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Biomedical subjects

R R Williams

Publications and source records attributed to R R Williams.

At least 181 records · Page 10Linked to original sources
PubMed1985

Urinary kallikrein: assay validation and physiological variability.

Decreased urinary kallikrein (UK) output has been suggested as a preclinical indicator of essential hypertension. In preparation for UK studies in hypertension prone Utah kindreds, we assessed selected UK assay parameters and physiological variability. Precision for the colorimetric kallikrein assay was quite acceptable, coefficient of variation (CV) less than 5% within run and 14% day-to-day at a concentration of 9.5 TU/l. The mean recovery was 105% and assay results were correlated with results from the 3H-TAME esterase method, r = 0.990. Urine specimens were stable at room temperature for up to 4 days, frozen at -20 degrees C for 6 weeks, or frozen at -80 degrees C after Sephadex treatment for a year. UK output varied significantly throughout the day with excretion highest in the morning. Urine collections at 10.00, 12.00 and 14.00 had significantly (p less than 0.05) more UK than the overnight collection. Intra- and inter-individual variations were of the same magnitude, mean 20%. In children UK output increased with age until the adult levels were reached at age 15. Male and female values were similar. Smoking; consumption of alcohol, coffee, tea, cola of chocolate; and female hormone medications did not significantly influence the 12-hour UK output in the 1110 caucasian subjects.

Adolescent↗
PubMed1985

Effects of household sharing on high density lipoprotein and its subfractions.

Household effects accounted for significant proportions of the observed variance of high density lipoprotein cholesterol (HDL-C) and subfractions HDL2 and HDL3. It was found that 19.3% of HDL-C variance could be attributed to a juvenile sib effect (under age 18); 17.4% of HDL2 variance could be attributed to a sib effect (of any age); and 22.1% and 32.6% of the HDL3 variance could be attributed to a parent-offspring effect and a sib effect (of any age), respectively. In addition, additive genetic effects accounted for 56.5%, 37.3%, and 28.3% of the variances of HDL-C, HDL2, and HDL3, respectively. These are maximum likelihood estimates obtained using a variance components model on 2,149 HDL-C levels measured on members of 54 Utah pedigrees, and 337 HDL2 and HDL3 levels measured on a subset of 14 pedigrees.

Adult↗
PubMed1985

Preventing coronary heart disease in high-risk families.

A preventive nursing intervention to reduce coronary heart disease (CHD) risk was tested. The sample was 19 families composed of 58 first-degreed relatives of young (age 30-55 years) victims of sudden cardiac death. Families were randomly assigned to control and experimental groups. The intervention at 3-5 months postdeath focused on assessment of health history, health behaviors, health beliefs, informing and educating about CHD risk factors, and methods for detecting and reducing these factors. The control group received mailed questionnaires and no intervention. The subject's reduction of CHD risk was measured at 7 months by changes in high risk CHD behaviors, changes in health beliefs, and adherence to screening for serum cholesterol and blood pressure determination. Analysis of covariance (covarying age and pretest scores) demonstrated no differences between groups for health beliefs; however, significant differences for health beliefs existed between the sibling subgroups. The intervention was correlated with a significant reduction in alcohol intake. Reductions in high fat meat consumption were in the desired direction. Greater percentages of subjects in the intervention group obtained blood pressure and cholesterol screening.

Adult↗
PubMed1985

Heritability of cardiac size: an echocardiographic and electrocardiographic study of monozygotic and dizygotic twins.

Because of the uncertainty as to the extent to which cardiac size is determined by exercise training vs genetic endowment, this study investigated familial (genetic plus common family environment) vs nonfamilial influences on cardiac size. College-age monozygotic twins (group 1, 31 sets), dizygotic twins (group 2, 10 sets), siblings of like sex (group 3, six sets), and nonrelated subjects (group 4, 15 sets) underwent echocardiographic and electrocardiographic tests, measurement of maximum oxygen uptake (VO2max), and evaluation of pulmonary and body composition; mean intrapair differences of the four groups were compared. Mean intrapair differences in cardiac size varied as much for subjects in group 1 as for those in groups 2 and 3. However, subjects in groups 1, 2, and 3 had less variation (p less than .05) than those in group 4. After the initial testing, 14 pairs of monozygotic twins, five sets of dizygotic twins, and six sets of siblings underwent 14 weeks of exercise training (both members participated) and all tests were repeated. After exercise training, subjects in group 1 still had as much intrapair variability in cardiac size as those in groups 2 and 3. The data suggest cultural familial influences are more important in determining cardiac size than nonfamilial influences or even genetic influences alone.

