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Ten chlorinated hydrocarbons (tetradifon, Chlorobenzilate, Kepone, lindane, Kelthane, toxaphene, dieldrin, hexachlorobenzene, dienochlor, and Aroclor 1254; see below) were evaluated in rats to assess agents which might selectively elevate high-density lipoprotein cholesterol (C-HDL). Single, nontoxic doses of Aroclor, dieldrin, and Kepone elevated C-HDL at day 7 (31%, 26%, and 24%, respectively, p less than 0.05). The C-HDL elevations were maintained at days 21 and 60 (28% and 31%, p less than 0.01) in the Aroclor group, while C-HDL returned to baseline in the dieldrin and Kepone groups. Liver function tests were unchanged from control, suggesting that the changes in C-HDL were not the consequence of hepatotoxicity. The hepatic microsomal cytochrome P-450 content of animals receiving Aroclor, dieldrin, and Kepone was 67%, 56%, and 44% higher than control values (p less than 0.02), indicating probable hepatic enzyme induction. If HDL (an antiatherogenic lipoprotein) is also selectively elevated by chlorinated hydrocarbons in man, then analogues might potentially be developed as antiatherogenic pharmacologic agents. Alternatively, the implications of man's exposure to halogenated hydrocarbons may be better understood.

This study focused on 124 octogenarians and 13 nonagenarians to extend data on lipid and lipoprotein distributions into the eighth and ninth decades of life and to assess relationships between lipids, lipoproteins, and longevity. The mean (±SD) ages of the 114 women and 23 men were 85 ± 4 and 84 ± 4 yr, respectively. Mean (±SD) total plasma cholesterol and high density lipoprotein cholesterol (C-HDL) were higher in women than in men, 219 ± 41 and 198 ± 31 mg/dl, 58 ± 16 and 50 ± 13 mg/dl respectively, p

A kindred with four generation vertical transmission of familial hypobeta-lipoproteinemia was ascertained by measurement of low levels of cord blood low density lipoprotein cholesterol (C-LDL) in a propositus neonate. Measurement of cord blood C-LDL in conjunction with family studies allows the neonatal diagnosis of familial hypobetalipoproteinemia.

To assess factors related to distinctive longevity, lipoprotein and kindred studies were carried out in 22 octogenarian kindreds self-referred by virtue of either two siblings or a parent and child living to age 80 or over. There was evidence for familial hyperalpha-lipoproteinemia in 7 kindreds, for familial hypobeta-lipoproteinemia in 3 kindreds, and for primary hyperalpha-lipoproteinemia and hypobeta-lipoproteinemia in an additional 2 and 2 kindreds respectively. First degreee relatives of probands with primary or familial hyperalpha- or hypobeta-lipoproteinemia had sharply reduced morbidity and mortality from myocardial infarction when compared to population controls, P P P

Two bile acid-sequestrant anion exchange resins, colestipol (U-26, 597A) and cholestyramine resin (Questran), were given in doses of 20 gm/day for four months each in a 14-month placebo crossover study to 25 patients with familial type II hyperlipoproteinemia. Plasma cholesterol and β-lipoprotein cholesterol were reduced to normal levels in 20 and 22 subjects, respectively, by one or both drugs. Coupled with low cholesterol, low saturated fat, polyunsaturate-rich diet, colestipol and cholestyramine provide parallel and alternative approaches to normalization of cholesterol and β-lipoprotein cholesterol in familial type II hyperlipoproteinemia.

Umbilical cord blood cholesterol was measured in 1800 consecutive unselected live births in a general hospital. Mean cholesterol (± 1 SD) was 63.8 ± 18.7, range 20–196 mg 100 ml . Cord blood cholesterol levels greater than 100 mg 100 ml (mean cord blood cholesterol ± 2 SD) were arbitrarily identified as elevated. Sixty-five neonates had cord blood cholesterol levels greater than 100 mg 100 ml . Of these 65 infants, both parents could be studied in 26 kindred, the mother only in 23 kindred, and neither parent in 16 kindred. Of the 26 parent pairs, nine mothers and two fathers were found to have Type II hyperlipoproteinemia. Of the 23 mothers of illegitimate, hypercholesterolemic infants, three were found to have Type II hyperlipoproteinemia. An infant and similarly affected mother or father with Type II hyperlipoproteinemia were then identified in 14 of 1800 consecutive live births. Five of ten siblings born to these 14 kindred had Type II hyperlipoproteinemia. Measurement of umbilical cord blood cholesterol in unselected populations offers promise in early diagnosis of neonatal and familial Type II hyperlipoproteinemia and should provide an opportunity for early therapy in a pediatric and young adult population prior to development of symptomatic or anatomic atherosclerosis.

