Search PubMed⌕ Search

Biomedical subjects

W R Clarke

Publications and source records attributed to W R Clarke.

At least 91 records · Page 5Linked to original sources

Multivariate models for human genetic analysis: aggregation, coaggregation, and tracking of systolic blood pressure and weight.

A multivariate path model parameterizing the sources of familial aggregation and coaggregation of systolic blood pressure and weight, as well as their tracking across time, is applied to longitudinal data collected in Muscatine, Iowa. Genetic, common household, and individual environmental effects, pleiotropy, and a direct regression effect of blood pressure on weight are parameterized. The sample consisted of 998 individuals distributed in 261 families of whom 601 were measured on four successive occasions. The data were divided with times 1 and 2 forming group 1, and times 3 and 4, group 2. Model fitting and estimation was performed using group 1, followed by testing the model and estimates using the data in group 2. Heritability estimates for systolic blood pressure and weight were .15 and .54, respectively. The genetic correlation between these traits was nonsignificant, but there was a significant direct regression effect. The results indicate that 30% of the full-sib correlation for systolic blood pressure is attributable to the aggregation of weight. In terms of tracking, 59% and 60% of the predicted systolic blood pressure and weight correlations, respectively, were attributable to genetic effects. Testing the model from group 1 in group 2 indicates that the qualitative relationships between blood pressure and weight are stable with time.

Adolescent↗

The Muscatine Cholesterol Family Study: familial aggregation of blood lipids and relationship of lipid levels to age, sex and hormone use.

The Muscatine Cholesterol Family Study includes data on first, second and third-degree relatives of school children who have the following cholesterol levels: above the 95th percentile in two consecutive school screens, N = 53; below the 5th percentile twice, N = 45; and a random sample between the 5th and 95th percentiles twice, N = 44. For males and females not taking estrogen the relationship of cholesterol to age was the same in high, middle, and low groups, although the overall level differed. For females taking estrogen, cholesterol levels rose more quickly with age in the high group as compared to the middle and low groups. The triglyceride levels of females taking estrogen is higher at younger ages and shows no significant change with increasing age. Among first degree relatives, the cholesterol correlations are between 0.25 and 0.30. Correlations in relatives of the middle group probands are higher than those in relatives of high or low group probands, but not significantly so. Correction for ascertainment increases the correlations in the high and low groups. Among second degree relatives cholesterol correlations in all three groups are approximately 0.20. There is negligible cholesterol correlation between spouses in the high and low groups, while the middle group spouse correlation is significantly greater than zero. Categorical analysis suggests the effect of the proband's cholesterol level is seen most upon the cholesterol level of parents, with siblings and second-degree relatives being less similarly affected.

Adolescent↗

The Muscatine Cholesterol Family Study: distribution of cholesterol levels within families of probands with high, low and middle cholesterol levels.

The Muscatine Cholesterol Family Study includes the relatives of three groups of schoolchildren: those with cholesterol levels above the 95th percentiles in two consecutive school screens, those with cholesterol levels below the 5th percentile twice, and random sample of those with cholesterol levels between the 5th and 95th percentiles twice. This paper examines the cholesterol distribution within and among these families for evidence of major gene effects. Three screening techniques are used: admixture analysis using maximum likelihood, comparison of within-sibship variances among groups, and regression of within-sibships variance on within-sibship mean. The results of the three techniques are consistent and indicate the existence of a major gene in a subset of the families with a proband above the the 95th percentile, but not in the other two groups of families. We estimate that 15% of schoolchildren with a cholesterol level above the 95th percentile twice, or 3 per thousand in the general population, have a dominant gene as a cause of the cholesterol elevation.

Adolescent↗

Coronary artery disease mortality in relatives of hypertriglyceridemic school children: the Muscatine study.

