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Biomedical subjects

J M van Rossum

Publications and source records attributed to J M van Rossum.

At least 19 recordsLinked to original sources
PubMed1996

Psychotropic drug use in a group of Dutch nursing home patients with dementia: many users, long-term use, but low doses.

The aim of this study was to describe the use of psychotropic drugs in a psychogeriatric nursing home, "Joachim en Anna", in Nijmegen, the Netherlands. To this end the medical records of 890 nursing home patients with dementia, admitted between 1980 and 1989, were analysed retrospectively. Each time pattern of psychotropic drug use was registered. Drugs were coded by means of the Anatomical Therapeutic Chemical classification system. The daily dose was expressed as the ratio of the mean prescribed daily dose and the defined daily dose. Side-effects and changes in prescription patterns throughout the years patients were admitted were analysed. A total of 3,090 time patterns of exposure to psychotropics were registered. Neuroleptics, benzodiazepines, and antidepressants accounted for 58, 32, and 9 percent of the time patterns, respectively. For almost every drug prescription the prescribed daily dose was lower than the defined daily dose. More than 75 percent of these nursing home patients had at least one prescription for a psychotropic drug during institutionalization. One or more side-effects were observed in 50 percent of the patients who used a neuroleptic. The total number of patients receiving psychotropics did not change throughout the study. Psychotropics were prescribed for long-term use, but in a low dose. Side-effects were frequently observed while the correct individual dose was being determined.

Antidepressive Agents↗
PubMed1993

[Use of psychotropic drugs in a group of nursing home patients with dementia: many users, long-term use but low dosages].

Of 890 nursing home patients with dementia, admitted between 1980 en 1989 to Dutch nursing home 'Joachim en Anna' in Nijmegen, each episode of psychotropic drug use was retrospectively registered. Drugs were coded by means of the Anatomical Therapeutic Chemical (ATC)-classification system and the daily dose was expressed as the ratio of the prescribed daily dose and the internationally agreed defined daily dose. Side effects were analysed as were changes in prescription patterns throughout the years of patient admittance. A total of 3090 episodes were registered. Neuroleptics, benzodiazepines and antidepressants accounted for 58, 32 and 9% of the prescriptions. In almost every drug-prescription the prescribed daily dose was lower than the defined daily dose. More than 75% of the patients had at least one prescription for a psychotropic drug during institutionalization. Half of those patients who used a neuroleptic showed one or more side effects. Neither the total amount of patients with psychotropics nor the duration of usage changed throughout the years of patient admittance. It is concluded that a majority of these nursing home patients got at least one prescription of a psychotropic drug during institutionalization. Psychotropics were prescribed for long-term usage, but in low doses. Side effects were frequently observed in determining the right dose.

Aged↗
PubMed1992

Interaction of legume lectins with the cellular metabolism of differentiated Caco-2 cells.

The binding of the legume lectins Phaseolus vulgaris E4 and L4, Glycine max agglutinin, Vicia faba agglutinin, and Pisum sativum agglutinin to intact differentiated Caco-2 cells and to brush border membranes of differentiated Caco-2 cells was investigated, and their impact on the cellular metabolism and the microvilli of these cells was assessed. P. vulgaris isolectin E4 showed the most intense staining after binding of fluorescein isothiocyanate-labeled lectin to intact Caco-2 cells. P. sativum agglutinin showed the weakest staining intensity. The dissociation constant for P. vulgaris isolectin E4 and P. sativum agglutinin binding was 0.11 x 10(-5) and 1.69 x 10(-5) mol/L, respectively. The values of the dissociation constants for P. vulgaris isolectin L4, G. max agglutinin, and V. faba agglutinin were situated in between these extremes. Stimulation of thymidine, glucosamine, and fucose incorporation was observed after exposure to P. vulgaris isolectins and soybean agglutinin. V. faba agglutinin had an inhibitory effect, whereas P. sativum agglutinin showed little or no effect. Compared with control cells and P. vulgaris isolectin L4- and P. sativum agglutinin-incubated cells, the microvilli of P. vulgaris isolectin E4-, soybean agglutinin-, and V. faba agglutinin-incubated cells were shortened significantly. The data provide evidence that a correlation exists, not only between the dissociation constants of the lectins and the fluorescent staining intensity, but also between the dissociation constants of the lectins and the extent of the legume lectin-induced changes in the cellular metabolism.

Colonic Neoplasms↗
PubMed1992

The methyl-5 alpha-dihydrotestosterones mesterolone and drostanolone; gas chromatographic/mass spectrometric characterization of the urinary metabolites.

