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Biomedical subjects

J H Pratt

Publications and source records attributed to J H Pratt.

At least 73 records · Page 4Linked to original sources

Stimulation of aldosterone secretion by metoclopramide in humans: apparent independence of renal and pituitary mediation.

Metoclopramide (MP), a dopamine antagonist, stimulates secretion of aldosterone by a mechanism which has not been defined. We examined a potential role for either the kidney or the pituitary to mediate MPs effect on aldosterone secretion. Responses to MP administered i.v. were measured in six anephric and six hypopituitary patients as well as in six normal subjects. MP increased the plasma aldosterone concentration (PAC) in normal subjects in a fashion similar to what had previously been reported. MP produced no increase in plasma levels of renin activity (PRA), cortisol, potassium, or sodium. Three of six anephric patients (all of whom had undetectable PRA) responded to MP with increases in PAC; the magnitude of these responses correlated with the plasma potassium concentration. All six hypopituitary patients showed increases in PAC after MP administration. MP increased plasma prolactin levels in normal subjects and anephric patients; one hypopituitary patient had high basal plasma prolactin levels which increased with MP. In conclusion, neither the kidney nor the pituitary is involved in the mechanism for MP stimulated aldosterone production. These observations suggest that MP may act on the adrenal to evoke secretion of aldosterone.

Adrenocorticotropic Hormone↗

The effect of sodium on aldosterone metabolic clearance.

The effect of sodium intake on the aldosterone metabolic clearance rate (MCR) was examined in 5 normal subjects. Measurements were made under conditions where dietary sodium ranged from 10 to 1500 meq/day. There were no consistent changes in MCR over these extremes of sodium intake, and the plasma level of aldosterone correlated only with the aldosterone urinary excretion rate. In an additional group of 6 normal subjects, a single dose of 100 meq sodium administered orally had no effect on the aldosterone MCR. The findings indicate that aldosterone metabolism is unaffected by sodium intake.

Adult↗

Increased aldosterone metabolic clearance in hypertensive patients treated with minoxidil: an effect of greater hepatic perfusion.

Since minoxidil was previously shown to raise plasma renin activity (PRA) but not the plasma aldosterone concentration (PAC), the effect of minoxidil on the rate of aldosterone metabolic clearance was studied. After the addition of minoxidil to the antihypertensive regimen of 7 hypertensive patients, the aldosterone metabolic clearance rate increased from 1,110 +/- 91 to 1,570 +/- 180 liters/day (p less than 0.01), an overall increase of 41%. Hepatic blood flow, estimated from the clearance from plasma of indocyanine green, was increased in a group of minoxidil-treated patients compared to a comparable group not treated with minoxidil (p less than 0.01). Thus, although minoxidil induces an increase in PRA, PAC does not change, since aldosterone metabolic clearance increases. Minoxidil increased hepatic blood flow, and it was probably by this mechanism that the drug accelerated the rate of aldosterone clearance.

Adult↗

The unnecessary hysterectomy.

After a short statement on unnecessary surgery, the background of the ripple effect of the McCarthy report of 1974 was briefly summarized. A review of the vaginal hysterectomies on my service for 1971 through 1976 revealed that hysterectomies for functional diagnoses comprised 46% of the total and that hysterectomy for sterilization is now the third major category. Many patients had anatomic lesions such as fibroids, adenosis, or relaxation, but indications for hysterectomy, as agreed on by patient and physician, were functional. The operations should be consistent with the preoperative diagnoses. Second opinions are only a second physician's opinion, but they can be very helpful in controversial problems. Hysterectomy per se can offer more to the "quality of life" than any other single operation.

Adnexal Diseases↗

Effects of propranolol on aldosterone plasma concentration and aldosterone metabolic clearance in hypertensive patients.

