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D H Catlin

Publications and source records attributed to D H Catlin.

At least 19 recordsLinked to original sources

Issues in detecting abuse of xenobiotic anabolic steroids and testosterone by analysis of athletes' urine.

Over the last decade the number of laboratories accredited by the International Olympic Committee (IOC) has grown to 25. Nearly half of the approximately 90,000 samples tested annually are collected on short notice-the most effective means to deter the use of anabolic androgenic steroids (AAS). The major urinary metabolites of AAS have been characterized and are identified by their chromatographic retention times and full or partial mass spectra. The process of determining if an athlete has used testosterone (T) begins with finding a T to epitestosterone (E) ratio > 6 and continues with a review of the T/E-time profile. For the user who discontinues taking T, the T/E reverts to baseline (typically approximately 1.0). For the extremely rare athlete with a naturally increased T/E ratio, the T/E remains chronically increased. Short-acting formulations of T transiently increase T/E, and E administration lowers it. Among ancillary tests to help discriminate between naturally increased T/E values and those reflecting T use, the most promising is determination of the carbon isotope ratio.

Anabolic Agents

Performance-enhancing drugs, fair competition, and Olympic sport.

Drug control has become an important component of Olympic sport. At the Atlanta Centennial Olympic Games, urine samples will be tested for prohibited substances, including stimulants, narcotics, anabolic agents, diuretics, peptides, and glycoprotein hormones as well as prohibited methods of enhancing performance, including blood doping and pharmacological, chemical, and physical manipulation of the urine. Drug testing programs must address short-acting stimulants, beta-blockers, and diuretics; training drugs such as anabolic steroids; and drugs affecting the detectability of other drugs. Programs include short- or no-notice testing during training periods, testing at qualifying competitions, and testing at the Olympic Games. Procedures and disposition that occur when a prohibited substance is found in an athlete competing in an Olympic sport are discussed. An analysis of the ethics of the use of performance-enhancing drugs in sports and of drug control in terms of fair competition and the impact of enhancement technologies of the meaning of sports also is presented.

Adrenergic beta-Antagonists

Improved method of detection of testosterone abuse by gas chromatography/combustion/isotope ratio mass spectrometry analysis of urinary steroids.

The current approach to detection of doping with testosterone is based on measuring the testosterone to epitestosterone ratio (T/E) in urine by gas chromatography/mass spectrometry. The median T/E for healthy males who have not used T is about 1.0. In a single urine, a T/E lower than six leads to a negative report even though it does not exclude T administration. A value greater than six indicates possible T administration or a naturally elevated ratio. It has been shown previously that the carbon isotope ratio of urinary T changes after T administration. In this study a potential confirmation method for T abuse was optimized. Gas chromatography/combustion/carbon isotope ratio mass spectrometry (GC/C/IRMS) was used to analyze two T precursors (cholesterol and 5-androsten-3 beta, 17 beta-diol) and two T metabolites (5 alpha- and 5 beta-androstane-3 alpha, 17 beta-diol) in addition to T itself in each of 25 blind urines collected from eight healthy men before, during or after T administration. The carbon isotope ratios of T and the metabolites were lower after T administration. The relationships among the variables were studied using multivariate analysis and beginning with principal components analysis; cluster analysis revealed that the data are composed of two clusters, and classified the samples obtained after T administration in one cluster and the remainder in the other; discriminant analysis correctly identified T users. The measurement of carbon isotope ratios of urinary androgens is comparable to the T/E > 6 test and continues to show promise for resolving cases where doping with T is suspected.

Adult

Urinary testosterone (T) to epitestosterone (E) ratios by GC/MS. I. Initial comparison of uncorrected T/E in six international laboratories.

Six laboratories in six countries collaborated to investigate the analytical method for estimating the testosterone to epitestosterone ratio (T/E) in urine by gas chromatography/mass spectrometry in the context of detecting the application of T as a doping agent in sport. The protocol specified many but not all details of reagents and instrument conditions. The design included the distribution and analysis of four urines with different T/E values, three replicates per value, and one standard. The ranges of mean T/E values for the four urines estimated by peak area (PA) were 0.32-0.42, 0.72-0.94, 0.91-1.14 and 3.19-5.48. The analyses of variance for these data and for the peak height (PH) data were significant for the laboratory factor (p < 0.0001). In addition there was a significant interaction between the urine factor and the laboratory factor which indicates the complexity of the analysis. T/E calculated using PA was not significantly different from that using PH. For within-laboratory precision all values for PH and PA were < 8.3%, and for between-laboratory precision all values were < 11.7% except for one (20.1%). The data represent a baseline for future experiments designed to elucidate the sources of within-and between-laboratory variance, and to harmonize estimates of T/E.

