Biomedical subjects
Publications and source records attributed to D Straumann.
A series of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives have been obtained and tested as non peptide AII receptor antagonists. Modification of the classical biphenyl moiety to a 4-arylthienyl fragment afforded interesting activities.
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In its original formulation, Listing's law referred only to eye positions during steady fixation. In recent years, however, several studies have suggested that Listing's law can be extended to the movements of the eyes, including during saccades and smooth pursuit. A major problem in deciding whether or not Listing's law is obeyed during eye movements is the influence of any spontaneous fluctuations in torsional eye position. To try to settle this question, the three-dimensional position of the eyes (around the three axes: horizontal, vertical, and torsional) was recorded with dual search coils in five normal subjects during fixations, 20 degrees saccades, blinks, and 20 degrees pursuit movements with a 20 degrees/s stimulus velocity. Eye movements across a wide range of horizontal positions were measured at different elevations of gaze during 11 min. Variability (as reflected in the standard deviation of torsional eye position) was used as a measure of the validity of Listing's law. After linear detrending single trials, each lasting 21.5 s, to remove the effects of drift over minutes, the reduction in the standard deviation of torsional position in tertiary eye positions was 54% assuming a planar and 58% assuming a second-order curved Listing's surface. We attributed this long-term fluctuation of the torsional signal to slippage of the coil on the eye. The remaining variability was mainly due to short-term fluctuation of eye torsion over seconds. The impact of hysteresis, associated with consecutive centrifugal-centripetal horizontal movements, on the variability of torsional eye position appeared negligible. Peak increases in the standard deviation from the fixation baseline after fitting individual Listing's planes for each trial were 348% during blinks, 141% during saccades, and 72% during pursuit movements (median value of five subjects). In conclusion, Listing's law during blinks, saccades, and pursuit is less valid than during fixations, which raises doubts about the existence of an internal "Listing's law operator" for eye movements. Possibly, central eye velocity commands do not comply with Listing's law.
In a patient with traumatic intracerebral lesions, we recorded two subsequent electroencephalograms with burst-suppression activity. Between the two measurements, the clinical condition of the patient deteriorated. The first EEG showed symmetrical interhemispheric asynchrony of bursts. In the second EEG, however, we noted synchrony from one hemisphere to the other, but asynchrony in the opposite direction. We propose a simple model that can explain why one-way asynchrony of burst-suppression activity is prognostically more severe than symmetrical asynchrony.
We demonstrated specific responses from the anterior and the posterior semicircular canal to irrigation of the outer ear canal with cold water in the Rhesus monkey. This required i) three-dimensional analysis of the evoked eye movements in the planes of the semicircular canals (canal plane vectors, CPV); ii) assessing these CPV responses in eight different head positions relative to gravity; iii) comparing the responses in 6 normal animals (12 ears) with responses after selective plugging of pairs of semicircular canals (all, both lateral, and right anterior + left posterior). The results showed: i) Irrigation of the outer ear canal with cold water induces thermoconvection also in the posterior and anterior semicircular canals. This can be inferred from the sinusoidal modulation of eye movement components with changes in position of the corresponding semicircular canal plane relative to gravity; ii) Specific vertical canal responses occur exclusively in the direction of the corresponding semicircular canal, though they are superimposed with response components of other origin, one probably related to endolymph shift in the lateral semicircular canal; iii) before possible clinical application, these different response components of vertical canals will need to be determined in humans.
The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) contains burst neurons whose activity precedes rapid eye movements with a vertical and/or torsional component. To ascertain their causal role in the generation of conjugate eye movements, we placed uni- and bilateral kainic acid lesions in that region. Unilateral inactivation of the riMLF leads to a loss of all rapid eye movements with an ipsitorsional component (ipsitorsional is defined as movement of the upper pole of the ipsilateral eye in a temporal direction). Vertical eye movements are impaired in an asymmetric way, with downward movements slowed and upward movements little affected. Listing's plane is shifted in the contratorsional direction, i.e., we find a constant torsional offset for all eye positions. With bilateral lesions one observes a total loss of all vertical and torsional eye movements, while Listing's plane retains its shape and position. These results show that burst neurons in the riMLF play a decisive role in generating rapid eye movements with a vertical and torsional component.
