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J H Pratt

Publications and source records attributed to J H Pratt.

At least 19 recordsLinked to original sources
PubMed1996

A comparison of the urinary excretion of bone resorptive products in white and black children.

Bone density is greater in blacks than in whites regardless of age. In adults, bone formation was shown previously to be much lower in blacks than in whites. A lower bone turnover in adult blacks may preserve a high bone density acquired earlier in life. Whether there is a difference in bone turnover in blacks and whites early in life is not known. Bone resorption is known to parallel bone formation, and thus in the present study we looked for racial differences in bone turnover in children by measuring the nocturnal urinary excretion of three markers of bone resorption: hydroxyproline and the pyridinium cross-links, pyridinoline and deoxypyridinoline. Sixty-four black and 145 white children ages 6 through 15 years were studied. We found excretion of hydroxyproline to be similar in whites and blacks. Urinary excretion of the cross-links was about 10% to 15% lower in blacks, but only the excretion of pyridinoline in boys was significantly lower in blacks (p = 0.031). Overnight urinary calcium excretion was about 30% lower in blacks than in whites (p = 0.0016 for boys and p = 0.008 for girls), as has been reported previously by others. In summary, the excretion rates of bone resorptive products in white and black children were similar, suggesting nearly equal bone turnover in the two racial groups, a finding that contrasts with observations made previously in adults.

Adolescent↗
PubMed1996

Racial difference in the relationship of an angiotensin I-converting enzyme gene polymorphism to serum angiotensin I-converting enzyme activity.

An insertion (I)/deletion (D) polymorphism of the angiotensin I-converting enzyme (ACE) gene that has been associated with certain cardiovascular disorders accounts for nearly half the variation in serum ACE level in white subjects. Whether a similar association of serum ACE with the I/D polymorphism occurs in other racial groups is not known. We studied the I/D polymorphism of ACE in relation to serum ACE activity in 141 white and 62 black healthy, unrelated children and adolescents (mean age, 14.7 years). The mean level of ACE activity in whites homozygous for the D allele was higher than in heterozygotes (P = .002) and in homozygotes for the I allele (P = .0001), consistent with an earlier study. In blacks, on the other hand, no significant difference in serum ACE activity between genotypes was observed. An additional finding was a significantly positive relationship between serum ACE activity and diastolic pressure (P = .009). In children and adolescents, serum ACE activity is related to the ACE gene I/D polymorphism in whites but not in blacks. The results indicate a potentially important ethnic variation in genetic regulation of serum ACE activity and the relationship of the I/D polymorphism to cardiovascular disease.

Adolescent↗
PubMed1995

Blood pressure effects of the angiotensin II receptor blocker, losartan.

BACKGROUND: Losartan potassium, the first nonpeptide selective blocker of angiotensin II at the AT1 receptor, has been shown to exhibit clinical antihypertensive effects. The aim of the present study was to characterize the efficacy and duration of action of losartan by ambulatory blood pressure monitoring. METHODS: The study was performed in nonblack hypertensive patients whose baseline untreated clinical diastolic blood pressures were 95 mm Hg or higher and whose average 24-hour ambulatory diastolic blood pressures were 85 mm Hg or higher. Patients were randomized, double-blind, into four treatment groups: placebo (n = 32) or losartan, 50 mg once daily (n = 29), 100 mg once daily (n = 30), or 50 mg twice daily (n = 31). Clinical and 24-hour ambulatory blood pressures were measured at baseline (off treatment for at least 4 weeks) and after 4 weeks of treatment. RESULTS: By clinical sphygmomanometer measurements at the end of the 24-hour or 12-hour dosing intervals (trough), all three losartan dosages were significantly more effective than placebo at decreasing systolic and diastolic blood pressures. By average 24-hour ambulatory systolic/diastolic blood pressure measurements, the decreases produced were 0.0/0.2 mm Hg for placebo and 9.2/6.9, 9.9/6.4, and 13.2/8.5 mm Hg, respectively, for losartan, 50 mg once daily, 100 mg once daily, and 50 mg twice daily. All drug effects were different from placebo (P < .01). The effects of losartan, 50 mg twice daily, were not significantly different from those of losartan, 100 mg once daily, but, as expected, the effects were greater than those of losartan, 50 mg once daily (P < .05). Addition of hydrochlorothiazide, 12.5 mg/d, during an additional 2-week treatment period in patients whose clinical diastolic blood pressure remained at 85 mm Hg or higher while receiving monotherapy produced additional and clinically meaningful blood pressure decrements that were similar in all four treatment groups. There was no clinically important difference in the incidence of adverse events among the losartan-treated and placebo groups [corrected]. CONCLUSION: Ambulatory blood pressure monitoring, which virtually eliminated antihypertensive placebo responses, demonstrated clear 24-hour efficacy for losartan, 50 mg once daily, as well as for higher doses of 100 mg once daily and 50 mg twice daily. This AT1 receptor blocker had antihypertensive effects that appeared additive when combined with low-dose diuretic therapy. Losartan was generally well tolerated.

