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Biomedical subjects

W E Connor

Publications and source records attributed to W E Connor.

At least 145 records · Page 8Linked to original sources

Comparative lymphatic absorption of sitosterol, stigmasterol, and fucosterol and differential inhibition of cholesterol absorption.

Studies have been conducted on the lymphatic absorption of sitosterol (24 alpha-ethyl cholesterol), stigmasterol (delta 22, 24 alpha-ethyl cholesterol), and fucosterol (24-ethylidine cholesterol) when administered intragastrically to rats. In addition, the effect of each sterol on absorption of endogenous cholesterol has been assessed by including tracer cholesterol in the administered test emulsion. Analysis of 24-h lymph collections by GLC-mass spectrometry demonstrated that all three sterols were poorly absorbed to the extent of only 3 to 4% of the administered dose of 50 mg. In contrast, cholesterol absorption under similar conditions was about 42% of the administered dose. Administration of either sitosterol or stigmasterol resulted in an equally effective inhibition of cholesterol absorption (54%). Under identical conditions fucosterol had no effect on absorption of luminal cholesterol. The data suggest that the mechanism(s) for intestinal discrimination of sterols for absorption may be independent of the mechanism for interference with efficient cholesterol uptake by the intestine.

Absorption↗

The composition and nutritional adequacy of subject-selected high carbohydrate, low fat diets in insulin-dependent diabetes mellitus.

The composition and nutritional adequacy of subject-selected high carbohydrate, low fat diets were investigated in six women with insulin-dependent diabetes mellitus. Subjects were randomly assigned to begin either the experimental diet with 65% carbohydrate, 20% fat, and 15% protein for 6 wk, or a control diet with 45% carbohydrate, 40% fat, and 15% protein for 4 wk. All subjects completed both dietary periods in a cross-over experimental design. Subjects were allowed free selection in their choice of carbohydrate-rich foods. The resulting selections produced diets with 51% simple and 49% complex carbohydrates and 50 g of dietary fiber during the experimental diet. Similar proportions were also selected during the control diet. Blood chemistries revealed no significant changes in thiamin, riboflavin, vitamin B6, pyridoxal 5'-phosphate, ascorbate, vitamin E, calcium, selenium, or zinc concentrations between the two dietary periods. With the exception of vitamin B6, all vitamin and mineral values were within normal respective ranges. Vitamin B6 status, as assessed by pyridoxal 5'-phosphate, were below or just above the levels of marginal deficiency (2.2 nmol/100 ml) in four of the six individuals, but the lower level observed occurred independent of the dietary treatments. The present study demonstrates that subject-selected high carbohydrate, low fat diets were much lower in complex carbohydrates and fiber than diets previously tested. In addition, the concentration of several nutrients did not appear to be adversely affected by these diets.

Adult↗

The origin of plant sterols in the skin surface lipids in humans: from diet to plasma to skin.

To test the hypothesis that plant sterols found in the skin surface lipids of humans originated from diet after their absorption from intestine into plasma and then transferred to skin, we studied the 24-h excretion of plant sterols and cholesterol from skin and in feces in a hyperlipoproteinemic (type IIa) patient fed formula diets providing varying quantities of plant sterols (0-30 g/day) and cholesterol (0-1000 g/day). Upon feeding a sterol-free diet, the beta-sitosterol excretion from the skin decreased progressively, from about 6 mg/day to 0.08 mg/day by 83 days and then completely disappeared. With addition of plant sterols (about 30 g/day) to the diet, beta-sitosterol reappeared in the skin surface lipids and rose to nearly 5 mg/day by 6 weeks. With feeding of the sterol-free diet, the fecal excretion of beta-sitosterol and the 2 other plant sterols decreased gradually and by week 4 disappeared completely from the feces and continued to be absent from the feces as long as the diet was free of plant sterols. The results demonstrated clearly that plant sterols which were absorbed into the plasma from the diet were excreted into the skin surface lipids after being transferred from the plasma to the skin.

Cholesterol↗

Lipids of human atherosclerotic plaques and xanthomas: clues to the mechanism of plaque progression.

