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Biomedical subjects

A H Clarke

Publications and source records attributed to A H Clarke.

At least 37 records · Page 2Linked to original sources
PubMed1998

Otolith and semicircular canal contributions to the human binocular response to roll oscillation.

Three normal human subjects were oscillated about their naso-occipital axis in a supine position at 0.4 Hz and 0.1 Hz, both in darkness and in the light with a structured fixation target. The same subjects were oscillated in roll about an upright position, at the same frequencies, in darkness; and also about axes directed 20 degrees and 40 degrees to the left and to the right of the midsagittal plane, at 0.4 Hz, in darkness. Three-dimensional binocular eye movements were recorded using video-oculography. All stimuli induced a predominantly torsional nystagmus with small disconjugate head-vertical (skew) and conjugate head-horizontal components. For roll oscillation, the torsional slow phase velocity gain was higher in the light and generally increased with the stimulation frequency. In darkness, only one subject had significantly higher torsional gains in the upright compared to the supine position (12% difference), suggesting that the otolith contribution to the roll response is minimal at the frequencies tested. The slow phase velocity gain of the skew increased with fixation in two subjects. but decreased in the third subject; these changes were related to changes in eye vergence. In the upright position, with oblique axes of rotation, the head-vertical eye movements were asymmetrical, with the outermost eye executing a larger amplitude movement. The disconjugate head-vertical eye movements observed can be explained by the pattern of vertical semicircular canal stimulation and their connections to the extraocular muscles. In humans, skewing of the eyes may compensate for the eccentricity of the foveae which lie in the temporal retina and undergo vertical translations in opposite directions when the eyes tort.

Adult↗
PubMed1997

On the origin of interindividual susceptibility to motion sickness.

According to the otolith asymmetry hypothesis for susceptibility to motion sickness, the interlabyrinthine asymmetry in the otoconial mass, which is normally compensated in the circuity of the vestibular system by appropriate neuronal weighting, becomes disrupted as a result of unfamiliar movement patterns or force environments. Measurements in various species have demonstrated a large scatter in the otoconial mass. As the utricle and saccule have distinct functions in the vestibular system it seems appropriate to deal with these organs separately. Results are presented on mass distribution and lateral preponderance of the otoconial mass in the utricles and saccules of the salmon (Salmo salar) and trout (Salmo irideus). The measurements revealed considerably larger dimensions of the saccular otoconia in these species, amounting to twenty-fold. This substantial difference indicates that different regulatory principles underlie the otoconial generation of each of the organs and is presumably related to their specific functions. The lateral preponderance was found to be normally distributed for both organs in both species, with standard deviations of approx. 4% except for the utricular otoconia of the salmon (13%). In a second set of experiments, fish were exposed to a Coriolis force environment. Their sealed aquarium was subjected to constant vertical axis rotation combined with pendular oscillation around the horizontal axis. The aquarium was illuminated by a light source fixed to project through the top, and a video camera recorded the movements of the fish. During combined rotation and pendular oscillation, one group of fish maintained an active compensatory swimming behaviour, whereas the movements of a second group became uncoordinated and often led to passive behaviour. Analysis of the otoconia of these two groups of fish promises to yield further evidence relevant to the otolith asymmetry hypothesis.

Animals↗
PubMed1996

The dynamic contributions of the otolith organs to human ocular torsion.

