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Biomedical subjects

W G Walker

Publications and source records attributed to W G Walker.

At least 55 records · Page 3Linked to original sources

Dissociation of the diurnal variation of aldosterone and cortisol in anephric subjects.

Diurnal variation of plasma aldosterone and cortisol concentration in man was studied in 13 anephric subjects and 7 normal subjects. All subjects were ambulatory and active throughout the study except during an 8-hour sleep period. Six anephric subjects received Kayexalate (sodium polystyrene sulfonate) during the studies to prevent potassium accumulation and increase in plasma potassium concentration. Diurnal variation of plasma aldosterone concentration with peak and nadir concentrations at 12:00 noon and 12:00 midnight respectively was demonstrated in the studies on normal subjects. Changes in plasma aldosterone concentration were not significantly correlated with changes in plasma concentration but were highly correlated with changes in PRA (P less than 0.001). There was a highly significant correlation between plasma aldosterone and potassium concentration in the anephric subjects studied without Kayexalate administration (P less than 0.001). In the anephric subjects who received Kayexalate, plasma aldosterone and potassium concentration remained stable, and no correlation could be demonstrated. No diurnal variation of plasma aldosterone concentration could be demonstrated in either group of anephric subjects, whereas plasma cortisol concentration varied as in the studies on normal subjects. Conclusion. Diurnal variation of plasma aldosterone concentration is dependent on continued stimulation by the renin-angiotensin system. Loss of this stimulation has no demonstrable effect on the diurnal variation of plasma cortisol concentration.

Adult↗

Renovascular hypertension: comparison of medical and surgical therapy.

1. Results of medical and surgical therapy were compared in 28 patients with hypertension and unilateral renovascular ischaemia. 2. Renal function remained normal in both groups throughout the study period. After 6 months of follow-up systolic and diastolic blood pressures were significantly lower in the surgically treated patients. After 12 months of follow-up there was no significant difference between the two groups in diastolic blood pressure and after 24 months of follow-up there was no significant difference between the two groups in either systolic or diastolic blood pressure. 3. Sixty per cent of surgically treated patients were cured 6 months after operation, but only 40% remained cured after 24 months of follow-up. 4. All patients cured at 6 months who subsequently required antihypertensive medication had arteriosclerotic renovascular disease.

Blood Pressure↗

The syndrome of inappropriate antidiuretic hormone secretion (SIADH): pathophysiologic mechanisms in solute and volume regulation.

1. Studies on eight patients were performed to clarify the mechanism(s) of altered sodium metabolism and volume regulation in SIADH. The mechanism controlling water excretion was also studied to determine whether there is evidence that altered osmoregulation may be the basis for inappropriate ADH secretion in some patients. 2. These studies show that cumulative sodium balance and aldosterone secretion rates in patients with SIADH are negatively correlated with water intake. There is also a negative correlation between aldosterone secretion and urinary sodium excretion. In the absence of normal urine diluting ability, this increased excretion of sodium becomes a mechanism that allows an increased quantity of water to be excreted despite the persistence of an ADH effect on the renal tubules. 3. Within the range of hyponatremia observed in our studies, changes in serum sodium concentration were accounted for by changes in solute and water balance. One patient, who was potassium deficient during the studies, retained large quantities of sodium and potassium that could not be accounted for by an increase in either serum osmolality or body weight. These observations suggest that intracellular osmotically active solute is either lost or "inactivated" in some manner as intracellular potassium is replenished. 4. Marked impairment of urine diluting ability was demonstrated in all patients. However, two patients with SIADH associated with pulmonary tuberculosis exhibited graded responses to water loading, which suggests that ADH secretion may have been suppressed as serum osmolality was progressively reduced. Whether this can be attributed to a basic alteration or "re-setting" or osmoreceptor function, or is merely an indication that greater than normal reductions of serum osmolality are required to inhibit potent nonosmotic stimuli, remains to be determined.

Adult↗

Plasma renin and angiotensin II in acute renal failure.

