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Biomedical subjects

M Garle

Publications and source records attributed to M Garle.

At least 19 recordsLinked to original sources
PubMed2000

Workplace drug testing (WDT) likely to increase in Europe. Report from the First European Symposium on WDT including selected abstracts.

Will it take a series of drug-related accidents that have already occurred in the USA before workplace drug testing (WDT) becomes accepted in Europe as a preventive measure? Currently, the development of WDT in most European countries lags some 10-15 years behind that in the USA. Labour authorities in Europe now ought to take initiatives to demand a mandatory programme for accrediting drug analytical laboratories for WDT. Companies should realise that illicit drug use is no longer only a problem at street corners, and that having a testing system in place is important, not just for public health, but also for their reputations as responsible societal actors. Improved networking among police and regulatory authorities is required to keep pace with the rapid appearance and dissemination of new substances of abuse. European research collaboration, including the newly formed European Workplace Drug Testing Group, is needed to assess the impact of drug-testing policies on accidents and other outcome variables, and thereby to convince the general public and politicians that drug testing is beneficial and necessary. A 1993-1994 survey of quality analysis in some 200 European laboratories reported from Institut Municipal d'Investigació Medica (IMIM), Spain, showed good agreement between nominal and found concentrations but that only 10% of the laboratories could both screen, identify and quantify samples. Experiences from Italy show that proficiency testing schemes lead to improved accuracy of results. These were some major conclusions of the First European Symposium on Drug Testing held at Huddinge University Hospital in Stockholm, Sweden, 30 March to 1 April 1998, organised by Karolinska Institute, with participants from 22 countries.

Europe↗
PubMed1996

Increased urinary testosterone/epitestosterone ratios found in Swedish athletes in connection with a national control program. Evaluation of 28 cases.

In connection with a national anti-doping control program, including analysis of 8946 urine samples, 28 athletes were found to have delivered samples free from xenobiotic anabolic steroids but with an increased testosterone/epitestosterone (T/E) ratio (> 6). Unannounced testing of the above athletes produced 2-4 additional urine samples during the next 2-3 months. A low degree of variation of the T/E ratio, with a C.V. below 30% was found in 17 of the subjects whereas 10 had a C.V. varying from 31% to 43%. One subject with a high urinary T/E ratio (10.5) had a C.V. of this ratio of 126% and also an extremely high ratio between testosterone and LH in urine. It has been reported that non-users of testosterone have T/E ratios fluctuating around a mean with a C.V. that will not exceed 30%. We found that administration of testosterone to seven healthy volunteers resulted in urinary T/E ratios that varied with a C.V. ranging from 67% to 130% during the following 4 weeks. It is concluded that among the above 28 cases, only one can be regarded as a clear case of testosterone doping. Although the vast majority of Swedish athletes have urinary T/E ratios below six, there is a subfraction with a constant higher ratio, possibly due to genetic factors.

Doping in Sports↗
PubMed1996

Determination of aglycones of ginsenosides in ginseng preparations sold in Sweden and in urine samples from Swedish athletes consuming ginseng.

Recently developed gas chromatographic and gas chromatographic-mass spectrometric methods were used to characterize 17 different commercial ginseng preparations sold in Sweden. The contents of total ginsenosides per capsule or per tablet varied from 2.1 to 13.3 mg. Unlike the other preparations, a red ginseng and three liquid ginseng preparations (after releasing the sugar moieties from ginsenosides) were shown also to contain significant amounts of 20-epimers of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol as well as their corresponding 24,25-hydrated compounds. In addition to the genuine and artificial sapogenins mentioned above, two epimeric pairs of prosapogenines (ginsenoside Rg3 and 20(S)-Rg3, ginsenoside Rh1 and 20(R)-Rh1) were also found in the liquid formulations. These results suggest that hydrolysis, epimerization and hydration in the side-chain of the aglycone moiety of ginsenosides may occur in the liquid formulations under weak acidic conditions (pH 3.0-3.5 with 9-10% of alcohol at room temperature). The new method was also used to determine the aglycones of ginsenosides in urine samples from Swedish athletes stating that they had consumed ginseng preparations within 10 days before urine collection. Out of the 65 samples analysed, 60 were found to contain 20(S)-protopanaxatriol. The concentrations of 20(S)-protopanaxatriol ginsenosides varied from 2 to 35 ng ml-1 urine. This is the first demonstration of uptake of ginsenosides in humans after oral administration of ginseng preparations.

