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Biomedical subjects

J R Gill

Publications and source records attributed to J R Gill.

At least 73 records · Page 4Linked to original sources
PubMed1980

The role of the prostaglandin system in the regulation of renal function in normal women.

The role of prostaglandins in the regulation of renal function was studied in seven healthy female volunteers taking a constant metabolic diet containing 59 meq of sodium and about 50 meq of potassium daily. Each subject underwent two renal clearance studies, during which vasopressin (priming dose, 200 mU; "sustainer," 200 mU/hour at 1 ml/min) was infused intravenously. The first clearance study served as the control; indomethacin (2 mg/kg/day) was given for seven days before the second clearance study to inhibit prostaglandin synthesis. Food and fluid were withheld for 12 hours before the studies. Urine was collected through an indwelling bladder catheter at 30 minute intervals. Glomerular filtration rate was estimated from inulin clearance and renal blood flow from para-aminohippurate (PAH) clearance. Indomethacin was associated with a significant increase in maximal urinary osmolality from 826 +/- 47 mosmol/kg H2) to 920 +/- 32 mosmol/kg H2O (P < 0.01). Minimal "free water" clearance was -1.40 +/- 0.02 ml/min before and -1.63 +/- 0.04 ml/min (P < 0.01) after the administration of indomethacin. Indomethacin did not affect urine flow, urinary sodium or potassium excretion, glomerular filtration rate or renal plasma flow. In addition, indomethacin did not affect the urinary excretion of cyclic adenosine monophosphate (AMP). Plasma arginine-vasopressin, measured in two subjects by radioimmunoassay, did not change with blockade of prostaglandin synthesis. It appears that prostaglandins antagonize the hydro-osmotic effect of antidiuretic hormone by an intrarenal mechanism, independent of changes in renal hemodynamics or cation excretion. This mechanism is probably mediated by an alteration in the water permeability of the collecting ducts. Since urinary cyclic AMP did not change during blockade of prostaglandin synthesis, whereas urinary osmolality increased, a change of vasopressin-dependent cyclic AMP production in the kidney was probably not reflected in urinary cyclic AMP.

Adult↗
PubMed1980

Effects of moderate short-term potassium depletion in normal humans. The role of prostaglandins.

The role of prostaglandins (PG) in the effects of potassium (K+)depletion was studied in six normal women. A mean K+-deficit of 220 mEq was induced with and without concomitant treatment with indomethacin (150 mg/day). Mean serum K+ concentration decreased from 4.2 +/- (S.E.) 0.1 to 3.2 +/- 0.1 mEq/L without indomethacin and from 4.1 +/- 0.1 to 3.2 +/- 0.1 mEq/L with indomethacin. "Supine" and "upright" plasma renin activity (PRA) and plasma norepinephrine concentration (NE) were unaltered by K+ -depletion alone but decreased with indomethacin. Plasma aldosterone (PA) was suppressed during K+-depletion (control: 7.2 +/- 2.6 ng/dl supine, 19.3 +/- 8.1 ng/dl upright; K+-depletion: 2.6 +/- 0.3 ng/dl supine, 5.5 +/- 1.3 ng/dl upright) and was paralleled by a decrease in urinary aldosterone. K+- depletion decreased urinary PGE2 from 667 +/- 133 to 343 +/- 60 ng/day (P less than 0.025) without a change in PGF2 alpha. The dose of exogenous angiotensin II (A II) which increased diastolic blood pressure by 20 mm Hg (pressor dose) was 7.1 +/- 1.4 ng/kg/min during control and increased to 11.0 +/- 0.7 ng/kg/min during K+-depletion (P less than 0.05). Indomethacin increased the sensitivity to A II both during control (pressor dose: 4.9 +/- 0.6 ng/kg/min) and K+ - depletion (pressor dose: 6.0 +/- 1.0 ng/kg/min). These results indicate that in healthy subjects, moderate short-term K+-depletion does not affect PRA or NE but decreases production of aldosterone and PGE2 by the kidney. The changes in vascular sensitivity to exogenous A II during K+-depletion and indomethacin and the decreases in plasma NE and PRA during indomethacin may be explained by changes in vascular vasodilator PG.

