Biomedical subjects

G Kobal

Publications and source records attributed to G Kobal.

At least 37 records · Page 2Linked to original sources

PubMed1998

Chemosensory event-related potentials change with age.

The study examined age-related changes in the perception of olfactory and trigeminal chemical stimuli using chemosensory event-related potentials (CSERP). Three groups of healthy volunteers, each comprised of 8 men and 8 women, were tested (age ranges 15-34, 35-54, and 55-74 years). Subjects underwent extensive psychological testing focusing on impairments of memory and attention. In addition, odor identification and discrimination ability was evaluated, as well as detection threshold sensitivity for two odorants. Odor discrimination scores exhibited a significant age-related decrease. Significant age-related changes were also observed for CSERP N1P2 and P2 amplitudes, and for the N1 peak latency. The age-related decrease of CSERP amplitudes appeared to follow a different time course for responses to trigeminal and olfactory stimulants.

Adolescent↗

PubMed1998

Relation of olfactory event-related potentials to changes in stimulus concentration.

OBJECTIVE: The aim of this study was to investigate the influence of odorant concentration on the olfactory event-related potential (OERP). METHODS: OERP were evaluated in 8 men and 8 women (17-34 years of age) in response to 4 concentrations of vanillin (7, 28, 56 and 84% v/v). Sixteen presentations of each concentration (stimulus duration 200 ms, interval 40 s, flow 81/min) were applied in a randomized order. EEG recordings were made at 3 midline sites (pos. Fz, Cz, Pz). Amplitudes and latencies of four peaks were measured (latencies in ms at Pz after stimulation with 84% v/v vanillin): P1 (277), N1 (348), P2 (412) and P3 (496). Statistical analysis was performed with MANOVAs ('concentration', 'recording site' = within-subject-factors; 'age' as covariate). RESULTS: With increasing stimulus concentration amplitudes became significantly larger; this was most pronounced for P3 (P1N1: F = 2.90, P < 0.05; N1P2: F = 5.15, P < 0.01; N1P3: F = 35.7, P < 0.001; P3: F = 38.6; P < 0.001). Correspondingly, latencies shortened with increasing concentrations (P1: F = 25.2; N1: 17.51; P2: 14.8; P3: 13.4; all P < 0.001). While there was no correlation between OERP amplitudes and butanol odor detection thresholds, latencies were the shorter the lower the subjects' thresholds (coefficients of correlations for peak latencies at Cz for 84% v/v: P1 rl5 = -0.59; N1 rl5 = 0.58; P2 r15 = -0.55; P3 r15 = -0.45). CONCLUSIONS: The results indicated that both OERP amplitudes and latencies are related to the concentration of olfactory stimuli. They also suggested that latencies exhibit a stronger relation to changes in stimulus intensity compared to OERP amplitudes.

Adolescent↗

PubMed1998

Handedness is a determining factor in lateralized olfactory discrimination.

The study aimed to re-investigate differences in olfactory thresholds and odor discrimination between the left and right sides in relation to the handedness of healthy subjects. Twenty left- and 20 right-handers participated; all were in excellent health with no indication of any major nasal or health problems, and all were non-smokers. The two groups were comparable in terms of sex and age (left-handers: 11 women, 9 men, median age 25 years; right-handers: 9 women, 11 men, median age 26 years). Odor thresholds did not differ in relation to handedness. However, in the odor discrimination task the left-handers performed significantly better at the left side compared with the right nostril; this pattern was reversed in the right-handers. The data indicate that, similar to other sensory systems, higher olfactory functions exhibit a certain degree of lateralization.

Adult↗

PubMed1998

Trigeminal chemosensitivity: Differences in relation to the time of the day.

Day-night differences of trigeminal chemosensitivity were investigated in 18 healthy volunteers employing both pain-related cortical potentials and pain ratings in response to stimulation of the nasal mucosa with CO2. Day-night differences were found with N 1 P2 amplitudes, P2 latencies and pain ratings. It is concluded that the time of the day must not be ignored when human chemosensitivity is investigated at suprathreshold levels.

