Search PubMed⌕ Search

Biomedical subjects

S C Hunt

Publications and source records attributed to S C Hunt.

141 records · Page 8Linked to original sources

Genetic analysis of sodium-lithium countertransport in 10 hypertension-prone kindreds.

The rate of sodium-lithium countertransport (SLC flux) across red cell membranes has been reported to be elevated in hypertensive persons and their relatives as compared to normotensive individuals without family histories of hypertension. We have investigated the inheritance of this trait in 434 persons from 10 kindreds. Relatives show positive correlation of SLC flux values, but there is no spouse-spouse correlation. Pedigree analysis favors a model of polygenic inheritance over models of major-gene inheritance. Major-gene index statistics and offspring-between-parent statistics provide similar results. The proportion of total phenotypic variance that is attributable to polygenic differences between persons is estimated at 71%. The SLC flux values of hypertensive persons in this study population are lower than those reported from Boston, but are similar to those reported from Europe. We found a broad overlap of SLC flux values for hypertensive and normotensive persons. We conclude that SLC flux probably is not useful as a preclinical marker for essential hypertension.

Adolescent↗

The treatment of myopia with atropine and bifocals. A long-term prospective study.

Two hundred fifty-three patients were followed for up to nine years (mean, 4 1/4 years). They were on a regimen of atropine 1% once a day in an attempt to retard myopic progression. Their rate of myopic progression prior to atropine treatment was compared with 146 controls. The rates of myopic progression during and after treatment were also compared to those of the controls. The results from several analyses showed a marked flattening in the rate of myopic progression during treatment, and the rate of myopic progression after treatment ran parallel to those in the control group. Age in relation to myopic progression was evaluated in subgroups. A variation existed in the rate of myopic progression in the controls. The fastest rate of myopic progression occurred between eight and 12 years of age, and the slowest rate of myopic progression developed in those patients over 18 years of age.

Adolescent↗

The relationship of plasma ionized calcium to cardiovascular disease endpoint and family history of hypertension.

Plasma ionized calcium and total calcium were measured on 271 individuals from 34 Utah pedigrees divided into groups defined by the method of pedigree ascertainment: 1) hypertension clusters, 2) early stroke death clusters and 3) clusters of early heart attack deaths. Normotensive individuals were also categorized by family history of hypertension. Members of stroke cluster pedigrees had higher mean plasma ionized Ca2+ than either hypertension pedigrees (p less than 0.05) or coronary artery disease pedigrees which had the lowest concentrations (p less than 0.001). Within the normotensive group, those subjects with a positive family history of hypertension exhibited significantly higher plasma ionized Ca2+ (2.18 +/- 0.10 (S.D.) mEq/l) than individuals without a family history of hypertension (2.12 +/- 0.08 mEq/l, p less than 0.01). In medicated hypertensives, both ionized (p less than 0.05) and total (p less than 0.01) plasma calcium were higher than calcium levels in the normotensive negative family history subjects. Plasma ionized Ca2+ in the adult normotensives (N = 134) had significant age corrected positive correlations with plasma sodium (r = 0.25, p less than 0.01), potassium (r = 0.29, p less than 0.001) and erythrocyte sodium-lithium countertransport values (r = 0.20, p less than 0.05). These findings provide additional evidence that plasma ionized calcium concentrations may be important to help define the heterogeneity of hypertension in adult Americans.

Adult↗

Magnified risks from cigarette smoking for coronary prone families in Utah.

The contribution of currently accepted risk factors to the familiality of early coronary heart disease (CHD) is poorly understood. In a telephone and mail survey, risk factor and disease morbidity and mortality data were collected from 100 proband and 185 control families encompassing about 40,000 person-years of experience. Probands were white married men who had died of CHD by age 45. There was a threefold increase in CHD incidence among first-degree relatives of probands compared with control families. In all, 67% of probands had at least one first-degree relative with early CHD, and 29% had two or more first-degree relatives with early CHD compared with 8% of the control families with two or more cases of early CHD. The most striking new finding of this study is the apparently magnified liability of cigarette smoking in families prone to have early coronary heart disease. This effect was seen strongly at younger ages (under 50). Furthermore, in about a third of all families with a history of early CHD, smoking seemed to be the only risk factor contributing to the familial occurrence of the disease. The findings show a large excess absolute risk for CHD among smoking members of proband families and further suggest a possibly heritable susceptibility to the deleterious effects of smoking in many families prone to early coronary disease. Modification of coronary risk factors, especially cigarette smoking, would be of greatest benefit among members of high-risk families.

Adult↗

Lack of association of diagonal earlobe crease with other cardiovascular risk factors.

