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Biomedical subjects

R H Knopp

Publications and source records attributed to R H Knopp.

At least 127 records · Page 7Linked to original sources
PubMed1987

Low fetal loss rates after ultrasound-proved viability in early pregnancy.

Once pregnancy is recognized clinically, it is accepted that 12% to 15% undergo spontaneous abortion. However, the actual time of fetal demise has not yet been determined. To address this question, the outcomes of pregnancies identified before 21 days of conception by serum beta-human chorionic gonadotropin assays were studied. All subjects underwent ultrasound examinations at eight and 12 weeks' gestation. Among 220 women who had a viable pregnancy at eight weeks, only seven (3.2%) experienced a fetal loss thereafter. The results of this study suggest that most clinically recognized spontaneous abortions manifested after eight weeks actually represent pregnancies in which fetal demise occurred before eight weeks. These findings have important implications with respect to the safety of chorionic villi sampling and to the identification of exogenous agents that cause fetal wastage.

Abortion, Spontaneous↗
PubMed1986

Prevalence and clinical correlates of beta-migrating very-low-density lipoprotein. Lipid Research Clinics Program Prevalence Study.

The prevalence and clinical associations of beta-migrating very-low-density lipoprotein (beta-very-low-density lipoprotein), an atherogenic lipoprotein associated with type III hyperlipidemia, were compared in men and women using and not using estrogen-containing hormones. Beta-very-low-density lipoprotein was more common in men, 0.54 percent or one in 185, than in women not taking hormones, 0.30 percent or one in 333, and was least common in women taking hormones, 0.04 percent or one in 2,500. Beta-very-low-density lipoprotein-positive men and women were heavier and had higher triglyceride, cholesterol, and very-low-density lipoprotein cholesterol levels compared with beta-very-low-density lipoprotein-negative subjects, but 30 percent of the men and 21 percent of the nonuser women did not have elevated triglyceride or cholesterol levels. The very-low-density lipoprotein cholesterol/total triglyceride ratio exceeded 0.30 in 55 percent and 54 percent of beta-very-low-density lipoprotein-positive men and women compared with 3.3 percent and 3.9 percent of beta-very-low-density lipoprotein-negative men and women. Ninety-three percent of the beta-very-low-density lipoprotein-positive subjects had some lipoprotein lipid abnormality and 60 percent had an abnormal glucose, liver, or renal function test result or high alcohol or dietary cholesterol intake. In conclusion, beta-migrating very-low-density lipoprotein is more common in men than in women, consistent with a protective effect of estrogen. About half of the time, beta-very-low-density lipoprotein is associated with an elevated very-low-density lipoprotein cholesterol/total triglyceride ratio, indicating that beta-very-low-density lipoprotein can be present independent of other markers of type III hyperlipidemia. Nonetheless, beta-very-low-density lipoprotein signifies abnormal lipoprotein metabolism of some kind in almost every instance, is frequently associated with treatable medical conditions, and may on pathophysiologic grounds be considered important in its own right in predicting atherosclerosis risk. Beta-very-low-density lipoprotein-associated conditions should attract medical attention.

Adult↗
PubMed1986

Effect of estrogen/progestin potency on clinical chemistry measures. The Lipid Research Clinics Program Prevalence Study.

