Varicocele scintigraphy: a simplified screening method for the detection of spermatic vein reflux.

Forty-three men underwent varicocele scintigraphy to exclude underlying varicocele as a possible cause of decreased semen quality. The total acquisition time for each study amounted to as little as 200 seconds. In four cases retrograde blood flow was seen in the left internal spermatic vein, with subsequent clear visualization of the pampiniform plexus. In three of four of these patients, pregnancy ensued after therapeutic intervention. Seven patients showed only increased scrotal activity locally, in the absence of retrograde blood flow. The remaining 32 patients showed a normal blood flow pattern. The existence of spermatic vein reflux in varicocele-related infertility is thought to be a major factor in proper patient selection for therapeutic ligation or embolization of the internal spermatic vein. It is suggested that this simplified scintigraphic method may be useful in the detection of retrograde blood flow in patients with varicocele, especially in small or subclinical varicocele.

Technetium-99m-MAG3 versus iodine-123-OIH: renal clearance and distribution volume as measured by a constant infusion technique.

The renal clearance and distribution volume of 99Tc-mercaptoacetyltriglycine (MAG3) and 123I-o-iodohippurate (OIH) were determined separately in six normal male volunteers using the constant infusion clearance technique in order to validate single injection clearance techniques and subsequently the normal values for these parameters. MAG3 renal clearance was 257 +/- 24 ml/min/1.73 m2, compared to the OIH clearance of 556 +/- 46 ml/min/1.73 m2 resulting in a MAG3/OIH clearance ratio of 0.47 +/- 0.06. The MAG3 and OIH apparent distribution volumes at steady-state were 14.8 +/- 3.7 and 19.4 +/- 5.3 liters, respectively, the latter value approximating the extra cellular fluid volume. Urinary excretion in the 0-30-min period after intravenous administration was 64.4 and 70.2% for MAG3 and OIH, respectively. This investigation revealed some significant differences in the normal values of the renal clearance and distribution volume of MAG3 compared with other studies.

Plasma oxalate concentration and oxalate distribution volume in patients with normal and decreased renal function.

In twenty-one patients (sixteen male, five female) with various kidney diseases including primary hyperoxaluria type I (four patients), the plasma oxalate level was calculated from the isotopically determined oxalate clearance and the chemically determined urinary oxalate excretion. The apparent oxalate distribution volume was assessed as well. In patients with impaired kidney function (n = 12), the oxalate clearance was lower and the biological half-life and plasma concentration were higher than in patients with normal kidney function (n = 10). No differences were found in the oxalate-to-creatinine clearance ratio (mean value 1.93), urinary oxalate excretion and apparent oxalate distribution volume. A linear relation was found between the oxalate and creatinine clearance, while the clearance ratio was independent of the degree of renal failure. The apparent oxalate distribution volume was 1.45 times the estimated extracellular fluid volume. Because the isotopically determined plasma oxalate levels are lower than chemically measured ones, a quick and better estimation of plasma oxalate can be made from the urinary oxalate excretion and the creatinine clearance.

Fractional oxalate clearance in subjects with normal and impaired renal function.

The 14C-oxalate clearance was determined in 13 healthy subjects and 22 patients with various diseases and varying degrees of renal function impairment, including 5 patients with primary hyperoxaluria (PH). The clearances of oxalate (Cox) and creatinine (Ccr) were correlated (r = 0.95). The regression line intersects the ordinate at the origin, while the regression coefficient is 2.0. This implies that the fractional Cox is constant, irrespective of the underlying disease and the degree of renal failure. Plasma oxalate (Pox), as calculated from the urinary oxalate excretion (Uox) and Cox, was elevated in patients with severely impaired kidney function and those with PH. Plasma creatinine (Pcr) and Pox were correlated as well (r = 0.83). Pox values of patients with PH were above the 95% confidence limits of the regression line. It is of practical importance that Pox can be estimated from Uox and Ccr when a 14C-oxalate clearance test cannot be performed. The reasons for the constancy of the Cox/Ccr ratio are discussed, and it is suggested that the effective renal plasma flow (ERPF) is the regulating factor for the tubular secretion of oxalate.

