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PubMed1996

The effects of vigabatrin on attention, concentration and mood: an investigation in healthy volunteers.

Ten healthy volunteers (six males; four females) completed this double-blind, crossover design study of vigabatrin vs placebo. Subjects were tested on four occasions; at the baselines of the placebo and the vigabatrin phase, and two weeks thereafter. At time of testing, the dose of vigabatrin was 2 g daily. Changes in cognition were assessed using the Sternberg, the PASAT, the Stroop, and Critical Fusion Flicker tests. Mood was assessed with the Mood Adjective Check List, the Beck Depression Inventory, and the Irritability, Depression and Anxiety scales. We found one drug, and one placebo, related significant difference on a measure of cognition.

Adult↗
PubMed1997

Magnetic resonance spectroscopy of isoflurane kinetics in humans. Part II: Functional localization.

We describe the first experiments to relate the cerebral kinetics of isoflurane (determined by fluorine magnetic resonance spectroscopy) to cerebral function. Using a surface receive coil we found two-compartment kinetics within the head with equilibrium half-times of 3.5 min and approximately 1 h with respect to expired isoflurane concentrations. Using critical fusion flicker frequency as an objective measure of the cerebral effect of isoflurane, we found evidence to identify the fast component as the brain. Responsiveness to command was lost at a brain partial pressure of 0.3% isoflurane. We conclude that the measured cerebral kinetics of isoflurane exactly matched the predictions of the classical perfusion-limited model.

Anesthetics, Inhalation↗
PubMed1997

Flicker perimetry in diabetic children without retinopathy.

OBJECTIVE: To determine the flicker fusion frequency in children and adolescents with insulin-dependent diabetes mellitus (IDDM) who did not have fluorescein angiographic signs of retinopathy. DESIGN: Cross-sectional study. SETTING: Antidiabetic Centre, departments of Ophthalmology and Pediatrics, University of Chieti, Chieti, Italy. PATIENTS: Forty-five patients aged 9 to 18 years with IDDM without fluorescein angiographic signs of retinopathy. Forty-five healthy subjects matched for sex and age constituted the control group. The patients were classified into two subgroups according to their metabolic control: good (percentage hemoglobin Alc 9% or less) or poor (percentage hemoglobin Alc greater than 9%). OUTCOME MEASURES: Retinal flicker fusion frequency, evaluated with an automated flicker perimeter in the central 30 degrees of the visual field. RESULTS: The subjects with poor metabolic control had a significantly lower mean flicker fusion frequency than the control subjects (27.43 Hz [standard deviation (SD) 5.16 Hz] vs. 38.72 Hz [SD 4.27 Hz]) and the patients with good metabolic control (33.94 Hz [SD 5.54 Hz]) (p < 0.001). There was a significant relation between flicker fusion frequency and the percentage of hemoglobin Alc (r = -0.533, p < 0.001). CONCLUSIONS: Our results show that children with poorly controlled IDDM without fluorescein angiographic signs of retinopathy have an impairment of retinal flicker sensitivity in the central 30 degrees of the central visual field and that this impairment is related to the degree of metabolic control. Flicker perimetry is a simple, noninvasive tool that may be useful to evaluate the eye function of diabetic children.

Adolescent↗
PubMed1997

The influence of established and new antiepileptic drugs on visual perception. 1. A placebo-controlled, double-blind, single-dose study in healthy volunteers.