Adult↗
PubMed1995

Identification of a splice variant of the rat and human mineralocorticoid receptor genes.

The sequence of a splice variant of the rat mineralocorticoid receptor (MR) gene is presented. A cDNA clone corresponding to rat MR was isolated from a rat brain cDNA library. Sequence analysis of the region corresponding to the DNA binding domain revealed the presence of a 12 base pair (bp) insertion. Analysis of mRNA from several rat tissues suggests that the variant is less abundant than the wild type in most tissues. The insertion variant is also a product of the human MR gene, the identical splice variant was also observed in human white blood cell mRNA. Unlike other splice variants reported for the MR, this variant alters the encoded protein by the addition of four amino acid residues in the DNA binding domain. The altered protein may influence the affinity of the MR for mineralocorticoid or glucocorticoid response elements.

Alternative Splicing↗
PubMed1995

Effects of losartan on a background of hydrochlorothiazide in patients with hypertension.

The purpose of this multicenter trial was to compare the antihypertensive efficacy and safety of losartan potassium (losartan), a selective angiotensin II receptor antagonist, when added to hydrochlorothiazide in hypertensive patients whose blood pressure was not adequately controlled by 25 mg hydrochlorothiazide monotherapy. After a 4-week monotherapy period of 25 mg hydrochlorothiazide, 304 patients with trough (22 to 26 hours postdose) sitting diastolic pressure between 93 and 120 mm Hg were maintained on 25 mg hydrochlorothiazide and randomized double-blind into treatment arms consisting of either 25, 50, or 100 mg losartan or placebo once daily for 12 weeks. The reductions in sitting diastolic pressure for patients treated with 25, 50, or 100 mg losartan concomitantly administered with 25 mg hydrochlorothiazide were significantly greater (P < or = .05) than the reductions observed in the 25 mg hydrochlorothiazide plus placebo group beginning 1 week after randomization. The antihypertensive response in all groups was greater at week 3 than week 1, with some additional decrease in blood pressure in some groups at later times. Sitting systolic pressures were also significantly reduced in each group over time. Standing blood pressures at week 12 were similar to sitting blood pressures. A dose-response relationship to losartan was observed in this patient population. The percentages of the total drug-related clinical adverse experiences as assessed by the investigator were generally similar in the 25, 50, and 100 mg losartan plus 25 mg hydrochlorothiazide groups (10.3%, 24.4%, and 20.0%, respectively) compared with the placebo plus 25 mg hydrochlorothiazide group (24.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children.

The T235 allele of the angiotensinogen gene (AGT) has been associated with hypertension. Blood pressure increases faster over time in black children than in white children, and in adults hypertension is more prevalent in blacks. We sought evidence for a role for angiotensinogen to contribute to racial differences in blood pressure in a study of 148 white and 62 black normotensive children (mean age, 14.8 yr). The frequency of the T235 allele was 0.81 in blacks and 0.42 in whites (chi 2 = 77.3, P = 0.0001). The mean angiotensinogen level was 19% higher in blacks than in whites (P = 0.0001 for males, P = 0.004 for females). Genotype was positively related to serum angiotensinogen in white children (P = 0.0001 for males, P = 0.004 for females), but a similar relationship was absent in blacks where the frequency of M235 may have been too low to discern an association. Longitudinal blood pressure (measured twice yearly) adjusted for body mass index showed a marginally significant relationship to the angiotensinogen level (P = 0.07). An independent relationship of serum angiotensinogen with body mass index (P = 0.0001) and race (P = 0.0003) was also observed. In summary, T235 was more frequent, and the level of angiotensinogen was higher in blacks than in whites. Such a racial difference in the renin-angiotensin system may contribute to the disparity in blood pressure levels of white and black young people.