Analysis of Variance

The effect of testosterone aromatization on high-density lipoprotein cholesterol level and postheparin lipolytic activity.

Stanozolol, an oral 17 alpha-alkylated androgen, increases hepatic triglyceride lipase activity (HTGLA) and decreases high-density lipoprotein cholesterol (HDL-C) levels, whereas intramuscular testosterone has comparatively little effect. In the present study, we tested the hypothesis that aromatization of androgen to estrogen blunts the lipid and lipase effects of exogenous testosterone. Fourteen male weightlifters received testosterone enanthate (200 mg/wk intramuscularly), the aromatase inhibitor testolactone (250 mg four times per day), or both drugs together in a randomized cross-over design. Serum testosterone level increased during all three drug treatments, whereas estradiol level increased only with testosterone alone (+47%, P < .05), demonstrating that testolactone effectively inhibited testosterone aromatization. Testosterone decreased HDL-C(-16%, P < .05), HDL2-C(-23%, NS), and apoprotein (apo) A-I (-12%, P < .05) levels, effects that were consistently but not significantly greater with simultaneous testosterone and testolactone administration (HDL-C, -20%; HDL2-C, -30%; apo A-I, -15%; P < .05 for all). In contrast, both testosterone regimens decreased HDL3-C levels by 13% (P < .05 for both). HTGLA increased 21% during testosterone treatment and 38% during combined testosterone and testolactone treatment (P < .01 for both). Lipoprotein lipase activity (LPLA) increased only during combined testosterone and testolactone treatment (+31%, P < .01), suggesting that estrogen production may counteract the effects of testosterone on LPLA. Testolactone alone had little effect on any lipid, lipoprotein, apoprotein, or lipase concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Left ventricular function is not impaired in weight-lifters who use anabolic steroids.

Recent reports suggest that anabolic steroid use might deleteriously affect left ventricular function. To examine this possibility, the present study measured left ventricular size and function with use of Doppler echocardiographic techniques in 23 weight lifters: 12 who were currently using anabolic steroids and 11 who reported that they had never used these drugs. Drug users had administered anabolic steroids to themselves for at least three cycles over the past year. All studies were interpreted by blind review and group assignment was confirmed by urine testing. Average age, years of exercise training and body weight, as well as heart rate and blood pressure at rest were similar in both groups. Cardiac dimensions (mean +/- SD) including left ventricular diastolic cavity diameter (57 +/- 3 vs. 56 +/- 5 mm), septal thickness (10 +/- 2 vs. 9 +/- 1 mm), posterior wall thickness (8 +/- 1 vs. 8 +/- 1 mm) and myocardial mass (149 +/- 27 vs. 135 +/- 21 g) did not differ between the anabolic steroid users and nonusers, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Dietary cholesterol and the origin of cholesterol in the brain of developing rats.

Milk substitutes containing cholesterol at concentrations lower, equal to or greater than the concentrations found in natural rat milk were fed to artificially reared rat pups from 5 d until 15 or 16 d after birth. Pups reared by their mother served as controls. In one experiment, D7-cholesterol was fed in the milk at four different concentrations. The purpose of the study was to determine whether cholesterol in milk influenced growth and the sterol composition of brain over the period of its most rapid accumulation in this organ. We found that body and brain weights were not different, irrespective of the concentration of cholesterol in the milk substitutes. High concentrations of cholesterol in milk caused a significant increase in cholesterol in liver and plasma, whereas the concentration of cholesterol in brain was not different from the concentration in the brain of controls. The amounts of D7-cholesterol in lung and liver, and in plasma and RBC that pass the brain, were consistent with the concentration fed in the milk and approached 70% of the total content of cholesterol in these organs at the highest concentration fed. Brain, by contrast, contained very small amounts of D7-cholesterol, which could readily be attributed to D7-cholesterol associated with the vascular system of the blood-brain barrier. We found that the sterol composition of brain is not influenced by the concentration of cholesterol in milk and that cholesterol exogenous to brain, even in a hypercholesterolemic condition, does not gain entry to the brain. We conclude that the brain biosynthesizes de novo all the cholesterol it requires.