Ginsenosides↗
PubMed1995

Serum and urinary markers of exogenous testosterone administration.

In an attempt to find optimal markers of exogenous testosterone (T) administration in male athletes, a number of compounds were measured in 11 healthy men before and after 3, 6 and 9 months of weekly administration of 250 mg i.m. T enanthate and in age-matched untreated controls. The following variables were measured in serum: T, 17 alpha-hydroxyprogesterone (17-OHP), sex hormone-binding globulin (SHBG), estradiol-17 beta, estrone (free + conjugated) and luteinizing hormone (LH). The following variables were measured in urine: T glucuronide (urinary T), epitestosterone glucuronide (urinary epiT), estrone (free + conjugated) and LH. Serum T, serum T/17-OHP ratio, serum T/LH ratio, serum T/SHBG ratio, serum and urinary estrogens, urinary T/creatinine-, T/epiT- and T/LH ratios increased whereas serum 17-OHP, SHBG and LH and urinary epiT/creatinine- and LH/creatinine-ratios decreased significantly during treatment. Levels above the upper reference limit were found in all subjects at 3, 6 and 9 months for serum T/17-OHP and serum and urinary T/LH ratios and at 6 months for the urinary T/epiT ratio. Levels below the lower reference limit were found in all subjects at 3, 6 and 9 months for serum LH and the urinary LH/creatinine ratio, at 3 months for the urinary epiT/creatinine ratio and at 9 months for serum 17-OHP. No other variable showed abnormal values in all subjects at the same occasion. Despite significant changes during treatment, steroid concentrations as such are poor indicators of T doping. Serum and urinary LH levels, T/LH ratios and serum T/17-OHP ratios seem to be the most reliable markers of exogenous T administration in males.

Age Factors↗
PubMed1993

Analysis of ginsenosides by chromatography and mass spectrometry: release of 20 S-protopanaxadiol and 20 S-protopanaxatriol for quantitation.

To facilitate studies on the possible presence of ginseng products in serum, tissues, and excretions, a procedure to optimize the analysis of the ginseng specific products, i.e., ginsenosides, had to be worked out. With the present method the two sapogenins, 20S-protopanaxadiol and 20S-protopanaxatriol, can be produced from ginsenosides Rb1, Rc, Rd, Re, and Rg1 in 80% yield by using an improved alkaline cleavage procedure. In contrast to previously described acid hydrolysis procedures for ginsenosides, our alkaline conditions caused no epimerization, no hydroxylation, and no cyclization of the side chain. Furthermore, no unchanged ginsenosides were recovered. The products of alkaline and acidic cleavage were separated, identified, and characterized by GC, GC-MS, and HPLC. In contrast to alkaline cleavage, treatment with acid afforded a number of side products. The C-20S-epimers of the ginseng sapogenins could be distinguished from C-20R epimers by difference in mass spectra and retention time after trimethylsilylation.

Chromatography, Gas↗
PubMed1992

Detection of testosterone administration by increased ratio between serum concentrations of testosterone and 17 alpha-hydroxyprogesterone.

An increased ratio between urinary testosterone (T) and epitestosterone (epiT) has been accepted by the International Olympic Committee as a marker for T doping. However, in a few subjects, we and others have observed constantly above-normal urinary T/epiT ratios that are unlikely to be related to exogenous T administration. To find a better test for T doping, we studied several serum and urinary androgens and androgen precursors, estrogens, and luteinizing hormone (LH) in seven healthy volunteers for 35 days after an intramuscular injection of 250 mg of testosterone enanthate. Among urinary analyses, only the T/epiT ratio was a suitable marker of T doping; of the serum assays, 17 alpha-hydroxyprogesterone (17OHP), T/17OHP ratio, LH, and T/LH ratio were fair to good markers of T doping. The serum T/17OHP ratio was the best marker of those tested, with all seven subjects having above-normal values for this in the first 3 days of the observation period. No other marker showed abnormal values in all subjects at any time. Moreover, the T/17OHP ratio was affected by neither diurnal variation nor physical stress. The value of this marker for T doping was further supported by the finding of normal T/17OHP ratios in a subject with increased urinary T/epiT ratios caused by an abnormally low testicular epiT production, probably related to genetic factors.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Fenfluramine treatment of twenty children with autism.