While the content of fatty streaks and fibrous plaques has been extensively studied in autopsied specimens, little is known about the lipid composition of advanced human atherosclerotic plaques requiring surgical removal. We have analyzed free cholesterol, cholesteryl ester, and the cholesteryl ester fatty acid content in 19 carotid and 7 femoral obliterative plaques obtained at endarterectomy. These were compared with values from each subject's plasma and from xanthomas removed from eight patients. The total cholesterol content was 75.1 mg/g dry weight for carotid plaques, 56.0 mg/g for femoral plaques, and 106.8 mg/g for xanthomas. The free cholesterol content was 56.6% and 50.4% of the total cholesterol for carotid and femoral plaques, respectively, while the free cholesterol of xanthomas was only 25.5%. The fatty acids of cholesteryl esters were analyzed in an attempt to identify the site of their esterification, i.e., within plasma or within plaque. This can be determined using the ratio of linoleic acid (18:2) to oleic acid (18:1) in the cholesteryl ester. The ratios were 0.36 for xanthoma, 1.62 for carotid plaque, 1.73 for femoral plaque, and 2.51 in plasma. These data emphasize two chemical changes occurring with evolution of the atherosclerotic process: 1) The cholesteryl ester fatty acid composition of the plaque becomes increasingly similar to that of plasma, and 2) there is a continuing increase in the percentage of free cholesterol. These alterations reflect a decreased metabolic efficiency within atherosclerotic lesions and may initiate events that enhance plaque progression.

Arteriosclerosis↗

Behavioral treatment of hyperlipidemia: techniques, results, and future directions.

The present review examines the role of several target behaviors in the treatment of hyperlipidemia, including diet, exercise, cigarette smoking, Type A pattern, and medication adherence. Modification of the typical American diet (high in cholesterol, fat, and sodium) is emphasized in the treatment of hyperlipidemia since a multitude of laboratory, clinical, and epidemiological studies have shown that diet plays a crucial role in the pathogenesis of this condition and an increase in coronary risk. Factors affecting patient compliance such as health beliefs and family support are discussed in terms of their impact on behavior change efforts aimed at reducing plasma lipids through dietary and drug regimens. Intervention studies are reviewed in the behavioral treatment of hyperlipidemia. These programs have focused on diet modification, exercise, and medication adherence to reduce plasma lipids and coronary risk. The role of other target behaviors (i.e., Type A pattern and smoking) is explored not only in determining coronary risk but also in terms of their direct impact on plasma lipids. Further research is necessary to clarify the relationship between these target behaviors and plasma lipid levels and to investigate the effects of innovative family- and group-based intervention procedures in promoting and maintaining habit change related to coronary risk reduction.

Behavior Therapy↗

Ciprofibrate in the therapy of type II hypercholesterolemia. A double-blind trial.

The hypolipidemic efficacy of ciprofibrate was evaluated in patients with type II hypercholesterolemia. Patients were randomized to placebo or ciprofibrate (50 mg or 100 mg/day) and, after a 6-week baseline period, received medication for a period of 12 weeks. Blood samples were analyzed every 2 weeks. Twenty patients completed the study (4 on placebo, 7 on 50 mg/day, and 9 on 100 mg/day ciprofibrate). The drug was well tolerated in all patients. Lipid values in the patients on active drug decreased and attained stable values after 4 weeks of treatment. Compared to baseline values, total and LDL cholesterol decreased 11% and 13% on the 50-mg dose whereas HDL increased 8%. Plasma triglyceride fell by 22%. In patients receiving 100 mg ciprofibrate, total and LDL cholesterol fell by 20% (334 leads to 269 mg/dl) and 24% (262 leads to 198 mg/dl), respectively. HDL increased 9.8% (51 leads to 56 mg/dl) and triglyceride decreased by 30% (102 leads to 69 mg/dl). Values in the placebo group remained stable. We conclude that once daily therapy with 100 mg ciprofibrate, is effective in reducing LDL levels in patients with type II hypercholesterolemia (mainly heterozygous FH) and that this decrease is paralleled by small rises in HDL.

Adult↗

The effect of shellfish in the diet upon the plasma lipid levels in humans.