The influence of single oral dosages of carbamazepine (CBZ), valproic acid, vigabatrin (VGB), lamotrigine (LTG), gabapentin (GBP), and losigamone (LSG) on visual perception was investigated in ten healthy volunteers according to a double-blind, placebo-controlled, cross-over study design. The test battery comprised visual acuity, the Lanthony-D-15-désaturé colour perception test, increment, postadaptation and transient tritanopia threshold measurements, perception threshold assessment for monochromatic and chromatic gaussian dots, monochromatic gratings and gratings of differing spatial frequency, and critical flicker fusion tests with various stimuli. The only consistent and partly significant effects were seen after VGB and GBP. After VGB, increment, postadaptation and transient tritanopia thresholds and the critical flicker fusion increased, whereas GBP led to a somewhat converse profile. The other tests were not influenced consistently by any antiepileptic drug (AED). We conclude that: (i) gamma-amino-butyric acid-(GABA)-related properties as under the prototype drug VGB result in specific alterations of the transient tritanopia phenomenon which is consistent with the physiological hypothesis for this retinal paradigm based on extracellular recordings in primates. The possible mechanisms why VGB improved critical flicker fusion as the only AED in this trial are discussed. The profile of GBP indicates a unique mechanism of action. We have not observed specific influences on visual perception under AEDs which act mainly via alterations of ion membrane conductance. The transient tritanopia and flicker fusion paradigms we used appear to be promising to investigate antiepileptic drugs with hitherto unknown modes of actions in human noninvasively.

Adaptation, Ocular↗
PubMed1981

Time course of mental and psychomotor effects of 30 per cent nitrous oxide during inhalation and recovery.

Two experiments were conducted testing the duration of action of nitrous oxide on human performance. In the first experiment, 11 subjects inhaled 30 per cent nitrous oxide for two periods of 40 min each, 45 min apart. Their mental and psychomotor skills were measured using free recall, tapping board, arithmetic and flicker fusion tests before and 2, 12, 22 and 32 min after establishing and end-tidal concentration of N2O of 30 per cent. Recovery was tested using the same tests 2, 12, 22 and 32 min after discontinuation of N2O. Eleven additional subjects inhaled oxygen only and served as a control group. In the second experiment, 8 subjects received both 30 per cent N2O and oxygen in cross-over fashion, and their flicker fusion threshold was measured. When compared to baseline or oxygen administration, N2O significantly impaired tapping rate, number of words recalled, and performance in arithmetic tests. The effects of N2O were maximal at 2 min and remained similar throughout the entire administration. In flicker fusion tests, the effects of N2O were similar to those of stimulant drugs; N2O improved the subjects' ability to discriminate the fusion of flickering light. Recovery was complete in 22 min. The effects of, and recovery from the second administration of N2O were similar to those of the first experiment. There was no evidence of development of tolerance to mental and psychomotor effects of the drug.

Adult↗
PubMed1978

Actions and interactions with alcohol of drugs on psychomotor skills: comparison of diazepam and gamma-hydroxybutyric acid.

Effects of gamma-hydroxybutyric acid (GOBA) on psychomotor skills related to driving were studied in healthy student volunteers. The effects of oral GOBA 1.0 and 2.0 g, alone or in combination with 0.5 g/kg of ethyl alcohol, were compared in double-blind cross-over trials against oral diazepam 10 mg (D), alcohol 0.5 g/kg, and lactose placebo. Reactive and co-ordinative skills, attention, flicker fusion, proprioception, nystagmus, Maddox wing, and subjective estimations were included. The first single-dose trial with 12 volunteers revealed that neither GOBA 1.0 g nor D modified attention. D impaired reactive skills whilst co-ordinative skills remained largely uninfluenced by D or GOBA. Both D and GOBA impaired leg proprioception. Only D was experienced as a sedative drug. In the second trial with 12 volunteers, GOBA 1.0 g slightly increased reaction mistakes whereas GOBA 2.0 g next day did not. Either dose of GOBA was ineffective on co-ordinative skills, critical flicker fusion frequency, and proprioception. Alcohol alone (0.41 +/- 0.047 mg/ml) improved rather than impaired skills. GOBA 1.0 g + alcohol (0.36 +/- 0.027 mg/ml) impaired reactive skills more than GOBA 2.0 g did but no potentiation was seen. D impaired reactive and co-ordinative skills and flicker fusion. When D was given on two consecutive days, some tachyphylaxis to the D response was seen on co-ordinative skills but not on reactive skills or flicker fusion. It is concluded that in the recommended anxiolytic doses used GOBA neither deteriorates driving skills nor importantly increases the effects of low doses of alcohol.