The effects of oral contraceptives of varied estrogen/progestin composition on clinical measurements of hepatic, thyroid, and renal function and carbohydrate metabolism were examined in 1,355 women in the Lipid Research Clinics Program Prevalence Study. In general, bilirubin and alkaline phosphatase levels are lower with both oral contraceptives and postmenopausal estrogen use, suggesting an estrogen effect. The least bilirubin reduction is seen with a progestin dominant oral contraceptive. A significant decrement in aspartate aminotransferase is observed in users of one high estrogen dose oral contraceptive and in postmenopausal Premarin users, while aspartate aminotransferase is higher in postmenopausal users of higher dose ethinyl estradiol. Globulins are slightly higher in all hormone use categories, suggesting an estrogen effect on hepatic secretion of this protein class into the circulation. Fasting glucose concentrations are generally slightly lower even in the progestin dominant oral contraceptives, where glucose intolerance has been described. Thyroxine concentrations are generally elevated in all women using oral contraceptives. A relationship to estrogen dose is seen in women with thyroxine concentrations greater than the 99th percentile and in postmenopausal estrogen users. Creatinine concentration is greater with the use of Ovral, a progestin dominant oral contraceptive, and lower with two estrogen dominant oral contraceptives and Premarin, suggesting a competitive effect of estrogen and progestin. Among the clinical laboratory tests considered here, oral contraceptive effects seem to be largely estrogen mediated with a suggestion of competitive effect of estrogen versus progestin only on bilirubin and creatinine levels. These observations differ from lipoproteins where opposing hormonal effects are more clearly reflected in changing lipoprotein concentrations.

Adult↗
PubMed1986

Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes.

The objective of this paper is to review the extent and mechanisms of lipoprotein alterations in pregnancy, present new data relating to placental lipid transport in normal humans and diabetic animals and consider possible effects on fetal growth and development in normal and diabetic pregnancy. The concentration of all lipoprotein fractions increases during pregnancy. VLDL cholesterol and triglyceride increase 2.5-fold over prepregnancy levels and LDL cholesterol increases 1.6-fold, all with peak levels at term. HDL cholesterol is maximally increased in midgestation by 1.45-fold and subsequently declines to 1.15-fold at term. The mechanisms of these lipoprotein changes have not been studied in humans but the hypertriglyceridemia in animal models is related to enhanced VLDL entry into the circulation. In addition, diminished adipose tissue lipoprotein lipase (LPL) activity in late gestation may cause a rerouting of triglyceride fatty acids to other tissues such as muscle and uterus for oxidation, rather than storage, since triglyceride transport is not reduced in pregnancy. All of these changes appear to be sex hormone mediated. In diabetic pregnancies, the available data indicate that triglyceride concentrations are increased and HDL cholesterol concentrations are decreased with reference to lipoproteins in nondiabetic pregnant women. Previously unpublished data show that a transplacental FFA gradient exists across the umbilical circulation in the direction of the fetus and is proportional to the maternal FFA concentration. No gradient is seen for triglyceride or total plasma cholesterol. However, transport of unmeasured amounts of triglyceride fatty acids may still occur via placental LPL and be exaggerated in diabetes where LPL declines in adipose tissue but not in placenta. The mechanism of transplacental cholesterol transport remains to be defined. Preliminary studies suggest that it depends on HDL as well as LDL since both can provide cholesterol for placental progesterone synthesis. In addition, fetal weight and length are associated with maternal apoproteins A-I and A-II, both major apoproteins of HDL. By lowering HDL in pregnancy, diabetes mellitus could negatively affect these relationships. In conclusion, sex hormone mediated modifications of lipoprotein physiology are described in pregnancy which may enhance triglyceride fatty acid transport to muscle for oxidation and LDL and HDL cholesterol delivery to growing maternal and fetal tissues, a process that diabetes could globally disrupt.

Animals↗
PubMed1986

Arteriosclerosis risk in women and the role of oral contraceptive progestins.

