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Microwave radiometry has provided valuable spaceborne observations of Earth's geophysical properties for decades. The recent SMOS, Aquarius, and SMAP satellites have demonstrated the value of measurements at 1400 MHz for observing surface soil moisture, sea surface salinity, sea ice thickness, soil freeze/thaw state, and other geophysical variables. However, the information obtained is limited by penetration through the subsurface at 1400 MHz and by a reduced sensitivity to surface salinity in cold or wind-roughened waters. Recent airborne experiments have shown the potential of brightness temperature measurements from 500-1400 MHz to address these limitations by enabling sensing of soil moisture and sea ice thickness to greater depths, sensing of temperature deep within ice sheets, improved sensing of sea salinity in cold waters, and enhanced sensitivity to soil moisture under vegetation canopies. However, the absence of significant spectrum reserved for passive microwave measurements in the 500-1400 MHz band requires both an opportunistic sensing strategy and systems for reducing the impact of radio-frequency interference. Here, we summarize the potential advantages and applications of 500-1400 MHz microwave radiometry for Earth observation and review recent experiments and demonstrations of these concepts. We also describe the remaining questions and challenges to be addressed in advancing to future spaceborne operation of this technology along with recommendations for future research activities.

Objective: To establish rates of skeletal mineralization in children and adolescents, and to identify factors that influence these rates., Design: Three-year observational study., Setting: University hospital., Subjects: Ninety white children, aged 6 to 14 years., Measurements: Bone mineral density of the radius, spine, and hip was measured at baseline and 3 years later. Physical activity was assessed by questionnaires at 6-month intervals and dietary calcium intake by diet diary 1 day per month for 36 months. Sexual maturation (Tanner stage) was determined by an endocrinologist at 6-month intervals, as necessary to classify children as prepubertal, peripubertal, or postpubertal., Results: Skeletal mineralization accelerated markedly at puberty in the spine (0.077 vs 0.027 gm/cm2 per year, peripubertal vs prepubertal) and greater trochanter (0.050 vs 0.027 gm/cm2 per year), less markedly in the femoral neck (0.047 vs 0.030 gm/cm2 per year), and only slightly in the radius. Nearly one third (15 gm) of the total skeletal mineral in the lumbar spine of adult women (approximately 52 gm) was accumulated in the 3 years around the onset of puberty. Increases in height and weight were the strongest correlates of skeletal mineralization: weight changes were more strongly correlated with trabecular bone sites and changes in height with cortical bone sites. Increases in calf muscle area were strongly associated with mineralization, particularly in peripubertal children, and physical activity was associated with more rapid mineralization in prepubertal children., Conclusions: Puberty has varying effects on skeletal mineralization depending on skeletal site; trabecular bone is apparently more sensitive to changing hormone concentrations. Physical activity and normal growth are also positively associated with skeletal mineralization, also depending on skeletal site and sexual maturation.

Background: Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain., Methods: We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years)., Results: The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit., Conclusions: In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.

Several studies have shown an inverse relation between blood pressure and plasma aldosterone levels. Since blood pressure is in part genetically regulated, we looked for evidence that genetic factors might also affect aldosterone production. The nocturnal urinary excretion rate was used to estimate aldosterone production, and electrolyte excretion rates were used to estimate sodium and potassium intakes. Studies were carried out in monozygotic (MZ) (n = 37 pairs) and dizygotic (DZ) (n = 26 pairs) twins, aged 6-17 years. Both groups of twins were white. The intraclass correlation coefficient for aldosterone excretion was 0.686 (p = 0.0001) for MZ twins, and 0.290 (p = 0.079) for DZ twins, indicating high heritability for the aldosterone excretion rate. In a second study, we looked for a racial effect on the genetic regulation of aldosterone excretion. Siblings from both black and white families (72 black siblings and 157 white siblings) were selected from an ongoing longitudinal study. Mean values for nocturnal aldosterone excretion, rates measured every 6 months over 1.5-3.5 years, were used in the analysis. The intraclass correlation coefficient for aldosterone excretion, adjusted for sodium and potassium excretion, was 0.510 (p = 0.001) for black siblings and 0.087 (p = 0.228) for white siblings, indicating a strong familial aggregation for aldosterone excretion in black children. In conclusion, studies in twins showed that regulation of urinary aldosterone excretion in children is determined partially by genetic factors. A familial component affecting the aldosterone excretion rate appears to be much stronger in blacks than in whites.

A group of 118 children, aged 5.3-14 years, were enrolled in a prospective study of calcium supplementation and bone mass. At entry to the study, questionnaires regarding the child's usual physical activity were administered to the children and their mothers. Repeated activity assessments at 6 month intervals indicated good within-person agreement for total activity and for most individual activities. Consistent positive associations were observed between bone mineral densities (BMD) in the radius, spine, and hip and most activities. A summary measure (total hours of weight-bearing activity) was significantly related to BMD in the radius and hip, independently of age or gender effects. Self-reported sports and play activities were associated with BMD, but neither time spent watching television nor hours of physical education classes were associated either positively or negatively with skeletal mass. These data suggest that important increments in skeletal mass may result from physical activity during childhood.