We measured human ocular torsion (OT) monocularly (using video) and binocularly (using search coils) while sinusoidally accelerating (0.7 g) five human subjects along an earth-horizontal axis at five frequencies (0.35, 0.4, 0.5, 0.75, and 1.0 Hz). The compensatory nature of OT was investigated by changing the relative orientation of the dynamic (linear acceleration) and static (gravitational) cues. Four subject orientations were investigated: (1) Y-upright-acceleration along the interaural (y) axis while upright; (2) Y-supine-acceleration along the y-axis while supine; (3) Z-RED-acceleration along the dorsoventral (z) axis with right ear down; (4) Z-supine-acceleration along the z-axis while supine. Linear acceleration in the Y-upright, Y-supine and Z-RED orientations elicited conjugate OT. The smaller response in the Z-supine orientation appeared disconjugate. The amplitude of the response decreased and the phase lag increased with increasing frequency for each orientation. This frequency dependence does not match the frequency response of the regular or irregular afferent otolith neurons; therefore the response dynamics cannot be explained by simple peripheral mechanisms. The Y-upright responses were larger than the Y-supine responses (P < 0.05). This difference indicates that OT must be more complicated than a simple low-pass filtered response to interaural shear force, since the dynamic shear force along the interaural axis was identical in these two orientations. The Y-supine responses were, in turn, larger than the Z-RED responses (P < 0.01). Interestingly, the vector sum of the Y-supine responses plus Z-RED responses was not significantly different (P = 0.99) from the Y-upright responses. This suggests that, in this frequency range, the conjugate OT response during Y-upright stimulation might be composed of two components: (1) a response to shear force along the y-axis (as in Y-supine stimulation), and (2) a response to roll tilt of gravitoinertial force (as in Z-RED stimulation).

Acceleration↗
PubMed1996

Immunologic responses following respiratory sensitization to house dust mite allergens in mice.

Allergens from the house dust mite Dermatophagoides pteronyssinus are a major cause of human respiratory diseases, including asthma. In order to help in understanding the early events in allergen sensitization, a murine model of allergic respiratory disease was developed. Mice were immunized by intranasal inoculation of Der p 1 or Der p 2 on days 0, 3, 7, 10, 14, 17, 21 and 29. T cell reactivity was determined using in vitro assays of allergen-specific cytokine production by cells from the spleen, the draining superficial cervical lymph nodes (SCLN) and the non-draining brachial and inguinal nodes. The cytokines assayed in supernatants were IL-4, as a measure of Th2 activation, IL-2 as a measure of Th 1 activation, and IL-3/GM-CSF as an overall marker of T cell stimulation. There was evidence of local and systemic T cell activation by day 7, with the release of IL-2 and of IL-3/GM-CSF by SCLN and spleen cells, respectively. IL-4 production by SCLN and spleen cells was not evident until day 21. T cell sensitization in non-draining node groups was not detected. Intradermal skin tests were performed at the above specified times and positive wheal responses indicated that specific IgE was present from day 3. The above data suggest that respiratory immunization to allergen is rapid and is associated with early systemic sensitization. In this model both Th1 and Th2 responses were evident, with the Th1 response occurring early and the Th2 following after repeated immunizations.

Allergens↗
PubMed1996

Ranitidine in a twice daily triple-therapy regimen for the eradication of Helicobacter pylori.

OBJECTIVE: To compare the efficacy and safety of ranitidine 300 mg twice daily plus amoxycillin 1000 mg twice daily for 2 weeks (RA2) with ranitidine 300 mg twice daily, amoxycillin 1000 mg twice daily, plus tinidazole 500 mg twice daily for 2 weeks (RAT2) for the eradication of Helicobacter pylori. DESIGN: Prospective, randomized, double-blind, parallel-group study in patients who were H. pylori positive on 13C urea breath test (13C UBT). SETTING: Twenty-four UK consultant gastroenterologists entered mostly hospital out-patients. PATIENTS: A total of 232 patients with gastric or duodenal ulceration or endoscopic appearances suggestive of gastritis (160 male, 72 female, mean age 51) were entered following routine endoscopy; 223 were H. pylori positive on 13C UBT. Patients with medical conditions or medications which could interfere with study response or measurements and those at risk of pregnancy were excluded. Two hundred and three patients completed the study. INTERVENTIONS: Patients underwent endoscopy with biopsy for rapid urease (CLO) test. Those who were positive had a 13C UBT. Patients were randomized to receive RA2 or RAT2. Eradication of H. pylori was assessed by 13C UBT 4 weeks after completion of therapy. Blood was taken for haematological and biochemical screening at the beginning and end of treatment. MAIN OUTCOME MEASURE: H. pylori eradication at least 28 days after end of treatment. RESULTS: In the intention-to-treat sample analysis, H. pylori was eradicated in 78/115 patients (68%) taking RAT2 and 42/108 patients (39%) taking RA2. In the per-protocol sample analysis H. pylori eradication was successful in 68/79 patients (86%) taking RAT2 and 36/71 patients (51%) taking RA2. One hundred and seventeen patients experienced 242 adverse events. CONCLUSION: Twice daily ranitidine triple therapy is a useful H. pylori eradication regimen.