UNLABELLED: Recent studies are reviewed to develop a perspective on the risk of arteriosclerotic heart disease occurring in women using various oral contraceptive (OC) formulations and postmenopausal estrogens. Evidence is provided in support of the following points: (1) arteriosclerosis risk increases in women after age 40 at a rate parallel to that in men; (2) arteriosclerosis risk is related to small changes in lipoprotein concentration, specifically LDL, HDL, and a subfraction of HDL, HDL2; (3) OC formulations alter LDL, HDL, and HDL2 concentrations in relation to the relative biologic effects (potency) of the estrogen and progestin components of the oral contraceptive pill, and/or the associated androgenic effect of the progestin component, with estrogen producing putatively favorable changes, and progestin, unfavorable changes; and (4) arteriosclerosis and myocardial infarction (MI) risk in young women using OC steroids is associated with increasing progestin potency, while postmenopausal women experience a reduced MI-related mortality and all-cause mortality, the latter attributable in part to an increase in HDL cholesterol concentrations. CLINICAL IMPLICATIONS: It is presently advisable to screen all subjects for hypercholesterolemia as a general measure, particularly those subjects who are contemplating the use of OCs. This national mandate is important in light of the data from the Lipid Research Clinics Coronary Primary Prevention Trial. This ten-year study showed that a 1% reduction in cholesterol yielded a 2% reduction in coronary risk. Therefore, small changes in a patient's lipid profile can have major ramifications later in life. OC steroids should be used with circumspection by women with existing cardiovascular disease risk factors and should be selected so as to minimize potentially adverse effects on lipoprotein physiology.

Arteriosclerosis↗
PubMed1986

Arteriosclerosis risk. The roles of oral contraceptives and postmenopausal estrogens.

Recent studies are reviewed to obtain a perspective on the risk of arteriosclerotic heart disease in women using various oral contraceptive formulations and postmenopausal estrogens. The evidence points to an increasing risk of arteriosclerosis in women after age 40 at a rate parallel to that of men. Arteriosclerosis risk is altered by small changes in lipoprotein concentration--in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) and in a subfraction of HDL, HDL2. There are indications that oral contraceptives alter LDL, HDL and HDL2 concentrations relative to the potency of their estrogen and progestin components and also to the progestin component's associated androgenic effect, with estrogen producing reputedly favorable changes and progestin, unfavorable ones. The risk of arteriosclerosis and myocardial infarction in young women using oral contraceptive steroids is associated with increasing progestin dose, but in most studies, postmenopausal women experience no change or reduced mortality from all causes, including myocardial infarction, with it related in part to increased HDL cholesterol concentrations. It is wise to screen all women patients for hypercholesterolemia, especially those contemplating the use of oral contraceptives. Oral contraceptive steroids should be used cautiously by women with cardiovascular disease risk factors. Formulations must be selected to minimize their potentially adverse effects on lipoprotein physiology.

Adult↗
PubMed1985

Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin.

To minimize the cutaneous flushing symptoms associated with niacin use, a time-release capsule form of niacin has been formulated. Thus study compares the effects of time-release niacin with those of unmodified niacin on lipoprotein lipids, including HDL2 and HDL3, apoproteins A-I and A-II, clinical chemistries, symptomatic side effects, and adherence to the medication regimen. Seventy-one primarily hypercholesterolemic subjects were randomized to either unmodified niacin or time-release niacin ad took medication for a six-month period. The two groups were closely matched on anthropomorphic and lipid variables. Adherence to the therapeutic regimen at a dose of 1.5 g/d in the first month of treatment was similar in the two groups. Thereafter, at a dose of 3.0 g/d, adherence was in excess of 90% among subjects taking unmodified niacin but only 64% among those taking time-release niacin, chiefly because of aggravated gastrointestinal symptoms; cutaneous flushing side effects, however, were slightly less common with time-release niacin. At these levels of adherence, LDL cholesterol (C) was reduced 21% by unmodified niacin and 13% by the time release form. Plasma total triglyceride was reduced more with unmodified niacin (27%) than with time-release niacin (8% maximum), and HDL-C and HDL2-C were increased significantly with unmodified niacin (26% and 36%) and were not significantly changed by time-release niacin. Increased to a similar degree on both regimens were HDL3-C (approximately 35%) and apoA-I (approximately 12%). ApoA-II was not affected by either drug regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Effects of pregnancy, postpartum lactation, and oral contraceptive use on the lipoprotein cholesterol/triglyceride ratio.