From 2655 healthy school children participating in the 1973 and 1975 Muscatine Coronary Risk Factor School surveys, two groups of index cases were selected for a detailed family study of coronary mortality: a group with fasting triglyceride levels greater than the ninetieth percentile on both surveys (n = 75) and a group with triglyceride levels less than the tenth percentile on both surveys (n = 47). Coronary mortality in adult (age 30 years or older) first- and second-degree relatives was not different between the two groups. When the families of the high-triglyceride group was further subdivided based on the cholesterol percentile of the index child, greater coronary mortality was observed in the relatives of index cases with high cholesterol (higher than the seventy-fifth percentile). This study suggests that family members of children with elevated triglyceride and low cholesterol levels do not have excess coronary mortality.

Adult↗

Electrocardiographic measures of left ventricular hypertrophy in children across the distribution of blood pressure: the Muscatine study.

We sought to test the effectiveness of the ECG as a measure of increased left ventricular wall mass in children with high blood pressure. One hundred eighty-one children, ages 9-18 years, were selected from the lowest, middle and highest quintile of systolic blood pressure from the Muscatine Study, based upon two biennial school screenings. After correction for age, sex, height, weight and skinfold thickness, children with the highest blood pressure had increased echocardiographic left ventricular wall mass (p less than 0.02). Voltage measurements of maximum R and S waves in the standard and precordial leads were measured by computer. We correlated blood pressure and echocardiographic measurements of the interventricular septum, left ventricular posterior wall and left ventricular wall mass to electrocardiographic combinations used to predict left ventricular hypertrophy in both children and adults. The electrocardiographic correlations ranged from -0.01 to + 0.17. Poor correlations were found between electrocardiographic measures and blood pressure, left ventricular wall thickness or left ventricular wall mass. Skinfold thickness and weight had negative correlations, suggesting a damping effect upon measured voltage. We conclude that the echocardiogram is a more sensitive measurement of increased left ventricular mass than the ECG in children with elevated blood pressure.

Adolescent↗

Blood coagulation changes after hypoxemia: a fetal lamb model.

The effects of fetal hypoxemia on blood coagulation (platelet count, prothrombin time, partial thromboplastin time, fibrinogen, factors II, V, VI, VIII, IX, X, XI, XII, XIII and von Willebrands activities, fibrin degradation products, and fibrin monomer) were evaluated in nine chronically catheterized fetal lambs early in the third trimester of pregnancy (107-110 days gestation). Seven chronically catheterized fetal lambs of similar gestational ages served as controls. The hypoxemic episode (pO2 14 mm Hg) was maintained for 1 hr in the experimental group during which time there were only minimal changes in PCO2, arterial pressure, heart rate, and pH. Epinephrine and norepinephrine levels increased significantly in stressed animals--22 pg/ml pre- to 1025 pg/ml postepinephrine, and 475 pg/ml pre- to 2292 pg/ml postnorepinephrine. There were no significant changes in blood coagulation factor activities related to the hypoxic stress although, one fetus who experienced acidemia did develop a transient increase in fibrin monomer. Slight through significant increases in VIII coagulant activity activity (4.0%), von Willebrand activity (5.9%), and factor XII activity (4.3%) occurred in both the hypoxemic and control fetal lambs. These changes were associated with minimal increases in the white blood cell count (15%) and slight decreases in the mean arterial pressure (3.9 mm Hg) hemoglobin (1.2 g), and hematocrit (2.9%) and may have been related to the blood loss of 25% that occurred as a result of sampling in both groups. There were no differences between the hypoxic and control animals' levels of coagulation factor activities when measured during an 18-day follow-up period except for a slight increase in factor X activity (10%) in the control animals not apparent in the nine hypoxic animals. Thus an episode of severe fetal hypoxemia in the absence of hypotension, acidosis, and hypercarbia does not lead to acute or chronic alterations in blood coagulation factor activities in the fetal lamb.

Animals↗

Forearm vascular resistance in the upper and lower quintiles of blood pressure in adolescent boys: The Muscatine Study.