Adult↗
PubMed1982

Antihistamines and visual function: studies on dynamic acuity and the pupillary response to light.

1 Effects of three antihistamines, triprolidine (10 mg) in a sustained release form, astemizole (10 mg) and terfenadine (60 mg), have been studied on dynamic visual acuity and on the response of the pupil to light, together with critical flicker fusion, digit symbol substitution and cancellation, and subjective assessment of mood. The study was double-blind and effects were observed from 0.5-4.0 h after ingestion. 2 Triprolidine impaired dynamic acuity and reduced the threshold for subjective fusion of a flickering light, but there were no changes with astemizole or terfenadine. The diameter of the pupil and its response to light were not changed by the drugs. 3 Performance on digit symbol substitution and cancellation was not altered by the drugs. 4 Astemizole and terfenadine are promising antihistamines for those involved in skilled activity.

Adult↗
PubMed1992

Exercise alters the pharmacokinetics of midazolam.

Six healthy volunteers received 15 mg midazolam, 50 mg ephedrine, or placebo orally before a 50-minute aerobic treadmill exercise and in a control session. Plasma drug concentrations for pharmacokinetic calculations were estimated from samples drawn up to 24 hours after drug intake. Heart rate, blood pressure, critical flicker fusion test, Maddox wing test, and visual analog scales relating to mood and feelings of tiredness were included in the sessions as pharmacodynamic measures. These tests were made at 35, 55, and 75 minutes and at 2, 2 1/2, 3 1/2, and 5 hours after drug intake. Exercise impaired the absorption of midazolam and counteracted the midazolam-induced decrement in flicker fusion threshold. Whether the effect on flicker fusion was caused mainly by the pharmacokinetic changes or by a general alerting effect of exercise cannot be verified by this experiment. The kinetics of ephedrine was not affected by exercise, but exercise enhanced the tachycardic response to ephedrine and abolished its pressor effect.

Adult↗
PubMed1987

The effect of diazepam on the responsiveness of human eccrine sweat glands to carbachol: influence of ambient temperature.

The effect of diazepam (10 mg, p.o.) on the responsiveness of eccrine sweat glands to intradermally injected carbachol and on critical flicker fusion frequency was compared in 6 male healthy volunteers under two ambient temperature conditions, 22 degrees C and 35 degrees C. Carbachol evoked dose-related increases in sweat gland activity. Responsiveness to carbachol was significantly enhanced under the 35 degrees C condition as compared to the 22 degrees C condition, this being reflected in a higher value of Emax of the dose-response curve for carbachol under the 35 degrees C condition. Diazepam had no significant effect on responses to carbachol under the 22 degrees C condition, but prevented the increase in responsiveness produced by high ambient temperature. High ambient temperature had no significant effect on critical flicker fusion frequency. Diazepam significantly reduced critical flicker fusion frequency under both temperature conditions. It is suggested that diazepam may block the increase in sympathetic outflow normally evoked by high ambient temperature, thereby preventing the development of sweat gland hyper-responsiveness.

Adult↗
PubMed1984

[An experimental study on the duration of a single spell of work on VDT (visual display terminal) performance].

