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Biomedical subjects

R H Knopp

Publications and source records attributed to R H Knopp.

At least 145 records · Page 8Linked to original sources

Relationships of gender, sex hormone use, and age with lipoprotein cholesterol/triglyceride ratios in an adult population. The Pacific Northwest Bell Telephone Company health survey.

UNLABELLED: Effects of gender, sex hormone use, and age on lipoproteins composition have been evaluated in 603 Caucasian subjects, ages 20-59, randomly selected from employees participating in the Pacific Northwest Bell Telephone Company Health Survey. Lipoprotein composition in this analysis is defined as the cholesterol to triglyceride (C/TG) ratio in each lipoprotein fraction. The lipoprotein C/TG ratio is inversely related to the lipoprotein triglyceride concentrations in VLDL, LDL and HDL; the ratio falling in each instance as lipoprotein triglyceride concentration increases. Plots of this relationship are virtually superimposable among women hormone users and nonusers and men in VLDL and HDL and between men and nonhormone taking women in LDL. A consistently lower C/TG ratio is observed in LDL for hormone-treated women compared to the other 2 groups. Age in these analysis is without effect. CONCLUSIONS: We hypothesize that a lower LDL (C/TG) ratio is hormone-treated women may render the lipoprotein less crystalline or smectic and potentially less atherogenic. No such difference exists in the lipoprotein C/TG ratio between men and nonhormone-treated women and therefore cannot explain the observed difference in atherosclerosis sick. Nonetheless, the C/TG ratios may predict atherosclerosis if the ratio is high in VLDL or in LDL. However, the significance of the HLD (C/TG) ratio remains to be established.

Adult↗

Distribution of lipoproteins triglyceride and lipoprotein cholesterol in an adult population by age, sex, and hormone use- The Pacific Northwest Bell Telephone Company health survey.

This report describes the distribution of lipoprotein triglyceride and lipoprotein cholesterol in employees of the Pacific Northwest Bell Telephone Company. Means, medians, and selected percentiles are presented for very low, low, and high density lipoproteins (VLDL, LDL, and HDL, respectively) in 606 randomly selected white subjects aged 20-59. Results are specific for age decade, sex, and female sex hormone usage. Women who use sex hormones have significantly higher concentrations of triglycerides in all of the fractions across all age decades from 20 to 59 than do women not taking hormones. The average VLDL, LDL, and HDL triglyceride levels in women taking hormones are 69, 25 and 18 mg/dl which are considerably higher than the corresponding averages of 44, 17 and 12 mg/dl noted in women not taking hormones. Men have the highest average VLDL triglyceride value (85 mg/dl) but their average triglyceride concentrations in the LDL and HDL fractions (18 and 12 mg/dl) approximate those of women not taking hormones. This study in a well-defined population provides references standards for lipoprotein triglyceride concentrations. These results can be used to evaluate the effect of sex hormone treatment on the lipoprotein triglyceride content in VLDL, LDL and HDL, and to assess triglyceride content as a potential risk factor in men and older women.

Adult↗

Lipid metabolism in pregnancy. VIII. Effects of dietary fat versus carbohydrate on lipoprotein and hepatic lipids and tissue triglyceride lipases.

UNLABELLED: We have asked, is hypertriglyceridemia in the fed state in pregnancy due to intolerance to exogenous fat, accumulation of endogenous triglycerides, or accumulation of remnants of d < 1.006 lipoprotein metabolism? To answer these questions, we fed fat-free diets high in starch or sucrose, or diets containing fat or fat plus cholesterol to pregnant and nonpregnant rats for 12 days until gestational day 21 (term = 22 days). Blood was obtained 0, 4, or 8 hr after removal of food from the cages. Lipid concentrations were determined in chylomicrons and very low, low, and high density lipoproteins. Hypertriglyceridemia in pregnancy exists on both starch and sucrose containing fat-free diets and is exaggerated 4 and 8 hr after food is removed from the cage. The triglyceride rise occurs in d < 1.006 lipoproteins. With fat feeding, chylomicron triglyceride concentrations are not significantly elevated in pregnant rats, 0 or 8 hr postabsorptively despite greater food intake in pregnancy. In contrast, very low density lipoprotein (VLDL) triglyceride concentrations are elevated at all times following fat feeding in pregnant compared to nonpregnant animals. A significant contribution of lipoprotein remnants to the triglyceride rise in d < 1.006 lipoproteins seems unlikely since an isolated increase in VLDL cholesterol is not observed. No statistically significant accumulation of hepatic triglycerides occurs on any diet in pregnancy. Diet induced shifts in adipose tissue and muscle lipoprotein lipase activity are exaggerated in pregnancy while hepatic lipase is unaffected. Fetal weight is similar on all diets except sucrose where weight is reduced. CONCLUSIONS: Hypertriglyceridemia in fed pregnant rats is due to an increase in endogenous triglycerides. Remnant lipid accumulation does not appear to contribute to the endogenous hypertriglyceridemia. There is no intolerance to exogenous (dietary) fat. The results are compatible with an unimpaired delivery of exogenous fat to fat oxidizing tissues thereby maximizing glucose availability for fetal growth.