The relationships among bone mineral measurements at hip, wrist, and spine sites and anthropometric measurements which provided estimates of frame size, skinfold thickness, and muscularity were examined in a population of 140 children. The average age of the children at the time of measurement was 9.5 +/- 2.5 years and all subjects were white. In this study population, the anthropometric measurements were generally highly intercorrelated. Univariate correlations among bone mass and density variables at the different sites were also high, especially in the female children. Model fitting procedures were employed to separate the effects of age, frame size, and fatness on the bone mass measures. Resulting models confirmed previous results which suggest that height is the best predictor of bone mass in children. As expected, models for bone mineral content and bone mineral density were similar. Models for hips and wrist sites were also similar in including an estimate of frame size, while in those for the spine hip circumference explained a greater percentage of the variance. It appears that there are several identifiable characteristics among the anthropometric variables which appear to exert differential effects on skeletal development in children.

Estimates of an individual's intake of specific nutrients is important in epidemiologic investigations of disease-diet relationships. The object of the present investigation was to determine the minimum number of daily food records required to estimate intake of specific nutrients in children. Both members of 70 pairs of twins (n = 140 children) completed a minimum of 3 and a maximum of 23 food records throughout a 2-y period. All subjects were white and range in age from 5 to 14 y. Assuming an attenuation of the correlation coefficient of 80%, the minimum number of daily food records required to estimate energy intake was seven for boys and eight for girls. As a group, the vitamin intakes were the most variable for both boys and girls, often requiring more than 20 records for either sex. Requirements for other nutrients generally fell between these two extremes. The results of the present investigation are particularly relevant to the interpretation and design of studies of associations with nutrient intake.

The rise in plasma vasopressin produced by infusion of hypertonic saline varies widely among healthy adults. To determine if these interindividual differences are reproducible, we used linear regression to analyze the relationship of plasma vasopressin to plasma osmolality during repeat hypertonic saline infusion in seven normal subjects. The results confirmed that the slope or sensitivity of the relationship differed widely between subjects (0.12 to 1.66 pg/ml/mOsm/kg) and revealed that these differences were highly reproducible. (r = 0.94 on repeat testing). The individual values for osmotic threshold were less variable (280 to 288 mOsm/kg) as well as less clearly reproducible (r = 0.61). To determine whether these differences are genetically influenced, we compared the vasopressin osmolality relationships within seven monozygotic and six dizygotic twin pairs. We found that the threshold and sensitivity values correlated significantly within monozygotes (r = 0.95 and 0.95) but not within dizygotes (r = 0.34 and 0.21). When the osmoregulation of thirst was similarly evaluated, the individual relationships were as variable as for plasma vasopressin, but only the threshold values in monozygotes correlated significantly (r = 0.92). In 80 healthy adults, the frequency distributions of the osmotic threshold and sensitivity of the vasopressin responses were essentially normal. We conclude that the sensitivity for vasopressin secretion as well as the osmotic thresholds for thirst and vasopressin demonstrate significant polygenetic variance among healthy adults.

To evaluate the effects of social support and home urine monitoring on success with dietary sodium reduction, 114 essential hypertensive adults and a household partner were recruited. One of the pair was required to be the food preparer. Patients with their partners were randomly assigned to either an active or passive partner condition. During dietary counseling in the active condition, both patient and partner were involved in instructions to change their diet to reduce their daily sodium intake to 80 mmol or less. In the passive condition, the partners were present during the dietary counseling, but no effort was made to involve them directly in the instruction or to encourage them to make personal dietary changes. Patients and active partners collected two 24-hr urine collections between each of the first two counseling sessions and received feedback on the sodium results by a telephone call. In the passive partner condition, only patients collected urine for feedback. At the end of the 6 week instructional period, all patients and partners collected a 24-hr urine and had their blood pressure assessed. Half of each group was also randomly assigned to have access to a system for periodic home-monitoring of urine for sodium content during a 3-month period beginning at week 6 of the study (immediate). The delayed feedback group received the home-monitoring three months after completion of the dietary instruction. All patients, but only active partners, used the feedback system during their assignment periods and collected a 24-hr urine monthly between 6 and 30 weeks of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

To identify characteristics that may contribute to salt sensitivity, we conducted studies of normal subjects who are at risk for hypertension, namely blacks, subjects older than 40 years of age, and first-degree relatives of subjects with essential hypertension. We also formulated definitions for salt sensitivity and resistance with a short-term volume expansion and contraction protocol and additionally from data derived from studies of long-term reduced dietary salt intake. We examined the effects of augmented potassium and calcium intake and also those of sodium as the chloride or the bicarbonate salt. Finally, we sought genetic markers that are associated with salt sensitivity. We found that salt sensitivity is a function of age and is more common in blacks than whites. These groups also have relatively delayed acute salt excretion compared with controls. We were unable to identify effects of gender. Haptoglobin phenotypes (HP 1-1) may facilitate identification of salt-sensitive individuals. A high potassium intake may make individuals less salt sensitive. Sodium chloride and sodium bicarbonate differ in their effects on blood pressure. Sodium chloride augments urinary calcium excretion, but sodium bicarbonate does not. Differences between susceptible and nonsusceptible groups, together with improved knowledge of electrolyte interactions, may facilitate our understanding of salt-sensitive hypertension.