The relationship between diagonal earlobe crease and coronary risk factors, controlling for age and sex effects, was tested in 686 persons. A positive correlation (rho=.86, P<.001) is obtained between age and percentage of persons with earlobe creases in each one-year age interval; no sex difference is seen. To test for associations between cardiovascular risk factors and earlobe creases, 67 persons with creases are compared with 67 controls (matched by age and sex) without creases, using the following variables: diastolic and systolic blood pressures, cigarette smoking, weight, height, scapular skinfold thickness, serum cholesterol level, high-density lipoprotein level, intracellular sodium, sodium-lithium countertransport, plasma renin level and the presence of diabetes and hypertension. None of these variables differs significantly between cases and controls, indicating that the previously documented association between earlobe crease and coronary heart disease may be independent of these risk factors. Although coronary heart disease has often been shown to aggregate in families, no familial aggregation is found for earlobe creases.

Adolescent↗

Sodium-lithium countertransport in erythrocytes of hypertension prone families in Utah.

Sodium-lithium countertransport was measured in July 1980-December 1982 in 841 persons from 48 Utah families prone to hypertension. Mean countertransport in 54 hypertensive adults (0.32 +/- 0.01 standard error of the mean) was significantly higher than in 511 normotensive adults (0.26 +/- 0.005, p less than 0.001) but with much overlap between the two groups. This difference was observed in both men and women. Only 26% of the subjects with essential hypertension had values above 0.40 (considered "high" by most other published reports). High values were seen in only 2% of 276 youths under age 18 years in contrast to 11% of the normotensive adults (p less than 0.001). Among normotensive adults, countertransport was higher in men than women, and correlated with weight, diastolic blood pressure, and age (all significant at p less than 0.01). None of these findings were seen in youths. In multivariate analyses, only weight continued to be significantly correlated with countertransport. The difference between countertransport levels in hypertensive vs. normotensive adults remained significant even after adjusting for weight. While confirming other reports of higher mean sodium-lithium countertransport in persons with essential hypertension, this study shows much overlap of values between groups and potential confounding effects of weight. When the authors compared their results with studies that show little overlap between hypertensive and normotensive adults, they found that the data for the normotensive adults in this study are similar to those reported in the other studies, but that the hypertensive adults include a larger percentage of individuals with low countertransport values.

Adolescent↗

A reproducible sodium-lithium countertransport assay: the outcome of changing key laboratory parameters.

This paper describes experimental conditions for reproducible measurement of sodium-lithium countertransport in red blood cells. The assay is sensitive to temperature (10% per degree C) and the condition of the red cells; it is affected little by changes in intracellular lithium over the range 2-7 mmol/1 or by red cell concentrations with laboratory hematocrits of 0.03 to 0.07. Repeated measurements of the same subjects give day-to-day coefficients of variation of 10% or less. The mean difference for interlaboratory comparisons is 11%.

Biological Transport↗

Breast cancer and reproductive history from genealogical data.

With the use of data from the Utah State Cancer Registry and Utah genealogical data, an analysis of 236 breast cancer patients and 937 controls matched on year of birth showed that a late age at the birth of the first child was most strongly associated with incidence of breast cancer (relative odds = 2.0; P less than 0.001). A strong interaction was found between age at first delivery (AFD) and age at last delivery (ALD). The association of AFD with breast cancer incidence was strongest for women with an ALD before 35 years of age even after adjustment for partly (relative odds = 4.1; P less than 0.001). Decreased parity was not significantly associated with breast cancer.

Adult↗

Type III dyslipoproteinemia in patients heterozygous for familial hypercholesterolemia and apolipoprotein E2. Evidence for a gene-gene interaction.

In four large pedigrees with heterozygous familial hypercholesterolemia (FH) genetically linked to the low density lipoprotein receptor locus, we have observed a strong interaction between the presence of FH and a single apolipoprotein (apo) E2 allele, resulting in a markedly increased prevalence of type III dyslipoproteinemia (DLPIII). DLPIII was defined by chemical criteria. None of the patients with DLPIII had tuberous or palmar xanthomas characteristic of classically defined type III hyperlipoproteinemia. After exclusion of four persons with apo E 2-2 phenotype, there were 89 FH patients and 110 non-FH subjects. Definite DLPIII (defined as a very low density lipoprotein [VLDL] cholesterol to plasma triglyceride ratio greater than 0.30 with plasma triglycerides greater than or equal to 150 mg/dl) was present in 26% of 43 FH patients with a single E2 allele compared with only 3.4% of 29 non-FH subjects with an E2 allele (p = 0.003). To further characterize this interaction we performed a two-way analysis of covariance, after adjustment for age, sex, and body mass index, to test for any interaction between FH and the apo E loci. There was a statistically significant interaction between FH and the presence of a single E2 allele for the ratio of VLDL cholesterol to plasma triglycerides and for a newly derived estimate of beta-VLDL cholesterol concentration. Estimated beta-VLDL cholesterol level was strongly correlated with age in the subgroup with FH and an E2 allele but not in other subgroups. There was no difference in estimated beta-VLDL cholesterol between sexes. Correlation between estimated beta-VLDL cholesterol level and body mass index in persons older than 18 years was of only marginal significance and of similar magnitude in persons with or without an apo E2 allele. Present knowledge suggests that beta-VLDLs are highly atherogenic; if so, then a sizable subset of FH patients having at least one apo E2 allele and DLPIII may be at increased risk for premature coronary heart disease.

