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Biomedical subjects

H Heuer

Publications and source records attributed to H Heuer.

At least 19 recordsLinked to original sources

Apparent size as a function of vertical gaze direction: new tests of an old hypothesis.

The hypothesis was tested that the decline of apparent size with elevated gaze results from a latent tendency of the eyes to diverge and thus increased vergence effort. Through the use of a method of category estimation, the decline of apparent size on elevation or depression of gaze was found not to be different between subjects with larger or smaller changes of dark vergence and thus vergence effort. In a 2nd experiment, vergence effort was varied by varying gaze elevation and the angle of convergence. With vergence effort constant, apparent size was dependent on the angle of convergence rather than being constant. It is concluded that apparent size does not depend on vergence effort and that the effect of gaze elevation on apparent size cannot be attributed to its concomitant effect on dark vergence.

Adolescent

Preferred vertical gaze direction and observation distance.

Hill and Kroemer (1986) and Kroemer and Hill (1986) found that the preferred vertical direction of gaze is lower with a nearer binocular stimulus than with a more distant one. A model is proposed that relates this phenomenon to characteristics of the resting state of the oculomotor system. Three predictions of the model were tested, based on measurements of the preferred vertical gaze direction and dark vergence in the same subject sample. On average the effect of observation distance on the preferred vertical gaze direction served to reduce the discrepancy between the resting state of vergence, operationally defined as dark vergence, and actual convergence during inspection of the binocular stimulus. Second, dark vergence data from individual subjects could be successfully used to predict whether they raised or lowered their eyes on inspection of a binocular stimulus as compared with the preferred vertical gaze direction while viewing a monocular stimulus. Finally, predictions of the size of the change of the preferred vertical gaze direction on introduction of a binocular stimulus produced only small and non-significant correlations.

Adolescent

PAF antagonism as an approach to the treatment of airway hyperreactivity.

Platelet-activating factor (PAF) would seem a good candidate for a mediator of airway hyperreactivity. It has been reported to induce a long-lasting, if modest, increase in hyperreactivity in both experimental animals and humans. Evidence (albeit often indirect) suggests increased levels associated with bronchial hyperreactivity or the related "late-phase reaction" of asthma. In experimental animals, specific inhibitors of PAF can suppress both allergen and PAF-induced hyperreactivity as well as the late-phase reaction to allergen. The mechanism by which PAF induces hyperreactivity is unknown, but the potent effects of PAF on the eosinophil, a cell characteristic of the inflammatory processes often associated with asthma and hyperreactivity, may be important. A number of potent and selective PAF antagonists are now available. The crucial test for the hypothesis that PAF has a role in human airway hyperreactivity will be the testing of substances such as these in appropriate double-blind, placebo-controlled clinical trials.

Allergens

[Preferred gaze direction and the vergence system at rest].

In two experiments the effects of binocular vergence, head tilt, and prolonged gaze inclination on the preferred vertical gaze direction were studied. Concurrently, dark vergence was measured to test a hypothesis on the effect that binocular vergence has on the preferred vertical direction of gaze. The previously reported influence of observation distance on the preferred gaze inclination was replicated. When the head was tilted backward, the preferred gaze inclination was lower and the effect of observation distance was reduced; when the head was tilted forward, the preferred gaze inclination was higher and the effect of observation distance was increased. After prolonged upward or downward gaze inclination the preferred vertical gaze direction was shifted up or down, respectively, while the effect of observation distance remained constant. Overall the change of the preferred vertical direction of gaze upon binocular fixation of near stimuli was accompanied by a reduced discrepancy between convergence and the resting state of the vergence system; additional implications of the hypothesis on the relation between individual resting vergence and the effect of observation distance on the preferred inclination of gaze could not be substantiated.

Adult

Safety, tolerability, and pharmacologic activity of multiple doses of the new platelet activating factor antagonist WEB 2086 in human subjects.