In five normal subjects, we analyzed uncalled for torsion (blips) during and after horizontal and vertical saccades. Torsion was defined as movement out of Listing's plane. During horizontal saccades in downward gaze the abducting eye extorted and the adducting eye intorted. The direction of the blips reversed in upward gaze. Peak torsional amplitudes (up to 1-2 deg) were always reached during saccades; drifts back to Listing's plane outlasted the saccades. Torsion of the extorting eye was larger than that of the intorting eye, producing a transient positive cyclovergence. Torsion and cyclovergence evoked by vertical saccades were also stereotyped in each eye, but showed idiosyncratic differences among subjects. We conclude that Listing's law is violated during saccades. Transient saccade-evoked torsion might reflect properties of the three-dimensional velocity-to-position integrator and/or the ocular plant.
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In Rhesus monkeys, distinct eye movement response components in the planes of the semicircular canals (canal plane vectors, CPV) were identified by 3-dimensional recordings of caloric nystagmus elicited in different head positions relative to gravity. Surgical plugging of single semicircular canals (SCC) was used to identify the generators of these response components. The lateral CPV is a sinusoidal function of head position, compatible with a thermovective mechanisms in this canal. Surgical plugging of the lateral SCC leaves only a small head position independent, lateral CPV, probably due to direct temperature effects on lateral SCC afferents. The posterior and anterior CPVs are complex responses composed of various components of which the present plugging experiments identified two generators: i) effects of thermovection in the lateral SCC, demonstrated by modifications of posterior and anterior CPVs after occlusion of the lateral SCC; and ii) thermovection in the vertical SCCs, demonstrated by effects of plugging a single vertical SCC exclusively on the corresponding CPV. This is the first definite identification of the vertical SCCs as contributors to the generation of nystagmus induced by caloric irrigation of the outer ear canal. It may provide a basis for the development of a modified caloric test measuring more than only lateral canal function in human patients.
The three-dimensional search coil technique provides a tool to dynamically study the laws on ocular cyclotorsion, which have already been formulated for the static situation, i.e. visual fixations, around 1850. Precise eye movement recordings show that Donders' law and Listing's law can even be violated under physiological conditions, e.g. during saccades. Conversely, experimental lesions of the mesencephalic vertical-torsional pulse generator only lead to small disturbances of Listing's law. Case studies of patients with torsional eye movement disorders indicate that a number of different vestibular and ocular motor pathologies can lead to violations of Listing's law.
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1. Although the eye has three rotational degrees of freedom, eye positions, during fixations, saccades, and smooth pursuit, with the head stationary and upright, are constrained to a plane by Listing's law. We investigated whether Listing's law for rapid eye movements is implemented at the level of the deeper layers of the superior colliculus (SC). 2. In three alert rhesus monkeys we tested whether the saccadic motor map of the SC is two dimensional, representing oculocentric target vectors (the vector or V-model), or three dimensional, representing the coordinates of the rotation of the eye from initial to final position (the quaternion or Q-model). 3. Monkeys made spontaneous saccadic eye movements both in the light and in the dark. They were also rotated about various axes to evoke quick phases of vestibular nystagmus, which have three degrees of freedom. Eye positions were measured in three dimensions with the magnetic search coil technique. 4. While the monkey made spontaneous eye movements, we electrically stimulated the deeper layers of the SC and elicited saccades from a wide range of initial positions. According to the Q-model, the torsional component of eye position after stimulation should be uniquely related to saccade onset position. However, stimulation at 110 sites induced no eye torsion, in line with the prediction of the V-model. 5. Activity of saccade-related burst neurons in the deeper layers of the SC was analyzed during rapid eye movements in three dimensions. No systematic eye-position dependence of the movement fields, as predicted by the Q-model, could be detected for these cells. Instead, the data fitted closely the predictions made by the V-model. 