Lipoprotein cholesterol/triglyceride ratio changes have been observed previously with sex hormone use. To determine if the lipoprotein cholesterol/triglyceride ratio is similarly changed by pregnancy and postpartum lactation, we examined pregnant subjects at 36 weeks gestation and the same women at 6 weeks postpartum and compared them to age-matched, nonpregnant women using or not using oral contraceptives. The cholesterol/triglyceride ratios were examined as means and medians and as curvilinear functions of increasing triglyceride concentration. Median ratios did not predict all ratio changes identified graphically. At very-low-density lipoprotein (VLDL) triglyceride concentrations below 40 mg/dL, the VLDL ratio is less than control in oral contraceptive users and further reduced in pregnant women. Above triglyceride concentrations of 40-60 mg/dL, the curves in the three groups are indistinguishable. No effect of lactation is observed. The low-density lipoprotein (LDL) cholesterol/triglyceride ratio is comparably lower in pregnant subjects and oral contraceptive users at all concentrations of lipoprotein triglyceride and again there is no effect of lactation. In high-density lipoprotein (HDL), there is no effect of either pregnancy or oral contraceptive use on the cholesterol/triglyceride ratio, while it is significantly higher with lactation. Postpartum decreases in the VLDL and LDL cholesterol/triglyceride ratio are seen at all lipoprotein concentrations independent of lactation. We conclude that triglyceride enriches VLDL at low concentrations and LDL at all concentrations in pregnancy and with oral contraceptive use, suggesting a common, hormonal mechanism. HDL is enriched with cholesterol during postpartum lactation, consistent with decreased transfer of cholesterol to other lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Effect of postpartum lactation on lipoprotein lipids and apoproteins.

To determine if postpartum lactation alters plasma lipoprotein lipid and apoprotein concentrations and composition, we studied 56 overnight fasting lactating and 16 nonlactating women approximately 6 weeks postpartum. Postpartum results are presented as absolute concentrations and as the difference from antepartum values determined at 36 weeks gestation. Antepartum lipoprotein lipid and apoprotein concentrations were generally not different in the 2 groups, with the single exception of whole plasma and low density lipoprotein (LDL) apoprotein (apo) B (probably a chance difference). When expressed as the antepartum and postpartum difference, the lactating and nonlactating groups were indistinguishable in very low density lipoprotein (VLDL) and LDL triglyceride, cholesterol, phospholipid, and apo B concentrations. However, lactating women had higher high density lipoprotein (HDL) cholesterol, phospholipid, apo A-I, and apo A-II concentrations than nonlactating women when results were expressed as differences from antepartum values or as absolute values. HDL triglyceride concentrations were not significantly different between lactating and nonlactating women by either analysis. There was no significant effect of lactation on VLDL or LDL composition, but there was a significant increase in the percent cholesterol content in HDL. We hypothesize that the increase in HDL constituents in lactation is generated in part by increased catabolism of triglyceride-rich lipoproteins by the lactating breast.

Adult↗
PubMed1985

Relationships of infant birth size to maternal lipoproteins, apoproteins, fuels, hormones, clinical chemistries, and body weight at 36 weeks gestation.

It has been hypothesized that plasma triglyceride fatty acids may traverse the placenta and contribute to infant adiposity particularly in GDM pregnancy. It has also been hypothesized that high-density lipoproteins (HDL) can both deliver cholesterol to and remove cholesterol from the placenta. To determine if these maternal parameters are related to fetal growth in normal pregnancy, we have examined relationships of lipoprotein lipids, apoproteins, hormones, fuels, clinical chemistries, and maternal weight at 36 wk gestation to infant birth weight, birth weight ratio (birth weight corrected for gestational age), birth length, and head circumference in a cohort of pregnant women attending a prepaid health plan, Group Health Cooperative of Puget Sound. Associations were examined using a multivariate regression analysis of several groups of related variables. Results show that the birth weight and/or birth weight ratio are weakly positively associated with maternal very-low-density lipoprotein (VLDL) triglyceride and statistically significantly positively associated with apoprotein A-I, placental lactogen, estradiol, bilirubin, and maternal prepregnancy weight and pregnancy weight gain. Glucose and insulin predict birth weight only in pairwise analysis. Significant negative predictors of birth weight or birth weight ratio include VLDL cholesterol, apoprotein A-II, SGOT, and creatinine. Significant positive predictors of birth length include apoproteins A-I, placental lactogen, and maternal weight. Apoprotein A-II negatively predicts birth length. Only maternal prepregnancy weight predicts head circumference.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Clinical chemistry alterations in pregnancy and oral contraceptive use.