Although propranolol administration produces a lowering of PRA, PAC does not decrease in a similar fashion. In the present study the effects of propranolol on the aldosterone MCR were examined. Eight patients with essential hypertension were studied while receiving treatment with a diuretic and again after propranolol (160 to 320 mg/day) was added to the therapeutic regimen. Propranolol therapy was associated with a 25% decrease in PRA (p less than 0.05) and changes in PACs that were variable but not significantly different from diuretic therapy alone. The aldosterone MCR decreased from 1420 +/- 120 to 1120 +/- 90 L/24 hr in response to propranolol (p less than 0.01). The average production rate of aldosterone (MCR X PAC) did not change after propranolol treatment despite a decrease in PRA. There were no changes in plasma concentrations of potassium or in ACTH secretion (as reflected by levels of cortisol) to explain a role for propranolol to sustain aldosterone secretion. Thus propranolol administered to hypertensive patients pretreated with a diuretic can affect circulating levels of aldosterone apart from changes in PRA. Propranolol therapy produces a moderate reduction in aldosterone MCR and appears to augment aldosterone production by a mechanism exclusive of known stimuli.

Adult↗

Diagnosis and localization of pheochromocytoma. Detection by measurement of urinary norepinephrine excretion during sleep, plasma norepinephrine concentration and computerized axial tomography (CT-scan).

The feasibility of differentiating patients with pheochromocytoma from other hypertensive patients by measuring urinary excretion rates of norepinephrine during sleep, a period of physiologic suppression of norepinephrine release, was investigated. The mean excretion rates of norepinephrine in 248 normal subjects and in 109 patients with essential hypertension were 1.03 +/- 0.03 and 1.12 +/- 0.06 (SEM) micrograms/hour, respectively, whereas the lowest excretion rate among the six patients with pheochromocytoma was about seven times higher. Plasma norepinephrine concentration in patients with pheochromocytoma was also consistently above the range observed in both normotensive and hypertensive subjects. CT scan correctly identified the same tumors visualized by selective arteriography. It is suggested that the usefulness of these approaches will provide simpler means of screening and detecting pheochromocytoma.

Adolescent↗

Minoxidil increases aldosterone metabolic clearance in hypertensive patients.

It has been shown that despite an effect of minoxidil to increase PRA, plasma levels of aldosterone do not change. We observed similar findings in seven hypertensive patients undergoing treatment with minoxidil; PRA activity increased markedly, whereas the plasma aldosterone concentration showed no consistent change. The aldosterone MCRs in these patients increased by 41% in response to minoxidil, from 1110 +/- 91 to 1570 +/- 180 (SEM) liters/day; this appeared to explain why plasma aldosterone levels did not increase in parallel with renin activity. Hepatic blood flow (estimated from the clearance of indocyanine green) in a group of patients receiving minoxidil was greater than that in an otherwise comparable group (P less than 0.02). This increase in hepatic perfusion may, at least in part, have accounted for the increase in aldosterone MCR.

Adult↗

The effect of extremely high sodium intake on plasma renin activity, plasma aldosterone concentration, and urinary excretion of aldosterone metabolites.

The effect of sodium intake on aldosterone production was examined in eight healthy men whose urinary sodium excretion approached their dietary sodium intake at levels of 10, 300, 800 and 1500 mEq sodium/day. Aldosterone secretion was estimated from the excretion rate of two aldosterone metabolites: Thaldo and aldosterone-18-glucuronide. Maximal suppression of aldosterone secretion appeared to have been reached when sodium intake was 800 mEq/day, since no further decrease in aldosteron metabolite excretion rates was observed at 1500 mEq/day dietary sodium. Both plasma renin activity and plasma aldosterone concentration were suppressed and approached or were below the detection limits of the respective radioimmunoassays when sodium intake reached 800 and 1500 mEq/day. Body weight and blood pressure significantly increased at each increment of sodium intake. Our findings show that when sodium intake is extremely high, aldosterone secretion does not decrease to zero but continues at a rate we estimate to be 10 to 30 microgram/day. We suggest that this nonsuppressible secretion of aldosterone may have contributed to the observed increases in weight and blood pressure.

Adult↗

Detection of adrenal tumors by computerized tomographic scan in endocrine hypertension.

Localization of adrenal lesions in various adrenal disorders can be difficult. An attempt to identify the adrenal tumors in ten patients with pheochromocytoma, Cushing's syndrome, or primary aldosteronism was made using computerized tomographic (CT) scans. The adrenal tumor was visualized in eight patients. The CT scan appears to be a promising noninvasive technique for localization of adrenal tumors.

Adrenal Gland Neoplasms↗

A giant fibroid uterus.