Adult↗
PubMed1985

Effects of age, sex, and body habitus on QRS and ST-T potential maps of 1100 normal subjects.

Body surface potential maps provide more detailed regional cardiac electrophysiologic information than the standard electrocardiogram. We performed a large-scale study of a normal population to form a comparison base for evaluation of the clinical utility of this technique. We analyzed body surface maps from 1113 normal subjects from 10 to 80 years old to detail map features as a function of age, sex, and body habitus. Maps were analyzed by visual inspection and by a spatial and temporal data reduction technique that allows statistical comparison of map features. On average, both QRS and ST-T potentials decreased with increasing age. Potential pattern distributions remained constant from 10 to 40 years. Beyond age 40, larger numbers of maps from normal subjects showed depolarization patterns consistent with delayed activation of the left anterior fasicle, despite normal 12-lead electrocardiograms. Only minor QRS potential amplitude and distribution differences were noted when male and female subjects were compared within groups of similar age and body habitus. Male subjects consistently showed greater average T potential amplitudes. Slender body habitus was associated with a more horizontal "zero" potential line. In female subjects over age 40 there were more extensive low-level negative potentials recorded over the precordium during the ST segment than in men. This study defines the range of normal body surface potential maps in a large clinically normal population and provides a basis for qualitative and statistical comparison with map features of patients with disease.

Adolescent↗
PubMed1985

The relationship of lithium-potassium cotransport and the passive lithium leak to hypertension in Utah subjects.

Rate constants for lithium-potassium cotransport (kLPC) and the lithium efflux into MgCl2 with furosemide (passive lithium leak) along with sodium-lithium countertransport (SLC) were measured in erythrocytes from 351 normotensive adults age 18 and over, 220 youth under age 18 and in 27 hypertensives. The kLPC was significantly higher in the hypertensives than the adult normotensives with means and standard deviations of 13.9 +/- 9.2 vs. 8.7 +/- 5.9 10(-3)/hr (p less than 0.01). Adjusting for the significant weight (p = 0.014) and sex (p = 0.066, normotensive males higher than females) associations with kLPC in an analysis of covariance, increased the significant difference between the hypertensives and normotensives (p = 0.0004). The passive lithium leak rate constant was also higher in hypertensives than normotensives (20.2 +/- 7.6 vs. 15.5 +/- 5.3 10(-3)/hr, p less than 0.01). Weight (p=0.0003), but not sex, was related to the leak but did not account for the difference between hypertensives and normotensives (p = 0.0009). Mean blood pressure was positively associated with the lithium leak but not the kLPC or SLC values in a multivariate regression.

Adolescent↗
PubMed1985

The goals and functions of a P & T committee.

The goals and functions of a productive and effective University Hospital P & T Committee are described. The primary responsibilities of the P & T Committee are to ensure high-quality drug therapy for hospital patients, provide liaison between the medical staff and the department of pharmacy services, and advise the Institutional Review Board of the University on the study of investigational drugs in humans. To meet its responsibilities, the P & T Committee maintains a formulary of medications approved for routine patient care, reviews drug use and adverse drug reactions, and establishes procedures for prescribing, dispensing,and administering drugs in the hospital. The P & T Committee acts on behalf of the Medical Board of the hospital, and actions of the Committee are subject to the Board's approval.

Drug Therapy↗
PubMed1985

Pregnancy in carriers of high-affinity hemoglobins.

Pregnancy in female carriers of abnormal hemoglobins with great avidity for oxygen provides a unique opportunity to assess the importance of the usual difference in oxygen affinity between fetal and maternal blood. Outcome of pregnancy was recorded for carriers of hemoglobins Bethesda, Osler, and Yakima, whose p50s (9.5, 9.1, and 12 mm Hg at pH 7.4) were far lower than that of a normal fetus (23 mm Hg at pH 7.3). Neither spontaneous abortions nor intrauterine growth retardation could be attributed to the presence of high oxygen affinity in the mothers. In vitro simulations suggested that neither maternal or fetal polycythemia alone was sufficient to adjust for perturbation of the normal situation, and increased uterine and/or fetal blood flow probably provided additional compensation.