In this study the effects of pregnancy and oral contraceptive use on plasma glucose concentrations, hepatic, renal, and thyroid function tests, and their relationships to plasma lipoprotein lipids after an overnight fast are compared. Observations were made in 546 pregnant women at 36 weeks' gestation, 56 women using oral contraceptive hormones, and 77 women not using sex hormones. All subjects were randomly selected from defined populations. Compared with nonpregnant women not using hormones, median plasma glucose concentrations are 3% lower with oral contraceptive use and 17% lower in pregnancy. Plasma total bilirubin concentrations are lowered by similar amounts in oral contraceptive users (29%) and in pregnancy (32%). Serum glutamic oxaloacetic transaminase is slightly lower among hormone users (9%) but is significantly higher (27%) in pregnancy. Alkaline phosphatase is significantly lower in oral contraceptive users (23%) but is higher in pregnancy (86%). Serum globulin concentrations are unaffected by pregnancy or oral contraceptive use. Compared with nonusers, thyroxine is 30% higher in oral contraceptive users and 100% higher during pregnancy. Serum creatinine is unaffected by sex steroid use but is 28% lower in pregnancy. Associations of these test results with plasma hormone concentrations corroborate hormonal mechanisms and suggest that some alkaline phosphatase and serum glutamic oxaloacetic transaminase come from the placenta. Relationships of these clinical measurements to lipoprotein lipids in pregnancy are generally weak and do not point to important controlling relationships, but effects similar to those seen in nonpregnant subjects are seen with hyperglycemia (associated with elevated triglyceride) and elevated thyroxine levels (associated with lower cholesterol and triglyceride).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Sex differences in the effect of diabetes mellitus on lipoprotein triglyceride and cholesterol concentrations.

We studied sex differences in the serum lipid abnormalities associated with diabetes mellitus in 111 patients with insulin-dependent diabetes and 270 patients with non-insulin-dependent diabetes, who were compared with 586 nondiabetic controls. Relative to control levels, the increases in triglycerides were 17 to 34 mg per deciliter greater in diabetic women than in diabetic men. The median low-density-lipoprotein cholesterol concentration in non-insulin-dependent diabetics was 1 to 4 mg per deciliter lower than the control level in women and 16 to 22 mg per deciliter lower in men, and was 30 mg per deciliter higher than control in insulin-dependent diabetic women and similar to control in insulin-dependent diabetic men. The decrease in median high-density-lipoprotein cholesterol in non-insulin-dependent diabetics was 2 to 7 mg per deciliter greater in women than in men, and the increase in high-density-lipoprotein cholesterol in insulin-dependent diabetics was 3 mg per deciliter less in women than in men. We conclude that diabetes has a greater adverse effect on triglyceride and lipoprotein cholesterol concentrations in diabetic women than in diabetic men, and that this may explain the greater increase in risk of arteriosclerosis in diabetic women.

Adult↗
PubMed1984

Lipid and lipoprotein triglyceride and cholesterol interrelationships: effects of sex, hormone use, and hyperlipidemia.