Absorption kinetics of oxalate from oxalate-rich food in man.

The absorption of oxalate was investigated in a healthy subject after ingestion of oxalate-rich meals (spinach and rhubarb) with and without addition of 14C-labeled oxalic acid and calcium oxalate, and after oxalate-free meals with addition of nonlabeled sodium oxalate and calcium oxalate. Under these conditions, calcium oxalate was absorbed to the same extent as soluble oxalate; only a small percentage (2.4 +/- 0.7) of the total oxalate load was absorbed. Significant oxalate absorption occurred within 1 to 8 h after ingestion. The results suggest that under normal conditions the proximal part of the small bowel is a major absorption site.

Urinary oxalate excretion, as determined by isotope dilution and indirect colorimetry.

A simple and reliable method for the determination of urinary oxalate excretion is described. Urinary oxalate is precipitated with calcium chloride, and the oxalate content of the precipitate is measured by an indirect colorimetric method developed by Neas and Guyon in 1972 [1]. For single urine samples, a correction is made for the incompleteness of the precipitation of calcium oxalate by isotope dilution. The range of normal values (5% limits) determined in 52 normal subjects was 0.121-0.325 mmol . 24 h-1 . m-2 for a 1-day collection period and 0.145-0.301 mmol . 24 h-1 . m-2 for a 3-day collection period. The within-assay CV of a control urine with a low oxalate concentration was 9% (n = 7) and the between-assay CV for the same control urine was 12% (n = 6). When the values obtained for oxalate excretion were normalized to body surface area, there was no significant difference between males and females; the main source of variation was the intra-individual variation.

Renal clearance of [14C]oxalate: comparison of constant-infusion with single-injection techniques.

1. The renal clearance of [14C]oxalate was assessed by the constant-infusion technique and single-injection technique (plasma sampling only: one-compartment and two-compartment model; plasma and urine sampling). Healthy volunteers and patients with renal stones were studied. 2. Results with the constant-infusion techniques (with and without urine sampling) were not significantly different from each other. 3. The renal clearance of [14C]oxalate measured with the single-injection technique as compared with the constant-infusion technique was overestimated in the single-injection one-compartment model (52%) as well as in the two-compartment model (30%). 4. The calculated level of plasma oxalate in the healthy volunteers ranged from 1.04 to 1.78 mumol/l (mean 1.39). 5. The biological half-life of [14C]oxalate, estimated by the cumulative excretion of 14C in urine after equilibrium had been established, was 128 min (range: 113-142). 6. The oxalate/creatinine clearance ratio in the healthy volunteers ranged from 1.73 to 2.22 (mean 2.01).

Determination of oxalic acid clearance and plasma concentration by radioisotope infusion. Results in a family with hyperoxaluria.

The renal clearance of 14C-oxalate was studied in a family with two children suffering from primary hyperoxaluria. The 14C-oxalate/creatinine clearance ratio ranged from 1.8 to 2.6 (mean 2.0) and appeared to be independent of the glomerular filtration rate. The calculated plasma oxalate concentrations in the three normo-oxaluric subjects ranged from 0.1 to 0.9 mumol/l, whereas values of 3.2 and 16.3 mumul/l were found in the two hyperoxaluric subjects. In the latter patient, the oxalate production decreased and the clearance increased after vitamin B6 treatment, resulting in a drop in the oxalate plasma level to 5.3 mumol/l. The apparent distribution volumes, expressed as percentage of body weight, ranged from 30 to 47% (mean 35). The mean biological half-life of 14C-oxalate was 2.7 hours in the subjects with normal renal function and increased with impairment of renal function. The recovery of 14C in the urine ranged from 87 to 112% (mean 101); all 14C activity was recovered as oxalate.

