Biomedical subjects

H Muijser

Publications and source records attributed to H Muijser.

At least 19 recordsLinked to original sources

PubMed2006

Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol.

As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans.

Adult↗

PubMed2003

Human volunteer study with PGME: eye irritation during vapour exposure.

The objective of this study was to establish the possible occurrence of eye irritation and subjective symptoms in human volunteers exposed to propylene glycol monomethyl ether (PGME) vapour at concentrations of 0, 100 and 150 ppm. Testing was conducted in 12 healthy male volunteers using a repeated measures design. Each subject was exposed for 2.5 h to each of the three exposure conditions that were spaced 7 days apart. The exposure sequences were counterbalanced and the exposure to the test substance and the effect measurements were conducted in a double-blind fashion. During all exposure sessions, 20 ppm diethyl ether was used as a 'masking agent' for vapour exposure. Measurements of pre- and post exposure eye redness, corneal thickness, tear film break-up time, conjunctival epithelial damage, blinking frequency, and subjective ratings on discomfort were used to evaluate the possible irritating effects of PGME. The results indicated no significant treatment effects for any of the objective parameters. Results of the subjective ratings indicated very slight effects on the eyes in the 150 ppm PGME condition only. No significant effects of treatment were found for the remaining questions concerning the perceived intensity of the smell in the room, the (un)pleasantness of the smell, the perceived effects on the skin, effects on the throat, shivering, muscle aching, and intestinal cramps. In conclusion, the results of the present study indicated minimal subjective eye effects at 150 ppm only, and no impact on the objective measures of eye irritation at either of the two exposure levels. It was concluded that the no adverse effect concentration for eye irritation due to PGME vapour was at least 150 ppm.

Adult↗

PubMed2001

Simultaneous exposure to ethyl benzene and noise: synergistic effects on outer hair cells.

The effects on hearing of simultaneous exposure to the ototoxic organic solvent ethyl benzene and broad-band noise were evaluated in rats. The effects of three ethyl benzene concentrations (0, 300 or 400 ppm) and three noise levels (95 or 105 dB(lin) SPL or background noise at 65 dB(lin) SPL) and all their combinations were investigated for a 5 day exposure at 8 h/day. Distortion product otoacoustic emissions and compound action potentials were affected after 105 dB noise alone, and after 105 dB noise in combination with ethyl benzene (300 and 400 ppm). However, the amount of loss for these combinations did not exceed the loss for 105 dB noise alone. Outer hair cell (OHC) loss after exposure to 300 ppm ethyl benzene was located in the third row of OHCs. At 400 ppm, the loss spread out to the second and first row of OHCs. Noise alone hardly affected the OHC counts except for a minor loss in the first row of OHCs after 105 dB SPL. Noise at 105 dB in combination with ethyl benzene at 300 and 400 ppm, however, showed OHC loss greater than the sum of the losses induced by noise and ethyl benzene alone.

Action Potentials↗

PubMed2000

Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) following whole-body exposure.

HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal Protocol on Substances that Deplete the Ozone Layer. The safety and pharmacokinetics of HFC 134a and HFC 227 were assessed in two separate double-blind studies. Each HFC (hydrofluorocarbon) was administered via whole-body exposure as a vapor to eight (four male and four female) healthy volunteers. Volunteers were exposed, once weekly for 1 h, first to air and then to ascending concentrations of HFC (1000, 2000, 4000, and 8000 parts per million (ppm)), interspersed with a second air exposure and two CFC 12 (dichlorodifluoromethane) exposures (1000 and 4000 ppm). Comparison of either HFC 134a or HFC 227 to CFC 12 or air gave no clinically significant results for any of the measured laboratory parameters. There were no notable adverse events, there was no evidence of effects on the central nervous system, and there were no symptoms of upper respiratory tract irritation. HFC 134a, HFC 227, and CFC 12 blood concentrations increased rapidly and in an exposure-concentration-dependent manner, although not strictly proportionally, and approached steady state. Maximum blood concentrations (C(max)) tended to be higher in males than females; in the HFC 227 study, these were statistically significantly (P < 0. 05) higher in males for each HFC 227 and CFC 12 exposure level. In the HFC 134a study, the gender difference in C(max) was only statistically significant (P < 0.05) for CFC 12 at 4000 ppm and HFC 134a at 8000 ppm. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. For the HFC 134a study, the t(1/2)alpha (alpha elimination half-life) was short for both CFC 12 and HFC 134a (<11 min). The t(1/2)beta (beta elimination half-life) across all exposure concentrations was a mean of 36 and 42 min for CFC 12 and HFC 134a, respectively. Mean residence time (MRT) was an overall mean of 42 and 44 min for CFC 12 and HFC 134a, respectively. In the HFC 227 study, t(1/2)alpha for both CFC 12 and HFC 227, at each exposure level, was short (<9 min) and tended to be lower in males than females. For CFC 12 mean t(1/2)beta ranged from 23 to 43 min and for HFC 227 the mean range was 19-92 min. The values tended to be lower for females than males for HFC 227. For both CFC 12 and HFC 227, MRT was statistically significantly lower (P < 0.05) in males than females and independent of exposure concentration. For CFC 12, MRT was a mean of 37 and 45 min for males and females, respectively, and for HFC 227 MRT was a mean of 36 and 42 min, respectively. Exposure of healthy volunteers to exposure levels up to 8000 ppm HFC 134a, 8000 ppm HFC 227, and 4000 ppm CFC 12 did not result in any adverse effects on pulse, blood pressure, electrocardiogram, or lung function.