The safety, tolerability, and pharmacologic activity of WEB 2086, a novel, specific platelet activating factor antagonist, were examined in two double-blind, placebo-controlled, within-subject crossover studies. In each study, WEB 2086 (three times 40 mg/day or three times 100 mg/day) was administered for 7 days to 12 healthy volunteers. Pharmacologic activity of the compound was monitored with ex vivo platelet activating factor-induced platelet aggregation. Multiple administration of WEB 2086 resulted in a continuous, almost complete inhibition of this aggregation. Nevertheless, no clinically significant drug-related effects on vital and laboratory parameters or obvious drug-dependent adverse reactions were observed. In conclusion, the performed studies confirmed earlier findings that WEB 2086 was an effective platelet activating factor antagonist in human beings and, furthermore, showed no side effects that would provide objections against further clinical trials with this substance in patients.

Adult

Vertical gaze direction and the resting posture of the eyes.

With horizontal gaze, the resting posture of binocular vergence typically corresponds to a distance of about 1 m. The effect of vertical direction of gaze on this basic resting posture was investigated. The dark vergence of twenty-four subjects was measured while they fixated a dim monocular light-point at vertical directions ranging from -45 degree (lowered) to +30 degrees (elevated). In one condition, gaze was varied by changes in eye position with the head held upright; in a second condition, gaze was varied by changes in head inclination with the eyes held in constant (horizontal) position with respect to the head. In both conditions, dark vergence shifted in the convergent (nearer) direction with lowered gaze and in the divergent (farther) direction with elevated gaze. The effect of varied eye inclination was larger, more variable across subjects, and more stable over time than that of varied head inclination. These findings indicate that multiple mechanisms contribute to gaze-related variations of the resting posture of the eyes. They may help to explain the variations of space perception and visual fatigue that are observed with different gaze inclinations.

Eye Movements

Structure-activity relationships and effects of platelet-activating factor antagonists in the hetrazepine series.

Thieno-triazolo-1,4-diazepines (hetrazepines) antagonize platelet-activating factor (PAF) induced platelet aggregation and inhibit the binding of [3H]-PAF. Introduction of a carboxamide alkyl side chain into the thiophene ring leads to compounds with less affinity to the benzodiazepine receptor and without sedative effects on the central nervous system (e.g., WEB 2086). By ring closure of the side chain, new tetracyclic compounds have been obtained. A parabolic relationship between either [3H]-PAF binding or PAF activity and the bulkiness of the alkyl substituents to the triazolo ring of the hetrazepines or of the bulkiness the 2-acyl moiety of the PAF analogues was found in quantitative structure-activity relationships. This suggests that perhaps the alkyl substituent of the hetrazepines fits the same receptor pocket as the 2-acyl moiety of the PAF agonists.

Azepines

[Rest position of the eyes and its effect on viewing distance and visual fatigue in computer display work].

A deviation between the angle of convergence during visual work and the resting level of the vergence system (vergence discrepancy) should be associated with costs; subjects should tend to reduce these costs by increasing the observation distance. The remaining costs should contribute to visual fatigue. Both hypotheses were tested using a sample of 40 subjects, mainly students. In agreement with the first hypothesis, subjects with large initial vergence discrepancy increased their observation distance more in the course of 1 1/2 hours of visual work than subjects with smaller initial vergence discrepancy. Visual fatigue was assessed using a set of questions developed in two pilot studies. Contrary to the second hypothesis, visual fatigue did not depend on effective vergence discrepancy, that is, the deviation between the resting level of the vergence system and the actual angle of convergence. In addition, such a relationship was not found for further dependent variables (performance, BMS questionnaire, critical flicker frequency, evaluation of conditions of work, postural complaints). The results are discussed with respect to the role of tonic and dynamic components of the vergence system for visual fatigue.

Adult

[Additive hypotheses of the effect of head and eye movement on dark convergence].

Dark vergence depends on the vertical direction of gaze; it decreases with raised gaze and increases with lowered gaze. The vertical direction of gaze can be varied by means or raising or lowering the eyes or by way of tilting the head forward or backward. The effects of both manipulations on dark vergence are different. According to Heuer (1988) the effects of head tilt and eye inclination on dark vergence are almost, but not exactly, additive. In Exp. 1 the hypothesis of additive effects of gaze direction and eye inclination was tested and could not be rejected. The two additive hypotheses (head tilt and eye inclination vs. gaze inclination and eye inclination) result in different predictions for dark vergence with "compensatory" head and eye inclinations, which leave the direction of gaze in space invariant. In Exp. 2 it was shown that predictions from both hypotheses deviated from the observed values of dark vergence. Thus none of the two additive hypotheses provides exact predictions of dark vergence for all possible combinations of head tilt and eye inclination. For practical purposes the approximation might be sufficient. In particular, although mean dark vergence cannot be predicted exactly, individual differences can be predicted quite accurately.