Nineteen 16 year old white boys whose systolic blood pressures were in the upper (r = 9) and lowest (r = 10) quintile of the distribution in two school surveys in 1975 and 1977 were selected. In 1979 forearm blood flow, blood pressure and heart rate were measured at rest, and during peak reactive hyperemia. Minimal forearm vascular resistance during peak reactive hyperemia was used to assess the structural contribution to vascular resistance. At rest the high quintile group again had significantly higher blood pressures than the low quintile group but their forearm vascular resistance was not significantly different. The high quintile group showed significantly higher minimal forearm vascular resistance at peak reactive hyperemia. The latter observation suggests that there is a difference in the structural contribution to forearm vascular resistance in adolescents with blood pressure in the upper versus lower quintile of the distribution.

Adolescent↗

Vasomotor dynamics associated with cardiac operations. I. Venous tone and the effects of vasodilators.

Vasomotor dynamics were studied in 52 patients undergoing direct coronary revascularization or mitral valve replacement utilizing cardiopulmonary bypass. Emphasis was placed on the study of venous tone. Operation resulted in a general vasoconstrictive response with increased arterial resistance and reduced venous capacitance. These changes were magnified in patients who underwent mitral valve replacement for mitral valve stenosis related or partially related to reduced cardiac performance before and after operation. Nine patients became hypertensive following coronary artery bypass and were treated with nitroprusside; eight patients were given nitroglycerin to reduce venous tone and prevent hypertension. A comparison of these two vasodilators, with their somewhat different actions on the vascular bed, reveals that afterload reduction and increase of cardiac output were equivalent with both. However, nitroglycerin had the effect of increasing venous capacitance, while nitroprusside had little effect on the venous circulation. In addition, nitroglycerin was especially effective in reducing venous tone and left ventricular preload following mitral valve replacement. Relative merits of pharmacologic reduction of venous tone as a part of overall relief of increased vascular resistance following cardiac operation should be considered when attempting to obtain an optimal hemodynamic state.

Adult↗

Decreased chemotactic activity in activated newborn plasma.

The roles of complement levels and CFI activity in the regulation of chemotactic factor generation were evaluated in newborn and adult plasmas. Plasma samples were obtained from 19 healthy adults, 19 neonates, and 12 3-day-old infants. CFI levels were determined in all samples, chemotactic activity in 15 of the 19 adult and newborn samples, and complement levels in 10 of these 15. Compared to adult plasmas, CFI activity was higher in newborn and infant plasmas and chemotactic activity was lower. A close reciprocal relationship was shown between these two activities (r=-0.958). When corrected for the effects of CFI, the difference in chemotactic activity between newborns and adults disappeared. Mean levels of C1, C3, C4, C5, C3 to C9, CH50, factor B, and properdin were lower in newborn plasmas; however, C2 levels were higher. Partial correlations between these complement components and the chemotactic activity were of small magnitude and statistically not significant. These data suggest that higher CFI activity, rather than lower complement levels, accounts for most of the differences in chemotactic activity between newborn and adult plasma. (J Lab Clin Med 99:331, 1982.)

Adult↗

Bone loss in the beagle tibia: influence of age, weight, and sex.

In a cross-sectional study, 154 Beagles (79 males, 74 females) ranging in age from 14 to 187 months were measured for bone mineral, bone width, and mineral-to-width ratio on the distal shaft of the right tibia using a photon absorptiometer. The measurements were evaluated with regard to age, sex and body weight. The results indicate that males were heavier than females in body weight, with weight being reduced in the older animals of both sexes. When compared on an age basis, males had more mineral, a wider tibia, and a greater mineral-to-width ratio than females. The males and females reach their peak mineral, and mineral-to-width ratio at about 6 years of age and then decline. On a body weight basis, mineral, width and mineral-to-width ratio all increase with increasing body weight, with bone width being the least affected by changes in body weight. The values for females are less than those for males in all parameters with the greatest differences occurring at the greater weights. The only variance from these observations was the greater mineral-to-width ratio in the lighter females. It is concluded that, when examining cortical bone, the Beagle is a model of age-related osteopenia, and body weight is an important consideration when explaining changes in bone mineral.

Aging↗

Vasectomy and coronary disease in men less than 50 years old: absence of association.