In order to document any hypercholesterolemic effects from the ingestion of shellfish, 6 normal men were given two diets containing different shellfish, each preceded by a low cholesterol baseline diet. Diet I contained 449 mg cholesterol per day from lobster, crab, and shrimp. Diet II contained clam, oyster, and scallop and provided 447 mg of sterols of which cholesterol constituted only 40 percent. The other sterols are uniquely characteristic of these shellfish (i.e. brassicasterol, 24-methylene cholesterol, etc.). In a second study, 2 normal men and 1 type II hypercholesterolemic woman were fed the baseline diet and shellfish diet II to provide 623 mg of sterols per day. The plasma cholesterol of the 6 subjects averaged 184 +/- 35 mg/dl during baseline, 192 +/- 35 mg/dl in shellfish diet I (p less than 0.05) and 182 +/- 24 mg/dl during shellfish diet II. In the second study, the plasma cholesterol of the 2 normal men did not change. The cholesterol of the hypercholesterolemic woman increased from 311 mg/dl (baseline) to 352 during the shellfish diet (p less than 0.05). Plasma triglyceride levels remained unchanged. Our data indicated that large quantities of lobster, crab, and shrimp were only mildly hypercholesterolemic in normals, but less so than other cholesterol-containing foods. Clams, oysters, and scallops were not hypercholesterolemic in normal subjects but were in a hypercholesterolemic patient.

Adult↗

Dietary cholesterol and the plasma lipids and lipoproteins in the Tarahumara Indians: a people habituated to a low cholesterol diet after weaning.

Eight Tarahumara Indian men participated in a metabolic study to measure the responsiveness of their plasma cholesterol levels to dietary cholesterol. They were fed isocaloric cholesterol-free and high cholesterol diets containing 20% fat, 15% protein, and 65% carbohydrate calories. On admission to the study, the Tarahumaras had a low mean plasma cholesterol concentration (120 mg/dl), reflecting their habitual low cholesterol diet. After 3 wk of a cholesterol-free diet their cholesterol levels were 113 mg/dl. The men were then fed a high cholesterol diet (1000 mg/day) which increased the mean total plasma cholesterol to 147 mg/dl (p less than 0.01) and also increased the low-density lipoprotein cholesterol concentration. Tarahumaras, habituated to a low cholesterol diet after weaning, had the typical hypercholesterolemic response to a high cholesterol diet that has been previously observed in subjects whose lifelong diet was high in cholesterol content.

Adult↗

The effects of age, body wight and family relationships on plasma lipoproteins and lipids in men, women and children of randomly selected families.

Two hundred thirty-three families were randomly selected from a designated population base. Data from 619 persons ages 6--65 years had distributions of lipid and anthropometric values typical for the U.S. population. The typical rise in plasma cholesterol and triglyceride with age was also demonstrated. The plasma cholesterol and low-density lipoprotein (LDL) correlated more strongly with age than body weight, whereas the plasma triglyceride was more related to body weight than to age. High-density lipoprotein (HDL) was inversely correlated with weight and plasma triglyceride. Family membership accounted for approximately 20% of the variability in cholesterol, LDL, HDL and weight. Related family members (father-child, mother-child and siblings) had strong correlations for plasma cholesterol, LDL and HDL. These measurements did not correlate in the spouse pairs. The plasma triglyceride did not correlate for the family as a whole nor for the individual family members. This study indicates the importance of both chronic environmental factors and genetic family relationships on plasma lipids and lipoproteins.

Adolescent↗

Corticosteroid production in abetalipoproteinemia: evidence for an impaired response ACTH.

The concept that an inherent absence of plasma LDLs may be associated with a reduced synthesis of steroid hormones has been evaluated in two patients with ABL. Basal production of adrenal corticosteroids, assessed by the concentrations of serum cortisol and the rates of excretion of urinary 17OHCS and 17KS and urine free cortisol, was normal in both patients with ABL. Prolonged stimulation (24 to 36 hr) with ACTH, however, disclosed an impairment in adrenal corticosteroid production in both patients with ABL (as compared to normolipidemic controls), which was manifest by lower serum cortisol levels, reduced rates of urinary excretion of 17OHCS and 17KS and a marked decrease in the excretion of urine free cortisol. These results provide in vivo evidence to support the view that plasma LDLs serve as an important source of cholesterol for adrenal corticosteroid synthesis during prolonged stimulation with ACTH but show that a total absence of LDL does not impair adrenal steroidogenesis in the basal state.