Administration, Inhalation↗

PubMed2000

Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.

Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.

Action Potentials↗

PubMed1999

The ototoxic effects of ethyl benzene in rats.

Exposure to organic solvents has been shown to be ototoxic in animals and there is evidence that these solvents can induce hearing loss in humans. In this study, the effects of inhalation of the possibly ototoxic solvent ethyl benzene on the cochlear function and morphology were evaluated using three complementary techniques: (1) reflex modification audiometry (RMA), (2) electrocochleography and (3) histological examination of the cochleas. Rats were exposed to either ethyl benzene (800 ppm, 8 h/day for 5 days) or to control conditions. The RMA threshold increased significantly by about 25 dB, 1 and 4 weeks after the exposure, irrespective of the stimulus frequency tested (4-24 kHz). Electrocochleography was performed between 8 and 11 weeks after exposure to the organic solvent. The threshold for the compound action potential increased significantly by 10-30 dB at all frequencies tested (1-24 kHz). Histological examination of the cochlea showed outer hair cell (OHC) loss, especially in the upper basal and lower middle turns (corresponding to the mid-frequency region) to an extent of 65%. We conclude that exposure to 800 ppm ethyl benzene for 8 h/day during 5 days induces hearing loss in rats due to OHC loss.

Administration, Inhalation↗

PubMed1994

A simple method for the calibration and equalization of whole-body startle measurements in the rat.

A dynamic calibration method for startle amplitude measurement systems for rats is described that is based on rotating weights. The calibration is dependent exclusively on: the mass of the weights, the eccentricity of the weights with respect to the rotation axis, and the rotation velocity in revolutions per second, all of which are easily and accurately measurable parameters. Because of the variability of the frequency spectrum of whole-body startle reactions, it is important to measure the frequency transfer function of startle measuring devices and if necessary to correct the transfer function in the preamplifier so that a flat transfer function in the relevant frequency range results.

Animals↗

PubMed1994

An indication for spatial integration in a non-Pacinian mechanoreceptor system?

It is generally accepted that threshold sensitivity for cutaneous vibrational stimuli has a Pacinian component and a non-Pacinian component. While the Pacinian receptor system exhibits spatial integration, such a property has, until now, not been found in any of the non-Pacinian systems. The present measurements of vibration sensitivity for stimuli with spatial contrast in six subjects revealed that at low frequencies (20-80 Hz) the threshold for a matrix of tiny pins is 13 dB lower than the threshold for a single pin, thus suggesting spatial integration in at least one class of non-Pacinian receptors. It is remarkable that the low threshold for matrix stimuli was found under the condition that adjacent rows of pins vibrated with opposite phase while the threshold for a matrix of pins all vibrating with equal phase was similar to the threshold for a single vibrating pin.

Adult↗

PubMed1994

Neurobehavioral effects of long-term exposure to xylene and mixed organic solvents in shipyard spray painters.