The role of raised plasma renin and angiotensin-II concentrations in the development of acute renal failure in man was examined in patients in shock from various causes and in patients in whom hypotension was used to promote haemostasis. Ten of the thirteen patients in shock had raised angiotensin-II concentrations in peripheral blood and acute renal failure manifested by oliguria, increasing serum-creatinine, a urine osmolality of less than 400 mos-mol/kg and a urine/plasma osmolality ratio of less than 1-5. Although patients who were hypotensive for periods of 1 h 45 min to 4 h to promote haemostasis during surgery had similarly raised plasma-renin activity and angiotensin-II concentrations in peripheral venous blood, they did not have acute renal failure. It is concluded that high plasma-angiotensin-II concentrations do not explain the pathogenesis of acute renal failure in patients in shock.

Acute Kidney Injury↗

Associations of hepatitis B surface antigenemia with HLA locus B specificities.

To test whether HLA histocompatibility phenotypes might be associated with circulating hepatitis B surface antigen (HBsAG), we performed chisquare and Scheffé analyses on findings in 144 renal patients with known HLA types and HBsAg status. A significant relation between locus B HLA type (or types) and HBS antigenemia was demonstrated (P = 0.01, adjusted for dual testing) with positive associations suggested between Bw15, Bw17 and Bw35 types and transient or persistent (or both) antigenemia. The latter associations individually were statistically significant only if multiple testing was disregarded, but the contrast by the Scheffé method between the three implicated specificities and all other specificities was significant, even after adjustment for multiple testing (P less than 0.02). Associations of genetically determined HLA specificities with hepatitis B infection may constitute the basis for previously observed population differences in HBS Ag prevalences, and suggest that susceptibility to hepatitis B infection may be in part genetically determined.

Alleles↗

Renal vein renin activity: a prospective study of sampling techniques and methods of interpretation.

Seventy patients undergoing renal arteriography were studied prospectively to define optimal techniques of renal venous sampling and to establish the most appropriate methods for interpretation of renal vein renin and activity (RVRA). Plasma renin activity values from the aorta, the antecubital vein and the lower inferior vena cava were nearly identical. The relationship between renal vein renin activity in the two renal veins was not influenced by lack of simultaneous sampling or by contrast administration. Thirty-one patients with normal arteriograms had a mean RVRA ratio (right over left) of 1.12 +/- .11 (mean +/- SEM) but RVRA difference (right minus left) of only 0.02 +/- .11 ng/ml/hr. In contrast 16 patients with "significant" (greater than 70%) narrowing of the main renal artery had a mean RVRA ratio (involved over uninvolved) of 4.3 +/- 1.2 and a mean RVRA difference (involved minus uninvolved) of 3.9 +/- 1.4 ng/ml/hr. Seven patients (22%) with normal arteriograms had "abnormal" RVRA ratios (greater than or equal 1.5) but corresponding RVRA differences within one standard deviation of the group mean. Thus the difference inRVRA between both renal veins may more accurately reflect a patient's renovascular status than does the corresponding RVRA ratio. An "abnormal" RVRA ratio alone inadequately indicates the presence of renal ischemia.

Humans↗

Biosynthetic studies with isolated kidney glomeruli.

Glomeruli were isolated from rat kidneys and were found active in protein and glycoprotein synthesis in vitro. The incorporation of proline, galactose and fucose into macromolecules was linear for at least 8 h. The intracellular pool of free proline and lysine was 52 and 32 nmol/mg glomerular protein respectively. Vinblastin and cytochalasin B, two agents which interfere with normal cellular secretory processes, inhibited galactose and fucose incorporation, possibly by a feedback mechanism. Experimental nephrotic syndrome was induced in rats by the injection of puromycin aminonucleoside; the rate of proline and galactose incorporation was reduced in glomeruli isolated from the nephrotic animals. The system of isolated glomeruli is deemed suitable for future studies of selected kidney diseases which affect the glomeruli.

Animals↗

Relation between plasma renin activity, angiotensin, and aldosterone and blood pressure in mild untreated hypertension.

