Peter Jaehnig - Academia.edu (original) (raw)

Papers by Peter Jaehnig

Vaccine, 2015

Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictabi... more Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictability of production to meet global demand. This study compared the safety and tolerability of TIVc with an egg-derived trivalent influenza vaccine (TIVf) in 4-17 year-olds. A Phase 3 observer blind, multicentre study enrolled 2055 healthy participants randomized 2:1 to receive either TIVc or TIVf, respectively (1372 TIVc and 683 TIVf evaluable subjects). Participants received one dose each on Days 1 and 28 (4-8 year-olds not previously vaccinated [NPV]) or one dose on Day 1 (4-8 and 9-17 year-olds previously vaccinated [PV]). Solicited adverse events (AEs) occurring within 7 days after each vaccination were assessed; participants were followed up for 6 months after their last dose for safety. Most solicited and unsolicited AEs were mild to moderate with <1% in the severe category. No withdrawals due to AEs, deaths or vaccine related SAEs were reported. TIVc and TIVf were similar in percentages of participants reporting solicited reactions in 4-8 years NPV group after the 1st dose: local reactions, TIVc: 48%, TIVf: 43%; systemic reactions, TIVc: 34%, TIVf: 32%; percentages were lower following the 2nd dose in TIVc; local reactions: TIVc: 40%; TIVf: 43%; systemic reactions: TIVc: 21%; TIVf: 22%. In 4-17 years PV group, solicited reactions were lower following TIVf, local reactions: TIVc: 53%; TIVf: 43%; systemic reactions: TIVc: 37%, TIVf: 30%. Injection site pain was the most common solicited reaction, and was similar following TIVc and TIVf in 4-8 year-olds (TIVc: 56%; TIVf: 55%), and lower following TIVf in 9-17 years group (TIVc: 52%; TIVf: 42%). Reporting of unsolicited AEs was similar for TIVc and TIVf across the two age groups. TIVc was well tolerated and had a safety and reactogenicity profile similar to that of TIVf in healthy 4-17 year-olds (NCT01857206).

Neuropsychobiology, 1995

The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic ... more The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic zopiclone (7.5 mg) on heart rate activity was studied in 16 elderly insomniacs in a placebo-controlled, randomised, 3-fold crossover trial. After digital preprocessing of the ECG, QRS complexes were automatically recognised by a detection technique based on adaptative thresholds. Both R-R periodicity and heart rate variability were analysed as a function of sleep stages and time of night. Under placebo, heart rate decreased significantly from the first to the second half of the night. The relationship between sleep stages and heart rate remained constant under both hypnotics. Although the two substances significantly modified the distribution of sleep stages, no relevant changes in ECG activity were observed when the proportion of the different sleep stages was taken into consideration.

Neuropsychobiology, 1992

The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern perso... more The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern personal computers however, it is possible to perform signal detection within a reasonable length of time automatically. This paper presents a method for signal processing based on matched filtering. This allows the detection of sleep spindles and K-complexes in a sleep EEG recording with a high degree of accuracy. First the technique is described, and the results of a validation study based on the comparison of visual evaluations and computer analysis are presented. Thereafter, results of an application study are presented. Sleep spindle and K-complex density under the influence of lormetazepam and zopiclone were examined. Under both medications sleep spindle density increased while K-complex density decreased. Computation of Pearson's correlation coefficients demonstrated that the interindividual sleep spindle and K-complex variations under both treatments are highly correlated. The data suggest that lormetazepam and zopiclone, although chemically different, have a similar mode of action and display comparable effects on the sleep EEG.

Neuropsychobiology, 1999

In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine an... more In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine and dexnafenodone, an antidepressant drug under development, were investigated in young, healthy volunteers. In contrast to placebo, both drugs suppressed REM sleep substantially after acute and repeated administration. As a consequence, REM sleep latencies increased under active treatment to mean values which were about two to four times larger than baseline values. Since the active inhibition of the muscle tone is a distinct feature of REM sleep, we studied the influence of the two antidepressant drugs on this variable. By means of computerised EMG analysis, tonic and transient EMG activity were computed for total recording time and for the different sleep stages. While tonic EMG activity during sleep was increased with both drugs, transient EMG events remained unaffected. Computerised analysis of the microstructure of sleep is an effective tool for studying the effect of antidepressant drugs on sleep.