A cross-sectional study was performed in shipyard painters exposed to organic solvents and age-matched referents. The work duties of the painters mainly involved spray painting with solvent-based paints containing > 50% xylene. Testing methods consisted of a symptoms questionnaire, measurement of peripheral sensory and motor nerve parameters and computerized performance tests. Results indicate that complaints regarding mood changes, equilibrium and fatigue were more severe in painters than in referents, but were not related to the estimated life-time exposure index. Decreased nerve function was observed in the lower extremities and to some extent in the upper extremities. The refractory period appeared to be a sensitive parameter in motor nerves. Most neurophysiological parameters investigated were significantly related to the exposure index. Behavioral testing revealed impairment of simple visuo-motor performance and complex perceptual coding. A relationship between effects on perceptual coding and the exposure index was also demonstrated.

Adult↗

PubMed1990

Special nerve functions and colour discrimination in workers with long term low level exposure to carbon disulphide.

Certain functions of the peripheral and autonomic nervous systems, and colour discrimination were examined in 45 workers (mean age 49; mean exposure to carbon disulphide (CS2) 20 years) and 37 controls (mean age 48). Conduction velocity and refractory period of the peroneal and sural nerves were determined. The conduction velocity of the slower fibres of the peroneal nerve was measured by means of an improved method that makes use of the refractory period. Function of autonomic nerves was assessed by measuring the variation in heart rate during rest, during deep breathing, and during isometric muscle contraction. Colour discrimination was evaluated by the Lanthony desaturated test. Individual cumulative exposure to CS2 was calculated on the basis of exposure in the past and individual job history. Mean cumulative exposure was 165 ppm-years. The peroneal nerves of exposed workers showed a decrease (-1.0 m/s) in conduction velocity of the slow fibres and a prolongation (0.1 ms) of the refractory period (mean 1.6 ms) compared with controls. These effects were related to cumulative exposure. No impairment of function of the sural nerve or of colour discrimination was found. The muscle heart reflex was decreased in the exposed group, but this was not related to cumulative exposure. This study has established more firmly that a decrease in conduction velocity of slow motor fibres occurs at low levels of exposure to CS2. Extrapolation of the results suggests that small effects may occur after 40 years of exposure to concentrations below the present threshold limit value (10 ppm).

Autonomic Nervous System↗

PubMed1990

The influence of spatial contrast on the frequency-dependent nature of vibration sensitivity.

Several stimulus configurations have been described for measuring the threshold for vibration perception. One such configuration, used primarily for screening for peripheral nervous system function, for example, consists of a matrix of 24 rows and 6 columns of tiny pins vibrating at 230 Hz, with the even rows of pins vibrating in opposite phase to the uneven rows. In order to determine which class of mechanoreceptors is being tested with such a stimulus, the frequency dependence of the threshold for vibration perception was measured with a similar stimulus configuration in a group of younger subjects and in a group of older subjects. Moreover, the stimulus configuration could be changed from opposite phase stimulation to equal phase stimulation, wherein all pins vibrated with equal phase. In the range above 160 Hz, it appeared that in younger subjects the threshold of the Pacinian receptor system was evaluated with both modes of stimulation, although the sensitivity for opposite phase stimulation was reduced relative to the sensitivity for equal phase stimulation. In the older subjects, equal phase stimulation also appeared to evaluate the Pacinian receptor system. However, with the opposite phase stimulation, the non-Pacinian receptors tended to be evaluated. Below 100 Hz, sensitivity was greater for opposite phase than for equal phase stimulation in both groups. Moreover, with both modes of stimulation, a sensitivity maximum at 40 Hz could be obtained, which was tentatively ascribed to the rapidly adapting class of mechanoreceptors.

Adult↗

PubMed1988

The effects of occupational exposure to styrene on high-frequency hearing thresholds.

Subchronic exposure to styrene has been reported to produce high-frequency hearing loss in rats. In humans, hearing thresholds for higher frequencies (greater than 8 kHz) are also more vulnerable to ototoxic drugs than those at lower frequencies. Since hearing loss at frequencies above 8 kHz does not seem to play a role in speech processing, hearing loss at frequencies above 8 kHz in workers exposed to styrene or other solvents might easily escape detection. Therefore, hearing thresholds were evaluated at frequencies up to 16 kHz in workers exposed to styrene and compared to those of a control group of unexposed workers. The airborne concentrations of styrene typically did not exceed 150 mg/m3 although individual exposures did, at times, reach higher values (up to 700 mg/m3). In accordance with the literature, an age-dependent increase in hearing thresholds at high frequencies was found. Compared to controls, workers exposed to styrene did not appear to demonstrate an aggravated age-dependent decrease in hearing high frequencies. A comparison, however, within the experimental group between the least exposed and the most exposed workers revealed a statistically significant difference on hearing thresholds at high frequencies.