Adult↗

PubMed1998

Lateralized and bilateral olfactory function in patients with chronic sinusitis compared with healthy control subjects.

Results of this study demonstrated that a new olfactory test, the "Sniffin' Sticks," can be used to distinguish hyposmic patients with chronic sinusitis (n = 63) from control subjects. Dirhinic testing yielded improved olfactory sensitivity compared with monorhinic testing. However, dirhinic results were not significantly different from results obtained for the best nostril.

Adolescent↗

PubMed1998

Olfactory and intranasal trigeminal event-related potentials in anosmic patients.

The aim of this study was to investigate the usefulness of chemosensory event-related potentials (CSERPs) in response to both olfactory and intranasal trigeminal stimulation in the diagnosis of anosmia. Forty-four patients participated. Gaseous CO2 was used for trigeminal stimulation, vanillin and H2S were used as olfactory stimulants. Event-related potentials to olfactory stimuli could not be obtained in any of the anosmic patients, indicating the complete loss of the sense of smell. However, all patients responded to stimulation of the trigeminal nerve with CO2. These data clearly demonstrate the clinical significance of CSERPs in the assessment of anosmia.

Adolescent↗

PubMed1998

Responses to nasal irritation obtained from the human nasal mucosa.

Responses to chemical irritation can be obtained from the human respiratory mucosa in response to stimulation with gaseous CO2; these negative mucosal potentials (NMPs) are thought to be summated receptor potentials from chemosensitive nociceptors. The present study aimed to investigate the relation of this response to both stimulus concentration and perceived intensity. A total of 29 healthy volunteers participated. Maximum negative amplitudes occurred 1.1 s after stimulus onset. The negativity exhibited a higher coefficient of correlation to intensity estimates of the painful sensations (r = .65) than to the stimulus concentration (r = .46); it appeared at the same time when the subjects' tracking of the painful sensations reached its maximum amplitude. These findings suggest that the NMP is suited for the investigation of peripheral nociceptive events in man.

Adult↗

PubMed1997

Comparison of the antinociception produced by two oral formulations of ibuprofen: ibuprofen effervescent vs ibuprofen tablets.

OBJECTIVE: The aim of this study was to compare the dose-related effects of both ibuprofen tablets and ibuprofen effervescent [placebo, 400 and 800 mg ibuprofen (Aktren)] on phasic pain. PATIENTS: Twenty volunteers participated in this randomized, double-dummy, fivefold crossover study. METHODS: Measurements were obtained before and 15, 60 and 240 min after drug administration. Pain was produced by CO2 pulses applied to the left nostril. Subjects rated the intensity of the painful stimuli by means of a visual analogue scale. In addition, chemosomatosensory event-related potentials were recorded. RESULTS: In line with previous work, ibuprofen produced a dose-related decrease in pain-related potential amplitudes P1N1, indicating its antinociceptive effects. Higher plasma concentrations of ibuprofen were reached 15-40 min after administration of the effervescent while ibuprofen tablets had a tmax 60-90 min after administration. In addition, 60 min after intake of the effervescent a prolongation of the latencies of the potentials was observed, possibly reflecting superior antinociceptive properties when compared to ibuprofen tablets. In addition, the effervescent appeared to have more consistent effects on intensity estimates compared to ibuprofen tablets.

Administration, Oral↗

PubMed1997

The negative mucosal potential: separating central and peripheral effects of NSAIDs in man.

