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Biomedical subjects

E Groen

Publications and source records attributed to E Groen.

10 recordsLinked to original sources

A comparison of the pharmacokinetics and tolerability of riluzole after repeat dose administration in healthy elderly and young volunteers.

The pharmacokinetics and tolerability of the novel antiexcitatory agent, riluzole, were compared in 18 healthy elderly and 18 healthy gender- and weight-matched young volunteers. All participants received riluzole 50 mg twice daily (the recommended dosage for patients with amyotrophic lateral sclerosis), administered orally for 5 days. The pharmacokinetics of riluzole, determined on the morning of the 5th day of dosing, were not significantly affected by age or gender. The mean terminal elimination half-life (t1/2), however, was statistically significant between elderly and young subjects. Riluzole was well tolerated upon repeat dose administration. Headache was the most frequent adverse event reported, and there was no overt difference in the type, frequency, or severity of adverse events between elderly and young volunteers or between genders. In conclusion, these results indicate that no dosage adjustments of riluzole are required in the elderly.

Adolescent↗

Contribution of the otoliths to the human torsional vestibulo-ocular reflex.

The dynamic contribution of the otolith organs to the human ocular torsion response was examined during passive sinusoidal body roll about an earth-horizontal axis (varying otolith inputs) and about an earth-vertical axis (invariant otolith inputs). Torsional eye movements were registered in 5 subjects by means of video-oculography. At a fixed amplitude of 25 degrees, the stimulus frequency was varied from 0.05 to 0.4 Hz. Additionally, at a fixed frequency of 0.2 Hz, the response was also measured at the amplitudes to 12.5 degrees and 50 degrees. The results showed that the gain and phase of the torsional slow component velocity (SCV) did not depend on stimulus amplitude, indicating a linear response. Contribution of the otoliths affected the ocular torsion response in three different ways. First, the gain of the SCV was slightly, but consistently, higher during rotation about an earth-horizontal axis than during rotation about an earth-vertical axis. With invariant otolith inputs the average gain increased from 0.10 at 0.05 Hz to 0.26 at 0.25 Hz. With varying otolith inputs, the average gain increased from 0.14 to 0.37. Second and more substantially, contribution of the otoliths improved the response dynamics by reducing the phase lead at frequencies up to 0.02 Hz. Third, the nystagmus showed considerably less anticompensatory saccades in upright conditions than in supine conditions, even though the SCV gain was lower in the latter. As a consequence, the average excursion of torsional eye position was highest during earth-horizontal rotation. This effect was observed in the entire frequency range. Thus, the otoliths controlled the human torsional VOR not only at low stimulus frequencies by keeping the slow component in phase with head motion, but also in a wider frequency range by modulating the saccadic behavior as to increase the amplitude of ocular torsion. We conclude that the primary concern of the otolith-oculomotor system during head tilt is to stabilize eye position in space, rather than to prevent retinal blur.

Adult↗

Motion sickness: only one provocative conflict?

In reviewing the various forms of motion sickness, the classic sensory rearrangement theory has been redefined by demonstrating that only one type of conflict is necessary and sufficient to explain all different kinds of motion sickness. A mathematical description is provided from the summarizing statement that "All situations which provoke motion sickness are characterised by a condition in which the sensed vertical as determined on the basis of integrated information from the eyes, the vestibular system and the nonvestibular proprioceptors is at variance with the subjective vertical as expected from previous experience."

Computer Simulation↗

Cervically induced ocular torsion: physiological and clinical aspects.

Ocular torsion was measured in five subjects during sinusoidal lateral tilt (amplitude 25 degrees, 0.2 Hz). The cervical contribution to ocular torsion was best visible as the difference between the signals obtained in conditions with only head tilt and conditions with whole body tilt. Contribution of the neck did not affect the slow component, but produced an anticompensatory modulation of the beating field offset by means of saccades (analogous to gaze shift). Static tilt conditions (25 degrees tilt) of the trunk only, the head only or the whole body showed similar data, although of smaller amplitude. The results from patients suffering from post-whiplash syndrome were similar to those of healthy subjects, showing large intersubject variability. The reduced tolerance to head tilt of whiplash patients restricts useful implementation of this sort of test in the clinic.