Amoxicillin↗
PubMed1996

Ocular counterrolling in response to asymmetric radial acceleration.

The fact that the labyrinths are positioned at approx. 3.5 cm from the head-centric axis leads to the generation of systematic radial acceleratory, or centrifugal, forces during physiological head rotations. Under physiological conditions, the forces exerted on the right and left maculae are generally assumed to be equal and opposite. In the present test, however, the subject was displaced eccentrically during constant angular velocity so that one labyrinth was aligned concentrically with the rotatory axis, whilst the other was exposed to the radial acceleration component generated by the chair rotation. In comparison with previous testing based on subjective setting of the visual vertical, three-dimensional eye movements were recorded in order to obtain an objective measure of the otolith-ocular response mechanisms in the brainstem. The results obtained from normal subjects demonstrate a predominant ocular counterroll (OCR) response to this asymmetric, or unilateral application of linear acceleration. The direction of the OCR response proved to be independent of direction of rotation. The findings demonstrate a symmetrical response magnitude for stimulation of the left and right maculae. In comparison with the OCR response to head-tilt, which can be described as critically damped, the time course of the present response appeared to be underdamped.

Acceleration↗
PubMed1995

Imaginary gaze effects on eye movements induced by linear acceleration: involvement of vestibular induced smooth pursuit eye movement.

We investigated smooth eye movements elicited i) by linear acceleration in a space-fixed imaginary gaze condition (smooth component of eye movement induced by linear motion: LSEM) and ii) during acoustic pursuit of a moving sound source (smooth component of eye movement induced by acoustic pursuit of a sound source: SSPEM). The two conditions were examined using the same test subjects. LSEM and SSPEM performance was found to be positively correlated across the subject population. From the comparison of LSEM and SSPEM we propose the following hypothesis: LSEM consists not only of a pure translational vestibular-ocular reflex (tVOR) component but also of a component based on the perception of otolithic information. Accordingly, this second component is instrumental in the pursuit of an imaginary visual target during linear self-motion.

Acceleration↗
PubMed1993

Vestibulo-oculomotor testing during the course of a spaceflight mission.

The experimental concept and findings from a recent manned orbital spaceflight are presented. In a single-case, longitudinal study, vestibulo-oculomotor function was examined by caloric testing and active head oscillations. The results from preflight, inflight, and postflight measurements of the human vestibulo-ocular reflex, together with those of ongoing terrestrial studies, should enable separation of the canalicular and otolithic contributions to ocular torsion. This analysis enables an accurate evaluation of the adaptation of the otolithic system to the inflight microgravity and, after landing, to the 1-g force environment. Video-oculography was employed throughout for the comprehensive measurement of eye and head movements. Caloric testing involved air insufflation at 15 degrees C over 90 s, followed by an observation interval of 2 min. During inflight testing this was continued with a 30-s free-floating interval. Active head oscillations were performed at four discrete frequencies (0.12, 0.32, 0.80, 2.0 Hz) and over a frequency sweep between 0.1 and 2.0 Hz. These head oscillations were performed in yaw, pitch, and roll and for three visual conditions (head-fixed target, space-fixed target, no target). The concomitant stimulation of the semicircular canals and otolithic receptors during these oscillations should yield different oculomotor responses under 1-g and 0-g adaptations. Both the short-form caloric test and the active head movement test were performed on 4 of the 5 available mission days. The results of the caloric tests yield a caloric nystagmus intensity (slow-phase velocity) of approximately 60% of that measured before flight and indicate an adaptation in response over the 10-day period after landing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Dynamic analysis of ocular torsion in parabolic flight using video-oculography.