Adolescent↗
PubMed1994

Familial influences on the adrenal androgen excretion rate during the adrenarche.

The regulation of adrenal androgen (AA) production in both children and adults has not been defined. We report here on two different studies that examined familial influences on AA production early in life when such production is accelerated, a period known as the adrenarche. AA production was estimated from measurements of excretion of AA in urine samples collected overnight. The first study used a twin model where genetic and environmental components to the variance in AA excretion were determined in white monozygotic (MZ) and dizygotic (DZ) twins. The intraclass correlation coefficient for weight-adjusted AA excretion was .730 (P < .0001) in MZ twins and .511 (P = .007) in DZ twins. There was a significant genetic component to the weight-adjusted AA excretion rate, with a heritability of 58%. Environmental effects accounted for 17% of the variation. Black children were previously shown to have higher AA levels than white children. Therefore, in the second study we looked for evidence that race affected familial influences on AA excretion. To estimate familial aggregation of AA excretion, intraclass correlations were determined in siblings from black and white families. AA excretion rates were measured twice-yearly for up to 4.5 years, and an individual's average excretion rate was used in the analysis. The intraclass correlation coefficient for the weight-adjusted AA excretion in black siblings was .492 (P = .0021), and for white siblings it was .372 (P = .0003). Intraclass correlation coefficients for AA excretion rates were not significantly different in the two racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1993

Evaluation of diagnostic tests in the differential diagnosis of primary aldosteronism: unilateral adenoma versus bilateral micronodular hyperplasia.

Effective management of primary aldosteronism is dependent upon correct localization of excessive aldosterone production. We report our results of localization studies in patients with biochemically and pathologically confirmed primary aldosteronism. Retrospective chart review identified 69 patients with unilateral adrenal adenoma and 11 with adrenal hyperplasia. Correct unilateral versus bilateral localization of excessive aldosterone production was predicted in 70% versus 71%, respectively, by adrenal venography, 100% versus 63% by adrenal vein hormone sampling, 46% versus 56% by adrenal nuclear scanning and 69% versus 13% by anomalous postural decline of aldosterone. Adrenal computerized tomography appeared to localize correctly 86% versus 80% of the lesions. Unilateral adrenalectomy normalized blood pressure in 79% of the patients with unilateral adenomas versus only 18% of those with adrenal hyperplasia. Once primary aldosteronism is confirmed, localization by adrenal vein sampling, adrenal venography and adrenal computerized tomography is most effective in directing antihypertensive therapy.

Adenoma↗
PubMed1993

Effect of recombinant human growth hormone on adreno-cortical function, and on sodium and potassium homeostasis.

In the present study we examined the effect of treatment with recombinant human growth hormone (rhGH) on adrenocortical secretory function, as well as sodium and potassium balance. rhGH, 100 micrograms/kg per day, was given for 4 days. Both glucocorticoid and androgen secretion were unaffected by treatment as evidence by unchanged levels of cortisol and dehydroepiandrosterone-sulfate. rhGH resulted in retention of sodium and potassium and a decrease in serum potassium concentration, but neither aldosterone plasma levels nor urinary excretion rates changed until after treatment. During the rhGH washout phase, a natriuresis ensued, but this occurred slowly possibly in part because a higher serum potassium stimulated aldosterone secretion. In summary, short-term treatment with rhGH had no immediate effect on adrenocortical function, but caused pronounced retention of electrolytes. In the posttreatment period, there were increases in aldosterone secretion accompanied by delayed recovery from the retention of sodium.

Adrenal Cortex↗
PubMed1993

Longitudinal assessment of blood pressures in black and white children.