Animals

Clinical assessment and urine testing for anabolic-androgenic steroid abuse and dependence.

The emerging epidemic of anabolic-androgenic steroid use, no longer confined to elite athletes, is associated with adverse health consequences for which users may seek treatment. As with other forms of drug abuse, patients may deny or hide their use of steroids while seeking treatment for bothersome side effects or other problems. Thus, clinicians may increasingly, but unknowingly, see patients who are using steroids. Early detection and treatment of steroid abuse and dependence is critical in order to prevent serious and potentially fatal consequences. Therefore, it is incumbent upon clinicians to know the signs and symptoms of using steroids, and to be familiar with the clinical indications for urine testing. Using case examples, the authors review the assessment of steroid abuse and dependence in clinical practice and illustrate the role of urine testing in the assessment process.

Adult

Testing for fluoxymesterone (Halotestin) administration to man: identification of urinary metabolites by gas chromatography-mass spectrometry.

Fluoxymesterone, an anabolic steroid, is metabolized in man primarily by 6 beta-hydroxylation, 4-ene-reduction, 3-keto-reduction, and 11-hydroxy-oxidation. These pathways of metabolism are suggested by the positive identification of 4 metabolites and the tentative identification of 3 other metabolites. Detection of the drug in urine is possible for at least 5 days after a single 10 mg oral dose to previously untreated adult males, by monitoring the presence of 2 metabolites, since the parent drug is not detectable more than 1 day after the dose.

Adult

Alteration in the pharmacokinetic disposition of ciprofloxacin by simultaneous administration of azlocillin.

Healthy subjects were given single intravenous doses of ciprofloxacin, azlocillin, and the two drugs simultaneously on separate occasions. High-pressure liquid chromatographic analysis was used to assay the concentrations of both drugs in serum and urine. Pharmacokinetic parameters were calculated by noncompartmental methods. The total body (CL), renal (CLR), and nonrenal (CLNR) clearances; steady-state volume of distribution (Vss); and fractional urinary excretion of ciprofloxacin were all markedly decreased with the simultaneous administration of azlocillin. The disposition of azlocillin was unchanged when it was given with ciprofloxacin compared to when it was given alone. The pharmacokinetic parameters (mean +/- standard deviation) of ciprofloxacin given alone versus in combination with azlocillin were as follows: CL, 52.2 +/- 9.2 versus 33.9 +/- 6.0 liters/h (P less than 0.0005); CLR, 26.5 +/- 4.8 versus 16.2 +/- 4.2 liters/h (P less than 0.0005); CLNR, 25.8 +/- 5.5 versus 17.7 +/- 4.0 liters/h (P less than 0.03); Vss, 224 +/- 30 versus 166 +/- 41 liters (P less than 0.01); fractional urinary excretion, 0.56 +/- 0.06 versus 0.43 +/- 0.04 (P less than 0.002), respectively. This interaction resulted in significantly higher and more prolonged concentrations of ciprofloxacin in serum, which may be beneficial in the treatment of serious gram-negative bacterial infections, but it could also produce greater toxicity or result in more pronounced effects on oxidative drug metabolism of other medications.

Adult

Analytical chemistry at the Games of the XXIIIrd Olympiad in Los Angeles, 1984.

The equipment, methods, logistics, and results of doping-control analyses for the 1984 Los Angeles Olympic Games are discussed in this article. Within 15 days, 1510 different urine specimens underwent 9440 screening analyses by a combination of gas chromatography, gas chromatography-mass spectrometry, "high-performance" liquid chromatography, and radioimmunoassay. These tests covered more than 200 different drugs and metabolites, including psychomotor stimulants, sympathomimetic amines, central nervous system stimulants, narcotic analgesics, and anabolic steroids. The results are summarized by class of drug. Less than 2% of the samples were found to contain a banned drug.

Adrenergic beta-Antagonists