Blending the old with the new. Interview by Damon Braly.
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Computer Systems↗
Biomedical subjects
A Edmiston
Publications and source records attributed to A Edmiston.
Using a symbiotic man/machine approach to evaluating visual clinical research data.
Some candidate medical expert system applications have a significant visual component. Knowledge engineers usually dismiss such task domains as potential expert systems applications. Our success in developing ESCA, a system for evaluating serial coronary angiograms, shows that such task domains should not be dismissed so quickly. We used a symbiotic approach between man and machine, where technologists provide the visual skills with an expert system imitating the conceptual skills of the expert, to produce a partially automated system that is more consistent and cost effective than one that is fully manual. The agreement between the system's conclusions and that of a panel of experts is good. The expert system actually has a slightly higher agreement rate with the expert panel than the agreement rate between two expert panel teams evaluating the same film pair.
Angiocardiography↗
Studies on the origin of androstanediol and androstanediol glucuronide in young and elderly men.
The in vivo origin of androstanediol (3 alpha diol) and its glucuronide was studied in six young and five elderly men undergoing cardiac catheterization. Constant infusions of [14C]testosterone and [3H]3 alpha diol were given, and blood was obtained from the aorta and hepatic vein in order to measure metabolic clearance, splanchnic extraction, and the possibility of splanchnic production of both 3 alpha diol and its glucuronide. In young elderly men, the concentrations of labeled and unlabeled testosterone, dihydrotestosterone, and 3 alpha diol were lower in the hepatic vein than in the aorta. The specific activities of dihydrotestosterone and 3 alpha diol were the same in blood entering and leaving the splanchnic compartment. The plasma concentration of 3 alpha diol was 18 +/- 2 in the young men and 15 +/- 4 ng/dl in the elderly group. However, the blood production rate of 3 alpha diol determined from the metabolic clearance and morning plasma concentration was reduced (324 vs. 199 micrograms/day) as a result of lower clearance in the elderly men. Plasma 3 alpha diol glucuronide concentrations were 197 +/- 68 and 96 +/- 35 ng/dl in the two groups. No difference in the concentration of 3 alpha diol glucuronide was observed across the splanchnic tissues by mass, radioactive levels, specific activity, or 14C to 3H ratios. The 14C to 3H ratio for 3 alpha diol glucuronide was 10 times higher than for the free steroid, indicating that more than 90% of the glucuronide originates from a pool separate from blood 3 alpha diol. Both the splanchnic extraction of 3 alpha diol and the metabolic clearance were reduced in elderly men. These studies indicate that both 3 alpha diol and its glucuronide in blood result from extrasplanchnic events. A major reduction in the plasma concentration of 3 alpha diol glucuronide occurs in the aging male, although no difference is seen in the levels of the unconjugated 3 alpha diol. 3 alpha diol and its glucuronide are derived principally by extrahepatic (target) tissue events.
Adult↗
Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia.
In vivo androgen kinetics were determined in six young (21--49 yr) and elderly men (62-77 yr) with prostatge hyperplasia (BPH). Steady-state infusions of [14C]testosterone and [3H]androstanediol (3 alpha diol) were given, which allowed determination of the conversions testosterone leads to dihydrotesterone (DHT) in equilibrium or formed from 3 alpha diol. These infusions also yield metabolic clearance data which, together with meaurement of nonisotopic steroid levels, yield estimations of blood production rates. The production rate for testosterone was 6.04 +/- 1.66 vs. 3.69 +/- 0.62 mg/d, whereas the production rate for 3 alpha diol was 319 +/- 57 and 193 +/- 34 micrograms/d (P < 0.05 both groups). The irreversible conversion rate of testosterone to DHT was 3.1 +/- 0.4 and 3.5 +/- 0.9% (NS). The back conversion of 3 alpha diol to dHT was high (68 +/- 25 vs. 81 +/- 17, NS) indicating that 3 alpha diol might cause BPH as a result of conversion to DHT in vivo. The conversion of DHT to 3 alpha diol is reduced in the elderly group (15.8 +/- 2.6 and 6.3 +/- 1.4, P < 0.001). Since DHT formation in the prostate is a key event in the development of BPH and blood DHT appears to be a measure of extrasplanchnic sexual target tissue activity, our in vivo studies suggest that the tissue increase in DHT may result from reduced metabolism and the activity of 3 alpha-oxidoreduction favors the oxidative pathway in elderly men.
Adult↗
Direct conversion of testosterone to dihydrotestosterone glucuronide in man.
Tritiated testosterone and [14C]dihydrotestosterone (DHT) were administered by constant iv infusion into five young and five elderly men undergoing diagnostic cardiac catheterization. The radioactivity concentrations of free and conjugated DHT in arterial and hepatic vein blood samples were then determined. The analysis of the 3H:14C ratio of free DHT in arterial and hepatic vein blood showed that in both groups, the 3H:14C ratio of free DHT was the same in arterial and hepatic vein blood, indicating that splanchnic tissue is not the source of blood DHT from testosterone. This is in agreement with data that the transfer constant across the liver ([rho]T-DHT SD) was undetectable. In both young and elderly men, a significant increase of the 3H concentration of DHT glucuronide in hepatic vein blood was observed, indicating that the splanchnic compartment could be the site of production of DHT glucuronide. The 3H:14C ratio of DHT glucuronide was much higher than that of free DHT in both groups, suggesting that DHT glucuronide is derived from the blood testosterone pool, and most of the DHT from testosterone seems to be conjugated before mixing with blood DHT. This study indicates that a large fraction of DHT produced in the liver from testosterone is efficiently conjugated or further metabolized, and this results in the lack of splanchnic production of free DHT in men.
Adult↗