OBJECTIVE: We wanted to test whether assessment of both a central pain-related signal (chemo-somatosensory evoked potential, CSSEP) and a concomitantly recorded peripheral signal (negative mucosal potential, NMP) allows for separation of central and peripheral effects of NSAIDs. For this purpose, experimental conditions were created in which NSAIDs had previously been observed to produce effects on phasic and tonic pain by either central or peripheral mechanisms. METHODS: According to a double-blind, randomised, controlled, threefold cross-over design, 18 healthy subjects (11 males, 7 females; mean age 26 years) received either placebo, 400 mg ibuprofen, or 800 mg ibuprofen. Phasic pain was applied by means of short pulses of CO2 to the nasal mucosa (stimulus duration 500 ms, interval approximately 60 s), and tonic pain was induced in the nasal cavity by means of dry air of controlled temperature, humidity and flow rate (22 degrees C, 0% relative humidity, 145 ml.s-1). Both CSSEPs as central and NMPs as peripheral correlates of pain were obtained in response to the CO2 stimuli. Additionally, the subjects rated the intensity of both phasic and tonic pain by means of visual analogue scales. RESULTS: As described earlier, administration of ibuprofen was followed by a decrease in tonic pain but-relative to placebo-an increase in correlates of phasic pain, indicating a specific effect of ibuprofen on the interaction between the pain stimuli under these special experimental conditions. Based on the similar behaviour of CSSEP and NMP, it was concluded that the pharmacological process underlying this phenomenon was localised in the periphery. By means of the simultaneous recording of interrelated peripheral and central electrophysiologic correlates of nociception, it was possible to separate central and peripheral effects of an NSAID. The major advantage of this pain model is the possibility of obtaining peripheral pain-related activity directly using a non-invasive technique in humans.

Adult↗

PubMed1997

Right-hemisphere preponderance of responses to painful CO2 stimulation of the human nasal mucosa.

We recorded whole-scalp cerebral magnetic fields from healthy adults to painful CO2 pulses (duration 200 ms, concentration 65-90%), led to the left or right nostril once every 20 or 30 s. The stimuli were embedded in a continuous airflow (140 ml/s, 36.5 degrees C, relative humidity 80%) to prevent alterations in the mechanical and thermal conditions of the nasal mucosa. The recording passband was 0.03-90 Hz and 16 single responses were averaged per run. Five out of the 9 subjects showed replicable and artifact-free responses 280-400 ms after stimulus onset. The main responses originated close to the second somatosensory cortex (SII), most frequently in the right hemisphere, and also in the rolandic areas, mostly on the left. The signals were considerably stronger over the right than the left frontotemporal region, with a right-to-left ratio of 2.3 for areal mean signal amplitudes calculated across 16 channels, for both left and right nostril stimuli. Air puffs delivered to the nasal mucosa resulted in a trend for right-hemisphere dominant responses, but responses to air puff stimulation of the lip and the forehead were symmetric. The right-hemisphere dominance of the SII responses may be associated with the painful, and thus unpleasant, nature of the CO2 stimulus, thereby suggesting involvement of the right hemisphere in emotional/motivational aspects of trigeminal pain, in agreement with the role of the trigeminal pathways as a general warning system.

Acute Disease↗

PubMed1997

'Sniffin' sticks': olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold.

'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance.

Adult↗

PubMed1997

Multiple olfactory activity in the human neocortex identified by magnetic source imaging.

To date, cortical regions activated by olfactory stimulation have not been identified precisely in humans. In this study we used magnetic source imaging to localize neuronal activity following olfactory stimulation with two odorants, hydrogen sulphide and vanillin. Peak latencies of the olfactory event-related magnetic fields corresponded to the ascending and descending slopes of the major deflections of the olfactory event-related potentials (OERP). At these latencies we obtained consistent activation of the anterior-central parts of the insula (agranular-periallocortical and dysgranular regions) the parainsular cortex and the superior temporal sulcus. No reproducible equivalent current dipoles were found in other brain areas, including the orbitofrontal cortex. For the first time, brain areas were identified that generate most components of olfactory bioresponses (OERPs) in humans.

Adult↗

PubMed1997

Chronobiology of nasal chemosensitivity: do odor or trigeminal pain thresholds follow a circadian rhythm?

Odor and trigeminal pain thresholds were studied four times each at 24:00, 04:00, 08:00, 12:00, 16:00 and 20:00 h in randomized order on different days in five healthy male volunteers. No circadian rhythm of olfactory or trigeminal thresholds were observed. However, the variability of odor, but not pain thresholds, increased from 04:00 h (thresholds between 0.4 and 1.2 p.p.m.) to 16:00 h (thresholds between 0.1 and 2 p.p.m.). It is hypothesized that environmental influences contribute to this increase in variance.