Adult↗
PubMed1985

Cost containment of the second-generation cephalosporins by prospective monitoring at a community teaching hospital.

All patients receiving cefoxitin and cefamandole were prospectively reviewed for appropriate and inappropriate utilization. There were two eight-week survey periods. In period 1, 81 (70%) of 115 patients received cefoxitin appropriately and six (40%) of 15 patients received cefamandole appropriately. In patients receiving antibiotics inappropriately, 12 (35%) of the 34 receiving cefoxitin and eight (89%) of the nine receiving cefamandole had infections that could have been treated with less expensive, equally efficacious antibiotics. Changes in antibiotic therapy were made in 79% of patients based on our recommendations. The estimated annual cost saving for these antibiotics was $40,290. During period 2, 73 (91%) of 80 patients were given cefoxitin appropriately and 14 (61%) of 23 patients received cefamandole appropriately. Forty-three percent of those receiving cefoxitin and 33% of those receiving cefamandole inappropriately could have been treated with a less expensive, equally efficacious antibiotic. In 88% of patients, the attending physicians followed our recommendations.

Bacterial Infections↗
PubMed1984

Hemodialysis does not affect erythrocyte sodium-lithium countertransport.

Sodium-lithium countertransport measurements on erythrocytes are currently of interest because some hypertensive subjects and their relatives have abnormally high values. Woods et al [1] reported that red cells taken from dialysis patients after hemodialysis had significantly lower sodium-lithium countertransport than before dialysis. They suggested that sodium-lithium countertransport is influenced by 'a dialyzable plasma factor'. We conducted experiments to further evaluate their observations relating to the 'dialyzable plasma factor'. However, we have been unable to confirm their findings. Neither an effect of hemodialysis on sodium-lithium countertransport in erythrocytes from maintenance dialysis patients nor any effect of dialysis on normal erythrocytes in vitro was evident. Our results do not support the existence of a dialyzable plasma factor affecting sodium-lithium countertransport.

Adult↗
PubMed1984

A simplified method for simultaneously determining countertransport and cotransport in human erythrocytes.

Both sodium countertransport and sodium-potassium cotransport are altered in erythrocytes from some hypertensive subjects and their relatives. Lithium can substitute for sodium in both of these transport mechanisms; they can then be monitored as sodium-lithium countertransport and lithium-potassium cotransport. Using erythrocytes loaded with lithium, we can determine both transport systems simultaneously by monitoring the rate of lithium efflux into three media: (1) NaCl, (2) MgCl2 and (3) MgCl2 with furosemide. The difference between the effluxes into NaCl and MgCl2 is the sodium-lithium countertransport; the difference between the effluxes into MgCl2 with and without the cotransport inhibitor furosemide is the lithium-potassium cotransport. At the intracellular Li concentrations used in these experiments, lithium-potassium cotransport is a linear function of the Li+ concentration and can be expressed by the equation for a first order reaction. The rate constant can be calculated by dividing the lithium-potassium cotransport by the intracellular lithium concentration and correlates well (r = 0.80, n = 30) with sodium-potassium cotransport measured by Dagher and Garay's method. The simultaneous measurement of countertransport and cotransport requires much less time, effort and material than measuring the two transports separately.

Biological Transport↗
PubMed1984

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↗
PubMed1984

The inheritance of high density lipoprotein cholesterol and apolipoproteins A-I and A-II.

A large pedigree was ascertained through cases of early myocardial infarction. High density lipoprotein cholesterol and apolipoproteins A-I and A-II were measured on family members. Likelihood analysis, using the polygenic/major gene mixed model, provided no evidence that major loci play a role in determining the levels of any of the three measurements. Heritability estimates, assuming polygenic inheritance, were 0.59 and 0.26 for HDL-C level and A-II level, respectively. No evidence of genetic transmission of A-I level was found.

Adult↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