The prevalence of hypertension is greater for blacks than whites. Whether black children have higher blood pressure than white children is less clear. We investigated this issue through a prospective longitudinal assessment of blood pressure in 345 white children and 164 black children. Each child had his or her blood pressure measured every 6 months for 2 to 5.5 years. The means for systolic and diastolic blood pressures for each individual were calculated, and the rate of change in blood pressure over time for each subject was estimated. The mean blood pressure and the mean rate were compared between gender-specific black and white groups. For both boys and girls, the mean systolic blood pressure was 2 mm Hg higher in black children than white children (P = .0008). Boys had a higher systolic blood pressure than girls (P = .0048). The mean diastolic blood pressure was 1.5 mm Hg higher in black children than in white children (P = .0270); no significant gender difference in diastolic blood pressure was observed. Age, weight, height, and body mass index were highly correlated with blood pressure. When accounting for these variables, for girls the racial difference in systolic blood pressure remained significant, whereas the difference in diastolic blood pressure in boys and girls was no longer significant. The rate of increase in blood pressure over time was significantly greater in blacks than whites: for systolic blood pressure, P = .0002, and for diastolic blood pressure, P = .009.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Racial differences in aldosterone excretion: a longitudinal study in children.

Aldosterone production, estimated from urinary excretion of aldosterone and the plasma aldosterone level, was found in a previous cross-sectional study to be lower in black children than white children. The present study examined aldosterone excretion longitudinally to determine whether the aldosterone excretion rate changed with time and if the racial difference in aldosterone excretion persisted. Urine samples were collected every 6 months for up to 5.5 yr in 351 white and 170 black children for measurements of aldosterone, sodium (Na+), and potassium (K+) excretion. Results were expressed per mumol urinary creatinine. Mean values for excretion rates for the total longitudinal period were determined. Na+ excretion was not significantly different in the two groups, whereas K+ excretion was 18% lower in blacks than whites (P = 0.0001). Body weight and urinary Na+ and K+ excretion were significantly related to aldosterone excretion. After adjusting for these variables, the aldosterone excretion rate was 35% lower in blacks than whites (P = 0.0001), a racial difference that did not change with age. Aldosterone excretion rates showed no longitudinal trend to either increase or decrease. The physiological relevance of the lower aldosterone excretion rate in black children remains unknown.

Adolescent↗
PubMed1992

The interaction of norepinephrine excretion with blood pressure and race in children.

OBJECTIVE: The purpose of this study was to examine the relationship between urinary norepinephrine excretion and blood pressure, and to determine the influence of race on this relationship. Urinary norepinephrine was used to estimate renal and systemic sympathetic nervous system (SNS) activity. DESIGN: Fifty black and forty-nine white normotensive children aged 9-14 years had their blood pressure measured, and provided an overnight urine sample. METHODS: Urinary norepinephrine was measured by radioenzymatic assay. Excretion rates of norepinephrine were expressed per milligram urinary creatinine. RESULTS: Black children had age-adjusted mean diastolic and systolic blood pressure which was higher than in white children. For both blacks and whites, nocturnal urinary norepinephrine excretion rates were positively related to age-adjusted mean diastolic blood pressure, but not to systolic blood pressure. Norepinephrine excretion was significantly lower in black children compared with white children. CONCLUSION: These findings suggest that the higher blood pressures in black children were not causally related to greater SNS activity. The SNS may have been suppressed in black children, possibly by a greater expansion of plasma volume, alternatively, black children may have been more sensitive to the influences of the SNS than white children.

Adolescent↗
PubMed1992

Genetic influences on the urinary excretion of aldosterone in children.

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.

Aldosterone↗
PubMed1991

Inhibition of aldosterone production by pinacidil in vitro.

