steroid use, HDLC was less than or equal to the age- race- and sex-specific 10th percentile in 11 of the 14 men, whereas while off anabolic steroids, HDLC was greater than or equal to the 90th percentile in 7 of the 13 men, and in the top quartile for 3 of the remaining 6 men. Mean LDLC was higher on androgenic steroids (150 +/- 44) than off (125 +/- 38 mg/dL), P less than .05 for paired differences. The ratio of LDLC/HDLC during exogenous steroid use (6.0 +/- 3.7) was nearly triple the ratio obtained when steroids were not taken (2.2 +/- 1.0), P less than .01 for paired differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary and familial hypoalphalipoproteinemia

Our specific aim was to assess within-family clustering of high-density lipoprotein cholesterol (HDLC) levels in kindreds identified through probands with primary hypoalphalipoproteinemia, and to determine whether, and to what degree, familial aggregation of HDLC less than or equal to the tenth percentile represents a heritable trait, familial hypoalphalipoproteinemia. Our probands were selected arbitrarily by virtue of HDLC less than or equal to the age-sex-race-specific tenth percentile as the sole dyslipoproteinemia, with an additional requirement that they be normotriglyceridemic (triglyceride levels less than the 90th percentile). The probands were also required to have primary hypoalphalipoproteinemia, not secondary to diseases and/or drugs. Fifteen of the 16 probands were men; 12 were referred because of premature myocardial infarction, angina, or stroke, 2 because of family history of premature myocardial infarction or stroke, and 2 because of low HDLC observed on routine health examinations. Two of the 16 kindreds exhibited three-generation vertical transmission of bottom decile HDLC. In three kindreds, there was also three-generation vertical transmission of bottom decile HDLC, but top decile triglycerides accompanied bottom decile HDLC in one or more generations. Eight kindreds displayed two-generation vertical transmission of bottom decile HDLC. After excluding probands, there were 11 critical matings (bottom decile HDLC by normal), with 30 living offspring, all of whom were sampled. Of these 30 offspring, 13 had bottom decile HDLC, 17 had HDLC greater than tenth percentile. The ratio of offspring with bottom decile HDLC to those of HDLC greater than tenth percentile was 13:17 (0.76/1), not significantly different from the ratio of 1/1, the ratio predictive of a dominant trait, X2(1) = 0.53, P greater than 0.4. The nearly 1:1 segregation ratio for the group of offspring was not due to the aggregation of sibships with, in general, most of the sibs, or none of the sibs affected; within-family expression of low HDLC was also not sex-linked. The 13 hypoalphalipoproteinemic offspring of 11 critical matings included only two subjects whose bottom decile HDLC was accompanied by top decile triglyceride. Our data suggests that not only (by selection) was low HDLC in the probands the sole dyslipoproteinemia, but that the segregation of low HDLC in offspring of critical matings was primarily accounted for by isolated low HDLC, not by hypoalphalipoproteinemia secondary to hypertriglyceridemia. Familial hypoalphalipoproteinemia is a heritable disorder with a pattern of transmission not significantly different from that expected by a hypothesis of mendel

High and low density lipoprotein cholesterols in adolescent boys: Relationships with endogenous testosterone, estradiol, and Quetelet index