Adult↗

PubMed1997

Lack of analgesic activity of morphine-6-glucuronide after short-term intravenous administration in healthy volunteers.

BACKGROUND: The analgesic activity of morphine-6-glucuronide (M-6-G) is well recognized for its contribution to the effects of morphine and its possible use as an opioid analgesic with a wider therapeutic range than morphine. The present study attempted to quantify the relative contribution of M-6-G to analgesia observed after systemic administration of morphine. METHODS: In a placebo-controlled, sixfold crossover study in 20 healthy men, the effects of M-6-G were assessed at steady-state plasma concentrations of M-6-G identical to and two and three times higher than those measured after administration of morphine. Morphine and M-6-G were administered as an intravenous bolus followed by infusion over 4 h. Dosage A was M-6-G-bolus of 0.015 mg/kg plus infusion of 0.0072 mg x kg(-1) x h(-1). Dosage B was M-6-G-bolus of 0.029 mg/kg plus infusion of 0.014 mg x kg(-1) x h(-1). Dosage C was M-6-G-bolus of 0.044 mg/kg plus infusion of 0.022 mg x kg(-1) x h(-1). Dosage D was a morphine bolus of 0.14 mg/kg plus infusion of 0.05 mg x kg(-1) x h(-1) for 4 h. Dosage E was M-6-G combined with morphine (doses A + D). Dosage F was a placebo. The analgesic effects of M-6-G and morphine were measured before administration of the bolus and after 3.5 h using an experimental pain model based on pain-related cortical potentials and pain ratings after specific stimulation of the nasal nociceptor with short pulses of gaseous carbon dioxide. RESULTS: Morphine significantly reduced subjective and objective pain correlates compared with placebo. In contrast, M-6-G produced no statistically significant effects. The addition of M-6-G to morphine did not increase the effects of morphine. Morphine produced significantly more side effects than M-6-G. CONCLUSION: After short-term intravenous administration at doses that produce plasma concentrations of M-6-G similar to those seen after administration of morphine, M-6-G had no analgesic effects in the present placebo-controlled study in healthy volunteers.

Adult↗

PubMed1997

Antinociceptive effects of the kappa-opioid receptor agonist RP 60180 compared with pentazocine in an experimental human pain model.

Agonists at kappa-opioid receptors may preserve the analgesic properties of mu-opioidergic agonists while avoiding their major adverse effects. The present study was aimed to investigate the antinociceptive effects of the new kappa-opioid receptor agonist RP 60180. An experimental pain model was used based on specific pain stimuli and event-related potentials. Effects of RP 60180 were compared to placebo and to pentazocine that served as positive control. Twenty healthy male volunteers participated in a placebo-controlled, randomized, double-blind, five-way cross-over study. Single peroral doses of RP 60180 (0.1, 0.5, and 1.0 mg), pentazocine (50 mg), and placebo were administered. Pain was induced by means of short pulses of gaseous CO2 applied to the nasal mucosa. In response to these stimuli, chemo-somatosensory event-related potentials (CSSERP) and pain ratings were recorded. Maximum antinociceptive effects were observed 2 h after the administration of 1.0 mg of RP 60180 and 50 mg of pentazocine. This was shortly after RP 60180 had reached the maximum plasma concentration and when highest plasma concentrations of pentazocine were measured. Both RP 60180 and pentazocine reduced pain-related CSSERP amplitudes by approximately 40% at this time. Pentazocine tended to produce more side effects. These results indicate the potential therapeutic value of kappa-agonist analgesics.

Adult↗

PubMed1997

Assessment of olfaction in multiple sclerosis: evidence of dysfunction by olfactory evoked response and identification tests.