The effects of fenfluramine were examined on 20 children with autism over a 48-week period utilizing a double-blind placebo-controlled crossover design. Blood and urine samples and psychological tests (Griffith's Developmental Scales and Real Life Rating Scale) were obtained at each crossover period. The only significant improvement was a decrease in abnormal motor behavior. We did not find any significant improvement in intellectual functioning or any correlation between good clinical response and low baseline serotonin levels or high baseline IQ. Serotonin decreased 53% after fenfluramine treatment and rebounded to a level 35% higher than baseline following a placebo period. Fenfluramine and the active metabolite norfenfluramine were determined in plasma samples.

Autistic Disorder↗
PubMed1987

The debrisoquin hydroxylation phenotype does not predict the metabolism of phenytoin.

Phenytoin plasma elimination kinetics and accrual of phenytoin metabolites in urine were studied in seven rapid and five slow hydroxylators of debrisoquin. There was no interphenotypic difference in phenytoin clearance, plasma half-life, volume of distribution, maximum rate of metabolism (Vmax), or Michaelis-Menton constant (Km). The total recovery of metabolites as percentage of given dose and the metabolite profiles in urine were similar for the two debrisoquin hydroxylator phenotypes. Similarly, no differences were observed between the groups with respect to stereoselective production of either dihydrodiol or para-phenolic metabolites of phenytoin. The debrisoquin hydroxylation phenotype was also investigated in 74 epileptic patients treated with phenytoin. Vmax and Km were graphically estimated from plasma concentrations at varying phenytoin dosage regimens in 36 of the patients. There was no correlation between the debrisoquin hydroxylation index and Vmax or Km. We conclude that the debrisoquin hydroxylation phenotype has no predictive value in guiding phenytoin dosage.

Adult↗
PubMed1986

Beta-blocking effect and pharmacokinetics of pindolol in young and elderly hypertensive patients.

The pharmacokinetics and beta-blocking effect of pindolol has been compared in 20 patients with essential hypertension (WHO Stage I), 10 below 25 years of age and 10 older than 60 years. Each patient received pindolol 10 mg p.o. once a day for 5 days. The area under the curve (AUC) of pindolol was larger in the old than in the young patients both on the first (p less than 0.05) and the fifth (p less than 0.01) days. The AUC of pindolol was 14% higher on the fifth day compared to the first day in the elderly group, indicating minor accumulation at steady-state. There was no change in AUC in the young patients. Endogenous creatinine clearance was lower in the old (80 +/- 9 ml/min) than in the young patients (150 +/- 45 ml/min). The beta-blocking effect did not differ between the groups at 2 h after administration of pindolol on Days 1 or 5. However, 24 h after the first and fifth doses approximately 60% of the beta-blockade persisted in the old group whereas 17 and 19% of the beta-blockade, respectively, persisted in the young group; the difference between the groups was statistically significant (p less than 0.01). The most probable explanation for the more sustained beta-blocking effect in the elderly is the physiologically decrease in renal function, which results in a more sustained plasma level of pindolol in those patients.

Adrenergic beta-Antagonists↗
PubMed1986

Extradural and parenteral pethidine as analgesia after total hip replacement: effects and kinetics. A controlled clinical study.

Twenty-one patients who had undergone total hip replacement were randomly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine im (I) and 20 mg (II) or 60 mg of extradural pethidine (III) in a double-blind design. The degree of analgesia, the adverse effects, and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale (VAS). Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine. Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry (GCMS). Hypoalgesia to pin prick test was evaluated. Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose. A significant difference in pain score compared with the im group was found after the higher extradural dose only between 0.5 and 1 h (p less than 0.05). The area under the curve (AUC) of pain score versus time (0-18 h) was not significantly different between groups. The recorded adverse effects were minor in all three groups. The terminal half-lives and plasma clearances of pethidine, and the time to peak concentration were not different between the groups. Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect. The present study shows that extradural pethidine produces shortlived analgesia, in contrast to the long-lasting effect of morphine found in other studies.

Aged↗
PubMed1984

Kinetics of morphine in cerebrospinal fluid after epidural administration.