Abstract The decrement in high density lipoprotein cholesterol (HDLC) during male adolescence has been postulated to result from increased testosterone (T) production. Although pharmacologic doses of exogenous T lower HDLC, in adults, HDLC and endogenous T correlate positively. Our specific aim was to assess whether and to what degree, endogenous testosterone (T) and estradiol (E2), Quetelet index (Q), and their interactions relate to HDLC, low density lipoprotein cholesterol (LDLC), and the ratio of LDLC to HDLC in adolescent boys undergoing sexual maturation. Using multiple regression analysis with E2, E22, T, T2, Q, Q2, and their interactions as explanatory variables, 47% of the variance of HDLC (p = 0.006), 76% of the variance of LDLC (p = 0.0001), 87% of the variance of the ratio of LDLC to HDLC (p = 0.0001), and 56% of the variance of triglycerides (p = 0.01) could be explained. For high levels of estradiol there was a negative association between HDLC and testosterone. For those with the highest estradiol levels, and at any given testosterone level, the higher the Quetelet index, the lower the HDLC. Boys with median estradiol levels had a slight increase in HDLC as testosterone increased. Boys with low estradiol levels had sharper increases in HDLC with increases in testosterone. At the highest estradiol levels, LDLC was negatively and curvilinearly related to testosterone, the decrement in LDLC becoming sharper at higher levels of testosterone. At high levels of estradiol, and at any given level of testosterone, low Quetelet index was associated with a lower LDLC. For median levels of estradiol, as testosterone increased, LDLC decreased. Only at low estradiol levels did LDLC increase along with testosterone levels. For the ratio of LDLC to HDLC, the higher the Quetelet index was, the higher the ratio tended to be. At high Quetelet indices, as testosterone increased, the ratio of LDLC to HDLC increased. Conversely, at low Quetelet index levels, as testosterone increased, the ratio of LDLC to HDLC fell. Within the Quetelet groups, estradiol levels allowed further discrimination, with the lowest ratio of LDLC to HDLC observed for boys with low Quetelet and low E2, and the highest LDLC to HDLC ratio observed for boys with high Quetelet and high E2. Overall, boys with the highest E2 had the greatest fall in HDLC and the highest ratio of LDLC to HDLC with increasing testosterone, with both trends accentuated by increasing ponderosity. We speculate that interactions of estradiol, testosterone, and Quetelet index in adolescent males may lead, in some subjects, to atherogenic changes in lipoproteins (lower HDLC, higher LDLC to HDLC ratios) and a higher risk of coronary heart disease later in life. In aggregate, changes in Quetelet index, testosterone, estradiol, and their interactions in boys during adolescence can account for a significant proportion of the dynamic changes observed in low and high density lipoprotein cholesterol.

Familial Aggregation of Lipids and Lipoproteins in Families Ascertained through Random and Nonrandom Probands in the Iowa Lipid Research Clinics Family Study

The aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] in families ascertained through random and nonrandom probands in the Iowa Lipid Research Clinics family study was examined. Nonrandom probands were selected because their lipid levels (at a prior screening visit) exceeded a certain pre-specified threshold. The statistical method conditions the likelihood function on the actual event that the probands value is beyond the threshold. This method allows for estimation of the path model parameters in randomly and nonrandomly ascertained families jointly and separately, thus enabling tests of heterogeneity between the two types of samples. Marked heterogeneity between the random and the hyperlipidemic samples is detected in the multifactorial transmission for TG and HDL, and moderate heterogeneity is detected for CH and LDL, with a pattern of higher genetic heritability estimates in the random than nonrandom samples. The observed pattern of heterogeneity is compatible with a higher prevalence in the random sample of certain dyslipoproteinemias that are associated with nonelevated lipids. For the random samples, genetic heritabilities are higher for CH and HDL (about 60%) than for TG and LDL (about 50%). For the nonrandom samples those estimates are about 45, 40, 35 and 30% for HDL, CH, LDL and TG, respectively. Little to no cultural (familial environmental) heritability is evident for CH and LDL, although 10-20% of the phenotypic variance is due to cultural factors for TG and HDL. These results suggest that the etiologies for lipids and lipoproteins may be quite different in random versus hyperlipidemic samples.

Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats

Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid content, were fed to partially nephrectomized rats; the effects were compared to those of feeding beef tallow. All three oils had favorable effects on progression of renal failure, salmon oil on kidney histology as well. The changes induced in platelet production of thromboxane A2, and in the renal production of various eicosanoids may explain the protective role of these oils.

The Cincinnati Myocardial Infarction and Hormone Family Study: family resemblance for dehydroepiandrosterone sulfate in control and myocardial infarction families.

Dehydroepiandrosterone sulfate (DHEAS) was examined in random (control) and nonrandom (case) families participating in the Cincinnati Myocardial Infarction and Hormone (CIMIH) family study. The case families were ascertained through white men who survived a myocardial infarction (MI) before the age of 56, whereas control families were recruited through advertisements and through an adolescent boy maturation study. Both familial correlations and genetic effects of DHEAS were investigated. First, maximum likelihood estimates of the sex-specific familial correlations (corrected for nonrandom ascertainment) suggested that there was significant heterogeneity between the two sampling types. This heterogeneity was isolated to the male sibling correlation, which was higher in the case than control families. Post hoc analyses suggested that the sibling group heterogeneity may be in part a function of age, since the control sample offspring were on average much younger than those in case families. No sex differences other than those for the siblings were noted in the familial correlations. Second, heritability was investigated in control families using a simple path model (TAU) that allowed for sex differences. The only significant model parameter was the sex-specific familiarity (combined polygenic and familial environmental effects), which was larger in females (74%) than in males (29%). In general, these analyses suggested that (1) DHEAS may play only a limited role in the increased risk for premature MI, and (2) the degree of heritable (familial) variation may be dependent on sex.