The relation between work load and the duration of a single spell of work on VDT performance studied in an experimental word processing task. Nine healthy male college students performed 2-hour visual tasks under the following three sets of work conditions. In the first set, subjects performed VDT work for two hours without intermission. In the second set, subjects had a 10-minute intermission after a 1-hour task. In the third set, there was a 5-minute intermission after a 30-minute task. Critical flicker fusion, near point distance, subjective fatigue symptoms, heart rate, respiratory rate, blinking counts, electromyogram in upper limb and performance score were measured. Results are as follows. Decrease in critical flicker fusion, increase in near point distance and subjective fatigue symptoms appeared in all three sets of experimental conditions after two hour tasks. Increased slow wave components on electromyogram and increased errors in performance appeared after 60-minute or more tasks without intermission. Effects on the critical flicker fusion, near point distance, subjective fatigue symptoms, electromyogram, blinking counts and errors in performance were least in the third set. The results of this study suggest that in order to reduce operators' fatigue on VDT work of the conversation type, countermeasures such as shortening the duration of a single spell of work to less than 60 minutes and taking frequent short intermission are necessary.

Adult↗
PubMed1985

Acrylamide effects on the macaque visual system. I. Psychophysics and electrophysiology.

Oral acrylamide produces axonal swelling and later degeneration and gliosis in the distal optic tract, especially within the lateral geniculate nucleus, of macaque monkeys. Measures of visual thresholds and cortical-evoked potentials were used to study the time course of visual changes during exposure to acrylamide in macaque monkeys. Contrast sensitivity, visual acuity, and flicker fusion frequency were reduced during exposure, and only flicker fusion recovered rapidly and completely after exposure. Pattern-reversal-evoked responses exhibited increased latency and reduced amplitude during dosing but substantially recovered after exposure. Visual acuity and contrast sensitivity for high spatial frequencies were decreased throughout the 140 days of testing after dosing. These results suggest an acute general depression of visual capacities as the initial effect of acrylamide exposure, whereas later effects were confined to high spatial frequencies.

Acrylamide↗
PubMed1995

150 mg fluconazole does not substantially increase the effects of 10 mg midazolam or the plasma midazolam concentrations in healthy subjects.

Fluconazole, an azole antifungal agent, moderately inhibits the CYP3A-mediated metabolism of midazolam in vitro. We therefore studied whether such an interaction takes place in vivo following oral administration of these drugs, given as relevant double blinded doses in capsule form. In study I parallel groups of healthy subjects received oral midazolam 10 mg (MID 10) or 15 mg (MID 15), placebo, or MID 10 mg + 150 mg fluconazole (FLU) given 2 h earlier. Objective and subjective performance tests were made before, and 30 and 90 min after the intake of midazolam. MID 10 and MID 15 moderately impaired performance on digit symbol substitution, letter cancellation and flicker fusion tests, and visual analogue scales revealed mild sedation. FLU + MID 10 had similar or slightly stronger effects than MID 10; it differed from MID 10 in that it lowered the flicker fusion threshold and produced subjective slowness and overall impairment. In study II 5 subjects received MID 10 after placebo, after FLU, and after 750 mg erythromycin (ERY) at 1-week intervals, following a crossover and double-blinded study design. Blood was sampled before MID intake and 30, 60 and 90 min after it, and performance was measured. FLU and ERY increased the effect of MID on flicker fusion and letter cancellation performances, and increased the HPLC-assayed plasma midazolam (ERY + 100%, FLU + 50%) in comparison to that measured after MID ingested alone. When the concentrations of midazolam together with its active metabolite alpha-OH-midazolam were assayed by radioreceptor technique the increases caused by ERY and FLU were less and compatible with the pharmacodynamic data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Flicker perimetry resists retinal image degradation.

