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Biomedical subjects

R A Maes

Publications and source records attributed to R A Maes.

At least 91 records · Page 5Linked to original sources

Improved screening method for beta-blockers in urine using solid-phase extraction and capillary gas chromatography-mass spectrometry.

An improved screening method for beta-blockers in urine is proposed, involving enzymatic hydrolysis, solid-phase extraction and capillary gas chromatography-mass spectrometry. Several extraction methods for beta-blockers, such as conventional liquid-liquid and solid-phase extraction procedures, have been evaluated for at least eight beta-blockers. Additionally, the gas chromatographic properties and mass fragmentation of the trimethylsilyl-trifluoroacetyl, trifluoroacetyl and cyclic n-butylboronate derivatives of beta-blockers have been compared and evaluated with respect to their efficiency for screening urine. The resulting screening method proved to be a specific and sensitive procedure, enabling these analytes to be detected and identified up to 48 h after the administration of a dosage, usually encountered in doping cases.

Adrenergic beta-Antagonists↗

The determination of non-steroidal anti-inflammatory drugs by GC-MS-MS in equine urine.

Results are given for a more sensitive screening procedure for non-steroidal anti-inflammatory drugs using GC-MS-MS. By monitoring a selected characteristic reaction for each drug very low detection limits are reached even in a difficult biological matrix such as equine urine. Detection down to 5 ng ml-1 for ibuprofen, ibufenac, alclofenac, fenoprofen, ketoprofen, naproxen and diclofenac is possible in contrast to the 0.5 microgram ml-1 limit for normal GC-MS detection. Examples are given of real positive cases for diclofenac and ibuprofen.

Animals↗

Why do doping control labs need a tandem mass spectrometer?

The International Olympic Committee requires a confirmation by gas chromatography/mass spectrometry for all positive doping cases. Because of the severe consequences involved they should be more specific about the required information and determine the differences allowed. The use of tandem mass spectrometry in dope control should be required before the Olympic Games in Barcelona in 1992. This article shows the power of tandem mass spectrometry in the definite identification of a drug.

Doping in Sports↗

Pharmacokinetics of morphine in cerebrospinal fluid and plasma after epidural administration in man.

The morphine concentration in serum as well as in cerebrospinal fluid (CSF) after epidural administration of 0.1 mg/kg morphine to 10 patients undergoing aortic abdominal surgery, was determined. Model independent pharmacokinetic parameters in serum and CSF i.e. mean residence time (MRT), clearance (Cl) and apparent volume of distribution were calculated from the concentration time curves using a non-linear square regression fitting programme. Peak concentration of morphine in serum (86 ng/ml) and in CSF (2610 ng/ml) was reached after 10 min respectively 40 min of epidural injection.

Adult↗

Long-term release of copper from two multiload IUD models: MLCu250 and MLCu375.

Decrease of mean copper content was assessed for two commercial types of Multiload IUD with different copper loads. Mean daily loss of copper amounted to about 18 mcg and 30 mcg for MLCu250 and MLCu375 devices, respectively. On the basis of these estimates, we conclude that both these IUD models can be considered long-lasting interceptive agents.

Copper↗

A comparative study of a monoclonal immunoassay reagent strip test and high pressure liquid chromatography for theophylline.

Our experience with the determination of theophylline in serum using a monoclonal immunoassay reagent strip test is reported. The day-to-day precision of a series of drug assay controls (n = 74) was investigated with a mean theophylline value of 15,3 +/- 1,2 mg/l. Interference and/or cross reactivity of structurally related compounds and metabolites of theophylline was tested. Serum samples from 148 asthmatic patients who were treated with theophylline were analyzed by the SERALYZER ARIS*) reagent strip test and by high pressure liquid chromatography. A correlation coefficient of 0.99 was found between these techniques using a linear regression analysis.

Antibodies, Monoclonal↗

Combination therapy of theophylline and terbutaline as sustained-release preparations in patients with asthmatic bronchitis.

In a group of ten patients with chronic asthmatic bronchitis, the effect of monotherapy with theophylline and terbutaline and the combination of both drugs, as sustained-release tablets, was compared to placebo, in a double-blind cross-over, triple dummy at random study. Lung function parameters, tremor measurements, c-AMP plasma levels, theophylline- and terbutaline-plasma levels were determinated. Monotherapy with theophylline and terbutaline in a relatively low dosage achieved a good lung function improvement without severe side effects, as compared to placebo. The combination of both drugs in the same dosage achieved a statistically significant enhancement of the lung function improvement, as compared to monotherapy, without an increase of side effects. An additional effect of theophylline and terbutaline on bronchodilation is demonstrated.