Month-to-month variability of lipids, lipoproteins, and apolipoproteins and the impact of acute infection in adolescents.

OBJECTIVE To assess month-to-month variability of total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), calculated low-density lipoprotein-cholesterol (LDL-C), apolipoprotein A1, apolipoprotein B, and lipoprotein (a), as well as factors that could influence variability, including recent acute infection in an adolescent population. METHODS Sixty-three high school students had fasting lipids and lipoproteins measured at 4 separate times during the school year and another venipuncture 3 to 7 days after recovery from an acute infection. Erythrocyte sedimentation rate was also measured. Coefficients of variation were calculated for each study variable. The influence of recent infection on variability was assessed. RESULTS The 50th and 95th percentiles, respectively, for the coefficient of variation for each variable were as follows: total cholesterol, 7.3% and 13.6%; triglycerides, 22% and 47.3%; HDL-C, 7.9% and 16.8%; LDL-C, 12.1% and 25%; apolipoprotein A1, 6.3% and 15.2%; apolipoprotein B, 9.5% and 17.2%; and lipoprotein (a), 19.3% and 40%. Recent infection significantly lowered HDL-C (4 mg/dL; P < .0001) and apolipoprotein A1 (7 mg/dL; P < .005). CONCLUSIONS Clinicians evaluating lipids and lipoproteins serially should expect significant visit-to-visit variation in triglycerides and calculated LDL-C values. Assessment of HDL-C and apolipoprotein A1 should not be done within 2 weeks of an acute infection. Apolipoproteins B and A1 have slightly less variability than their respective lipoprotein cholesterol values (LDL-C and HDL-C).

Definition and application of the discretionary screening indicators according to the National Cholesterol Education Program for Children and Adolescents

OBJECTIVES (1) To propose definitions for the discretionary screening indicators described by the National Cholesterol Education Program for Children and Adolescents (NCEP-Peds); (2) to examine the relative prevalence of major screening indicators (family history of premature heart disease and parental plasma cholesterol concentration > or = 6.21 mmol/L (240 mg/dl)) and discretionary screening indicators (excessive consumption of fat or cholesterol or both, smoking, diabetes, hypertension, and steroid use) in a family population; and (3) to evaluate the relative value of the major and the discretionary indicators in detecting high serum levels of low-density lipoprotein-cholesterol (LDL-C) (> or = 3.36 mmol/L (> or = 130 mg/dl)). DESIGN Control cohort from a case-control study. SETTING Lipid research clinic. PARTICIPANTS White children and adolescents < 20 years of age from 232 nuclear families who participated in the Cincinnati Myocardial Infarction Hormone Study. MAIN OUTCOME MEASURES (1) Number of children who have major and discretionary screening indicators; (2) sensitivity and specificity of the major and the discretionary screening indicators in identifying children with LDL-C concentrations > 3.36 mmol/L (130 mg/dl) (high LDL-C). RESULTS With cutoff points of the 90th percentile for blood pressure, the 85th percentile for obesity, and the 80th percentile for dietary fat and cholesterol, and self-report for diabetes, smoking, and corticosteroid use, 54% of the 232 children in the cohort had one or more discretionary indicators. Additionally, applying the major screening indicators raised the percentage of children identified to 74%. Twenty-eight percent had both major and discretionary indicators. Having a discretionary screening indicator did not increase the probability of having a major indicator. Applying both discretionary and major screening indicators to the cohort identified 96% of the children who had a high concentration of LDL-C; 30% of the children with high LDL-C levels were discovered solely by the discretionary indicators. Similar sensitivity and specificity were noted between the major and the discretionary indicators. Children with high LDL-C concentrations were more likely to have multiple screening indicators. CONCLUSION Discretionary and major screening indicators suggested by the National Cholesterol Education Program for Children and Adolescents identify different subsets of children at risk of having premature cardiovascular disease. Both major and discretionary indicators contribute to the identification of children with high LDL-C concentrations.