Adipose Tissue↗

Dietary management of the pregnant diabetic.

The tendency of the pregnant diabetic to fasting ketosis limits the extent to which calorie restriction (particularly negative calorie balance) can be used in the treatment of the obese, adult-onset, pregnant diabetic. In addition, the vagaries of measuring excess weight gain and detecting extraneous sources of weight gain in diabetic pregnancy, and the difficulty of accurately enforcing a caloric prescription without forcing the subject to weigh her food, make the determination of an accurate degree of caloric limitation difficult at best. A greater reliance on the mother's appetite center may be more accurate and rewarding in most instances than any devices available to the clinician. Important considerations in the diet of the pregnant diabetic are adequate protein, minerals, and vitamins, an amount of carbohydrate that is constant from day to day but not necessarily restricted, carbohydrate intake in an unrefined form that maximizes the intake of associated fiber, and a reproducible meal and snack schedule which complements in insulin regimen. Insulin must remain the primary therapeutic tool if the effects of maternal diabetes on fetal morbidity and mortality are to be minimized.

Adipose Tissue↗

Lipid metabolism in pregnancy. IV. C Apoprotein changes in very low and intermediate density lipoproteins.

In vitro studies indicate that relative amounts of apolipoproteins CII and CIII in plasma may alter lipoprotein lipase mediated triglyceride removal from very low density lipoprotein. Therefore, we have determined relative amounts of these peptides in pregnant women in late gestation (mean 36 weeks) and 6 and 20 weeks postpartum. Very low density (d less than 1.006) and intermediate density (d 1.006-1.019) lipoproteins have been examined because they are affected similarly in pregnancy. Triglyceride and cholesterol in these two fractions increased 3 1/2 to 4 1/2-fold in pregnancy in keeping with previous reports. On a relative basis, apo CII was decreased and apo CIII1 and CIII2 increased in both VLDL and IDL at 36 weeks gestation. At 6 and 20 weeks postpartum relative amounts of C peptides returned to identical levels and were unaffected by lactation. It remains to be seen if in vivo triglyceride removal in pregnancy is altered by the reduction in apo CII relative to apo CIII.

Adult↗

Effect of intravenous glucagon on urinary catecholamine excretion in normal man.

We have evaluated intravenous glucagon as pharmacologic stimulus to adrenal catecholamine secretion in normal human subjects. Urinary epinephrine and norepinephrine were measured at two hourly intervals before and after the intravenous injection of saline, 4 mg glucagon, or 0.1 mu/kg crystalline insulin. Urinary epinephrine was increased 2.3-fold over baseline after both saline and glucagon. By contrast, insulin hypoglycemia produced a 24-fold rise in urinary epinephrine. No rise in urinary norepinephrine was detected in any test. Under the conditions of this study, we conclude that epinephrine excreted after glucagon injection is due to the stress of the test itself. In normal man, glucagon either does not stimulate adrenal catecholamine secretion, or the effect is too small to measure. By contrast, in pheochromocytoma, glucagon may be specific for catecholamine secretion, based on data from the literature. In normal subjects, insulin hypoglycemia remains the only proved method for assessing adrenal catecholamine reserve.

Adrenal Glands↗

Effects of aspartame in young persons during weight reduction.

Given the potential use of a low-calorie sweetener during weight reduction, a toxicity study of chronic aspartame ingestion was conducted. Particular attention was given to possible long-term effects of aspartame on the fuel hormonal alterations characteristically caused by weight reduction. As a group mean age was 19.3 yr, body weight was 164.6 lb, and mean height was 65.4 in. Subjects were an average of 33% in excess of ideal body weight. The aspartame dose was 2.7 g/day and was compared on a double-blind randomized basis with a lactose placebo. Both materials were given in gelatin capsules. An average of 6.9 +/- 1.5 lb was lost by the aspartame group during the 13-wk study on a calculated 1,000-calorie diet. The placebo group lost 4.5 +/- 1.2 lb (no significant difference between the two groups). After an overnight fast, reductions in glucose and immunoreactive insulin were seen in both groups, while rising trends in immunoreactive glucagon were observed. These changes are all characteristic of calorie restriction. In no instance was there a detectable effect of the ingested aspartame. No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol, nor on any other parameter of hematologic, hepatic, or renal function that was measured. Similarly, side effects were equally distributed between asparatame and placebo.

Adolescent↗

Quality, efficiency, and cost of a physician-assistant-protocol system for managment of diabetes and hypertension.

Briefly trained physicians assistants using protocols (clinical algorithms) for diabetes, hypertension, and related chronic arteriosclerotic and hypertensive heart disease abstrated information from the medical record and obtained history and physical examination data on every patient-visit to a city hospital chronic disease clinic over a 18-month period. The care rendered by the protocol system was compared with care rendered by a "traditional" system in the same clinic in which physicians delegated few clinical tasks. Increased thoroughness in collecting clinical data in the protocol system led to an increase in the recognition of new pathology. Outcome criteria reflected equivalent quality of care in both groups. Efficiency time-motion studies demonstrated a 20 per cent saving in physician time with the protocol system. Coct estimates, based on the time spent with patients by various providers and on the laboratory-test-ordering patterns, demonstrated equivalent costs of the two systems, given optimal staffing patterns. Laboratory tests were a major element of the cost of patient care,and the clinical yield per unit cost of different tests varied widely.

