Biomedical subjects
G de Groot
Publications and source records attributed to G de Groot.
Wheelchair ergonomics and physiological testing of prototypes.
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Centrally induced respiratory arrest: main cause of death in beta-adrenoceptor antagonist intoxication.
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Calcium interferes with the cardiodepressive effects of beta-blocker overdose in isolated rat hearts.
Propranolol, timolol and sotalol were compared with respect to their cardiotoxic properties in isolated, spontaneously beating rat hearts. Propranolol and timolol induced a dose-dependent decrease in myocardial contractility. A high dose of sotalol had only modest negative inotropic effects. Similar reductions in myocardial contractility were observed in isolated, ventricle-stimulated rat hearts. These observations were similar to those in a previous study in which spontaneously beating and ventricle-stimulated reserpinized rat hearts were investigated. Spontaneously beating rat hearts were perfused with a high-, a normal- and a low-Ca++ medium, each with and without propranolol, timolol and sotalol. Addition of each beta-blocker to a normal-Ca++ medium induced a decrease of myocardial contractility and of heart rate and an increase of AV-conduction time when compared with the drug-free medium. In a high-Ca++ medium containing the same concentration of each beta-blocker, a less pronounced decrease of myocardial contractility was observed. Heart rate decreased and AV-conduction time increased to the same extent as after perfusion with the drug containing normal-Ca++ medium. With respect to the corresponding drug-free medium perfusion with a low-Ca++ medium with each beta-blocker enhanced the decline in myocardial contractility, most pronounced in propranolol and timolol containing media. For propranolol and sotalol the decrease in heart rate and increase in AV-conduction time were similar to the results after administration of the same beta-blocker in a high- and a normal-Ca++ perfusion media. Timolol caused an electromechanical dissociation. It was concluded that in beta-blocker intoxication the negative-inotropic phenomena cannot be explained by an action of the drugs on the beta-receptor since the results in reserpinized and non-reserpinized rat hearts were similar. Other effects have to be responsible for the observed cardiotoxic phenomena. The present results indicate that these phenomena can be influenced by Ca++ and or can be attributed to differences in lipophilicity.
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.
The control of speed in elite female speed skaters.
From ten participants in the World Championships Speed Skating for Ladies 1983 a number of selected mechanical parameters were measured and correlated with speed and external power. The parameters were derived by means of video and film analysis of strokes at the four distances: 500 m, 1500 m, 3000 m and 5000 m. The results show that these speed skaters control the different speeds at different distances mainly by changing their stroke frequency and not by changing the amount of work per stroke. However, at the same distance the relatively small interindividual differences in performance level appeared not to be correlated to differences in stroke frequency but were correlated to differences in push-off mechanics. Better performers gain some potential energy during the gliding phase and show a more horizontally directed push-off in the frontal plane. Maximal knee extension velocity did not show any correlation with performance. The fact that this might be connected to the absence of a plantar flexion during push-off is discussed.
Two different T-cell systems in humans, one of which is probably equivalent to Qa or Tla in mice.
Two different alloantigenic systems, expressed mainly on TG and TM lymphocytes and called TCA and TCB, respectively, are described. Alloantisera from parous women are absorbed with Epstein-Barr virus-transformed B cell lines from the husband of the serum producer to remove all anti HLA-A,B,C and DR antibodies. The absorbed sera are tested against a random panel and against lymphocytes from families. Family studies indicate that the TCA system might be encoded by a gene linked to HLA and located on the telomeric side of HLA-A. The total lod scores for the material of 15 informative families is +3.301 at a recombination fraction of 15%. Furthermore we can show that the TCA molecule is associated with beta 2-microglobulin by blocking with turkey anti-beta 2 microglobulin. The antigens are dimers of peptides with a molecular weight of approximately equal to 42,000 daltons and 12,000 daltons, respectively. This implies that TCA might be equivalent to either Qa or Tla in the mouse. For the TCB system no evidence is found for linkage with any known genetic marker. Only in random population studies is an association seen between TCB and Gm.
Respiratory arrest as main determinant of toxicity due to overdose with different beta-blockers in rats.