OBJECTIVE: To resolve whether the olfactory pathways are affected in multiple sclerosis. METHODS: Olfaction was assessed by: (1) The University of Pennsylvania smell identification test (UPSIT, which uses microencapsulated odours that are released when scratched with a pencil) in 72 patients with multiple sclerosis and 96 controls, (2) olfactory evoked potentials (OEP) to 20 ppm H2S by volume, and 50% CO2 in air for 45 patients with multiple sclerosis and 47 controls. The abnormality rate in patients with multiple sclerosis for both tests (1) and (2) was compared with that for visual evoked potentials measured using a standard checquerboard technique. RESULTS: By comparison with controls, patients exhibited significantly low scores on the smell identification test with 15% of patients scoring outside the 95% confidence intervals for controls. The UPSIT was occasionally abnormal when the visual evoked potential (VEP) was normal. In general UPSIT scores correlated well with the H2S-evoked response in controls and patients. For H2S, there was a statistically significant increase of latency and decrease of amplitude for patients compared with controls. Increased H2S latency and reduced UPSIT score correlated with greater disability on conventional rating scales. Overall, H2S responses were abnormal in about one quarter of patients with multiple sclerosis. The sensitivity of UPSIT and OEP was similar although disorder on one test did not necessarily indicate abnormality in the other. The visual evoked potential was found to be a more sensitive indicator of disease than OEP or UPSIT. CONCLUSION: These findings confirm the existence of olfactory dysfunction in multiple sclerosis and validate a new evoked potential technique.

Adult↗

PubMed1997

Chemosensory event-related potentials in response to trigeminal and olfactory stimulation in idiopathic Parkinson's disease.

Decrease of olfactory function in patients with Parkinson's disease (PD) has been reported by several authors. The current study investigated olfaction in PD patients using olfactory event-related potentials (OERPs) as an electrophysiologic correlate of olfactory function in combination with psychophysical testing. A specific focus was the influence of antiparkinsonian drugs. We investigated PD patients treated with antiparkinsonian drugs (n = 13) and PD patients who received no pharmacologic treatment (n = 18). They were compared to age- and sex-matched control subjects (n = 38). To obtain OERPs, stimulants were chosen to stimulate specifically the olfactory nerve (2.1 ppm vanillin, 0.8 ppm H2S). In addition, chemosomatosensory event-related potentials were recorded after trigeminal stimulation with 52% v/v CO2. Moreover, the subjects' ability to identify and to discriminate odorants was tested by means of a "squeeze bottle" technique. The study yielded the following major results: (1) Odor identification was impaired in PD patients. It was not influenced by treatment with antiparkinsonian drugs. (2) The OERP latencies were prolonged in both PD patients taking and not taking antiparkinsonian drugs; however, this effect was more pronounced in PD patients taking antiparkinsonian drugs. (3) The intranasal chemosensory trigeminal system seemingly was neither affected by the neuronal degeneration seen in PD nor by treatment with antiparkinsonian drugs.

Adult↗

PubMed1997

Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation.

The Working Group on Neurogenic Inflammation proposed 11 testable hypotheses in the three domains of neurogenic inflammation, perceptual and central integration, and nonneurogenic inflammation. The working group selected the term people reporting chemical sensitivity (PRCS) to identify the primary subject group. In the domain of neurogenic inflammation, testable hypotheses included: PRCS have an increased density of c-fiber neurons in symptomatic tissues; PRCS produce greater quantities of neuropeptides and prostanoids than nonsensitive subjects in response to exposure to low-level capsaicin or irritant chemicals; PRCS have an increased and prolonged response to exogenously administered c-fiber activators such as capsaicin; PRCS demonstrate augmentation of central autonomic reflexes following exposure to agents that produce c-fiber stimulation; PRCS have decreased quantities of neutral endopeptidase in their mucosa; exogenous neuropeptide challenge reproduces symptoms of PRCS. In the domain of perceptual and central integration, testable hypotheses included: PRCS have alterations in adaptation, habituation, cortical representation, perception, cognition, and hedonics compared to controls; the qualitative and quantitative interactions between trigeminal and olfactory systems are altered in PRCS; higher integration of sensory inputs is altered in PRCS. In the domain of nonneurogenic inflammation, testable hypotheses included: increased inflammation is present in PRCS in symptomatic tissues and is associated with a heightened neurosensory response; PRCS show an augmented inflammatory response to chemical exposure. The working group recommended that studies be initiated in these areas.

Chemoreceptor Cells↗