Adult↗

PubMed1988

Experimental exposure to alcohol as a model for the evaluation of neurobehavioural tests.

The performance characteristics of 4 computerized psychological tests were studied using alcohol as a model compound. Subjects received alcohol (0.5 ml/kg) or placebo in a cross-over design and performance was assessed using the Simple Reaction Time test, the Switching Attention test, the Hand/Eye Coordination test and the Color-Word Vigilance test. Analyses indicated an overall significant effect of alcohol at blood-alcohol levels of 0.03% with response speed on the Color-Word Vigilance test being the most sensitive parameter.

Adult↗

PubMed1987

Lead exposure during demolition of a steel structure coated with lead-based paints. II. Reversible changes in the conduction velocity of the motor nerves in transiently exposed workers.

In a group of workers exposed to high levels of lead during five months nerve conduction velocity parameters were evaluated at the termination of exposure, and also three and fifteen months later. At the termination of exposure the mean blood lead level was 4.0 mumol/l, and motor conduction velocities in the median and the ulnar nerves were slower and the distal latencies in the median nerve were longer compared to the values measured 15 months later. Sensory conduction velocities, measured distally in the same nerves, were not depressed compared to the values measured three or fifteen months later. It was tentatively concluded that the effect of lead on the conduction velocity of the motor nerves has an initial reversible phase, dependent on the duration of exposure.

Adult↗

PubMed1986

Vibration sensitivity as a parameter for detecting peripheral neuropathy. I. Results in healthy workers.

Two methods of evaluating the threshold for vibration perception were compared. Surprisingly it appears that the theoretically attractive, adaptive forced choice method does not result in lower variability than the method of limits. Moreover two devices were used to evaluate the threshold: the Optacon Tactile Tester and the "multirod". Based on the characteristics of these devices and the known properties of mechanoreceptors, it is argued that the two devices test different mechanoreceptor systems. The high correlation of threshold with age (r = 0.9) found by Arezzo and Schaumburg in measurements with the Optacon could not be reproduced.

Adult↗

PubMed1986

Envelope detection of amplitude-modulated high-frequency sinusoidal signals by skin mechanoreceptors.

High-frequency (1000-2000 Hz) sinusoidal vibrations of the skin, which are normally imperceptible, induce distinct sensations when amplitude modulation is applied in the frequency region around 200 Hz. This phenomenon appears to be initiated in the mechanoreceptor, as a result of rectification in the mechanoelectrical transduction process. The curve for sensitivity to modulation frequency resembles the frequency-sensitivity curve of the Pacini receptor system. The low-frequency slope is flatter than that of comparable psychophysical frequency-threshold curves for sinusoidal stimuli. This finding suggests that mechanical filtering (in the capsule of the Pacinian corpuscle and the surrounding skin tissue) contributes to the detection threshold. The characteristics of such a mechanical filter are estimated.

Fingers↗

PubMed1981

Effects of extracts of denervated muscles on the morphology of cultured muscle cells.

Previously, trophic effects of extracts from whole chick embryos and from innervated muscles on cultured muscle cells were described. The present study demonstrated similar effects of extracts from 10-days denervated chick muscles. Extracts from innervated as well as from denervated muscles exsanguinated in vivo with saline prior to dissection showed only marginal trophic activity, suggesting a major contribution of serum components to the trophic effects of tissue extracts. Indeed, serum of adult chicks appeared to have a trophic action similar to that of chick embryo extract.

Animals↗

PubMed1981

Measurement of the electrotonic length constant in cultured muscle fibres.

The measurement of passive electrical membrane properties in cultured muscle cells is complicated by the fact that the electrotonic length in these cells often exceeds their actual length, leading to serious deviations from the simple infinite cable behaviour. By using very short current pulses for these measurements and integrating the responses, the cells can be made to behave as infinite cables.

Animals↗