Propranolol, timolol and sotalol were compared regarding their toxicological effects on the cardiovascular and respiratory system. Each drug was administered intravenously to anaesthetized spontaneously breathing and artificially ventilated rats. After the start of infusion in spontaneously breathing rats each drug induced an expected decrease in arterial blood pressure and heart rate. An increase in PQ, QRS and QT interval was observed. From 5/8 of the survival time onwards these changes were accentuated. PaO2, pH and respiratory rate decreased and PaCO2 increased. The rats died as a result of respiratory arrest. Artificial ventilation of rats infused with the same doses increased the survival time significantly. The total doses administered before the animals died as a result of cardiovascular failure were significantly higher for each drug. The initial decreases in arterial blood pressure and heart rate were similar to those in spontaneously breathing rats. Thereafter, significantly smaller decreases were observed. The increases in PQ, QRS and QT interval were significantly less than in spontaneously breathing rats. Blood gases remained unchanged except for a decrease in pH in case of timolol.
Dopamine and isoproterenol in imipramine intoxication in the dog.
Artificially ventilated anesthetized dogs were given imipramine 7.5 mg/kg/hr i.v. In the first group (n = 6) mechanical cardiac activity was no longer detectable after a cumulative dose of 20.0 +/- 6.6 mg/kg (mean +/- sd). When aortic flow had decreased to 75% of its initial value, in a second group (n = 5) of experiments dopamine 10 micrograms/kg/min and in a third group (n = 5) isoproterenol 1 microgram/kg/min were administered i.v.. The doses of dopamine and isoproterenol were doubled when aortic flow had again decreased to 75% and 100%, respectively, of the original values. Cardiac mechanical activity was not detectable after a cumulative dose of 43.8 +/- 13.3 in the dopamine and 42.5 +/- 8.0 mg imipramine/kg in the isoproterenol group. These values differed significantly from that in the reference group (both 0.01 greater than p greater than 0.001). In the first group plasma imipramine concentrations at the end of the experiments were 3.06 +/- 0.66, in the second 3.36 +/- 0.66 and in the third 3.32 +/- 1.10 mg/1. Desipramine concentrations were 0.078 +/- 0.06, 0.162 +/- 0.076 and 0.383 +/- 0.09 mg/1 respectively. Dopamine induced a hemodynamic profile of low output and high pressure and isoproterenol one of low pressure and high output. It is concluded that dopamine combined with isoproterenol might be effective in counteracting the cardiodepressant action of imipramine.
Aerobic energy expenditure of handicapped children after training.
The effect is reported of a 10-week physical training program, consisting of three sessions with a total duration of two hours weekly, on the physical work capacity and efficiency of physically handicapped children aged 8 to 14 years. The program for the experimental group (n = 6) was an intensification of the usual school physical education activities. The control group (n = 5) received the usual physical education. The intensity of training was measured by heart rate recording. In the experimental group attempts were made to achieve heart rate values higher than 160 beats/min as long as possible. The relationship of oxygen uptake (VO2) to heart rate and to workload was determined before and after the end of the training program by submaximal bicycle ergometer tests. After the training program a significant decrease in VO2 at different workloads was found (delta oxygen uptake/delta workload remained unchanged). No effect of the training program on the relationship of oxygen uptake and heart rate was found. The implication of this study is that the children can perform the same amount of external work after training as before training but with a lower expenditure of aerobic energy. The decrease of the oxygen uptakes for the workloads used could be induced by enhanced coordination of movement.
Science and technology in an institute of public and environmental health.
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Thallium concentrations in body fluids and tissues in a fatal case of thallium poisoning.
A fatal case of thallium poisoning is described in which the thallium concentration was quantitated in plasma and urine during treatment and in tissue samples obtained on postmortem examination. As ileus paralyticus and the onset of renal failure were already manifested on admission of the patient, charcoal hemoperfusion and this technique in combination with hemodialysis were applied which showed to be tenfold more effective than the simultaneous renal elimination. The highest thallium concentration was found in the heart and not in kidneys as reported previously in animal experiments. Evidence is presented that thallium distribution in kidneys is dose dependent.