To evaluate factors influencing hemodynamic responses to psychological and physical stress, 117 normotensive college students were studied. The standardized tests included arithmetic, Stroop word-color, mirror draw, isometric handgrip and cold pressor challenges. The responses of blood pressure and pulse during the tests were compared to the baseline measurements. All the challenges produced a significant (P less than 0.01) increase in systolic and diastolic pressure and pulse rate, with the greatest increase being seen with the isometric handgrip test. The increases in the systolic and diastolic pressure and the heart rate to the psychological stressors were highly correlated (P less than 0.001). The responses to the physical stressors were correlated for the diastolic pressure (P less than 0.01) and the heart rate (P less than 0.001), but not for the systolic pressure. The responses of the systolic and diastolic pressure, but not the heart rate, to the isometric handgrip correlated with the responses to the psychological stressors. The responses of the diastolic pressure and the heart rate, but not the systolic pressure, to the cold pressor stimulus correlated with the responses to the psychological stressors. The gender influenced the response to all the stressors with males having a greater (P less than 0.05) blood pressure response and a lesser (P less than 0.001) heart rate response than females. Black subjects had greater blood pressure responses to the cold pressor test and a greater diastolic pressure response to the handgrip, but there were no observed racial differences in the responses to the psychological stressors.(ABSTRACT TRUNCATED AT 250 WORDS)

A study was undertaken to determine whether genes associated with herpes simplex virus (HSV) neuroinvasiveness in mice influence the growth of HSV in man, the virus's natural host. HSV-2(186), a nonneuroinvasive HSV strain, was found to replicate poorly (less than 3-fold) in cultures of phytohemagglutinin (PHA) stimulated human peripheral blood mononuclear cells (PBMC). In contrast, seven other HSV strains all multiplied 40- to 100-fold. The paucity of HSV-2(186) growth in PBMC was not due to a failure of this strain to grow in primary human cells because high titers (greater than 10(8) PFU/ml) were obtained following infection of human foreskin fibroblasts. The genetic basis for the deficient growth was analyzed by marker rescue experiments. Recombinant HSV-2 strains were generated in marker rescue experiments utilizing HSV-2(186) DNA and plasmids containing a cloned DNA polymerase gene isolated from a neuroinvasive HSV strain possessing the capacity to replicate in human PBMC. Progeny which rescued DNA from the cloned HSV DNA polymerase gene replicated 40- to 100-fold in PHA-stimulated PBMC. Moreover, unlike the HSV-2(186) parent, HSV-2(186) isolates possessing rescued DNA grew well in the eye, trigeminal ganglion, and brain of mice and induced fatal encephalitis. The results indicate that nucleotide sequences responsible for increasing the capacity of HSV-2(186) to grow in PBMC of man are identical to those responsible for increasing the capacity of this strain to grow in mouse tissues and to spread from the eye to the brain.

To test the utility of a qualitative chloride titrator strip in facilitating compliance with a reduced sodium intake diet, we enrolled 32 patients into a randomized crossover trial comprising two study periods of four weeks each. The study periods were begun after the patients had undergone extensive instruction in the diet and the use of the strip. A high degree of correlation between the patient's and the laboratory's interpretation of the strip result was identified in 29 of the subjects. Ability to use the strip was not related to level of education. A total of 12 patients achieved compliance with the diet when using the strips. Of these, nine were able to achieve compliance without the strips. Ten patients (30%) had significantly lower sodium intake when using the strips than when they did not use them. We conclude that the use of the chloride titrator strip can be mastered by most patients and, in conjunction with dietary counseling, can facilitate compliance with a reduced sodium intake diet.

To examine the effects of dietary sodium on blood pressure 149 healthy, normotensive children (64 males, 85 females) participated in a study to restrict sodium intake to 60 mEq/day or half of the usual intake for 3 months. Sodium excretion was significantly decreased during the study period (100.6 +/- 3.4 mEq vs 46.5 +/- 2.0 mEq, P less than .001). As a group there was no significant change in systolic and a small decrease in diastolic blood pressure (54.2 +/- 0.8 mmHg vs 53.0 +/- 0.7 mmHg, p less than .03, one tailed). Adjustment of blood pressure for weight and age and analysis of residuals yielded significant decreases in both mean arterial (p less than .05) and diastolic blood pressure (p less than .05). In the potassium supplement study, comparison of supplementation to post-supplement periods in 31 children (13 male, 18 female) showed a significantly lower (p less than .05) systolic blood pressure during supplementation (101.3 +/- 2.1 mmHg vs 103.3 +/- 20 mmHg). Analyses of diastolic pressures, sodium excretion and weight were not significant. These studies show heterogeneity in the blood pressure response to sodium restriction and suggest that sodium restriction and potassium supplementation have different effects on blood pressure in children.