Before including the detection of the methyl-5 alpha-dihydrotestosterones mesterolone (1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) and drostanolone (2 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) in doping control procedures, their urinary metabolites were characterized by gas chromatography/mass spectrometry. Several metabolites were found after enzymatic hydrolysis and conversion of the respective metabolites to their trimethylsilyl-enol-trimethylsilyl ether derivatives. The major metabolites of mesterolone and drostanolone were identified as 1 alpha-methyl-androsterone and 2 alpha-methyl-androsterone, respectively. The parent compounds and the intermediate 3 alpha,17 beta-dihydroxysteroid metabolites were detected as well. The reduction into the corresponding 3 beta-hydroxysteroids was a minor metabolic pathway. All metabolites were found to be conjugated to glucuronic acid.

Androstanols↗
PubMed1991

Rapid and sensitive gas-chromatographic determination of caffeine in blood plasma, saliva, and xanthine beverages.

A gas chromatographic procedure is reported for the determination of caffeine in plasma, saliva, and xanthine beverages. Using a 75 cm column packed with OV-17, nitrogen-sensitive detection, and 1 ml samples, a suitable limit of analysis (coefficient of variation (CV) = 10.2%) of 50 ng/ml was obtained in plasma. Within-day CVs at caffeine concentrations of 0.1-0.5-2.0-7.5-15.0 micrograms/ml in plasma were 7.7-5.6-4.8-3.8-3.4%, respectively. The limit of detection, defined as the injected quantity of caffeine giving rise to a signal to noise ratio of 2, is 40 pg, corresponding to a plasma concentration of 1 ng/ml. The procedure involves addition of the internal standard 7-pentyl theophylline and alkaline extraction of the sample with dichloromethane. The method described rivals any gaschromatographic assay published so far in rapidness and accuracy. Plasma and saliva caffeine concentrations were determined in a healthy male volunteer after swallowing 400 ml of coffee. The calculated pharmacokinetic parameters, assuming complete absorption of caffeine from the G.I. tract, agree well with previously published values.

Adult↗
PubMed1991

Chaos and illusion.

Pharmacology is the study of the interaction of drugs with living organisms, especially humans. The body is a very complicated system, which suggests that the 'effect' induced by a drug is not a single entity but a change in several variables at the same time, all of which are interrelated in a nonlinear fashion. Research on nonlinear systems in other fields of science--commonly known as chaos theory--may therefore be of use in understanding pharmacology, as explained here by J. M. van Rossum and J. E. G. M. de Bie. They argue that in the study of drug effects, several variables should be measured simultaneously. Many pharmacologists prefer to construct an illusion of reality, studying just one of the essential variables and averaging data in a population of subjects, thus losing the opportunity to understand what a drug really does to a patient.

Animals↗
PubMed1991

Doping control of testosterone and human chorionic gonadotrophin: a case study.

Doping control for testosterone and human Chorionic Gonadotrophin (hCG) requires special attention as a difference must be made between the endogenous and exogenous origin of both substances. The detection of exogenous testosterone is based on the ratio of testosterone- to epitestosterone-glucuronide (T/E) in urine. The problems with this ratio are discussed. For hCG analysis in urine the utilization of sandwich-type hCG specific assays instead of hCG/hCG beta competitive assays is recommended. A case study in which an athlete self-administered testosterone and hCG before a competition is described. The T/E ratio and hCG concentration in urine were followed during this period of self-administration. The results demonstrate the relevance of the T/E ratio and of the selected hCG assay. The ratio of testosterone to human Luteinizing Hormone (T/hLH) in serum also indicated the use of hormones. Although the athlete's urine was negative for exogenous testosterone directly after competition, he would have been found positive for hCG.

Chorionic Gonadotropin↗
PubMed1989

Pharmacokinetics from a dynamical systems point of view.

The pharmacological action of many drugs depends on several variables at the same time and therefore will be dominated by an attractor of a dimension greater than zero. The pharmacokinetic behavior is likely to be dominated by a zero dimensional point attractor so that it is highly predictable. Pharmacokinetics is discussed from a dynamical systems point of view, whereby the transport of drugs in the tissues and organs is considered a stochastic process characterized by density functions of transit times and blood flows. In the body, the tissues and organs are arranged in parallel, in series, and in a feedback-loop fashion. Consequently, the single-pass transport of drugs through the body is again a stochastic process characterized by the density function of total body transit times, the cardiac output, and the total body extraction. The drug molecules, however, may pass through the body several times before ultimately leaving the system by metabolism or excretion. As a result, the body may be regarded as a positive feedback system with the pulmonary circulation (and its tissues) as the forward transfer function and the systemic circulation (with all its tissues) as the feedback transfer function. Consequently, the total body transport function (closed loop) is again a stochastic process characterized by a density function of total body residence times. The relationship between the body transit time distribution and the body residence distribution is determined by the feedback-loop arrangement, the cardiac output, and the extraction ratio which can easily be written in the Laplace domain. The pharmacokinetic parameters logically follow from the systems approach. They are the cardiac output, the mean transit time, the extraction ratio, the clearance, the volume of distribution in steady state, the mean residence time, and the average number of recirculations. The dynamic systems approach in pharmacokinetics has been illustrated with some examples notably with caffeine.

