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Biomedical subjects

M H Gault

Publications and source records attributed to M H Gault.

At least 55 records · Page 3Linked to original sources

Identification of progesterone and cortisol as immunoreactive plasma digitalis like factors in pregnancy.

Plasma values for immunoreactive digitalis like factors (DLF) in 3 women during the third trimester of pregnancy were 0.13, 0.13 and 0.40 ng digoxin equivalents/ml. Progesterone accounted for 39%, 35% and 19% of the total DLF in the three women respectively, and cortisol 4%, 18% and 7% based on HPLC analysis. Both progesterone and cortisol displaced [125I]-digoxin from digoxin antibody and [3H]-ouabain from hog brain Na,K-ATPase in a concentration-dependent manner, but only progesterone in the plasma concentrations found in these patients would appreciable influence Na,K-ATPase. HPLC separation of the plasma DLF from two of the women showed several peaks. Two of these were identified as progesterone and cortisol by retention time, immunoassay and by GC-mass spectrometry.

Blood Proteins↗

Disposable-column radioimmunoassay for serum digoxin with less interference from metabolites and endogenous digitalis-like factors.

A preparative extraction step using disposable C18 low-pressure chromatography columns greatly improved the specificity of a commercially prepared digoxin radioimmunoassay (RIA). Elution solvents were isopropanol/water (15/85 by vol), which extracted most immunoreactive digitalis-like factors and metabolites, and methanol, which extracted digoxin for RIA. Many different digoxin RIA kits could be used. The coefficients of variation for replicates and duplicates were 4.6% and 5.2%. Analytical recoveries of digoxin standards in serum of 1.0, 0.5, and 0.1 microgram/L were 96%, 95%, and 88%, respectively. Serum digoxin was assayed by this method in 200 patients, 47 of whom were studied by HPLC-RIA. Values correlated better with "true digoxin" by HPLC-RIA (r = 0.93) than did values found by direct assay (r = 0.63). The mean for the isopropanol fraction as a percentage of the mean direct RIA value was higher for the 21 dialysis-dependent patients than was that found for the 179 nondialysis patients (P less than 0.004). The method is suggested as being most useful when metabolites or digitalis-like factors are known to be often high and values for digoxin are disproportionate to the dose.

1-Propanol↗

Evidence for an adrenal contribution to plasma digitalis-like factors.

Digitalis-like factors (DLF) were assayed on plasma collected serially using antibody to digoxin: (1) after intravenous ACTH (n = 3 patients) and (2) after 0.15 U/kg crystalline insulin, 50 micrograms gonadotropin-releasing hormone and 0.2 mg thyrotropin-releasing hormone (n = 7) as a combined pituitary function test. Patients had either hypothalamic-pituitary or ovarian problems. Mean values for DLF rose fourfold after ACTH, and by a factor of 2.3 with the combined pituitary function test. DLF rose at least 50% in all 10 subjects. In 3 dogs, adrenal vein values for DLF were on average more than double values in either adrenal artery or lower vena cava. These results suggest that certain DLFs have an adrenal origin.

Adrenal Glands↗

Congestive heart failure in dialysis patients.

To determine the prevalence of congestive heart failure in dialysis patients and the disorders with which it is associated, 85% of 153 nondiabetic patients who were undergoing maintenance dialysis had echocardiography and gated cardiac scan. Ten percent (n = 15) had congestive heart failure, 53% (n = 8) of whom had dilated cardiomyopathy, and 47% (n = 7) had hypertrophic hyperkinetic cardiomyopathy. Ischemic heart disease was an additional independent risk factor for congestive heart failure. Significantly more of those patients with dilated cardiomyopathy were smokers and none were hypertensive, whereas all those patients with hypertrophic cardiomyopathy were hypertensive. The prevalence of hypertrophic hyperkinetic disease was 11%, of dilated cardiomyopathy 18%, and of symptomatic ischemic heart disease 18%. We concluded that congestive heart failure in dialysis patients is associated not only with dilated cardiomyopathy but also with hypertrophic cardiomyopathy, a disease that requires echocardiography for diagnosis and that has different risk factors and management.

Cardiomyopathy, Dilated↗

Low-output left ventricular failure in end-stage renal disease.