17-Hydroxycorticosteroids↗

Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia.

The death of a 13-year-old boy from coronary atherosclerosis prompted the study of an Amish family. Five of his twelve sibs had tendon and tuberous xanthomas, and increased plasma plant sterols, particularly beta-sitosterol. The plasma level of the major apoprotein of low density lipoprotein (LDL), the B protein, was very high (mean 173 mg/dl) in these five sibs, while the LDL cholesterol level was moderately increased (209 mg/dl). Four other sibs and both parents had an increased LDL B protein level with a normal or mildly raised plasma total and LDL cholesterol level (hyperapobeta-lipoproteinaemia). Evidence for coronary artery disease was found in both parents and three xanthomatous sibs. The original family with beta-sitosterolaemia and xanthomatosis, described in 1974, was re-examined. The proband and her sister had persistent phytosterolaemia and normocholesterolaemia but increased LDL B protein levels. Both parents, two uncles, and three of four grandparents had increased LDL B protein levels and normal total and LDL cholesterol levels. The proband's father had atypical angina pectoris. People with the full syndrome (phytosterolaemia, xanthomas, and hyperapobetalipoproteinaemia) are most probably homozygous for a mutant allele. An increased LDL B protein level permits the identification of heterozygotes in these families, even though in the fasting state they show no phytosterolaemia. The homozygote and probably the heterozygote are at increased risk for cardiovascular atherosclerotic disease.

Adolescent↗

Colestipol plus nicotinic acid in treatment of heterozygous familial hypercholesterolaemia.

Thriteen patients with heterozygous familial hypercholesterolaemia (FH) were sequentially treated with: a low-cholesterol, fat-restricted diet; diet and colestipol; and diet and colestipol and nicotinic acid. Concentrations of plasma cholesterol decreased from 415 +/- 69 mg/dl on diet alone to 327 +/- 54 mg/dl on colestipol and fell to 246 +/- 49 mg/dl on the combined drug regimen. Plasma concentrations of LDL cholesterol declined 24% on colestipol; the subsequent addition of nicotinic acid resulted in a further 31% fall so that values on the combined drug regimen were 47% below those seen on diet alone. HDL cholesterol levels were similar on both the diet (40 mg/dl) and colestipol (43 mg/dl) treatment periods but increased to 53 mg/dl on the combined drug regimen. Treatment resulted in significant decreases in the LDL:HDL ratio which fell from 8.4 on diet to 3.3 on the colestipol plus nicotinic acid regimen. In most patients with heterozygous FH, combined use of a bile acid sequestrant and nicotinic acid affords the opportunity to maintain a normal lipid profile. Prolonged use of this regimen may reduce the incidence of premature coronary atherosclerosis which naturally occurs in these patients.

Adult↗

The effects of dietary cholesterol upon the hypercholesterolemia of pregnancy.

The hypercholesterolemia which accompanies the normal human pregnancy is not known to be influenced by diet or other factors. The present experiment in fourteen pregnant women was designed to document this phenomenon under controlled metabolic conditions and to study the effect of dietary cholesterol upon this usual increase in serum cholesterol. The subjects included twelve normal subjects, one juvenile diabetic, and one type II familial hypercholesterolemic subject. They were fed controlled, nutritionally adequate diets which were equivalent except for the cholesterol content, which was cholesterol-free or 600-1000 mg from egg yolk daily. Calories were adjusted to permit weight gain of 1.4 kg per mo. The cholesterol-free diet lowered th mean serum cholesterol level in the 12 normal pregnant women from 234-187 mg/dl, a 20% decrease (-47 +/- 37 S.D.) (p less than 0.005). The addition of cholesterol to the diet invariably elevated the mean serum cholesterol concentrations to 223 mg/dl, a 19% increase (+36 +/- 12) (p less than 0.001). The mean serum triglyceride levels increased steadily throughout pregnancy regardless of diet, up to 198 +/- 43 (S.D.) mg/dl at term. Both serum cholesterol and triglyceride concentrations decreased strikingly 1 wk after parturition. These serum cholesterol and triglyceride responses occurred similarly in the familial hypercholesterolemic and the diabetic women. The increased serum cholesterol levels during the high cholesterol diets occurred largely in the low density lipoprotein (LDL) fraction. Despite the inevitable alterations of cholesterol and lipoprotein homeostasis which occur in pregnancy, the results of this study indicated that the usual hypercholesterolemia of pregnancy in women eating the general American diet was greatly ameliorated by a very low cholesterol, nutritionally adequate diet.