Aldosterone↗
PubMed1980

Correction of increased prostacyclin synthesis in Bartter's syndrome by indomethacin treatment.

The role of prostacyclin and thromboxane A2 in the pathogenesis of Bartter's syndrome was investigated by measurement of the urinary excretion of 6-keto-PGF1 alpha and thromboxane B2, respectively, in five patients. The prostaglandin metabolites were extracted from urine by a reproducible method and measured by specific radioimmunoassays. The patients with Bartter's syndrome excreted about four-times as much 6-keto-PGF1 alpha as the normal controls. In contrast, there was no significant difference in the urinary excretion of thromboxane B2 between the patients and the controls. In a second part of the study, three patients were treated with indomethacin (150 mg/day for four days), an inhibitor of prostaglandin synthesis. This regimen suppressed urinary excretion of 6-keto-PGF1 alpha by 43% and that of thromboxane B2 by 46%. It is suggested that the increase in prostacyclin production is responsible for both the hyperreninemia and and the other endocrine derangements as well as the hyporesponsiveness of blood pressure to intravenous infusion of vasopressors in patients with Bartter's syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Evolution of the surgical management of primary aldosteronism.

During the past two decades 50 patients were operated on for primary aldosteronism. Diagnosis was based on high aldosterone excretion or secretion during a high sodium intake and, more recently, low stimulated plasma renin activity. Computed tomography and adrenal venography with selective adrenal vein catheterization for determination of aldosterone/cortisol ratios were helpful in the distinction between adenoma and bilateral hyperplasia. As a result of preoperative localization, unilateral posterior or flank approach to the adrenal has replaced transabdominal as the approach of choice. Overall in-hospital mortality in this series was 10% and occurred exclusively with a transabdominal approach in the early part of the series. Adrenalectomy has been curative in 66% of patients with adenoma and in 38% of patients with hyperplasia which includes patients with adenomatous (dominant macroscopic adenoma, 1 cm or greater) hyperplasia when the cure rate was 75%. Currently, only patients who have unilateral adrenal hyperfunction, who respond to spironolactone with a fall in blood pressure, and who are a good operative risk are considered for operation by posterior or flank approach. These guidelines for the management of primary aldosteronism, used since 1974, have been associated with an excellent response (92%), zero mortality and reduced morbidity.

Adenoma↗
PubMed1979

Prostacyclin overproduction in Bartter's syndrome.

Urinary excretion of 6-keto-prostaglandin F1alpha and thromboxane B2, the major metabolites of prostacyclin and of thromboxane A2, respectively, was measured by specific radioimmunoassays in five female patients with Bartter's syndrome and in five normal female controls. The patients with Bartter's syndrome excreted about four times as much 6-keto-PGF1alpha as the controls; their excretion of thromboxane B2 was no different from that of the controls. These data suggest that overproduction of prostacyclin mediates both the hyper-reninaemia and the hyporesponsiveness of blood-pressure to pressor agents in Bartter's syndrome.

Adolescent↗
PubMed1979

Prolactin in primary aldosteronism.

1. This study was done to examine the possibility that escape from the sodium retention produced by aldosterone may be associated with an inhibition of prolactin secretion. Plasma prolactin concentrations were determined in seven patients with adrenal adenoma and aldosteronism, before and after unilateral adrenalectomy, at a time when they were in balance on a sodium intake of 109 mmol/day. 2. After operation, plasma aldosterone was normal [before operation, 52.7 +/- 12.1 (supine), 64.6 +/- 9.1 ng/dl (upright); after operation, 6.8 +/- 1.5 (supine), 11.1 +/- 3.0 ng/dl (upright)], while plasma prolactin remained unchanged [before operation, 19.6 +/- 2.8 (supine), 15.5 +/- 3.3 ng/ml (upright); after operation, 23.8 +/- 2.3 (supine), 11.1 +/- 3.0 ng/ml (upright)]. 3. Our results do not support a role for prolactin in the renal response to aldosterone in man.

Adrenalectomy↗
PubMed1979

Preoperative diagnosis and localization of aldosteronomas by measurement of corticosteroids in adrenal venous blood.