Costs and Cost Analysis↗

Lipid metabolism in pregnancy. II. Postheparin lipolytic acitivity and hypertriglyceridemia in the pregnant rat.

Plasma postheparin lipolytic activity (PHLA) has been measured in rat pregnancy to qualitatively assess mechanisms of triglyceride removal from the circulation. This assessment can be made if the larger plasma volume of pregnancy is considered. A supramaximal dose of heparin avoids dilution of the heparin stimulus to PHLA release. Dilution of the released PHLA is corrected using measurements of plasma volume. In addition, no evidence of circulating inhibitors is present, and timing of PHLA appearance is unaffected by pregnancy. Prior studies of postheparin lipolytic activity in human pregnancy have not taken the effect of plasma volume into account and must therefore be reconsidered in light of the present results. We observed a biphasic pattern in PHLA over the course of gestation. Levels were increased in midgestation (day 12), declined to normal by day 19, and fell rapidly to one-half of control by day 21. Assuming a functional role for the triglyceride lipases represented in PHLA, the data suggest the following hypothesis: triglyceride removal is increased or normal for the greater part of gestation and is decreased only at term. If this hypothesis proves true, the hypertriglyceridemia of pregnancy should be due largely to overproduction, with decreased removal contributing only near term.

Adipose Tissue↗

Plasma glucagon and insulin in rat pregnancy. Roles in glucose homeostasis.

To determine if pancreatic glucoregulatory hormones can be implicated in the glucose fall of pregnancy, we have measured plasma immunoreactive insulin and glucagon (IRI and IRG) in rats. Fed rats in midgestation show a rise in IRI without a corresponding increase in IRG. In late gestation, IRG rises significantly, but only enough to keep pace with a further rise in IRI. On a molar basis, IRI remains the predominant hormone despite a marked fall in blood glucose. After a 48-h fast IRI falls to comparably low levels in pregnant and virgin rats. A small rise in IRG is seen in virgin but not in pregnant rats despite frank hypoglycemia in the latter. Thus, IRG secretion in pregnancy is diminished relative to IRI in the fed state and fails to increase in the fasted state despite the stimulus of a lower glucose in both instances. To evaluate IRG secretory reserve, the IRG response to i.v. alanine was assessed in late gestation. In fed rats a greater IRG increase is seen in pregnancy; after fasting no difference is seen between pregnant and virgin rats. These results preclude an absolute deficiency in glucagon secretion. Pancreas hormone stores were alos measured in an effort to explain the altered secretory state. We find reciprocal changes in IRI and IRG content favoring IRG in midgestation and IRI in late gestation. Thus, pancreas hormone storage is altered in pregnancy but does not account for the changes in hormone secretion. Rather, pregnancy exerts an effect on the islet secretory process itself. Release of IRI is enhanced relative to IRG regardless of the blood sugar level. These observations suggest that in the pregnant rat circulating levels of insulin and glucagon may act to limit hepatic glucose output. Available evidence from the literature supports the concept of restrained glucose production. It is proposed that a lower blood glucose production. It is proposed that a lower blood glucose in rat pregnancy may be a lesser liability teleologically than would be the obligate nitrogen wasting which accompanies gluconeogenesis.

Alanine↗

Lipid metabolism in pregnancy. II. Altered lipid composition in intermediage, very low, low and high-density lipoprotein fractions.

The hyperlipidemia of pregnancy consists primarily of an increase in triglyceride with lesser rises in cholesterol and phospholipid. As a further characterization, we have analyzed all lipids in the major lipoprotein subfractions in fasting pregnant and non-pregnant women. An elevated triglyceride in the major lipoprotein fractions in pregnancy is confirmed. The triglyceride rises in VLDL and IDL (density 1.006-1.019 lipoprotein) are associated with proportional rises in cholesterol and phospholipid. The result is a 3-4-fold increase of compositionally unchanged lipoprotein lipid. Contrasting changes are seen in LDL, density 1.019-1.063 lipoprotein, and HDL. In these fractions, triglyceride rises more than cholesterol and phospholipid. As a result, an increase in triglyceride on a percentage basis tends to reduce the contribution of the other two lipids. Nonetheless, on an absolute basis HDL cholesterol is not significantly reduced. The proportional increases in all lipids of VLDL and IDL fractions are consistent with increased VLDL production in pregnancy as suggested by data from animal systems. However, alterations in removal are not rules out. Maintenance of the HDL cholesterol level distinguishes pregnancy from other endogenous hypertriglyceridemias where HDL cholesterol is reduced. One may speculate that these physiological adaptations in material lipid transport can serve the increased energy needs of the mother, supply steroid hormone precursors for the placenta, and provide cholesterol and essential fatty acids for the fetus.

Cholesterol↗