Adolescent↗

Apolipoprotein, low density lipoprotein subfraction, and insulin associations with familial combined hyperlipidemia. Study of Utah patients with familial dyslipidemic hypertension.

Familial dyslipidemic hypertension (FDH) is a syndrome recently described from sibships selected for early familial hypertension and found to have one or more of three fasting lipid abnormalities [high triglycerides, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol]. In further analyses of these same 131 hypertensive subjects, apolipoprotein A-I and B, fasting plasma insulin (adjusted for body mass index), and detailed anthropometrics were different in two subgroups of FDH. Of 63 FDH patients, 19 met the criteria for familial combined hyperlipidemia (FCHL); 44 did not, but still had high triglyceride and/or low HDL cholesterol levels. When compared to 20 normolipidemic hypertensive patients, the 19 hypertensive patients with FCHL had 196% higher very low density lipoprotein cholesterol (p = 0.0001), 33% higher apolipoprotein B (p = 0.0002), smaller LDL particles (p = 0.007), and 73% higher fasting insulin (p = 0.003), but no significant differences in body mass index or skinfold thicknesses. The other 44 FDH patients without FCHL had 33% lower HDL (p = 0.0001), with only 8% lower apolipoprotein A-I levels (p = 0.20); significantly higher subscapular skinfolds (p = 0.02), weights (p = 0.002), body mass index (p = 0.006), knee widths (p = 0.0007), and wrist circumferences (p = 0.0009); smaller, denser LDL subfractions (p = 0.001); and increased apolipoprotein B levels (p = 0.01) compared to the normolipidemic hypertensive group. Increased fasting insulin levels were similar to the normolipidemic group and significantly lower than the FCHL group after adjustment for body mass index, suggesting a relationship between obesity and fasting insulin levels only in the non-FCHL group. We conclude that FDH consists of at least two subgroups: 1) FCHL with high apolipoprotein B, small LDL particles, and increased fasting plasma insulin levels, and 2) a less well-defined residual having upper central obesity with low HDL cholesterol and high triglyceride levels. Elevated insulin levels found in both groups, but possibly originating through different physiological mechanisms, may provide the pathophysiological connections between dyslipidemia, obesity, and hypertension.

Apolipoprotein A-I↗

Three red cell sodium transport systems in hypertensive and normotensive Utah adults.

Sodium-lithium countertransport (SLC), sodium-potassium cotransport (CoT), and ouabain binding to sodium-potassium adenosine triphosphatase (Na, K-ATPase) sites were measured on fresh erythrocytes from hypertensive and normotensive Utah subjects with and without a first-degree relative with hypertension. SLC was measured as Li+ efflux into NaCl and MgCl2 media from Li+-loaded cells (5-7 mM). CoT was measured by monitoring Na+ and K+ efflux from cells loaded to 20-30 mM Na+ and 20-30 mMK+. Ouabain binding was determined for fresh cells using 3H-ouabain. Subjects were selected from pedigrees that showed a prevalence of hypertension. SLC was significantly elevated in 26.5% of the hypertensive subjects (p less than 0.001) as well as in 12.8% of the normotensives with a hypertensive first-degree relative (p less than 0.05). Although elevated SLC and decreased CoT have previously been associated with hypertension, no hypertensive subject in this study exhibited both abnormalities. All subjects with elevated SLC had normal CoT. A positive correlation between SLC and CoT was observed. Few hypertensive subjects (11.8%) had decreased CoT. In the majority of subjects studied, both SLC and CoT were normal: hypertensives 61.8%, normotensives with a hypertensive first-degree relative 61.7%, and other normotensives 58.7%. The number of ouabain-binding sites was not significantly altered among hypertensives, or their relatives, even though there was a positive correlation between SLC and the number of ouabain-binding sites.

Adult↗