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Biomedical subjects

M H Gault

Publications and source records attributed to M H Gault.

At least 73 records · Page 4Linked to original sources

Dehydroepiandrosterone sulfate as a digitalis like factor in plasma of healthy human adults.

Plasma values for digitalis like factors (DLF) and dehydroepiandrosterone sulfate (DHEA-S) in 11 healthy adults were (mean +/- SD) 44 +/- 6 pmol digoxin equivalents/L and 11 +/- 3 mumol/L respectively. DHEA-S accounted for 62-100% of the total plasma DLF. DHEA-S and plasma DLF displaced [125I]digoxin from digoxin antibody, inhibited hog brain Na,K-ATPase and displaced [3H]ouabain from ATPase in a concentration dependent manner similar to digoxin. Plasma extracts (11 subjects) inhibited Na,K-ATPase and displaced [3H]ouabain from Na,K-ATPase with mean values +/- SD of 1.7 +/- 0.22 and 1.8 +/- 0.25 nmol digoxin equivalents/L plasma respectively. HPLC fractionation of plasma DLF showed several peaks. The major peak was due to DHEA-S, identified by its retention time, radioimmunoassay of DHEA-S and mass spectrometry.

Adult↗

Combined liquid chromatography/radioimmunoassay with improved specificity for serum digoxin.

This method for assaying digoxin in serum with improved specificity combines small-column extraction of serum, "high-performance" liquid chromatography, and RIA of the eluted fractions. Analytical recoveries of 1.0, 0.5, and 0.1 microgram/L standards were 95%, 93%, and 84%, respectively. The CVs for duplicates and replicates of sera with values of 0.5 to 1 microgram/L were 4 to 6%. Fifty-nine sera from 50 patients receiving digoxin were so studied. All digoxin metabolites appear to cross react with antibody to digoxin to various degrees. The most polar metabolites were quantitatively the most important, their average cross reactivity being 33%. For eight patients the value for digoxin by the present method was less than 60% of the RIA value. Sera from nine patients not taking digoxin but with falsely high digoxin values were also studied by the present method. The digoxin peak was well resolved from those for (a) digoxin metabolites (except dihydrodigoxin), (b) digitalis-like factors in neonates and in patients with renal failure or combined hepatic and renal failure, and (c) two cross reacting drugs and their metabolites.

Adult↗

Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling.

Few reports are available on the age-related risk of relatives of affected persons to manifest adult polycystic kidney disease (APKD). For 371 persons in 17 kindreds, at risk for APKD by virtue of having an affected first degree relative, we calculated the estimated probability of clinical diagnosis of APKD to be 0.011 by age 20, 0.041 by age 30, 0.115 by age 40, 0.299 by age 50, and 0.404 by age 60 years (expected = 0.50). Ultrasonographic examination of 172 asymptomatic persons at risk showed definite APKD in 60. The probability of ultrasonographic detection of asymptomatic APKD is estimated as 0.222, 0.657, and 0.855 at age 5, 15, and 25 years, respectively. The probability of having APKD following normal ultrasonogram results (conservatively assuming 90% specificity) is estimated as 0.46, 0.28, and 0.14 for persons at 50% risk in their first, second, or third decade. The marginal benefit of ultrasound as a diagnostic test for APKD for persons in the second or third decade is estimated as 0.37 and 0.41, respectively for a "positive" test and 0.22 and 0.37 for a "negative" test.

Adolescent↗

Assessment of specific gravity determined by Ames N-Multistix-SG.

Specific gravity (SG) was determined in 204 urines by N-Multistix-SG solid phase test strip. Seventy-seven of the urines were from patients with known renal disease or were positive for protein or glucose, or had pH greater than 6.4 (Group I) and were assayed for osmolality, SG by urinometer and refractometer, and several other parameters, intercorrelations were calculated. Osmolality was used as the gold standard. In Group I, correlation of osmolality with N-Multistix SG (r = 0.66) was not significantly different (p greater than 0.1) from that found with SG determined by refractometer (r = 0.72), or urinometer (r = 0.60). The correlation coefficient for 45 N-Multistix-SG values determined by two staff members was 0.91. For the 127 Group II normal urines, the correlation coefficient between Multistix-SG and SG by refractometer was 0.85. Multistix-SG avoids the errors related to large molecules such as glucose and radiographic contrast media seen with SG determined by urinometer and refractometer (uncorrected for glucose) and was found to have comparable accuracy to these two methods when compared with osmolality, in patients with known renal disease or abnormal urinalysis.

Humans↗

Digoxin biotransformation.