Oxalic acid concentration in serum measured by isotopic clearance technique. Experience in hyper- and normo-oxaluric subjects.

In a family from which two children suffered from primary hyperoxaluria the renal clearance of (14C) oxalate was studied. The (14C) oxalate/creatinine clearance ratio ranged from 1.76-2.63 (mean: 2.03) and appeared to be independent of glomerular filtration rate (GFR). The calculated plasma oxalate concentrations in normo-oxaluric subjects ranged from 0.1-0.9 mumol/L, whereas in hyperoxaluric subjects values between 3.2-16.3 mumol/L were found. The mean biological half-life of (14C) oxalate was 2.7hr in subjects with normal renal function and increased proportionally with renal functional impairment. Recovery of (14C) oxalate ranged from 87-112% (mean: 101%). All urine (14C) activity was found in the oxalate fraction.

Interaction of delta-5-androstene-3beta, 17beta-diol with estradiol and dihydrotestosterone receptors in human myometrial and mammary cancer tissue.

Specific receptor binding of estradiol (E-2) and dihydrotestosterone (DHT) was studied in human myometrial tissue and in human mammary cancer tissue. The inhibition of binding for E-2 and DHT by E-2, testosterone (T), DHT, dehydroepiandosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), androstendione (A) and 5-androstene-3beta, 17beta-diol (Adiol) was tested with the use of dextran-coated charcoal separation of bound and free E-2, respectively, and DHT. The percentage of binding inhibition was calculated with reference to the inhibition obtained with nafoxidine in a molar concentration ratio of 1,000 for E-2 binding, respectively, with cyproterone acetate in a molar concentration ratio of 10,000 for DHT binding. In 15 samples of myometrium tested, receptors were found for both E-2 and DHT. From 19 samples of mammary carcinoma tissue one showed no binding activity, three samples did bind E-2 only, five samples DHT only, and ten samples showed binding of both steroids. A 50% inhibition of E-2 binding, in myometrial as well as in tumor tissue, required a molar concentration ratio of 40 for Adiol, of more than 2,000 for DHEA. No significant inhibiting activity could be found for A up to a molar concentration ratio of 10,000 and for DHEA-S up to 40,000. With regard to DHT binding, Adiol is more active than E-2 and less active than T. Of the substances tested Adiol is therefore the only one which exerts a significant inhibiting influence at a molar ratio not far beyond the physiological range. This signifies that Adiol might interfere at the receptor level in the estrogenic stimulation of mammary cancer cells.

PIP: Specific receptor binding of estradiol-17beta (E2) and dihydrotestosterone (DHT) was studied in human myometrial tissue and in human mammary cancer tissue. The inhibition of binding for E2 and DHT by E2, testosterone (T), DHT, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), androstenedione (A) and 5-androstene-3beta, 17beta-diol (Adiol) was tested with the use of dextran-coated charcoal separation of bound and free E2, respectively, and DHT. The percentage of binding inhibition was calculated with reference to the inhibition obtained with nafoxidine in a molar concentration of 1000 for E2 binding, respectively, with cyproterone acetate in a molar concentration ratio of 10,000 for DHT binding. In 15 samples of myometrium tested, receptors were found for both E2 and DHT. From 19 samples of mammary carcinoma tissue 1 was without binding activity, 3 samples bound E2 only, 5 samples DHT only, and 10 showed binding of both. A 50% inhibition of E2 binding in myometrial as well as in tumor tissue, required a molar concentration ratio of 40 for Adiol, of more than 2000 for T and for DHT, and of about 20,000 for DHEA. Significant inhibiting activity for A up to a molar concentration ratio of 10,000 was absent. This was also true for DHEA-S up to 40,000. With regard to DHT binding, Adiol is more active than E2 and less active than T. Thus Adiol was the only substance which exerted a significant inhibiting influence at a molar ratio near physiological range. Adiol might interfere at the receptor level in the estrogenic stimulation of mammary cancer cells.