Adrenal venous aldosterone/cortisol ratios were determined in 14 patients with primary aldosteronism. Of 12 patients diagnosed as having an adrenal adenoma, ten underwent surgery in which an adenoma was found. Bilateral adrenal hyperplasia was thought to have developed in two other patients. Measurement of adrenal vein cortisol and establishment of aldosterone/cortisol ratios were done to correct for catheter placement and dilute adrenal efflux. Determination of steroids after ACTH stimulation was helpful in distinguishing quiescent from suppressed adrenal in two patients and in confirming the diagnosis of the others.

Adenoma↗
PubMed1979

Neural control of renal tubular sodium reabsorption.

Renal adrenergic nerves are in contact with the basement membranes of tubule cells and, when these nerves are stimulated or ablated, proximal tubular reabsorption of sodium is increased or decreased, respectively. Renal adrenergic nerve activity appears to be regulated by low-pressure cardiopulmonary receptors and high-pressure arterial baroreceptors in response to changes in blood volume. Thus, a decrease in blood volume or in effective circulating blood volume leads to an increase in renal nerve activity, release of norepinephrine, alpha-adrenergic stimulation and increased tubular reabsorption of sodium, whereas an increase in blood volume leads to a decrease in renal nerve activity, a decreased release of norepinephrine, an increased release of dopamine, possible beta-adrenergic stimulation and a decreased tubular reabsorption of sodium.

Animals↗
PubMed1979

Computed tomography in adrenal tumors.

Computed tomography (CT) was used to evaluate 26 patients with a variety of adrenal lesions. Surgical proof was available in 22 patients and clinical confirmation with a variety of other studies in the other four patients. Nine patients ahd aldosterone-producing adrenal adenomas and CT correctly identified seven. Four patients had cortisol-producing adenomas and five patients had cortisol-producing carcinomas; CT identified each of these tumors. Prominent but normal shaped glands were seen in each of the four patients with adrenal hyperplasia. Adrenal metastases from malignant melanoma in two patients were identified. Only one of two pheochromocytomas in two patients could be seen on CT. CT is a noninvasive method of localizing adrenal tumors and may be helpful in distinguishing adenomas from adrenal hyperplasia.

Adenoma↗
PubMed1978

Prostaglandin synthetase inhibitors in Bartter's syndrome. Effect on immunoreactive prostaglandin E excretion.

Urinary excretion of immunoreactive prostaglandin E (iPGE) was measurably increased in five of seven patients with Bartter's syndrome. The effects of indomethacin were compared with those of either aspirin or ibuprofen in four patients. Indomethacin produced notably greater suppression of urinary iPGE, greater sodium and potassium retention, greater increases in serum potassium, and decreases in plasma renin activity and in creatinine clearance than the other inhibitors. This demonstration that there is a close correlation between the suppression of urinary iPGE excretion and the extent of correction of the clinical abnormalities in Bartter's syndrome, regardless of the chemical structure of the prostaglandin synthetase inhibitor, is further evidence for the importance of prostaglandins in the pathogenesis of this syndrome.

Adolescent↗
PubMed1978

Evidence for a prostaglandin-independent defect in chloride reabsorption in the loop of Henle as a proximal cause of Bartter's syncrome.

Maximal free-water clearance was measured in five patients with Bartter's syndrome and in five patients with the hypokalemic alkalosis of persistent psychogenic vomiting. Hypokalemic alkalosis, hyperreninemia, hyperaldosteronism and excessive renal production of prostaglandin E2 were present in the patients with both disorders. Maximal free water clearance was abnormally low, in association with a high clearance of chloride, in all the patients with Bartter's syndrome; it was normal in all the patients with psychogenic vomiting. In the patients with Bartter's syndrome, apparent distal delivery of proximal tubular fluid was inversely related to glomerular filtration rate and was excessive only in those patients with a low glomerular filtration rate. Patients with psychogenic vomiting showed mean distal fractional chloride reabsorption of 0.92 +/- 0.04 (standard error [SE]). In the patients with Bartter's syndrome, distal fractional reabsorption of chloride was 0.49 +/- 0.08 and was the same (0.46 +/- 0.06) during inhibition of prostaglandin synthesis with indomethacin therapy. Thus, a prostaglandin-independent defect in chloride reabsorption in the loop of Henle is the most proximal cause for the abnormalities in Bartter's syndrome thus far identified.

Bartter Syndrome↗