We evaluated the utility of chloride titrator sticks for facilitating the assessment of dietary salt intake, in a systematic series of clinical trials. These inexpensive devices were applied daily to 24-h or nocturnal urine specimens, thereby avoiding the inter- and intra-subject variability in salt excretion which confounds the use of occasional 24-h urine collections. Chloride and sodium concentrations in urine were highly correlated (r greater than 0.92) in either nocturnal, diurnal, or 24-h collections. The quantitative chloride titrator estimates and measured chloride concentrations were highly correlated as well (r greater than 0.99). The qualitative chloride titrator was graded on a simple scale, and was successfully employed by outpatients attempting to limit their salt intake. Commonly used antihypertensive medications did not interfere with the determinations. Additional chloride intake, such as supplemental potassium chloride, interfered with estimates of salt ingestion, but if the daily amount of potassium chloride supplement was constant, adjustments in interpretation could be made. Renal insufficiency introduced a systematic over-estimation of salt intake by the qualitative chloride tirator, but only at high salt intakes. Relative estimates of salt intake in subjects with renal failure were still possible. We conclude that chloride titrators can facilitate the management of patients who require a prescribed salt intake.

This paper reviews investigations by the Indiana University Medical Centre Hypertension Research Centre into genetic influences on blood pressure control systems in man. Our studies have used the families of adult identical twins to partition the relationships of age, sex and body size to the genetic contribution to blood pressure variability. These studies provide little evidence for environmental influence on the familial aggregation of blood pressure and suggest that at least 63% of the variability is due to genetic factors. Studies on the renin-angiotensin-aldosterone system and on the kidney's ability to excrete sodium were also undertaken in identical and fraternal twins, as well as in black and white subjects, and provided unequivocal evidence of genetic control. Studies in first degree relatives of patients with essential hypertension have demonstrated higher plasma renin levels and a decreased ability to excrete a sodium load when compared to first degree relatives of normotensive subjects. Blacks in the U.S.A. have a decreased ability to excrete a sodium load and a greater rise in blood pressure with sodium loading than do whites. We suggest that the heritability of blood pressure is directly related to a genetic influence on the level of renin and that this increase in renin level results in subtle increases in angiotensin II. These chronic elevations of angiotensin II directly increase blood pressure and decrease the kidney's ability to excrete sodium by either a direct renal effect or indirectly by stimulating aldosterone-dependent sodium retention.

A randomized, double-blind, placebo-controlled trial was conducted to examine the effect of calcium supplementation on blood pressure in normotensive black (n = 21) and white (n = 54) men, aged 19 to 52 years. After a four-week baseline period of weekly blood pressure measurement, subjects were randomly assigned within racial groups to either a treatment (calcium, 1500 mg/d) or placebo group for a 12-week period. During the experimental period, multiple blood pressure measurements were taken every two weeks in both the seated and supine positions, using a random baseline sphygmomanometer. A repeated-measures analysis of covariance yielded a modest but significantly lower seated mean arterial pressure in the treatment group compared with the control group, but no differences between the races. Results were similar for supine blood pressure. Calcium supplementation, in comparison with placebo, resulted in lower mean arterial pressure in normotensive white and black men during a 12-week period. The overall blood pressure-lowering effect was not correlated with the response of serum levels of total and ionized calcium, total inorganic phosphorus, or parathyroid hormone, or overnight urinary electrolyte values.

While the familial and genetic nature of hypertension has long been recognized, the mechanisms involved are not clear. Recent studies suggest that an environmental factor, increased dietary sodium intake, may be required for the expression of this genetically determined form of hypertension. The evidence for this conclusion is based on physiological studies of humoral factors, renal function and the blood pressure response to sodium and volume expansion and reduction in several carefully characterized human populations.

To examine potential mechanisms responsible for the greater prevalence of hypertension among relatives of hypertensives than among relatives of normotensives, we subjected 43 normotensive first-degree relatives of known essential hypertensives and 43 age-, race-, and sex-matched normal subjects with no family history of hypertension to sodium loading and depletion. The data show that the relatives had higher blood pressures than did controls. They also had higher PRA values before and after a 2 L intravenous saline infusion over 4 hr. In addition, the relatives excreted less (p less than 0.05) sodium on the day of the infusion than did the controls. PA values and UNe excretion in the two groups did not differ. In the relatives, age correlated with systolic and diastolic blood pressure. Age correlated inversely with the 24 h urine sodium excretion on the sodium loading day. These correlations were not observed in controls. Normotensive first-degree relatives of hypertensives differ from relatives of nonhypertensives in that they have higher PRA values and a blunted natriuretic response to a saline load. These features may predispose them to the development of hypertension.