Forty patients undergoing arthroscopy were given an epidural dose of 0.05 mg morphine-HCl in 0.1 ml saline/kg body weight to study the disposition of morphine in the cerebrospinal fluid (CSF). In each patient one to three CSF samples were collected (86 samples in total). A mean peak concentration of 13 890 nmol/l was achieved 75 min after morphine administration. The compiled data show an elimination half-life of 162 min (r = 0.98). Individual half-lives in seven patients with three samples ranged from 61-172 min. Large interindividual variations were found in CSF-concentrations of morphine, 9- and 8-fold at 3 and 8 h, respectively, after the dose. However, 16 h after administration no patient had a concentration less than 81 nmol/l. At 8 h after the dose, CSF concentrations of morphine were significantly higher (P less than 0.05) in a group of patients (n = 5) kept uptilted (80 degrees), as compared to those in the supine position (n = 5). Such a difference was not observed 3 h after the dose. The sampling procedure and age also seemed to influence CSF concentrations of morphine. There was no correlation between the dose given in mg and the CSF concentrations achieved. Strict standardization is thus mandatory when studying the disposition of opiates in CSF after epidural or intrathecal administration. Since our calculated half-lives of morphine in CSF were similar to those reported in plasma, the long-lasting effect is probably related to the high initial morphine concentrations in CSF.

Adult↗
PubMed1984

Simultaneous treatment with terbutaline and theophylline.

The bronchodilating effect and side-effects of theophylline and a beta 2-adrenoceptor stimulating drug (terbutaline) alone and in combination were studied in 10 adult asthmatic patients. Initially, each individual's pharmacokinetic parameters for theophylline were determined. On 3 separate days, theophylline was infused to defined steady-state concentrations (0, 7.5, and 15 micrograms/mL, respectively) followed by the administration, at intervals of 1 h, of incremental intravenous doses of terbutaline. Theophylline caused a plasma concentration-dependent increase in the volume of air expelled in the first second of forced expiration (FEV1). Theophylline itself had no significant effect on objectively recorded skeletal muscle tremor or heart rate but enhanced the terbutaline-induced increase in both. At the highest steady-state concentration (15 micrograms/mL), 2 of the patients experienced nausea. Terbutaline caused a plasma concentration-dependent increase in FEV1, heart rate and tremor. The plasma levels of terbutaline at the given doses did not differ significantly between individuals or within individuals at different theophylline levels. The combination of theophylline and terbutaline resulted in an additive effect on bronchodilatation. At comparable levels of bronchodilatation, the combination of theophylline and terbutaline caused a lesser degree of side-effects than either drug alone.

Adult↗
PubMed1984

Morphine glucuronidation in the rhesus monkey: a comparative in vivo and in vitro study.

The kinetics of morphine in the rhesus monkey after i.v. or oral administration including the hepatic extraction ratio determined directly in the portal and hepatic veins were compared with the glucuronidation of morphine in liver microsomes from the same animals. The plasma half-lives varied between 102 and 202 min and the apparent volume of distribution was 2.68 to 3.15 l X kg b.wt.-1. The systemic blood clearance (9.2-21.3 ml X min-1 X kg b.wt.-1) was in the same range as the estimated hepatic blood clearance (9.7-23.9 ml X min-1 X kg b.wt.-1). After i.v. administration, the blood concentrations of morphine-3-glucuronide ( M3G ) were 8 to 11 times higher than those of morphine. The molar blood concentration ratio between morphine-6-glucuronide and M3G was 0.04 or less. The ratio between the metabolite levels in blood was similar to the relative formation rates for M3G and morphine-6-glucuronide in liver microsomal preparations (less than .039). The intrinsic hepatic metabolic clearance of morphine as estimated from the apparent enzyme kinetic constants Vmax and Km for the formation of the major M3G metabolite was used to predict the hepatic extraction ratio. The predicted values of the hepatic extraction ratio (0.09-0.14) were, however, underestimates of the experimentally determined hepatic extraction ratio, which varied between 0.61 and 0.74. This indicates that unknown factors in the liver microsomal glucuronidation preclude the use of enzyme kinetics parameters obtained in vitro for the prediction of the hepatic extraction ratio of morphine. For some drugs that are oxidized it has been shown previously that such prediction from in vitro data is possible.

Animals↗
PubMed1982

Extradural and parenteral morphine: kinetics and effects in postoperative pain. A controlled clinical study.

In a controlled clinical study of 20 patients undergoing arthrotomy a single dose of morphine 0.05 mg kg-1 administered extradurally resulted in more pronounced and prolonged pain relief than morphine 0.1 mg kg-1 i.m. in the period immediately after operation. This difference was significant between 2 and 11 h after morphine administration. The maximum analgesic effect for nine patients in the extradural group was obtained about 2 h after injection. Two of 10 in the extradural group experienced urinary retention. Other side-effects were mild for both groups. Plasma concentrations of morphine were measured in five patients in each group. Four hours after administration, morphine was not detectable in plasma in any of the extradural group and in two of the i.m. group. Our study gives further support for the theory that extradural morphine acts on the spinal cord.

Adult↗