The influence of refractive defocus and artificial media opacities on perimetric thresholds in automated light-sense and flicker perimetry was investigated in 20 eyes of 20 normal subjects. Thresholds were determined at 13 locations in the central visual field up to 25 degrees. Refractive defocus was induced by blurring with glasses of +1, +2, +3, +6 and +9 diopters spherical. Three diffusers were used as artificial media opacities, causing a mean reduction of visual acuity to 0.46, 0.08, and 0.02. Blurring of the retinal image by a small defocus or by slight artificial media opacities causes a measurable reduction of light-difference sensitivity. Mean sensitivity (MS) and defocus are related logarithmically (log(MS)/defocus, r = -0.9297; P < 0.0001). The correlation between MS and the luminance factor l15, characterizing the artificial media opacities, is linear (MS/l15, r = -0.9736; P < 0.0001). Flicker fusion frequency resists retinal image degradation much better. Mean flicker frequency (MF) and defocus are related logarithmically (log(MF)/defocus, r = -0.4960; P < 0.0001). The correlation between mean flicker frequency (MF) and the luminance factor l15 is nonlinear (MF/[l15]2, r = 0.8693; P < 0.0001). The results of the present study show that perimetric methods that use temporal threshold criteria, such as flicker fusion frequency, should be more suitable than methods that use static criteria for detecting neuronal damage in the presence of factors that disturb retinal image quality.

Adult↗
PubMed1975

Side effects and skills related to driving after intramuscular administration of bupivacaine and etidocaine.

Eleven healthy subjects were injected intramuscularly with a saline placebo, 1.3 mg/kg of 0.5% plain bupivacaine, or 2.6 mg/kg of 1.0% plain etidocaine in a double-blind cross-over fashion. Before and at 1/2, 2 and 4 h after injection, side effects were recorded, and psychomotor skills related to driving were measured. Fatigue, dizziness, and sore thighs were significantly more common with etidocaine than with bupivacaine or the saline solution. Bupivacaine significantly impaired eye-hand cooridination and flicker fusion discrimination during the whole observation period. Etidocaine impaired flicker fusion discrimination only. The subjects' adaption to darkness, sensitivity to brightness, and visual discrimination ability in bright counterlight remained unaltered after each treatment. The results suggest that such psychomotor performance as driving ability is impaired for at least 2 h after a patient receives 1.3 mg/kg of plain bupivacaine or 2.6 mg/kg of plain etidocaine intramuscularly.

Acetanilides↗
PubMed1983

The H1-antagonist mequitazine: studies on performance and visual function.

The effects of single oral doses of mequitazine (5 and 10 mg), terfenadine (60 mg) and triprolidine (10 mg) as active controls, and placebo were evaluated on visuo-motor coordination, digit symbol substitution, critical flicker fusion and dynamic visual acuity, and on subjective assessments of mood and well-being in six normal female volunteers. The study was double-blind. Mequitazine (5 mg) impaired visuo-motor coordination 7.5 h after ingestion (considered to be a chance result), but there was no effect on digit symbol substitution, critical flicker fusion threshold or dynamic visual acuity. Mequitazine (10 mg) impaired visuo-motor coordination and reduced the number of substitutions on the digit symbol substitution test. Terfenadine (60 mg) had no effect on performance or on subjective feelings. Triprolidine (10 mg) impaired visuo-motor coordination, reduced the number of substitutions on the digit symbol test, lowered the critical flicker fusion threshold and reduced dynamic visual acuity. Mequitazine (5 mg) and terfenadine (60 mg) are likely to prove acceptable H1 antagonists when sedation must be avoided.

Adult↗
PubMed1987

Multi-point flicker recognition apparatus and its application for video display terminal work.

The apparatus to measure multi-point critical flicker fusion frequency (MCFF) was devised for more precise determination of the critical flicker fusion frequency (CFF). Using this apparatus, the variations in flicker value after the work load of the television (TV) game, the Kraepelin using the video display terminal (VDT-Kraepelin) and the paper-Kraepelin were examined in order to test its practical applicability. The following results were obtained. The degree of decrease in the CFF values of some peripheral eye fields was larger than that on the central field of both eyes (ordinary CFF) after work load. The variation rates of the central and the peripheral flicker values were measured before and after loading in each work, and the correlations of variation rates between two CFF values among them were calculated. The numbers of peripheral eye fields showing significant correlation of variation rates between two eye fields in the TV game and the VDT-Kraepelin, were greater than those in the paper-Kraepelin.

Adult↗