Adult↗

A sustained hyper-g load as a tool to simulate space sickness.

In April 1989 the three European scientist astronauts of the D1 Spacelab Mission were exposed to a 1.5 hours +3G centrifuge run in supine position, resulting in a linear acceleration along the subjects' x-axis. Afterwards, severe motion sickness symptoms were provoked by head movements (Sickness Induced by Centrifugation: SIC). The astronauts mentioned close similarities with what they experienced in space during the D1-Spacelab Mission in 1985, where head movements also provoked motion sickness symptoms (Space Adaptation Syndrome: SAS). Moreover, the astronauts agreed that the rank order of their susceptibility to SAS was the same as for SIC. It was therefore postulated that with this method SAS could be simulated on earth. Additionally, in otolith function tests following the centrifuge run, changes in visual-vestibular interaction were observed, which replicated objective findings obtained with the same astronauts immediately after the D1 Spacelab Mission. During the last couple of years a series of experiments has been carried out to determine the nature of the stimulus causing SIC, the incidence of SIC, and the underlying cardio-vascular and/or vestibular mechanisms. These experiments were carried out on several astronauts and some 50 'normal' healthy subjects. In the next sections the main findings of all these experiments and the implications are summarized.

Acceleration↗

Ocular torsion before and after 1 hour centrifugation.

To assess a possible otolith contribution to effects observed following prolonged exposure to hypergravity, we used video oculography to measure ocular torsion during static and dynamic conditions of lateral body tilt (roll) before and after 1 h of centrifugation with a Gx-load of 3 G. Static tilt (from 0 to 57 degrees to either side) showed a 10% decrease in otolith-induced ocular torsion after centrifugation. This implies a reduced gain of the otolith function. The dynamic condition consisted of sinusoidal body roll (frequency 0.25 Hz, amplitude 45 degrees) about an earth horizontal and about an earth vertical axis (respectively, "with" and "without" otolith stimulation). Before centrifugation the gain of the slow component velocity (SCV) was significantly lower "with" otolith stimulation than "without" otolith stimulation. Apparently, the contribution of the otoliths counteracts the ocular torsion response generated by the semicircular canals. Therefore, the observed increase in SCV gain in the condition "with" otolith stimulation after centrifugation, seems in correspondence with the decreased otolith gain in the static condition.

Adult↗

Saccular impact on ocular torsion.

When someone is tilted laterally, the shear force on the maculae of the utriculus and the sacculus is described by the sine and the cosine of the angle of tilt, respectively. So both the sacculus and the utriculus are stimulated, but in the literature, ocular torsion is normally attributed to utricular function alone (and, thus, seen as a response to y-axis linear acceleration). However, on the base of a series of experiments on a tilt chair, a linear track, human centrifuges, and during parabolic flights, we conclude that the sacculus contributes to ocular torsion as well (there is a response to z-axis linear acceleration). The data suggest that the ratio of the utricular and saccular impact on ocular torsion is 3:1. The utriculus generates conjugate and the sacculus disjunctive torsional eye movements.

Adult↗

Determination of ocular torsion by means of automatic pattern recognition.

A new, automatic method for determination of human ocular torsion (OT) was developed based on the tracking of iris patterns in digitized video images. Instead of quantifying OT by means of cross-correlation of circular iris samples, a procedure commonly applied, this new method automatically selects and recovers a set of 36 significant patterns in the iris by the technique of template matching as described by In den Haak et al. Each relocated landmark results in a single estimate of the torsion angle. A robust algorithm estimates OT from this total set of individually determined torsion angles, thereby largely correcting for errors which may arise due to misjudgement of the rotation center. The new method reproduced OT in a prepared set of images of an artificial eye with an accuracy of 0.1 degree. In a sample of 256 images of human eyes, a practical reliability of 0.25 degrees was achieved. To illustrate the method's usefulness, an experiment is described in which ocular torsion was measured during two dynamic conditions of whole-body roll, namely during sinusoidally pendular motion about either an earth horizontal or earth vertical axis (that is "with" and "without" otolith stimulation, respectively).

Algorithms↗