Adolescent↗

Does egg feeding (i.e., dietary cholesterol) affect plasma cholesterol levels in humans? The results of a double-blind study.

In order to study the effects of dietary cholesterol in outpatients eating their usual home diets, we fed whole eggs and an egg substitute in a double-blind design to 16 normal volunteers. One-half cup of whole eggs (approximately 500 mg cholesterol) and a cholesterol-free egg substitute product were incorporated into the subjects' customary home diets for 4 wk each in a random order. Dietary cholesterol intake changed from a mean +/- SD of 196 +/- 112 mg/day during the egg substitute period to 728 +/- 119 during the whole egg period (p less than 0.001). The mean plasma cholesterol concentration during the whole egg period (243 +/- 39) was increased (p less than 0.01) 9% above the baseline level (223 +/- 40) and was increased (p less than 0.01) 11% above the egg substitute period (219 +/- 44). The mean plasma cholesterol concentration during the egg substitute period was not different from base-line. The feeding of whole egg in a double-blind study in outpatients eating their customary diets had a hypercholesterolemic effect compared to a cholesterol-free product.

Adult↗

Lymphatic absorption of shellfish sterols and their effects on cholesterol absorption.

Studies have been conducted on the absorbability of individual sterols from a mixture of oyster sterols when administered intragastrically to rats with indwelling catheters in the left thoracic duct. In addition, the effect of oyster sterols on cholesterol absorption has been assessed using [4-14C] cholesterol in the mixture, and comparison against absorption of cholesterol alone. The order of absorbability (percentage absorption) of individual sterols from the mixture of oyster sterols was: cholesterol greater than or equal to 26-carbon sterols greater than or equal to dehydrocholesterol greater than 24-methylene cholesterol greater than brassicasterol greater than plant sterols. The absorption of noncholesterol sterols was 8.2 +/- 0.8% of the fed dose, or less than half of that for an equivalent level of cholesterol alone. The presence of these sterols in mixtures containing cholesterol reduced lymphatic absorption of cholesterol by 25 to 40% compared to absorption of the same amount of cholesterol administered alone, or to an amount of cholesterol equal to the total oyster sterols, respectively. These studies suggest that shellfish sterols are poorly absorbed, and, like plant sterols, effectively reduce dietary and/or endogenous cholesterol absorption from the intestine.

Absorption↗

Familial hypercholesterolaemia and primary hypothyroidism: coexistence of both disorders in a young woman with severe hypercholesterolaemia.

Severe hypercholesterolaemia in a 7-year-old girl was found to be due to the coexistence of heterozygous familial hypercholesterolaemia and chronic lymphocytic thyroiditis with primary hypothyroidism. Her cultured skin fibroblasts showed a 70-75% reduction in the binding, internalization and degradation of 125I-labelled low density lipoprotein and several other family members were hypercholesterolaemic. Replacement therapy with L-thyroxine reduced the concentrations of total and low density lipoprotein cholesterol and apoprotein B in the patient's plasma to values similar to those in other sibs with only heterozygous familial hypercholesterolaemia. Severe hypercholesterolaemia attributable to coexistent heterozygous familial hypercholesterolaemia and hypothyroidism in teenage girls may be estimated to occur with a frequency of between 1 and 500 000 and 1 in 10(6). This value is similar to the gene frequency for homozygous familial hypercholesterolaemia.

Adolescent↗