Because recent experiments in primates suggest a relationship between vasectomy, and the development and promotion of atherosclerosis a case control study was performed to explore this possibility in humans. The prevalence of prior vasectomy was determined in 55 men less than 50 years old with onset of documented coronary disease and in a matched control group of close relatives (45 brothers and 10 first cousins) free of coronary disease. The prevalence was the same in each group, 25.5 per cent (14 of 55), and there was no significant difference between study groups in the mean interval since vasectomy. Thus, within the limitations of this study no association of coronary disease with prior vasectomy was found. Further work is needed to evaluate whether the animal findings pertain to humans.

Coronary Disease↗

Postnatal age-related renal responses to hypoxemia in lambs.

The role of normocapnic hypoxemia (arterial PO2 33 +/- 7 torr for 30 minutes) in asphyxial renal failure and its modification by maturation of renal function was studied in 50 chronically catheterized, unanesthetized lambs of 2-38 days postnatal age. Arterial pH and PCO2 did not change significantly in response to hypoxemia in these lambs. Normocapnic hypoxemia was associated with (1) significant percent increases in arterial serum osmolality (1.82 +/- 2.96%, P = 0.0001), arterial blood lactate concentration (1009 +/- 2092%, P = 0.0018), arterial blood hematocrit (6 +/- 12%, P = 0.0016), arterial hemoglobin concentration (4.6 +/- 6.5%, P = 0.0004), arterial plasma vasopressin (2370 +/- 3340%, P = 0.0001), arterial plasma renin activity (153 +/- 230%, P = 0.0001), arterial plasma aldosterone (91.3 +/- 143%, P = 0.0001), and fractional sodium excretion rate (120 +/- 240%, P = 0.007); and (2) significant percent decline in glomerular filtration rate (-22.6 +/- 32.6%, P = 0.0003). Several responses to hypoxemia correlated significantly with postnatal age, including (1) positive correlation of postnatal age with percent change in blood osmolality (r = 0.36, P = 0.010), hematocrit (r = 0.48, P = 0.0005), hemoglobin (r = 0.59, P = 0.0004), and lactate (r = 0.72, P = 0.0001), suggesting greater water movement from the intravascular compartment in response to hypoxemia in more mature lambs; and (2) positive correlation of postnatal age with change in urinary flow rate (r = 0.66, P = 0.0001), urinary sodium excretion rate (r = 0.65, P = 0.0001), and osmolar clearance rate (r = 0.60, P = 0.0002), suggesting a greater effect of hypoxemia on the renal tubules to decrease sodium reabsorption in more mature kidneys. Thus, normocapnic hypoxemia may play a role in asphyxial renal failure, and the immature kidney does not have increased susceptibility to this condition.

Aging↗

Development of blood coagulation--a fetal lamb model.

To study the normal development of blood coagulation factor activities in a growing fetus while avoiding the effects of labor and delivery, a chronic fetal lamb model was developed in which serial blood samples from 10 fetuses were studied during the third trimester of pregnancy and 24 hr after birth. Under operating room conditions with sterile technique, a polyethylene catheter to which heparin had been bound to both internal and external surfaces was inserted into the femoral artery of the fetus. The catheter was brought out through a skin pouch to the side of the ewe and enclosed in a zip lock bag. Blood samples were withdrawn from the catheter three times each week for measurement of coagulation factor activities. Levels of coagulation factor activities at birth in noncatheterized animals were not different from those found in catheterized animals except for factor IX activity which was 12% higher in the catheterized animals (0.02 less than P less than 0.05). The patterns of development for each of the coagulation factors were similar in all 10 animals studied. Fibrinogen, prothrombin, and factor VII show a decrease in activity early in the last trimester of pregnancy. Both factors VIII and IX show a significant increase in activity (23% factor VIII and 12% factor IX) associated with the process of delivery. The levels of coagulation factor activities at birth in the lamb relative to adult sheep normals are similar to those found in humans with the exception of factor XIII. Factor XIII is at normal levels in the newborn lamb and is reported to be at levels approximately 50% of the adult level in human infants.

Animals↗