Changes in electrolyte intake have been advocated to lower the prevalence of hypertension in the normal population. To elucidate the potential impact of such strategies, we conducted a comprehensive analysis of data from three interventions, namely, salt (NaCl) restriction, calcium (Ca) supplementation, and potassium (K) supplementation in normal volunteers. Eighty-two adults lowered their Na intake from 157 +/- 6 S.E. to 68 +/- 3 mEq/day for 12 weeks. Population mean systolic and diastolic blood pressure decreased less than or equal to 2 mm Hg. Ca supplementation, 1.5 g daily for 12 weeks in 37 men, decreased blood pressure compared to 38 men receiving placebo. Ca supplementation, 1 g daily for 8 weeks in an older group of 44 normal subjects, decreased supine diastolic and standing systolic blood pressure. K supplementation with a nonchloride salt in 64 normal adults for 4 weeks had no effect on systolic or diastolic blood pressure even though urinary excretion was increased by 20 mmol/day. The responses to all interventions were Gaussian in distribution. A potentially adverse effect on blood pressure in some normal individuals cannot be excluded on the basis of the currently available data. Although all three interventions may benefit some hypertensive and some normal individuals, the data from these relatively short-term cross-sectional studies are insufficient to warrant generalized dietary recommendations for the normal population.

The present study undertook to examine aldosterone excretion during sleep as an integrated measurement of aldosterone production. A 24-hour urine collection was divided into awake and sleep fractions. Urinary aldosterone and electrolyte excretion were measured in 26 healthy children (mean age, 8.9 +/- 1.9 [SD] years) and 28 adults (mean age, 29.9 +/- 9.5 years). Aldosterone excretion in children was 5.6 +/- 3.9 (SD) micrograms/g creatinine during the awake period, which was significantly different from the 3.9 +/- 4.1 micrograms/g creatinine value recorded during sleep (p less than 0.002). In adults, awake aldosterone excretion was significantly greater than that during sleep; 4.9 +/- 2.7 versus 3.2 +/- 1.6 micrograms/g creatinine (p less than 0.001). Sleep aldosterone excretion values were highly correlated with the corresponding 24-hour aldosterone excretion values (r = 0.85, p less than 0.001) in children and in adults (r = 0.64, p less than 0.001). Sleep aldosterone excretion was correlated with 24-hour potassium excretion (p less than 0.02) only in children. Sleep aldosterone excretion correlated with neither sleep nor 24-hour sodium excretion in children or adults. Sleep electrolyte excretion rates were highly correlated with 24-hour excretion rates in both children and adults. Dexamethasone, 1 mg, administered the night before to suppress the normally high morning levels of endogenous adrenocorticotropic hormone, had no discernible effect on sleep aldosterone excretion. These results indicate that measurement of aldosterone excretion in an easily collected sleep urine sample provides a reliable index of aldosterone production in children and adults.

Offspring of monozygotic (MZ) twins form half-ships that permit a direct test of maternal effects and differentiate several sources of between-family environmental variance. Combined with conventional twin data, these genetic half-sibships provide a unique data set for estimating sources of variation in quantitative traits. To illustrate, genetic and environmental parameters were estimated for Identical Pictures Test data obtained from children of MZ twin parents and an (approximate) age-matched cohort of like-sex twins. Analyses of variance of the data, standardized for age and sex, yield 12 mean squares to which gene-environment models were fit. Maximum-likelihood estimation revealed a complete absence of maternal influences and shared environmental effects; a simple two-parameter model, assuming random mating and attributing variation in test scores to additive genes and within-family environment, adequately accounts for the familial data.

To examine the effect of modest dietary sodium ion restriction in treated hypertensive individuals, we studied 114 hypertensive patients undergoing individualized dietary counseling with a research dietitian to achieve reduction in dietary sodium ion intake. A significant reduction in mean sodium ion intake was achieved after the first of three lessons and was maintained for 30 weeks with no change in potassium ion intake. Significant falls in blood pressure and body weight were observed with no significant correlations noted between the two variables, implying independence of these effects. Individuals compliant with the dietary sodium ion restriction goal (urinary excretion, less than or equal to 80 mmol/d [less than or equal to 80 mEq/24 h]) were more likely to have a reduction in number of medications than those not reaching that goal. Ninety-eight of the 114 patients completed the entire 30 weeks. Patients who dropped out tended to have lower diastolic blood pressures and required fewer medications for blood pressure control than those who completed the 30 weeks. For these reasons, patients in the former group may have been less highly motivated to complete the study. These observations suggest that modest dietary sodium ion restriction is feasible in treated hypertensive patients and that adherence to such a regimen may permit blood pressure control with fewer medications.

The multiple relationships which exist within families of adult monozygotic (MZ) twins permit evaluation of genetic and environmental variance and provide a direct test of maternal effects. Systolic blood pressure (SBP) was measured in 610 members of the families of 76 MZ twin pairs. Age and sex effects on BP were removed via a Z-transformation. Correlations for SBP were .72 for MZ twins and .23 for full siblings. Regression of offspring on single parent was .26. The husband-wife correlation was significant, but it was no higher than the resemblance of a twin to the spouse of his co-twin. Comparisons of maternal and paternal half-siblings provide no evidence of maternal influences on SBP. To evaluate whether familial resemblance of BP is mediated by body size, the original systolic pressures were adjusted by stepwise multiple regression of age, sex, height, weight and skinfold thickness. Adjusting BP for effects of body size reduced regression of offspring on mid-parent from .40 to .23. The authors conclude that familial aggregation of systolic pressure reflects additive genetic variance mediated, in part, by body size and augmented by social homogamy arising from non-random mating.