Dynamic ocular torsion was investigated in a group of healthy subjects during the course of parabolic flight by means of our video-based eye movement recording method-video-oculography. This technique enables a non-invasive dynamic measurement of all three dimensions of eye movement in a harsh experimental environment such as parabolic flight. The test subjects were positioned so that the changing resultant gravito-inertial field in the aircraft was aligned with their interaural (y) axis, primarily stimulating the utricular organs. The analysis of the torsional component of eye movement during the change of gravity between 1.8-0 and 0-1.8 g demonstrated a static component--well known as the ocular counter roll--and a dynamic component, which leads to a slight overshoot in the torsional response. These static and dynamic component of ocular torsion correlate with previous neurophysiological findings.

Acceleration↗
PubMed1993

Three-dimensional aspects of caloric nystagmus in humans: I. The influence of increased gravitoinertial force.

The influence of increased gravitoinertial force on the horizontal vertical and torsional components of caloric nystagmus response was examined. Video-oculographic (VOG) recordings were made on a group of 10 human subjects so that all three components of eye movement could be evaluated. The caloric nystagmus response at all tested g-levels included nystagmus components around all three rotation axes. Over the tested range of 1.0 g to 3.0 g, the results demonstrate that nystagmus intensity does not increase linearly with effective gravitoinertial force but appears to saturate at levels of 2.0 g and beyond. It is proposed that the vertical and torsional nystagmus components were elicited both by caloric stimulation to the (anterior) vertical canals and direct thermal mediation to the otolithic sensory cells. Vertical LZ-nystagmus response was also observed during centrifuge runs (previous to caloric irrigation) at all g-levels and in all subjects. The caloric-induced vertical nystagmus response was also clearly recognisable. The observation of a reduction and inversion of nystagmus intensity during g-transitions agrees with earlier findings and is attributable to the stimulation to the canals during centrifuge acceleration, respectively deceleration.

Caloric Tests↗
PubMed1993

Three-dimensional aspects of caloric nystagmus in humans: II. Caloric-induced torsional deviation.

The oculomotor response to caloric stimulation was recorded using video-oculography (VOG), yielding measures of eye rotation about all three orthogonal axes. During an ongoing caloric nystagmus response, a slow torsional deviation of the eye in the direction of the slow phase of the torsional component of nystagmus was observed. The effect appeared to be systematically influenced by the gravitoinertial force employed during a centrifuge study (see Part I, this issue), and was observed in all tested subjects. Furthermore, in subsequent laboratory tests warm and cold irrigations elicited opposite responses, as did stimulation to right and left ears. Testing in the supine and prone positions, however, did not lead to a reversal of direction, as is the case with the horizontal, vertical and torsional nystagmus components as such. The rate of torsional deviation was of the order of 0.05 degrees/s, well below the physiological transduction range of the cupular organs. Testing with a torsional optokinetic stimulus produced only the expected OK nystagmus without any slow deviation. This would argue against a central vestibular integratory, or oculomotor origin for the phenomenon. It is proposed that this caloric-induced, torsional deviation is of peripheral otolithic origin, most likely elicited by way of direct thermal stimulation to the hair cells of the utricular maculae.

Caloric Tests↗
PubMed1993

Evaluation of the torsional VOR in weightlessness.