Absorption↗
PubMed1989

Systems dynamics in clinical pharmacokinetics. An introduction.

Pharmacokinetics is in essence the study of the input/output relationships of the (human) body, which is considered as a system characterised by a density function of residence times. The input is the dosage rate, and the output is the concentration in the blood. The body transport function is first derived in a model-independent fashion, assuming linear kinetics. It is subsequently defined on the basis of a positive feedback loop of transport through the pulmonary and systemic circulation. Thus, the residence times distribution is based on transit times distributions and recirculation. The relevant dynamic systems parameters are cardiac output, extraction ratio, clearance, volume of distribution, mean transit time and mean residence time. In the case of drug absorption, mean absorption time and bioavailability are also important. In this review, the systems approach in pharmacokinetics is illustrated by clinical and computational experiments.

Biological Transport↗
PubMed1988

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↗
PubMed1988

The pharmacokinetics of intradural morphine in major abdominal surgery.

The pharmacokinetics of intradural morphine used for major abdominal surgery were evaluated. Lumbar spinal fluid and plasma concentrations were measured at intervals after morphine 0.05 mg/kg had been injected intradurally in 21 patients scheduled for elective abdominal aortic surgery. The CSF morphine concentrations were fitted by a biexponential function. A non-compartmental model based on statistical moment theory was used for calculating the intradural morphine disposition. Mean residence time was 137 +/- 54.9 minutes, mean initial volume of distribution 15 +/- 5.49 ml, mean volume of distribution at steady-state 42 +/- 18.25 ml and mean clearance 0.34 +/- 0.18 ml/min (0.02 +/- 0.01 L/h). The moments of the morphine concentration-time curves and the pharmacokinetic parameters varied between the patients. They were not significantly different with regard to morphine dosage, or patient sex or age. Free morphine could not be detected in plasma. Morphine-3-glucuronide appeared in plasma at 5 minutes, increased to a maximum at 240 minutes and fell below the detection limit at about 16 hours after morphine administration. Possible clinical causes of interindividual variations in the CSF morphine concentrations and the pharmacokinetics of intradural morphine are discussed.

Adult↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

Action of lombazole, and inhibitor of fungal ergosterol biosynthesis, on Staphylococcus epidermidis.

Lombazole had no effect on respiration at any tested concentration and had little effect on the K+ permeability of Staphylococcus epidermidis. Of the major metabolic processes investigated in this bacterium, only de novo synthesis of the cell envelope was inhibited by lombazole well in advance of an effect on growth. The time course of inhibition indicated that lombazole exerted its primary effect via inhibition of lipid synthesis; other induced changes, such as reduced synthesis of lipoteichoic acid and cell wall components, were considered to be secondary effects. Although the precise site of action in S. epidermidis has to be established, the absence of alterations in lipid patterns after treatment with lombazole suggests the toxicant may affect an essential step in lipid biosynthesis. In Candida albicans, lombazole inhibited the sterol C-14 demethylation step in the ergosterol biosynthesis pathway.

Anti-Bacterial Agents↗
PubMed1986

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↗
PubMed1985

Disposition of disodium azodisalicylate in healthy subjects. A possible new drug for inflammatory bowel disease.

The disposition of disodium azodisalicylate and salicylazosulfapyridine was studied in 6 healthy volunteers. After a single oral dose (1.0 g disodium azodisalicylate; 2.3 g salicylazosulfapyridine) maximum serum concentrations of the intact compound ranged between 1.4 and 6.8 mumol/L and 32 and 114 mumol/L, respectively. Mean residence time and serum half-life of disodium azodisalicylate were considerably longer than those of salicylazosulfapyridine, probably because of a higher apparent volume of distribution. Both compounds were largely split by colonic bacteria and comparable amounts of the active moiety, (acetyl-)5-aminosalicylic acid, were recovered in feces. During long-term ingestion of disodium azodisalicylate (1.0 g/day) it took 6-19 days to reach a steady state. Serum concentrations of disodium azodisalicylate at steady state were low: 2.2-8.4 mumol/L. The serum half-life was 6-10 days. It is concluded that the disposition of disodium azodisalicylate is similar, in important respects, to that of salicylazosulfapyridine. Disodium azodisalicylate, therefore, deserves therapeutic trial.

Administration, Oral↗