Giant uterine fibroids are those weighing greater than 25 lb (11.4 kg). Such a fibroid may appear as a solitary tumor or as a conglomerate mass of uterine fibroids presenting as a single uterine tumor. The challenge of these tumors lies in their proper surgical management. Combined preoperative and postoperative mortality is approximately 15%. The paucity of recent reports encountered in the literature of uterine fibroids of this magnitude reflects their rarity.

Female↗

Panniculectomy and abdominoplasty.

The series involved 123 patients who had 126 excisions of the abdominal wall. In 84 patients, a large pannus of fatty tissue and skin was excised to expedite the approach to intra-abdominal disease or the repair of hernias. In 39 patients, the operation was an abdominoplasty done to improve the appearance of the abdomen or to excise relaxed or redundant tissues. Complications were minimal. The experience suggests that the surgeon should consider and utilize techniques to improve the general function and appearance of the abdominal wall and yet not compromise the treatment of the patient's major problem.

Abdominal Muscles↗

A new approach to the difficult assessment of aldosterone secretion in anephric patients.

A new method for the assessment of endogenous formation of aldosterone in anephric patients is described. (1, 2-3H) aldosterone was administered i.v. to patients 1-2 days before hemodialysis, and then the specific activity (SA) of tetrahydroaldosterone glucosiduronate, the major aldosterone metabolite, was measured in the dialysate using a specific radioimmunoassay. The aldosterone secretion rate was determined from the extent of isotope dilution by endogenous metabolite. Aldosterone secretion rates measured in 10 patients were for the most part low. The secretion rate determined in blood from the aldosterone metabolic clearance rate and plasma aldosterone concentration closely approximate secretion rate values obtained by the isotope dilution method in 3 of 4 patients. In 2 patients in whom ACTH was administered chronically, radio-labeled aldosterone was administered at the start of the study and then the day to day aldosterone secretory response to ACTH was determined from the SA of tetrahydroaldosterone in blood. Aldosterone secretion continuously increased for as long as ACTH was administered.

Adolescent↗

Aromatization of androgens by muscle and adipose tissue in vivo.

[7-3HA1Androstenedione and [4-14C]estrone or [7-3H]testosterone and [14C]estradiol were infused at constant rates into brachial arm veins of 15 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle, and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In seven men the mean +/- SE value for the fractional conversion of androstene tissue. In eight men the mean +/- SE value for the fractional conversion of testosterone to estradiol was 0.0007 +/- 0.0001 for muscle and 0.0012 +/- 0.0002 for adipose tissue. Both of these values were significantly (P less than 0.01) less than the respective values of androstenedione aromatization to estrone. If constancy of tissue aromatization throughout the body is assumed, the muscle accounts for 25-30% and adipose tissue for 10-15% of the total extragonadal aromatization of androgens to estrogens.

Adipose Tissue↗

Estriol production rates and breast cancer.

We have infused [6,7-3H]estrone or [6,7-3H]estradiol and [4-14C]estriol into seven women who had had breast cancer and into five normal postmenopausal women. We measured the endogenous concentrations and the metabolic clearance rates of estrone, estradiol, and estriol and calculated the blood production rates for these steroids in each group. There were no significant differences between the respective measurements for each group. Our data does not support the argument that physiological amounts of estriol are protective against breast cancer development in women.

Adult↗

Relationship between urine and plasma estrogen ratios.

Normal young and postmenopausal women were placed into groups according to the ratio of the estrogens in their urine. Women whose ratio was greater than 1.3 if young and greater than 3.2 if postmenopausal were compared to women whose ratio was less than 0.7 and less than 2.1 for young and postmenopausal, respectively. Between the respective high- and low-ratio groups, there were no significant differences for circulating levels of estriol, metabolic clearance rates of estriol, or blood production rates of estriol, estrone, or estradiol. Women who had had breast cancer were compared to a group of normal controls and were also found to have similar blood production rates for estriol, estrone, and estradiol. The ratios of the blood production rates of estriol to estrone and estradiol were similar for the high and low groups for young and postmenopausal women and also between the breast cancer women and their controls. It appears, therefore, that the difference in urinary estrogen ratios is primarily due to different pathways of metabolism of the free circulating estrogens and not to differences in the production rates of the estrogens. Estriol is produced at only 10% the rate of estrone and estradiol.

Breast Neoplasms↗