Pinacidil, an antihypertensive agent that opens potassium channels, lowers plasma aldosterone levels in hypertensive patients by an unknown mechanism. In the present study, pinacidil's direct effects on production of aldosterone were assessed using isolated cells from bovine adrenal glomerulosa. Pinacidil was found to inhibit aldosterone production, both basally and during stimulation with either potassium, angiotensin II (Ang II), or adrenocorticotropic hormone (p less than 0.001), with half maximal inhibition occurring at 10(-5) M. As assessed by the exclusion of trypan blue from cells, pinacidil did not inhibit secretion through injurious effects on glomerulosa cells. Also, washing of cells previously exposed to pinacidil restored secretory responsiveness. Pinacidil did not alter cytosolic calcium (Ca2+) concentrations when aequorin was used as a photoluminescent indicator of Ca2+ levels, suggesting that pinacidil acted by a non-Ca(2+)-mediated mechanism. Consistent with direct inhibition of the late pathway in steroidogenesis was that pinacidil decreased conversion of pregnenolone and corticosterone to aldosterone. Pinacidil did not block binding of Ang II to its receptor, nor did it appear to affect adrenocorticotropic hormone-receptor binding, since stimulation by cyclic AMP, the post-receptor second messenger of adrenocorticotropic hormone, was also inhibited. In summary, pinacidil inhibited directly the adrenal's production of aldosterone. The mechanism whereby the inhibition occurred was unclear.

Adrenocorticotropic Hormone↗
PubMed1990

Dehydroepiandrosterone sulfate quantification in serum using high-performance liquid chromatography/mass spectrometry and a deuterated internal standard: a technique suitable for routine use or as a reference method.

A thermospray high-performance liquid chromatography/mass spectrometry method for determination of serum dehydroepiandrosterone sulfate is described. The steroid was measured intact using [7,7-2H2]dehydroepiandrosterone sulfate as internal standard. The analysis was carried out in the negative ion mode by determining the peak height ratio of the molecular anions of the analyte and internal standard. The method was used to determine the steroid in serum from 15 male and female normal adults and the following values were obtained: males, 272 +/- 45 micrograms/dl (range, 197 to 331 micrograms/dl) and females, 215 +/- 67 micrograms/dl (range, 107 to 347 micrograms/dl). In addition, dehydroepiandrosterone sulfate was measured by high-performance liquid chromatography/mass spectrometry and radioimmunoassay (a commercial kit) on 25 individuals of all age groups. There was strong correlation between the values obtained, but the radioimmunoassay values were generally double those obtained by high-performance liquid chromatography/mass spectrometry. Three other steroid sulfates, androsterone sulfate, epiandrosterone sulfate, and androst-5-ene-3 beta, 17 beta-diol sulfate, were also assayed. In males, these had mean values of 112, 44, and 13 micrograms/dl and, in females, they had mean values of 84, 25, and 6 micrograms/dl, respectively. Radioimmunoassay cross-reactivity measurement for these steroids (as reference compounds) showed that they were unlikely to contribute greatly to the discrepancy between radioimmunoassay and high-performance liquid chromatography/mass spectrometry values.

Adult↗
PubMed1990

Adrenal androgen excretion during adrenarche. Relation to race and blood pressure.

We have previously shown that black children have higher blood pressures than white children. In the present study, we examined whether a possible racial difference in adrenal androgen production during adrenarche might contribute to the racial disparity in blood pressure. Adrenal androgen production was estimated from urinary excretion of adrenal androgen metabolites that showed cross-reactivity with antisera to dehydroepiandrosterone sulfate (DHEA-S). Urine samples were collected overnight in 798 children, one third of whom were black. Analyses were performed for two different age groups, less than 10 years and 10 years or more of age. In children less than 10 years of age, adrenal androgen excretion rates were 17% higher in blacks than in whites (p = 0.0099); adrenal androgen excretion rates tended to be higher in older black children as well, but differences here were not statistically significant. Adrenal androgen excretion rates were positively correlated with diastolic blood pressure in the older age group only (p = 0.014). However, when the relation of race to blood pressure was examined along with adrenal androgen excretion adjusted for age, sex, and weight, race remained an independent contributor to the level of blood pressure, suggesting that a difference in adrenal androgens could not explain the racial differences in blood pressure. In summary, black children produced more adrenal androgen, but this did not explain their higher blood pressures. In older children, where adrenal androgen excretion rates were higher, diastolic blood pressure and adrenal androgen excretion were positively related, suggesting that adrenal androgens participate in establishing the level of blood pressure in young people.

Adrenal Glands↗