The experimental concept and findings from a recent manned orbital spaceflight are described. Together with ongoing terrestrial and parabolic studies, the present experiment is intended to further our knowledge of the sensory integrative processing of information from the semicircular canals and the otolithic receptors, and to quantify the presumed otolithic adaptation to altered gravito-inertial force environments in a more reliable manner than to date. The experiment included measurement of the basic vestibulo-oculomotor response during active head rotation about each of the three orthogonal axes. Priority was given to the recording of ocular torsion, as elicited by head oscillation about the roll axis, and thus due to the concomitant stimulation of the semicircular canals and otolith receptors. Videooculography was employed for the measurement of eye movements; head movement was measured by three orthogonally arranged angular rate sensors and a triaxial linear accelerometer device. All signals were recorded synchronously on a video/data recorder. Preliminary results indicate alterations in the torsional VOR under zero-g conditions, suggesting an adaptive modification of the torsional VOR gain over the course of the 6-day orbital flight. In addition, the inflight test findings yielded discrepancies between intended and performed head movement, indicating impairment in sensorimotor coordination under prolonged microgravity conditions.

Aerospace Medicine↗
PubMed1992

Telescience testbed: operational support functions for biomedical experiments.

A telescience testbed was conducted to study the methodology of space biomedicine with simulated constraints imposed on space experiments. An experimental subject selected for this testbedding was an elaborate surgery of animals and electrophysiological measurements conducted by an operator onboard. The standing potential in the ampulla of the pigeon's semicircular canal was measured during gravitational and caloric stimulation. A principal investigator, isolated from the operation site, participated in the experiment interactively by telecommunication links. Reliability analysis was applied to the whole layers of experimentation, including design of experimental objectives and operational procedures. Engineering and technological aspects of telescience are discussed in terms of reliability to assure quality of science. Feasibility of robotics was examined for supportive functions to reduce the workload of the onboard operator.

Aerospace Medicine↗
PubMed1991

A compact equipment package for vestibular experiments during spaceflight.

A compact measurement and stimulus equipment package for vestibular testing is described. The package is designed on a modular concept so that a customised version can be assembled for each experimental situation. Although primarily conceived for space-related research, the equipment has also been introduced successfully into the clinical diagnostic procedure. An essential function of the equipment is the recording and evaluation of eye movements. This is performed by a video-based measurement system which permits evaluation of horizontal, vertical and torsional components of eye movement. Objective testing of the vestibulo-ocular reflex in all three orthogonal planes is therefore possible. Furthermore evaluation of the otolithic function in weightlessness is made feasible by the possibility of measuring dynamic ocular counterrolling. Some applications of the equipment are described.

Equipment Design↗
PubMed1991

Measuring three dimensions of eye movement in dynamic situations by means of videooculography.

A primary function of the vestibular system is the stabilisation of the eye during head movement. Consequently, evaluation of reflex eye movements represents an essential means to both clinical diagnosis and researching of the vestibular function. Movements in the eye can be resolved into three orthogonal components, i.e. horizontal, vertical and torsional. As an improvement on most current techniques, which provide only measurement of the horizontal and vertical components, videooculography (VOG) facilitates non-invasive measurement of all three of the defined components. To date, only the scleral coil technique, which involves the semi-invasive placement of coil rings onto the bulbi, yields a continuous measure of eye torsion. Employment of suitable solid-state devices permit the integration of a compact, high resolution video recording system. In the basic configuration, eye movements can be observed and simultaneously recorded for later analysis or documentation. The video images of the eye are obtained by means of a miniaturised CCD video sensor mounted on a light-occluding mask. Image processing of the acquired video images determines horizontal and vertical coordinates of eye position online. Ocular torsion, as reflected by the rotation of the natural iris, is measured for each video frame. The VOG algorithm has been implemented on a PC based workstation, which permits online observation, recording and evaluation of eye movements. In addition, the technique has found clinical application as a portable eye-movement observation and recording system, allowing bedside examination and recording of transient symptoms. Preliminary results from various studies, including the objective evaluation of positional nystagmus (BPPN), are presented.

Eye Movements↗