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Biomedical subjects

J van der Steen

Publications and source records attributed to J van der Steen.

6 recordsLinked to original sources

Foveation dynamics in congenital nystagmus. I: Fixation.

Congenital nystagmus (CN) has been described as a 'fixation' nystagmus implying an inability to fixate a target. However, each cycle of CN contains a target-foveation period during which the eye velocity is at, or near, zero. Prolongation of foveation time, reduction of retinal image velocity and cycle-to-cycle foveation repeatability all contribute to increased visual acuity. We developed several methods to accurately measure the dynamics of foveation in CN; their use is illustrated on an individual with typical idiopathic CN and no afferent defects. During eight 5-second intervals of fixation on a stationary target, the horizontal standard deviation (SD) of the mean foveation position (FPOS) was 12.82 minarc and the SD of foveation velocity was 118.36 minarc/sec. The SD of the means of total eye position and of the non-foveating peak of the CN were 43.17 and 25.32 minarc respectively. The mean foveation-time interval (eye velocity less than or equal to 4 degrees/sec) was 57.27 msec. The SD FPOS for the best 1-second interval (4 successive CN cycles), in a typical 5-second record, was 0.71 minarc. Histograms revealed peaks of eye position at 0 +/- 10 minarc and of eye velocity at 0 +/- 240 minarc/sec. The small vertical component of the CN (16 minarc peak-to-peak) had a SD of 6.56 minarc. A nystagmus foveation function related to visual acuity was derived that was more sensitive than CN intensity. The increased visual acuity resulting from the use of convergence or base-out prisms was due to increased foveation time. Although it might appear that CN is a defect of fixation, this individual with CN had strong fixation reflexes in the sense that he was able to accurately (within 1 minarc) achieve (interbeat) and maintain (intrabeat) target foveation for appreciable periods of time. Our data support the hypothesis that individuals with idiopathic CN do not have a primary disturbance of fixation.

Fixation, Ocular

Foveation dynamics in congenital nystagmus. II: Smooth pursuit.

It has been shown that, during 5 seconds of fixation, an individual with congenital nystagmus (CN) can repeatedly (beat-to-beat) foveate (SD = 12.87 minarc) and maintain low retinal slip velocities (SD = 118.36 minarc/sec). Smooth pursuit data from several CN subjects showed that eye velocities during these foveation intervals approximated target velocity. Despite some claims that CN is caused by absent or "reversed" smooth pursuit, those with CN hardly ever experience oscillopsia or exhibit any accompanying symptoms of such deficits in pursuit; they are able to master sports requiring tracking of rapidly moving small objects (e.g. racquetball or handball). We developed and describe several new methods to accurately assess the function of smooth pursuit in an individual with typical idiopathic CN. We investigated the dynamics of CN foveation periods during smooth pursuit to test the hypothesis that eye velocities would match target velocities during these periods. Unity or near-unity instantaneous (beat-to-beat) pursuit gains of both experimenter-moved and subject-moved targets at peak velocities ranging from only a few deg/sec up to 210 degrees/sec were measured. The dynamic neutral zone was found to shift oppositely to target direction by amounts proportional to the increase in target speed. Our methods proved that eye velocity is made to match target velocity during the foveation intervals and support the conclusion that smooth pursuit in individuals with CN is functioning normally in the presence of the CN oscillation. In addition, we hypothesize that the same fixation mechanism that prevents oscillopsia during fixation of stationary targets, also does so during pursuit.

Fovea Centralis

Foveation dynamics in congenital nystagmus. III: Vestibulo-ocular reflex.

It has been shown that, during fixation of a stationary target with a fixed head, an individual with congenital nystagmus (CN) can repeatedly (beat-to-beat) foveate (within 13 minarc) and maintain low retinal slip velocities (less than 4 degrees/sec). With the head in motion, vestibuloocular reflex (VOR) data showed eye velocities during these foveation periods that approximation head velocity. Despite some claims that the VOR of CN subjects was deficient or absent, individuals with CN hardly ever complain of oscillopsia or exhibit any of the symptoms that would accompany such deficits in the VOR, whether during simple walking and running or while skiing down a mogul field. We developed and describe several different and unrelated methods to accurately assess the function of the VOR in an individual with typical idiopathic CN. We investigated the dynamics of CN foveation periods during head rotation to test the hypothesis that eye velocities would match head velocities during these periods. At about 1 Hz, horizontal VOR instantaneous (beat-to-beat) gains were 0.96 in the light and 0.94 in the dark while imaging a stationary target. Vertical VOR gains were 1.00 and 0.99 for these two conditions at the same frequency; the CN was horizontal. Also, during the VOR there is a CN neutral-zone shift comparable to that found during smooth pursuit. Our methods demonstrated that gaze velocity was held constant during foveation periods and we conclude that the VOR in this subject is functioning normally in the presence of the CN oscillation. Based on our findings in this and previous studies, we hypothesize that CN may be due to a peripheral instability.