Bicycle ergometry and speed skating performance.
A comparison between maximal power output during cycling and skating was made, and correlates of skating performance with bicycle performance and skating technique were investigated. Twenty-five well-trained speed skaters performed two bicycle tests and a 500-m and 1500-m ice skating race. The power (P) during skating is calculated from ice and air friction losses: at 500 m P500 = 344 +/- 60 W and at 1500 m P1500 = 283 +/- 65 W. Stroke frequency and pre-extension knee angle as principle determining factors of P were determined. The two bicycle tests (of 30" and 2'30" duration, maximal performance) yield P30C = 875 +/- 86 W and P2.30C = 420 +/- 52 W with VO2max = 4.76 +/- 0.45 l/min. The highest correlate of P500 as well as of P1500 appeared to be P30C, respectively, r = 0.78 and r = 0.85. Correlation coefficients between the power during skating and P2.30C or VO2max have a value of about 0.6. If the stroke frequency and P30C are correlated with the power during skating, then high multiple correlation coefficients are obtained: at 500 m R = 0.85 and at 1500 m R = 0.90. The correlation of P30C suggests that the interindividual differences of skating performance at 500-m and 1500-m distances can be attributed substantially to differences in anaerobic power. Yet, the predictive value of the bicycle test for speed skating performance is low. The difference observed between maximal power output during cycling and skating is discussed.
Urinary excretion of cadmium, protein, beta-2-microglobulin and glucose in individuals living in a cadmium-polluted area.
Urine was collected from 289 inhabitants of a cadmium-polluted quarter of Stadskanaal. The excretion of cadmium, protein, beta-2-microglobulin and glucose were determined. After being divided according to sex and to smoking habits, the results of the inhabitants were compared with those of 293 controls. In inhabitants as well as controls, cadmium excretion was age-dependent. Cadmium excretion in females increased faster with age than in males. In male-smoker controls, cadmium excretion was significantly higher (p less than 0.001) than in male-non-smoker controls. In male-non-smoker inhabitants, cadmium excretion (p = 0.05), protein excretion (p less than 0.01) and glucose excretion (p less than 0.01) were significantly higher than in corresponding controls. In male-smoker inhabitants, protein excretion (p less than 0.01) and glucose excretion (0.01 less than p less than 0.05) were significantly higher than in corresponding controls. In female-non-smoker inhabitants glucose excretion was significantly higher (0.01 less than p less than 0.05) than in corresponding controls. For some categories, living in the polluted area was associated with an increased cadmium excretion in urine and a slight difference in renal function, possibly related to a difference in cadmium body burden. It was concluded that, considering the actual values of each parameter, the observed differences were not relevant in terms of potential health hazards.
Different toxicological profiles for various beta-blocking agents on cardiac function in isolated rat hearts.
Propranolol, timolol and sotalol were compared regarding their cardiotoxic properties in isolated, perfused and catecholamine depleted rat hearts. Catecholamine depletion was performed in order to exclude interference of the drugs with beta-adrenergic receptors. The results demonstrate that both in spontaneously beating and atrial- stimulated hearts propranolol (3 - 30 micrograms/ml) and timolol (30 - 300 micrograms/ml) induced a dose dependent decrease in myocardial contractility, stimulus formation and stimulus conduction. Lacking local anesthetic properties as evidenced by effects on coronary flow and threshold voltage in the heart it can be deduced that the negative inotropic effect and an impaired stimulus conduction due to timolol can neither attributed to beta-adrenoceptor antagonism nor membrane stabilising activity. In addition, both propranolol (5 micrograms/ml) and timolol (200 micrograms/ml) reduced myocardial contractility to the same extent in ventricular-paced hearts. Therefore, a direct myocardial depressive effect rather than an indirect effect due to a reduced heart rate must be responsible for the negative inotropy. The hydrophilic beta-blocker sotalol demonstrated a slight cardiodepressant activity either in the spontaneously beating and atrial-stimulated hearts (30 - 300 micrograms/ml) or ventricular-paced hearts (300 micrograms/ml). It is concluded that the toxicological profile of various beta-blocking drugs might be determined by an yet unknown pharmacological property apart from beta-adrenoceptor blockade or membrane stabilising activity. Furthermore, the degree of lipophilicity of the drug might be an important determinant for the cardiotoxic profile of this class of drugs.