In order to determine whether the specific activity in a single serum sample estimates calcium absorption, six healthy children participated in a study using stable isotopic calcium tracers, one given orally and the second intravenously. High-resolution, fast atom bombardment mass spectrometry was used to quantify the 44Ca and 42Ca tracers in serum and urine. Subjects ingested 250 mg of calcium (215 mg calcium enriched with 35 mg 44Ca) in the form of a chewable calcium citrate malate tablet with a standard meal, followed 30 min later with an i.v. injection of 42Ca tracer. Blood for tracer determinations was obtained at 90, 120, 150, 180, and 300 min after oral ingestion, and a urine sample was obtained 24 h after oral calcium tracer administration. The average calcium absorption estimated from the ratio of urinary tracers was 41.4 +/- 8.2%. This study indicates that the level of oral tracer in serum taken 150 min post-ingestion is significantly correlated (r = 0.85, p less than 0.05) with calcium absorption, as determined by the tracer levels in the urine. These results show that an oral stable isotopic tracer coupled with a single blood sample can be used to estimate calcium absorption in children.

Blacks are more likely to have hypertension, have lower levels of plasma renin activity, and typically consume less potassium than whites. Whether blacks and whites secrete different amounts of aldosterone is less clear. We estimated aldosterone secretion indirectly in 715 children, 249 of whom were black, by measuring their nocturnal rates of urinary excretion of aldosterone. Dietary sodium and potassium intakes were estimated from their excretion rates. The mean (+/- SE) aldosterone-excretion rate was lower in the black children than in the white children (0.045 +/- 0.003 vs. 0.078 +/- 0.004 nmol per micromole of creatinine per kilogram of body weight; P less than 0.001). The potassium-excretion rate was also lower in the black children than in the white children (0.13 +/- 0.01 vs. 0.18 +/- 0.01 mmol per micromole of creatinine per kilogram; P less than 0.001). Aldosterone excretion was highly correlated with potassium excretion (P less than 0.001), but the lower aldosterone-excretion rate in blacks was explained only in part by their lower dietary intake of potassium. Systolic blood pressure was higher in black children (P less than 0.001), as was diastolic pressure (P = 0.037). In a second study of 99 children, the plasma aldosterone level was found to be significantly lower in black children than in white children (230 +/- 30 vs. 400 +/- 30 pmol per liter; P less than 0.001). Plasma renin activity and plasma cortisol levels were the same in both groups. In summary, we found that black children secrete about 40 percent less aldosterone than white children. The role of the lower aldosterone-secretion rate in the genesis of the higher blood pressures observed in black children is not known.

To assess the influence of heredity on factors that help regulate the arterial blood pressure in man, we conducted sodium-loading and depletion studies in monozygotic and dizygotic twins, normotensive first-degree relatives of essential hypertensives, and in normotensive control subjects matched for age, sex, and race. Following sodium-loading, we found evidence for the influence of genetic variance on the natriuretic responses, plasma renin activity (PRA), plasma aldosterone concentrations (PA), and plasma and urinary norepinephrine. Relatives of hypertensives differed from controls in that they had higher blood pressures, greater renin values, and relatively sluggish natriuretic responses. Since renin and fractional sodium excretion values were inversely correlated in all subject groups, it is possible that the heritable influences we observed on sodium excretion were mediated by the renin-angiotensin-aldosterone system.

To investigate the effect on blood pressure of a modest increase in dietary potassium intake, 38 healthy, free-living families were enrolled in a study involving 4 weeks of potassium supplementation. This was preceded by collection of five baseline measurements of blood pressure and urinary electrolyte excretion and followed by a 4-week recovery period. Although there was a significant increase in urinary potassium excretion during supplementation in both adults and children (p less than 0.001), there were no significant changes in systolic, diastolic, or mean arterial blood pressure. Height and weight increased significantly in children (p less than 0.001), and weight increased in adults (p less than 0.01) over the course of the study. Multivariate analysis of variance of blood pressure controlling for these confounding variables failed to reveal any effect of the potassium supplementation on blood pressure. These results suggest that increasing intake of dietary potassium alone in a healthy, free-living normotensive population is unlikely to have a discernible effect on blood pressure.

Heritable influences on venous plasma norepinephrine (PNe) and urinary norepinephrine (UNe) values were examined in normotensive monozygotic and dizygotic twins during volume expansion and contraction. The presence of genetic variance was tested by calculating the within-pair estimate of genetic variance. Significant genetic variance was found to influence PNe during recumbency before and after a 4-h iv infusion of 2 liters saline. Similarly, heritable influences on UNe excretion were observed in a 10-h urine collection after the sodium load. Heritable influences on PNe or UNe were not observed after postural stimulation or volume contraction. The data suggest that sympathetic nervous system activity is influenced by heritable factors which may contribute to the development of hypertension in some individuals.