Adult↗

Terbutaline sustained-release treatment during one week 5 mg b.i.d. compared to one week placebo: terbutaline plasma levels, c-AMP plasma levels, lung function and tremor measurement.

In a group of ten patients with chronic asthmatic bronchitis, a good improvement of the lung function was achieved by a sustained-release terbutaline preparation (Bricanyl Retard) in a dosage of 5 mg twice daily. Tremor measurements and c-AMP plasma level showed a statistically significant increase. A good patient compliance was achieved with this dosage of terbutaline two times daily. The sustained-release preparation caused a rather constant and low terbutaline plasma level. We think that this relative low terbutaline plasma level is the most important reason for the lack of side effects.

Adult↗

Pharmacodynamics (lung function tests, tremor measurements and cAMP determinations) of a single dose of 0.5 mg terbutaline subcutaneously during sustained-release theophylline medication in patients with asthmatic bronchitis.

A group of 10 patients with chronic asthmatic bronchitis was titrated with slow-release theophylline (Theolin Retard) to a steady state plasma theophylline level of 10 mg/l. After one week of this treatment a single s.c. dose of 0.5 mg terbutaline (Bricanyl) at 10:30 a.m was administered. Lung function at 8:15 a.m. on this day was better than on the reference day without any medication, but the differences were not statistically significant. At 11:00 p.m., 30 min after s.c. administration of terbutaline all lung function parameters (VC, FEV1, MMEF and sGaw) were significantly raised compared to the values of 8:15 p.m. cAMP levels and tremor were significantly higher after the combined medication (30, as well as 150 min after s.c. administration of terbutaline) than on the reference day. This observation implies that we have to be careful with the administration of terbutaline s.c. to patients on theophylline treatment in the daily practice of the lung function laboratory.

Adult↗

Lung function improvement, tremor measurements and c-AMP determinations in a group of ten patients with asthmatic bronchitis after one week sustained release theophylline medication (theophylline plasma level +/- 10 mg/l) compared to one week placebo.

After one week theophylline therapy with a sustained release preparation (TheoDur 200 and 300 mg), a mean theophylline level of 10 mg/l was obtained in a group of ten patients with chronic asthmatic bronchitis with a mean dosage of 760 mg theophylline/24 h. A good improvement of the lung function was achieved, although only statistically significant for the mid maximal expiratory flow rate (MMEF) and the end expiratory specific airway conductance (sGaw) compared to placebo therapy. Tremor measurements and cyclic-AMP determinations showed a slight increase after theophylline therapy compared to placebo, although not statistically significant.

Asthma↗

Pharmacokinetics of morphine after epidural administration in man.

The concentration of morphine and morphine glucuronide in serum after epidural injection of 9 patients with aortic abdominal surgery was measured using gas chromatography-mass fragmentography. The decline of morphine serum concentration after epidural administration of 0.1 mg/kg was described by a bi- or triexponential decay equation with a mean terminal half-life (t1/2) of 134.7 +/- 107.9 min. Pharmacokinetic parameters were calculated from the fit parameters mean values for clearance and apparent volume of distribution were 1.16 +/- 0.65 l/min, and 156.6 +/- 107.3 l, respectively, for free morphine and 0.19 +/- 0.09 l/min and 37.2 +/- 17.7 l, respectively, for morphine glucuronide. Peak concentration of morphine 79 +/- 19 ng/ml was reached within 10 min after administration. Haemodynamic values, ECG, end-expiratory CO2 concentration, temperature, acid-base status, hemoglobin, Na+, K+, total Ca++, lactate, glucose concentration in the blood and the urine were registered before, during and after the operation.

Aged↗

Identification of N alpha-acetyl-alpha-endorphin and N alpha-acetyl-gamma-endorphin isolated from the neurointermediate lobe of the rat pituitary gland.

The peptides that represent the major components with alpha-endorphin- and gamma-endorphin-like immunoreactivity in the rat neurointermediate lobe were purified to homogeneity and chemically characterized. Rat neurointermediate lobes were extracted by boiling and homogenization in acetic acid. Peptide purification was based on gel filtration, followed by two high-pressure liquid chromatography steps. Pools containing peptides with the size and immunochemical properties of alpha- and gamma-endorphins were resolved by reverse-phase high-pressure liquid chromatography into multiple immunoreactive components. The major forms were finally purified by paired-ion high-pressure liquid chromatography. The amino acid compositions of these peptides fitted the beta-endorphin sequences 1-16 and 1-17. Tryptic mapping, aminopeptidase M digestion, chromatographic characterization, and immunoreactivity to an antiserum recognizing the N alpha-acetylated terminus of endorphins showed that these peptides were indistinguishable from N alpha-acetyl-alpha-endorphin (N alpha-acetyl-beta-endorphin 1-16), and N alpha-acetyl-gamma-endorphin (N alpha-acetyl-beta-endorphin 1-17). The NH2-terminal residue of the peptides was identified by mass spectrometry as N alpha-acetyltyrosine, substantiating the identity of the peptides. The results demonstrate the existence of N alpha-acetylated alpha- and gamma-endorphin as endogenous peptides in the neurointermediate lobe of the rat pituitary gland. In view of their occurrence and biological properties they should be considered significant members of the pro-opiomelanocortin family.