Fovea Centralis

Visually induced cycloversion and cyclovergence.

Binocular cyclorotatory (torsional) eye movements in response to visual patterns, which oscillated sinusoidally in the frontal plane, were recorded with scleral induction coils in human subjects. Conjugate cycloversion and disjunctive cyclovergence were directly compared by in-phase and out-of-phase oscillation of the same pattern. Stimulus motion had a frequency of 0.2 Hz and amplitudes of 2-8 deg. Both response types had a similar and low gain (about 0.2 averaged over all subjects). Cycloversion showed no time lag, while cyclovergence lagged by about 600 msec. Non-fusible patterns were effective in eliciting cycloversion, but not cyclovergence. Apart from this, the nature of the pattern (randomly distributed dots, regular rows of dots, horizontal or vertical grating, Julesz stereogram or images with a pictorial significance) had only the slightest effect on the magnitude of the responses.

Adult

Injections of beta-noradrenergic substances in the flocculus of rabbits affect adaptation of the VOR gain.

Noradrenaline (NA) has been implicated as a neuromodulator in plasticity, presumably facilitating adaptive processes. Recent experiments by others have suggested a modulatory role of NA in adaptive changes in the vestibulo-ocular reflex (VOR). These experiments showed that general depletion of brain NA resulted in a decreased ability to produce adaptive changes in the VOR gain. In order to identify the specific brain region responsible for these effects, as well as the nature of the adrenoceptors involved, we injected beta-adrenergic substances bilaterally into the flocculus of rabbits. The flocculus is known to receive noradrenergic afferents and, moreover, ablation of the flocculus interferes strongly with the normal adaptive changes in the VOR gain. We injected the beta-agonist isoproterenol and the beta-antagonist sotalol, and compared the adaptive capacity of the rabbits after these injections to that in a situation without injection. The rabbit was oscillated in a direction opposite to the direction of motion of the platform on which the rabbit was mounted, a condition which normally results in an increase in the VOR gain, measured either in light or in darkness. Injection of the beta-agonist did not greatly affect the adaptation of the VOR measured in the light. In darkness, the increase in gain after the injection of isoproterenol was larger than in the non-injection experiments in 9 out of 10 rabbits. The beta-antagonist sotalol reduced the adaptation of the VOR gain significantly in the light, as well as in darkness. In a control condition without pressure for adaptation (only intermittent testing of the VOR gain over a period of 2.5 h), the gain of the VOR either remained unaffected or was only slightly affected by similar injections of beta-adrenergic agents in individual rabbits. For the group as a whole, these effects were insignificant. We conclude from these results that noradrenergic systems facilitate the adaptation of the VOR gain to retinal slip in rabbits, without affecting the VOR gain directly. At least part of this influence is exerted through beta-receptors located in the cerebellar flocculus.

Adaptation, Physiological

Two stable Fenton oxidation products of cyclophosphamide (NSC-26271) as precursors of 4-hydroxycyclophosphamide (NSC-196562) under physiologic conditions.

Cytostatic and chemical properties of two cyclophosphamide (CP) 4-peroxides, 4-hydroperoxycyclophosphamide and 4-hydroxycyclophosphamide anhydro-dimer, that were earlier isolated and identified after Fenton oxidation of CP, are summarized and discussed. Their cytostatic toxicities, which are quantitatively comparable to those of the primary metabolite of CP, 4-hydroxycyclophosphamide, are explained from their apparent spontaneous conversion to mono-oxidized forms of CP, both in vitro and in vivo. The conversion is shown to proceed via autocatalyzed reactions, which are thought to imply the occurrence of free radicals during deoxygenation. The point is raised whether any qualitative difference in cytotoxicity might be caused by the action of these free radicals. Current dose-effect studies of residual colony-forming ability after treatment of 3T6 mouse fibroblasts and Yoshida sarcoma cells in suspension culture are introduced. Further studies on the local toxic action of the radicals under in vivo conditions are necessary if the peroxides are to be introduced in local or regional clinical treatments.

Acrolein