Persons participating in a 5-day diagnostic protocol were routinely typed for ABO, Rh, MNS, Kell, Kidd, Duffy, P, Haptoglobin, phosphoglucomutase-1 (PGM-1), and acid phosphatase (AcP). The study population was composed of 164 normotensive whites, 34 normotensive blacks, 161 whites and 43 blacks with essential hypertension, and 52 whites with secondary forms of hypertension (18 atherosclerotic renovascular hypertensives, 17 patients with fibromuscular disease, and 17 patients with primary aldosteronism). There were no significant differences in phenotype frequencies in ABO, Rh, Kidd, Kell, Duffy, P, Haptoglobin, PGM-1 or AcP in any of the comparisons. However, there was a significantly different distribution of MNS phenotypes in comparisons of essential and atherosclerotic renovascular hypertensives with normotensive controls. Essential hypertensives had a lower frequency of the S gene and a higher frequency of s in whites (X2 = 12.21, p less than 0.005). Atherosclerotic renovascular hypertensives differed from the normotensive population in the frequencies of both MN (X 2 = 4.34, p less than 0.05) and Ss (X2 = 4.21, p less than 0.05). The finding of disease-blood group associations supports the hypothesis that there may be significant physiological differences between individuals of different blood types.

Age-related changes in blood pressure, renal function, and sodium homeostasis suggest that sodium sensitivity of blood pressure may also be influenced by age. Blood pressure was measured in 378 normal volunteers and 198 patients with essential hypertension after an intravenous infusion of normal saline and after sodium and volume depletion. Those whose mean arterial blood pressure decreased more than 10 mm Hg after sodium and volume depletion were considered sodium-sensitive, whereas those with a decrease of less than 5 mm Hg were considered sodium resistant. The normal and hypertensive subjects were divided into groups of those above and those below 40 years of age. The blood pressure responses of both older and younger groups were normally distributed, indicating that blood pressure could either decrease or increase following volume depletion. Older hypertensive and normotensive subjects are more likely to be sodium sensitive. They usually have lower renin values than do younger subjects, but substantial heterogeneity is found. Age and renin status do not reliably predict sodium sensitivity. Volume contraction and dietary sodium restriction are more likely to decrease blood pressure in older than in younger subjects, but regimens must be tailored individually.

Sensitivity and resistance to the effects of sodium were evaluated in normotensive and hypertensive humans by two approaches. Blood pressure was measured after an intravenous infusion of 2 L of normal (0.9%) saline and after sodium and volume depletion induced by a low sodium diet and furosemide administration in 378 normal volunteers and 198 subjects with essential hypertension. Those in whom mean arterial blood pressure decreased by at least 10 mm Hg after sodium and volume depletion were considered sodium-sensitive, and those with a decrease of 5 mm Hg or less (including an increase in pressure) were considered sodium-resistant. The second study utilized the blood pressure response to modest dietary sodium restriction in 74 normotensive subjects to identify sodium sensitivity and resistance. In both studies the responses were heterogeneous. In the first study significantly more hypertensive subjects were sodium-sensitive, as compared with those in the normotensive group (p less than 0.001). Plasma renin activity (low, normal, or high) did not predict sodium responses. In both groups sodium-sensitive individuals were significantly older (p less than 0.001) and had lower baseline renin values than sodium-resistant subjects. Factors related to the change in mean arterial blood pressure after sodium and volume depletion included baseline pressure (r = -0.54, p less than 0.001) and age (r = -0.16, p = 0.002 in the normotensive group; r = -0.28, p less than 0.001 in the hypertensive group). The response to dietary sodium restriction was also correlated with baseline pressure (r = 0.61, p less than 0.001) and the initial urinary sodium excretion (r = 0.27, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the impact of large scale population screening for elevated total cholesterol, a city-wide event was scheduled in Indianapolis during nine days in February 1987. Altogether, 29,954 individuals were screened, and more than 32% were found to be at moderate or high risk using the classification recommended by the National Institutes of Health at the time of the screening for heart disease on the basis of their total plasma cholesterol concentrations. Although larger numbers of females and whites volunteered to be screened, the screened population represented a broad range of age and education levels. Results of a followup questionnaire returned by 18% of those at moderate of high risk revealed that after receipt of an elevated cholesterol result, 67% of the respondents scheduled a physician visit. The majority of those not doing so (53%) contacted their physician for other reasons or by telephone. Results of the followup indicate that screened subjects responded appropriately to the results received. The results of this project indicate that mass screening is only one tool to successfully identify individuals at risk. Given the biases present in the screened population, other strategies should be used to identify at-risk members of population groups unlikely to participate in similar screening events.