Plasma renin activity, arterial and venous angiotensin II (A II), plasma aldosterone, and sodium excretion were measured in a group of 101 patients with mild essential hypertension. For the total hour; arterial A II was 5.2 +/- 1.0 pg/ml; venous A II was 4.2 +/- 0.6 pg/ml; and plasma aldosterone was 5.0 +/- 0.45 ng/100 ml. All values were lower corresponding values for normal subjects on a high salt intake despite the fact that salt intake in the normal subjects exceeded that for the hypertensive group more than 3-fold. Moreover, when the range of diastolic blood pressure up to 114 mm Hg was divided into three successive class intervals of increasing severity, there was a negative correlation between diastolic blood pressure and both PRA and plasma aldosterone. Arterial A II showed an anomalous increase in the class interval 105-114 mm Hg, despite the fact that this group exhibited the lowest level of PRA. At diastolic blood pressures above 114 mm Hg, the PRA appears to rise again. The anomalous increase in arterial A II in the presence of marked suppression of PRA is consistent with the presence of a renin activator or accelerator factor in hypertensive plasma as postulated by others. It also identifies a possible mechanism whereby even small increases in PRA could exert an adverse effect on the hypertensive state.

Adolescent↗

Arterial and venous angiotensin II in normal subjects. Relation to plasma renin activity and plasma aldosterone concentration, and response to posture and volume changes.

Plasma renin activity, arterial and venous angiotensin II (A II) concentrations, and plasma aldosterone concentration were measured in 16 normal subjects (mean age = 34 years) after 8 hours of recumbency, following 2 hours of ambulation, and again 30 minutes after administration of furosemide intravenously. Measurements were obtained during periods of sodium restriction and again during sodium surfeit. Both arterial and venous A II exhibited a 3-fold increase from low values of 8.8 +/- 2.5 and 8.6 +/- 2.5 pg/ml of plasma, respectively, during recumbency on high sodium intake to values of 23.9 +/- 4.1 and 26.5 +/- 6.2 pg/ml, respectively, following intravenous furosemide during sodium restriction. Corresponding values for aldosterone exhibited a 5-fold rise from 5.6 ng/100 ml to 32.0 ng/100 ml, whereas plasma renin activity (PRA) measured by an in vitro assay exhibited a 20-fold rise from 0.6 +/- 0.2 ng of angiotensin I (AI) generated per ml per hour to 13.1 ng/ml per hour. Despite the disparity in the magnitude of these increases, significant correlations were identified between all four of the measured parameters, indicating a major role of the renin-angiotensin system in regulating aldosterone output in response to volume and posture-related stimuli. Values of arterial and venous immunoreactive A II were closely correlated ( r = +0.72, P less than 0.005), but significant differences were demonstrated between low and high salt periods, suggesting that changes in metabolism of A II in the peripheral circulation may occur during sodium restriction.

Adult↗

Therapeutic implications of gentamicin accumulation in severly diseased kidneys.

We evaluated the influence of severe disease in human kidneys (12 patients) on gentamicin sulfate accumulation characteristics in such tissue and compared the results with intrarenal tissue concentration data derived from the study of healthy dogs (54 kidneys) during variation in hydration and urinary pH. Our results indicate that, in the management of pyelonephritis complicating preexisting renal disease, if the minimal inhibitory gentamicin concentration for an infecting organism is greater than the usual therapeutic an nontoxic serum levels of the compound, then it may be appropriate to use alternate antibiotics that demonstrate lesser reduction in tissue drug accumulation in diseased kidneys.

Animals↗

Pharmacokinetic characteristics of doxycycline accumulation in normal and severely diseased kidneys.

Intrarenal concentrations of doxycycline were measured in 48 normal canine kidneys during wide variations in urine pH and the systemic state of hydration of the experimental animals. The results were compared with the renal parenchymal levels achieved in 10 severely diseased human kidneys. Although the state of hydration, the urine pH, and renal disease all significantly influenced the urinary concentrations and rate of renal clearance of doxycycline, there was no detectable difference between concentrations in normal renal tissue and those in severely diseased kidneys. This result is in contradistinction of the findings for previously evaluated antibiotics. The levels of doxycycline measured in renal tissue averaged twice the concentration in serum without notable difference among levels in renal cortex, medulla, and papilla. Prospective clinical trials will be necessary for identification of any solid correlation between the remarkable characteristics of accumulation of doxycycline in diseased renal parenchymal tissue and the clinical, therapeutic importance of such an observation.

Animals↗