6. In two monkeys, both SC were reversibly inactivated by symmetrical bilateral injections of muscimol. The frequency of spontaneous saccades in the light decreased dramatically. Although the remaining spontaneous saccades were slow, Listing's law was still obeyed, both during fixations and saccadic gaze shifts. In the dark, vestibularly elicited fast phases of nystagmus could still be generated in three dimensions. Although the fastest quick phases of horizontal and vertical nystagmus were slower by about a factor of 1.5, those of torsional quick phases were unaffected. 7. On the basis of the electrical stimulation data and the properties revealed by the movement field analysis, we conclude that the collicular motor map is two dimensional. The reversible inactivation results suggest that the SC is not the site where three-dimensional fast phases of vestibular nystagmus are generated.(ABSTRACT TRUNCATED AT 400 WORDS)
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Juvenile rhesus monkeys, placed on a motorized turntable, were rotated at constant velocity and then decelerated about an Earth-vertical axis. The animals were implanted with dual search coils to measure eye movements in three dimensions. By changing the monkey's body position (upright, ear-down, supine), postrotatory nystagmus was elicited in the horizontal, vertical, or torsional direction. Peak slow phase eye velocity and time constant of velocity decay were compared between decelerations in the dark and in the light. In all nystagmus directions, illumination reduced the time constant (Tc) to values around 5 sec. Peak velocity (Vp) was markedly attenuated in the horizontal and vertical directions (around 50%), but the effect of light on Vp in the torsional direction was small (less than 20%). These findings were independent of the velocity step size. Our hypothesis is that the two dynamic components of optokinetic nystagmus, as they interact with postrotatory nystagmus during visual suppression, differ in their dimensionality: the early component (fast component, direct pathway, pursuit system) is mainly activated in the horizontal and vertical directions, while the late component (slow component, indirect pathway, optokinetic system) effectively operates in all three dimensions.
A procedure is described to calibrate three-dimensional eye position with a dual-search coil implant in rhesus monkeys using a two-field magnetic system. The method allows one to determine the sensitivity of the search coils taking into account the presence of d.c. offset voltages. The orientation of the implant on the eye relative to a space-fixed reference frame is computed using fixations of targets arranged vertically. The critical steps of the procedure are discussed and documented by experimental data.
In three rhesus monkeys three-dimensional eye positions were measured with the dual search coil technique. Recordings of spontaneous eye movements were made in the light and in the dark, with the monkeys in different static roll or pitch positions. Eye positions were expressed as rotation vectors. In all static positions eye rotation vectors were confined to a plane, i.e. Listing's plane was conserved. Tilt about the roll axis shifted the plane along this axis, i.e. a constant torsional component was added to all eye positions. Tilt about the pitch axis changed the pitch angle of Listing's plane.
The aim of this study was to investigate whether caloric nystagmus contains response components that can be attributed to a stimulation of the vertical semicircular canals. Three dimensional eye movement recordings with a dual search coil technique revealed important horizontal, vertical and torsional nystagmus components following irrigation of the external ear canal with cold water in various head positions relative to gravity. Horizontal nystagmus components, i.e. lateral semicircular canal vectors, followed a cosine function of both the pitch and yaw angle of the head relative to gravity, confirming a mainly thermovective mechanism for stimulation of the horizontal canals. Vertical and torsional nystagmus components behaved differently following left and right ear irrigations. Right-left symmetrical vectors emerged only when the vertical and torsional components were transposed into vectors of single semicircular canal directions. The intensity of these vertical semicircular canal vectors as a function of the position of the corresponding canal relative to gravity, however, excludes important thermovective mechanisms acting at the vertical canals. It remains an open question whether these vertical canal vectors represent a non-thermovective caloric stimulation of vertical canal afferents.