Charcoal hemoperfusion in the treatment of two cases of acute carbamazepine poisoning.
Charcoal hemoperfusion is effective in the treatment of acute carbamazepine (CBZ) poisoning, its efficacy depending on the metabolic capacity of the patient involved. This was assessed in two cases of CBZ poisoning in which CBZ and its metabolite carbamazepine-10,11-epoxide (CBZO) were monitored. One patient had not been treated with CBZ or other enzyme-inducing drugs before the overdose ingestion. The CBZO/CBZ plasma concentration ratio of this patient was 0.15 +/- 0.01 (mean +/- s.d.), indicating a normal metabolic capacity. The average clearance values obtained with the Haemocol were 85 ml/min for CBZ and 81 ml/min for CBZO. The other patient had been on long-term treatment with anticonvulsive drugs before. The CBZO/CBZ ratio was 1.58 +/- 0.16, indicating a high metabolic capacity and, consequently, a high intrinsic clearance. The average clearances obtained with the Adsorba 300 C were 129 ml/min for CBZ and 133 ml/min for CBZO. Saturation of a charcoal column can occur during a four hours treatment, in particular if the plasma CBZO concentration is high. CBZ and CBZO were also monitored in erythrocytes. The erythrocyte/plasma concentration ratios of CBZ were 0.90 +/- 0.11 (mean +/- s.d.) and 1.36 +/- 0.10. CBZO was 30-40 per cent more concentrated in erythrocytes than was CBZ. The erythrocyte/plasma concentration ratios of CBZO were 1.36 +/- 0.10 and 1.80 +/- 0.23.
Some technical, physiological and anthropometrical aspects of speed skating.
Five elite speed skaters and fourteen well trained skaters of a lower performance level performed three maximal tests: a 3,000 m race from which the skating position and the stroke frequency were derived, an oxygen consumption test both during skating and during a bicycle ergometer test. From all subjects anthropometric measures were taken. The elite group showed a VO2 during cycling of 64.4 +/- 3.5 ml . kg-1 . min-1 and 59.4 +/- 3.7 ml . kg-1 . min-1 during skating. The elite skaters showed: a shorter upper leg length with respect to total leg length, higher aerobic power during cycling, higher stroke frequency, smaller pre-extension knee angle coupled to higher work per stroke, higher "efficiency" during skating and higher external power during skating and during cycling when compared with the group of lower performance level. It is concluded that an important pre-requisite for speed skating appears to be the possibility to skate at a small pre-extension knee angle without an excessive claim to anaerobic metabolism.
Differences in oxygen consumption and external power between male and female speed skaters during supramaximal cycling.
Differences in performance levels between elite male and female endurance athletes are often explained by differences found in VO2 max even when expressed in VO2 max per kilogram lean body mass (VO2/LBM). Such an explanation is only a matter of course when less or no difference exists in mechanical efficiency, anaerobic power and technical variables like friction constants between males and females. Particularly during supramaximal exercises. In this study five elite male speed skaters were compared with five elite female speed skaters with respect to oxygen consumption and external power during a 3 min supramaximal bicycle ergometer test. The training background and training history of both groups were comparable. Although the elite males showed a 20% higher VO2/BW and 8% higher VO2/LBM (71.0 versus 65.01 x min-1 . kg-1) than the females, the female group showed the same mean external power Pc per kilogram body weight, and a surprising 12% higher Pc/LBM than the males (6.47 versus 5.79 W x kg-1). Hence the female group delivered 22% more external power per liter of oxygen consumption. With the help of additional data from 14 male and 11 female sub-elite skaters it is shown that the differences between the elite groups are mainly due to sex differences. In the light of differences between men and women reported in other studies, it seems likely that the differences found in this study are due to a difference in mechanical efficiency which particularly occurs in supramaximal tasks.(ABSTRACT TRUNCATED AT 250 WORDS)