To determine the factors associated with low-output left ventricular failure (LVF) in endstage renal disease (ESRD), we performed echocardiography and gated cardiac scan on 217 nondiabetic dialysis and transplant patients. The prevalence of low-output LVF (ejection fraction less than 55% and left ventricular end diastolic diameter greater than or equal to 5.5 cm) in dialysis patients was 18% and in transplant patients 2%. The 26 patients with LVF were compared to 52 controls without LVF, matched by age, sex and year of starting treatment for ESRD, but not for current ESRD therapy. Mean age was 55 +/- (SEM) 14 years; 73% of the patients in both groups were males. Duration of treatment for ESRD was 5.6 +/- 4.3 years in patients, compared to 5.1 +/- 4.1 years in controls. Significant differences between LVF patients and controls included current treatment (73% of cases were on hemodialysis and 8% were transplanted, compared to 48 and 42%; chi 2 = 9.9, p less than 0.01), high serum creatinine, smoking and high serum alkaline phosphatase. There were no differences for current blood pressure, proportion on treatment for hypertension, left ventricular wall thickness, symptomatic ischemic heart disease, proportion with functioning vascular access, degree of weight gain between dialyses, hemoglobin level or high transfusion requirement. Multiple logistic regression demonstrated the most significant and independent variables associated with LVF were high alkaline phosphatase (suggestive of hyperparathyroidism), smoking and high serum creatinine levels (reflecting degree of uremia). Dialysis patients with LVF (n = 23) were compared to dialysis patients who had normal echocardiograms (n = 29).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗

False-positive digoxin measurements due to conjugated metabolite accumulation in combined renal and hepatic dysfunction.

A 41-year-old man with combined renal and hepatic dysfunction was noted to have marked elevations in serum digoxin concentration subsequent to the discontinuation of digoxin therapy. These elevations (peak value 8.6 ng/ml), as measured by both radioimmunoassay and fluorescence polarization immunoassay, were not associated with electrocardiographic evidence of digitalis toxicity. Using a combined high-performance liquid chromatography/radioimmunoassay, accumulation and immunoassay cross-reactivity of conjugates of digoxigenin monodigitoxoside (cardioinactive metabolites of digoxin) were found to be the basis of the observed false elevation in digoxin concentration.

Acute Kidney Injury↗

Staphylococcal epidermidis infection of a hemodialysis button-graft complex controlled by vancomycin for 11 months.

A 54 year old woman had a Bentley DiaTAP button implanted in her thigh for hemodialysis access. She had been started on continuous ambulatory peritoneal dialysis (CAPD) because of intractable vascular access problems. Unfortunately, CAPD had to be discontinued because of fungal peritonitis. Transplantation had not been possible because of circulating cytotoxic antibodies. The prosthetic complex soon became infected with Staphylococcus epidermidis and blood cultures were intermittently positive for 11 months. However, with continuing vancomycin therapy she remained in her usual state of health, without side effects from vancomycin, until venous thrombosis resolved and it became possible to remove the infected prosthetic complex and implant a button in an arm. As a last resort, it may be possible to maintain a patient on dialysis in reasonable health with a DiaTAP button graft complex infected with Staphylococcus epidermidis and intermittent positive blood cultures using long term vancomycin therapy. Such management probably would not be appropriate for any other organism.

Arteriovenous Shunt, Surgical↗

Plasma endogenous digitalis-like factors in healthy individuals and in dialysis-dependent and kidney transplant patients.

Plasma digitalis-like factors (DLF), dehydroepiandrosterone sulfate (DHEAS) and cortisol were assayed in 20 healthy subjects, 22 dialysis dependent subjects and 30 patients with kidney transplants. DLF were assayed on plasma extracts by digoxin radioimmunoassay (RIA), and by Na,K-ATPase inhibition and [3H]-ouabain displacement using hogbrain Na,K-ATPase. Values for the 3 methods strongly intercorrelated (r = 0.99, p less than .001). Mean values for plasma DLF, assayed by all three methods, were significantly greater in dialysis dependent subjects, than in healthy subjects (p less than .0001). Mean plasma DLF values measured by digoxin RIA in renal transplant recipients, were significantly lower than in dialysis dependent subjects (p less than 0.0001) and higher than in healthy subjects. Plasma DLF values correlated inversely with creatinine clearance (p less than 0.01). Plasma DHEAS levels were significantly lower and contributed substantially less to digoxin antibody reactivity and ouabain displacement in dialysis subjects and in renal transplants compared with healthy subjects. There was no change in plasma immunoreactive DLF, DHEAS or cortisol measured before and after dialysis. DHEAS is a major digoxin like immunoreactive DLF and a minor Na,K-ATPase inhibitor in healthy subjects but makes only a minor contribution to DLF in dialysis and transplant subjects. We found the assays involving Na,K-ATPase inhibition and [3H]-ouabain displacement from Na,K-ATPase to be more sensitive for plasma DLF than the digoxin RIA, but because of the strong correlation between the methods, we suggest the RIA on plasma extracts can be used as a screening procedure.

Adult↗

Bile salts as endogenous digitalis like factors.

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.

Acute Kidney Injury↗