Very low density lipoprotein triglyceride turnover rate, fractional turnover rate, and half-life were studied using Glycerol −3H to label VLD-TG in 16 patients with familial Type IV hyperlipoproteinemia. The patients were maintained on an isocaloric diet with determination of triglyceride turnover after 2 wk of placebo, and a second determination after 2 wk of Oxandrolone (an anabolic-androgenic synthetic steroid). On placebo, mean very low density lipoprotein triglyceride (VLD-TG) was 539, falling on Oxandrolone to 254 mg100 ml (p < 0.05). Mean half-life (T12) was 10.3 hr on placebo and was shortened to 5.2 hr on drug (p < 0.05). The fractional turnover rate (FTR) on placebo was 0.104 ± 0.016 hour−1, and rose to 0.166 ± 0.016 on drug (p < 0.05). Mean turnover rate (TR) rose slightly from 17.6 mg/kg/hr on placebo to 19.04 mg/kg/hr on Oxandrolone. Both postheparin lipolytic activity (PHLA) and postheparin triglyceride lipase (TGL) were appreciably increased on drug, rising respectively from 0.297 μeq FFA/ml/min and 11.7 mμeq FFA/ml/hr (on placebo) to 0.396 and 23.7 (on drug). The changes (Δ) in VLD-TG on Oxandrolone correlated with Δ T 12 (R = 0.761) and with Δ FTR (R = −0.532). Oxandrolone may lower very low density lipoprotein triglyc eride by substantially increasing fractional turnover rate and shortening half-life while slightly augmenting turnover rate and improving efficiency of VLD-TG removal.

A spectrum of musculoskeletal findings, not readily classifiable into a recognised rheumatic entity, is described in association with hypertriglyceridaemia with predominant increase in pre-beta-lipoprotein (type-IV hyperlipoproteinaemia). Patients were primarily of middle age with acute or insidious onset of morning stiffness, arthralgias of usually asymmetric distribution involving variable numbers of both large and small joints, limitation of joint motion, and, on occasion, severe periarticular hyperaesthesia. Symptoms were often aggravated by exertion, temperature, and humidity change. Although recurrent joint swelling was described by patients, effusions were infrequent, were of a non-inflammatory nature, and lacked significant lipid abnormality. On physical examination, evidence of overt inflammation was rare. The most prevalent finding was tenderness which was occasionally severe and incapacitating. Such musculoskeletal findings, though not specific, should suggest the possibility of an underlying type-IV hyperlipoproteinaemia which is potentially correctable by diet and/or drugs.

In a subject homozygous for familial hypercholesterolemia (FHC) placental lipids (PL), enzymes (E), and insulin receptors (IR) were studied to determine if changes in PL were associated with change in E or IR. Levels of FHC placental phospholipids, free fatty acids, triglycerides, cholesterol esters, and cholesterol were respectively .031, .106, .045, .149, and .044 mg/g placenta, with (X±SD) values in 6 normal placentas being .11±.02, .07±.01, .09±.004, .15±.04,and .13±.03. The FHC placenta had much less phospholipid, triglyceride, and cholesterol and more free fatty acids than normals. Placental palmitic acid in all lipid classes of the FHC was twice that of normals, while FHC placental linoleic acid was increased and arachidonic acid decreased. Marker E content and localization in the FHC placenta was normal. FHC placental alkaline phosphatase, 5′ nucleotidase, Ca++ and Mg++ ATPase, and IR concentrations were normal when compared to 6 normal term placentas. Microvillus brush border membranes were enriched 10-12 fold with marker E, as compared to activities in the whole placental homogenate in FHC and normals. The IR concentration at 12 × 10−10M I-125 insulin in the FHC and normal placentas was 33.7 vs. 37±8.2 × 10−6 nmoles/mg protein respectively, an insignificant difference. Despite changes in placental membrane lipids in the FHC, there were no changes in marker E or IR concentration, implying normal placental function as measured (indirectly) by these parameters, and by the successful butcome of this pregnancy and birth of a healthy obligate heteroygote male neonate.

Since high density lipoprotein cholesterol (C-HDL) levels in adults are inversely related to risk of coronary heart disease, male(M): female(F) C-HDL differences may be important. Cord blood total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(C-LDL) were studied in 464 live births (248 M, 216 F) to determine whether M:F differences in adults an in later childhood were also expressed in cord blood. In 873 schoolchildren (ages 6-17) from the Lipid Research Clinic prevalence study, F had higher TC and TG than M, slightly higher C-LDL, and ,at the end of adolescence, higher C-HDL. Mean ± SD TC, TG, C-HDL, C-LDL, and the ratio of C-HDL to C-LDL for the neonates were: At birth, F had higher TC(p .1, and C-HDL/C-LDL ratios in F and M did not differ, p>.1. Lipid and lipoprotein levels are under combined genetic and environmental control. M:F differences in C-HDL in adults and adolescents are manifested in cord blood, as are the higher schoolchild F levels of TC and C-LDL. C-HDL levels are higher in adult blacks (vs. whites), and in Russian vs. American males, but do not differ in cord blood. M:F C-HDL differences may be “genetic” while racial and cross-cultural differences may in part, reflect environmental effects.

Cord blood triglyceride (TG) concentrations were determined in 60 neonates whose parents had normal plasma cholesterol and triglyceride levels, and in 57 neonates with one parent having primary hypertriglyceridemia. The 95th percentile value for cord blood triglyceride in both groups of neonates was 70 mg/100 ml, and this level was arbitrarily used as a cutoff point in the definition of cord blood hypertriglyceridemia. In 2,000 consecutive live births, 56 neonates had cord blood triglyceride levels > 70 mg/100 ml (mean TG 111±33, range 71 to 218 mg/100 ml). Forty-six neonates with triglyceride levels