Adolescent

PAF-induced platelet aggregation ex vivo as a method for monitoring pharmacological activity in healthy volunteers.

Platelet aggregation induced ex vivo by aggregating factors such as adrenaline, ADP, collagen or PAF may be useful as a model for describing drug effects in humans. In the two studies reported here, PAF-induced platelet aggregation ex vivo was used as an indicator of the pharmacological activity in healthy volunteers of the newly developed specific PAF-antagonist WEB 2086. In intravenous and inhalative single rising dose tolerance trials this method proved useful for monitoring the pharmacological action of the compound tested. After administration of placebo no relevant pharmacological activity was observed. In both studies increasing dosages of the test substance showed clear, dose-related inhibition of PAF-induced platelet aggregation. Ex vivo PAF-induced platelet aggregation thus provides a simple and rapid means of assessing functional PAF antagonism during trials of PAF-antagonists in human volunteers.

Adult

Effect of the PAF-antagonist WEB 2086 on anaphylactic lung reaction: comparison of inhalative and intravenous challenge.

The specific and potent antagonist of platelet activating factor (PAF), WEB 2086, has been used to investigate the putative role of PAF in anaphylaxis in the guinea-pig. Intravenous (i.v.) challenge with ovalbumin has been compared to inhalative provocation. When actively sensitized guinea-pigs were challenged by the i.v. route, in the presence of mepyramine (5 micrograms/kg i.v.), oral WEB 2086 (0.05-0.5 mg/kg) inhibited the anaphylactic bronchoconstriction but not the hypotension. In passively sensitized guinea-pigs, i.v. WEB 2086, in the presence of mepyramine, protected the animals from both anaphylactic bronchoconstriction and blood pressure changes. When the antigen was inhaled by actively sensitized guinea-pigs, WEB 2086 inhibited the anaphylactic reaction without the administration of any additional antihistamine. These results suggest that PAF plays an important role in anaphylaxis. PAF may be (a) more important in passive than in active anaphylaxis and (b) may be involved during inhalative challenge in active anaphylaxis.

Administration, Inhalation

Inhibitory effect of oral WEB 2086, a novel selective PAF-acether antagonist, on ex vivo platelet aggregation.

WEB 2086 is a novel PAF-acether antagonist, whose pharmacological action in man has only been preliminarily defined. Twelve healthy male volunteers received oral doses of 5, 30 and 90 mg and over the following 24 h inhibition of 5 x 10(-8) M PAF-acether-induced platelet aggregation ex vivo was studied as an indicator of pharmacological activity. WEB 2086 inhibited PAF-acether-induced platelet aggregation in all the doses tested, with the maximum effect 1 to 2 h after administration. After 2 h 5- 30- and 90-mg doses caused, respectively, 87, 98 and 100% inhibition. The magnitude and duration of the inhibitory effect was dose-dependent, with a significant action still detectable 10 h after administration of all three doses, and 12 h after administration of the two highest doses (30 and 90 mg). The subjects did not complain of any significant adverse effect and all completed the study.

Adult

The effects of sustained vertical gaze deviation on the resting state of the vergence system.

Vergence of the eyes in the dark depends on the vertical direction of gaze. In three experiments this phenomenon was studied using eye inclinations and head tilts of 5 min duration during which monocular or binocular near and distant stimuli were inspected. The effects of eye inclination and head tilt on dark vergence were temporally stable; they exhibited even a tendency to increase with the passage of time. On return to horizontal gaze, positive aftereffects were found, that is dark vergence was biased towards its value with a vertically deviated gaze. The effect of vertical gaze direction turned out to be additive to the effect of binocular near fixation. These findings represent evidence against the hypothesis that the effect of vertical gaze direction on dark vergence is mediated by a feedforward signal that is related to voluntary effort in raising or depressing the eyes.

Adaptation, Ocular