Serum digoxin and metabolites were assayed in plasma and urine by HPLC in 10 dialysis-dependent patients with end-stage renal failure (group I) and in five patients with comparatively normal renal function (group II) after ingestion of 150 muCi 3H-digoxin-12 alpha. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts, were 3 beta-digoxigenin and its mono- and bis-digitoxosides, and 3-keto and 3 alpha(epi)-digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7 to 76) of the radioactivity in plasma 6 hr after drug, and 60% (11 to 88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation, mainly, we suggest by hydrolysis, oxidation, epimerization, and conjugation to polar end-metabolites.

Administration, Oral↗

Prognosis of adult onset polycystic kidney disease re-evaluated.

To appraise the prognosis of adult onset polycystic kidney disease (APKD), an inception cohort containing 140 subjects from 17 kindreds was assembled. Multiple renal cysts, demonstrable by ultrasonography, or clinical APKD, or both were present in 100 subjects. APKD was predicted in 32 subjects unavailable for ultrasonography and could not be excluded in eight deceased subjects. All had been at risk for endstage renal disease (ESRD) since birth. The probability of either developing ESRD, requiring dialysis or transplantation, or dying was estimated using a time-to-event analysis. The earliest age at which ESRD occurred was 36 years. For those with APKD, the probability of being alive and not having ESRD was 77% by age 50, 57% by age 58, and 52% by age 73 years. Excluding those predicted to have APKD changes these probabilities to 75, 53, and 47%, respectively. The serum creatinine values were less than 1.5 mg/dl for most subjects who had not developed ESRD. The prognosis for subjects with APKD is much better than most reports suggest and can be estimated from the time-to-event data presented.

Adult↗

HLA and urolithiasis.

Frequencies of persons having particular HLA-A, -B, and -C antigens were compared for 113 urolithiasis clinic patients, a subset of 24 patients who had hypercalcuria , and 225 controls. The frequency of HLA- A30 was significantly elevated among the patients. A suggestion (S afwenberg et al. 1978) that HLA-B27 frequency is elevated among hypercalcuric patients with recurrent kidney stones was not confirmed.

Adult↗

Rising serum digoxin without further dosage in acute renal failure.

A 73-year-old man was given a total of 1 mg of digoxin intravenously over 3 days, close to the time that he developed acute renal failure with oligo-anuria. He received no cardiac glycosides before or after this 3-day period. 2 days after the last dose, the serum digoxin concentration (SDC) was 2.9 ng/ml, yet a peak value of 4.2 ng/ml was reached only 11 days later. The SDC remained above 2 ng/ml for another week, until urine output began to increase appreciably. As renal function improved, the SDC gradually fell to become undetectable 32 days after the last dose. Values for apparent volume of distribution calculated from the total dose, and also determined after injection of tritiated digoxin, suggest that the rise in SDC in the absence of additional doses was due in large part to a decrease in the apparent volume of distribution. Dosage and parameters of toxicity should be carefully monitored in patients receiving digoxin who develop acute renal failure.

Acute Kidney Injury↗

Human adenine phosphoribosyltransferase: characterization from subjects with a deficiency of enzyme activity.

Adenine phosphoribosyltransferase (APRT) was characterized with respect to specific activity and immunoreactive protein (CRM) levels in hemolysate from 18 members of an APRT-deficient kindred. In addition, lymphoblastoid cell lines were established from six of these subjects and APRT from these cells was characterized in a similar fashion. Levels of specific activity and CRM in patients homozygous for the deficiency were less than 1% of normal. Heterozygous subjects had higher levels of activity and CRM in lymphoblasts than in erythrocytes and, in all cases, the APRT present was normal in terms of isoelectric point, subunit molecular weight, and heart stability. The higher levels of activity and CRM found in lymphoblasts may be due either to expression of a mutant gene product stabilized in a normal:mutant dimer or to autologous regulation.

Adenine Phosphoribosyltransferase↗

Declining incidence of analgesic nephropathy in Canada.

Surveys of nephrologists in Canada indicate that the incidence of analgesic nephropathy has decreased by about 50% in less than a decade in association with the removal of phenacetin from the market and restrictions on the availability analgesic mixtures containing acetaminophen and acetylsalicylic acid. The number of patients presenting with end-stage renal disease attributed to analgesics has shown a similar drop. These decreases have occurred in spite of increased consumption of acetaminophen as a single analgesic. Analgesic nephropathy should not be expected to disappear, however, since there is evidence that the drugs still in use have the potential to cause renal damage.

Canada↗