Sodium sensitivity and resistance of blood pressure were examined in 117 normotensive and 85 hypertensive subjects by means of a protocol using rapid extracellular fluid volume expansion with intravenously administered saline (2 L over 4 hours) followed by a day of low dietary sodium intake (10 mEq) and volume contraction induced by a diuretic (furosemide, 120 mg orally). Genetic markers were also examined. Both hypertensive and normotensive subjects with haptoglobin 1-1 phenotype were significantly more (p less than 0.05) likely to be sodium-sensitive than were those with 2-1 or 2-2 phenotypes, and subjects with 2-2 phenotypes were more apt to be sodium-resistant. A second population was examined in which both adults and children with haptoglobin 1-1 phenotype were found to have significantly (p less than 0.05) higher casual systolic and diastolic blood pressures. These two studies independently confirm a relationship between haptoglobin phenotypes and blood pressure and suggest an environmental factor (sodium) as well.

Three different dosages of vitamin C, dependent on body weight, were administered to 44 school-aged monozygotic twins for five months using a double-blind, co-twin control study design. The mothers recorded daily observations of cold symptoms, and multiple biochemical, anthropometric, and psychological measurements were made at the beginning and end of the study. Paired comparisons showed no significant overall treatment effect on cold symptoms, but the response was not uniform in all sub-groups. Treated girls in the youngest two groups had significantly shorter and less severe illness episodes, and an effect on severity was also observed in the youngest group of boys. The seven treated twins in the latter group also grew an average of 1.3 cm more than their untreated co-twins during the five-minth period of the study.

To investigate the effect of dietary sodium restriction on blood pressure in healthy, normotensive adults, 82 individuals (36 men, 46 women) participated in a study of restricted sodium intake (less than or equal to 75 mEq/day) for a period of 12 weeks. For the entire population there was a small but significant (p less than 0.01) decrease in mean arterial pressure during sodium restriction. The change in blood pressure was significantly correlated with age (r = 0.23, p less than 0.05). Division of the population at age 40, showed that the older individuals were more likely to have a decreased blood pressure during sodium restriction, while as a group younger adults showed no change. The individual blood pressure responses were heterogeneous with increases in pressure observed in some subjects. These results suggest that "sodium sensitivity" of blood pressure may be more evident with increasing age. Further, sodium restriction in all normotensive adults may not be innocuous.

Utilization of several genetic models (twins, families of monozygotic twins, characterized hypertensives and normotensive first-degree-relatives of essential hypertensives) has permitted us to probe for evidence of genetic mediation of several components of the blood pressure control system in humans. These studies have identified evidence for genetic mediation of systolic blood pressure in a cross-sectional study of normotensive subjects covering a wide age span. Further, this effect was independent of body size. The twin model, studied under conditions of sodium loading and sodium and volume depletion, demonstrated a genetic component in the response of plasma renin activity, aldosterone, norepinephrine and renal sodium excretion to these maneuvers. Among hypertensive subjects and unexpected abnormality in the distribution of a specific MNS blood group pattern was seen in renal vascular hypertensives. This may provide a new genetic marker for identifying individuals at increased risk to develop this abnormality.

To investigate the influence of hereditary on plasma renin activity (PRA), plasma aldosterone concentrations (PAC), blood pressure, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man, we studied 37 pairs of monozygotic (MZ) and 18 pairs of dizygotic (DZ) twins. Volume expansion was achieved by the intravenous infusion of 2L normal saline; volume contraction was accomplished by a low-sodium diet and 120 mg oral furosemide. The presence of genetic variance was tested by calculating the within pair and among component estimates of genetic variance. Outpatient 24-hour-urine collections suggested that MZ and DZ twins ingested diets similar in sodium and potassium content, and failed to reveal genetic influences on the dietary preferences for these electrolytes. The PRA values suggested heritable influences during both the volume expanded and contracted state with the added stimulus of upright posture. Heritable influences were observed on PAC and were most apparent in the basal state on the day of volume expansion. An influence of heredity on blood pressure was most apparent during volume contraction. Urinary sodium excretion (UNaV), urinary potassium excretion (UKV), fractional excretion of sodium (FENa), and fractional excretion of potassium (FEK) revealed evidence of significant genetic variance under the condition of volume expansion. in that state, systolic blood pressure was directly correlated with PRA, PAC, and inversely with FENa. The data suggest that the renal regulation of sodium and potassium excretion is in part influenced by heritable factors that may in turn contribute to the development of hypertension in some individuals.

Possible genetic influences on glomerular filtration rate and electrolyte excretion were investigated in 55 (37 monozygotic, 18 dizygotic) young adult white twin pairs. Subjects were studied during a five-day hospitalization involving sodium loading and sodium depletion. No evidence of genetic variability was found in the control levels of serum or urine sodium and potassium. Following a saline infusion it was possible to detect genetic influence in electrolyte handling. Creatinine clearance, used as a measure of glomerular filtration rate, did not appear to be genetically mediated. The results indicate that genetic factors are important in sodium handling in normal individuals and that this is independent of glomerular filtration rate.