The interrelationships of lipid and lipoprotein cholesterol and triglyceride concentrations in normolipidemic and hyperlipidemic employees of the Pacific Northwest Bell Telephone Company were examined bivariately using correlation analysis and multivariately by factor analysis. Application of the latter resulted in the identification of three distinct lipoprotein lipid clusters, which succinctly describes their metabolic relationships. Among normolipidemic subjects, the interrelationships were found to be similar in male and female subjects, but hormone use by women considerably altered interrelationships that involved high-density lipoprotein cholesterol (HDL-C) and triglyceride. Among hyperlipidemic subjects, we found that elevation in cholesterol level alone rarely altered relationships, but elevation in triglyceride level either alone or in conjunction with an elevation in cholesterol concentration was associated with substantial changes in relationships involving the low-density lipoprotein (LDL) fraction. In many instances, positive relationships between LDL cholesterol (LDL-C) and other lipoprotein lipids became inverse in the presence of triglyceride elevation. We conclude that hormone use by women and hypertriglyceridemia with or without an elevation in cholesterol level clearly alter lipoprotein relationships, whereas pure hypercholesterolemia does not. These alterations provide a basis for investigating pathophysiologic mechanisms in hypertriglyceridemia.

Adult↗
PubMed1983

Malformations in infants of diabetic mothers: problems in study design.

Infants of diabetic mothers have a two- to threefold increased risk of having congenital malformations. Primary prevention of these malformations may be possible if the teratogenic mechanisms in diabetes can be identified. The Diabetes in Early Pregnancy Study (DIEP) addresses the questions of high malformation rates and fetal losses using an innovative study design. Women are recruited prior to pregnancy, monitored to ensure prompt diagnosis of pregnancy, and followed carefully for diabetic problems or fetal losses. To date, 450 diabetic and 550 normal control prepregnant women have been recruited. A basal body temperature monitoring system has been successful in identifying pregnant women within 21 days of conception. Before initiating such a study, problems of feasibility, study design, and possible bias had to be solved. This report summarizes our experience in designing and conducting a prospective pregnancy study. The DIEP demonstrates that a truly prospective pregnancy study is feasible.

Congenital Abnormalities↗
PubMed1983

First trimester serum zinc concentrations in human pregnancy.

Serum zinc concentrations in the 1st trimester of human pregnancy were evaluated in 106 women whose dates of conception were precisely determined by basal body temperature monitoring and human chorionic gonadotropin levels. Data are reported by intervals of postovulatory days. Sera were analyzed for zinc by atomic absorption spectrophotometry after acid digestion. Mean 1st trimester serum zinc concentrations, determined by 20-day increments from ovulation, were 0.97 +/- 0.22, 0.68 +/- 0.14, 0.77 +/- 0.18, and 0.70 +/- 0.15 micrograms/ml; differences between means were significant at p less than 0.005, less than 0.005, and less than 0.01, respectively. These differences could not be related to diet, supplement use, or hematocritic changes. No differences were apparent between diabetic and nondiabetic subjects. Of the 25 samples from women who aborted spontaneously, zinc concentration of seven were lower than interval means.

Abortion, Spontaneous↗
PubMed1982

Effects of oral contraceptives on lipoprotein triglyceride and cholesterol: relationships to estrogen and progestin potency.

Hormone formulation and estrogen/progestin potency were evaluated in relation to triglyceride and cholesterol concentrations in total plasma and lipoprotein fractions and in relation to lipid composition among a random sample of female telephone company personnel. Triglyceride concentrations in whole plasma, very low-density lipoprotein, and high-density lipoprotein (HDL) were elevated in response to increasing estrogen potency as were triglyceride concentrations in low-density lipoprotein (LDL). LDL cholesterol rose with increasing estrogen potency in contraceptive users but was slightly lower in postmenopausal estrogen-treated women. Plasma HDL cholesterol varied according to estrogen and progestin levels. The LDL cholesterol/triglyceride ratio was reduced for all combination oral contraceptives examined. Sequential oral contraceptives of postmenopausal estrogens did not significantly alter the cholesterol/triglyceride ratio in any lipoprotein fraction. Potential arteriosclerotic risk from sex hormone use may vary among oral contraceptive formulations.

Adult↗