Amino Acids↗

An evaluation of the efficacy of charcoal haemoperfusion in the treatment of three cases of acute thallium poisoning.

The efficacy of intermittent charcoal haemoperfusion in combination with forced diuresis and Prussian blue therapy was evaluated in three cases of thallium poisoning. At a blood flow of 300 ml/min the average blood clearance values obtained with haemoperfusion were 72 +/- 11 ml/min (mean +/- SD) at a starting blood concentration above 2 mg/l and 120 +/- 23 ml/min (mean +/- SD) below this blood level. As a result of the combined intensive treatment, the thallium half-lives in blood observed during the period monitored were only 25-41 h. Removal of thallium by haemoperfusion is faster per unit of time than simultaneous excretion by forced diuresis. When forced diuresis was combined with intermittent (4-20 h intervals) haemoperfusion therapy, the total elimination by each technique was about equivalent over the period of combined treatment. Saturation of the Adsorba 300 C columns occurred during treatment. As a result, the clearance obtained did decrease to half the initial value in 2-3 h. As this decrease in efficacy is related to the blood concentration, haemoperfusion is more efficient at lower blood concentrations. This is in contradistinction to forced diuresis, of which the excretion is proportional to the blood concentration.

Acute Disease↗

Kinetic aspects of misonidazole and its major metabolite in radiotherapy.

Oral doses of misonidazole between 0.75 and 1.3 g/m2 were administered during 3-5 days per week to 21 patients with various malignancies. Mean plasma levels of misonidazole and desmethylmisonidazole at the times of radiotherapy were in the range 20-50 and 2-12 mg/l respectively. Slight accumulation of misonidazole and desmethylmisonidazole in plasma was observed with a dosage interval of 24 h. In patients with anticonvulsant comedication plasma elimination half-lives of misonidazole of 4.1-8.9 h were found. Observed side-effects were nausea and vomiting (9%), exanthema or rashes (14%) and mild peripheral neuropathy (9%).

Adult↗

Pharmacokinetics and pharmacodynamics of three sustained-release theophylline preparations (Theograd, 350 mg Theolair Retard, and 300 mg Theolin Retard) in steady state in six normals and six patients with chronic asthmatic bronchitis--Part II: Lung function.

The lung function profiles of a group of six healthy volunteers and six patients with moderately severe asthmatic bronchitis were compared after one theophylline infusion and after oral administration of Theograd (350 mg), Theolair Retard (350 mg), and Theolin Retard (300 mg) all given twice daily for 1 week. The group of patients showed a good reversibility of bronchoconstriction after intravenous theophylline administration; however, only minor improvement was observed at the levels reached after relatively low oral doses.

Adult↗

Tissue distribution of amiodarone and desethylamiodarone in rats after multiple intraperitoneal administration of various amiodarone dosages.

Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was studied after repeated intraperitoneal administration of the drug. Tissue and serum concentrations of amiodarone and desethylamiodarone were determined by high-performance liquid chromatography. The levels of amiodarone and desethylamiodarone in serum and tissues obtained after repeated intraperitoneal application of doses varying from 25 mg to 200 mg/kg show that the accumulation of amiodarone and desethylamiodarone in the rat is dose-dependent and both drugs are preferentially distributed in decreasing order in adipose tissue, lung, liver, kidney and thyroid gland. The penetration of the drug and its metabolite into brain was poor and with all the applied dosages brain levels were considerably lower than the corresponding serum levels. Desethylamiodarone serum and tissue concentrations were substantially lower than the corresponding amiodarone concentrations and varied from 1 to 48% (mean 15%) depending on the dosage used and the kind of tissue. The amiodarone tissue/serum concentration ratios were exceptionally high in adipose tissue (1,000-4,000) and moderate to high in the other tissues except brain (5-90), and indicate an extensive distribution of the drug with fat as a reservoir with a large storage capacity. The levels of amiodarone and desethylamiodarone, obtained with 50 mg/kg and 100 mg/kg dosages, showed in function of time clearly an increase in serum and tissues. The observed amiodarone tissue/serum ratios in function of time revealed no further significant increase (p less than or equal to 0.05) after 3 injections over a 6-day period, indicating the attainment of "steady-state".(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