Neuropsychobiology, 1995

Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances o... more Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances on the central nervous system (CNS) activity. A standard technique is to measure the EEG under vigilance-controlled and resting conditions for a short duration, for example 5 min. The aim of the present study was to investigate the stability of 5-min EEG recordings. While the time course of the EEG was fairly stable during the recording session under the vigilance-controlled condition, systematic trends became apparent under the resting condition. Pharmaco-sensitivity of the EEG and its reliability increased with the recording duration. Five minutes of EEG recording seem to be sufficient and well chosen to evaluate the influence of drugs on the EEG.

Clinical Pharmacology & Therapeutics, 2003

Sleep

Sleep onset latency (SOL) is frequently defined as the time between lights-out and the first epoc... more Sleep onset latency (SOL) is frequently defined as the time between lights-out and the first epoch of sleep stage 2. In practice, SOL can be quantified easily on the basis of visual examination. We have developed a computer algorithm allowing an automatic estimation of this parameter. The agreement between both strategies, visual and computer analysis, was tested using data from a pharmacological sleep study with 16 elderly insomniacs, which was aimed at comparing the effects of lormetazepam and zopiclone on polysomnography. A high correlation was found between the visual and the computer-based determination of SOL. Drug-related differences in SOL could be shown with both approaches.

Sleep

A method for the automatic detection of episodes of wakefulness during sleep is presented. The al... more A method for the automatic detection of episodes of wakefulness during sleep is presented. The algorithm is based on the evaluation of the alpha slow-wave index (ASI), a measure that has been developed to detect fluctuations of vigilance in daytime pharmaco-electroencephalogram studies. Its application to sleep data was validated with polysomnographic recordings from 16 elderly insomniacs and 16 young healthy subjects. The rate of agreement between the computerized procedure and the visual scoring of wakefulness was 94.0% for the insomniacs and 96.9% for the healthy subjects. The decision criterion used by the computer allowed the definition of a subject-adapted threshold for the detection of wake episodes. The method opens new perspectives for the automatic analysis of continuous 24-hour sleep-wake recordings.

Journal of Infectious Diseases, 2014

Background: A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an avai... more Background: A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.

Klinische Neurophysiologie, 1993

Vaccine, 2004

This study investigated the immune response and safety in 430 adults, when boosted more than 3 ye... more This study investigated the immune response and safety in 430 adults, when boosted more than 3 years after primary or booster TBE immunisation as measured by neutralization test (NT) and ELISA. Tested by NT, the post-booster day 21 geometric mean titer (GMT) was 331 and 142 for the 18-49 and ≥50 years old, respectively. The post-/pre-booster geometric mean titer ratio (GMR) was 2.29 for the 18-49 years old and 3.21 for the ≥50 years old. An at least four-fold increase of neutralizing TBE antibodies was observed in only 26 and 38% of subjects aged 18-49 and ≥50 years, respectively. The booster effect in subjects with only the primary vaccination course prior to study entry clearly depended on the time elapsed since last TBE vaccination with an estimated annual decline rate of 15%. In subjects with at least one additional booster vaccination virtually no antibody decline was observed. This study clearly indicates that (1) adults may be effectively and safely boosted with a different TBE vaccine and (2) following four immunisations protective antibodies can be detected far beyond a period of 3 years, thus, strongly supporting the reconsideration of currently recommended booster intervals.

Vaccine, 2004

A descriptive evaluation of protective immunity was performed on subjects with a complete primary... more A descriptive evaluation of protective immunity was performed on subjects with a complete primary tick-borne encephalitis (TBE) immunization (and additional regular boosters) more than 3 years after primary or booster TBE immunization, as measured by neutralization test and two different ELISA systems. The study population (n = 430) was stratified for age (i.e., 18-49 or 50 years of age) and for the number of years since last TBE vaccination. GMTs (NT) of all subgroups (at the time of the present evaluation) were above detection limit: 144 and 44 for the 18-49-and 50-year-old subjects, respectively. One percent of subjects aged 18-49 years, and 6% of subjects aged 50 years were ELISA-negative. A detailed sub analysis revealed that subjects with either low NT and/or negative to borderline ELISA test results are usually older and constitute a higher number of subjects without any TBE booster vaccination compared to the respective test-positive subject group. From the fourth year (exceeding 3 years after last vaccination) titers show a decline rate of 6-7%. This study indicates that after multiple TBE (booster) immunizations protection surpasses the currently advised TBE booster interval of 3 years, thus supporting reconsideration of the recommendations for booster intervals.

Psychopharmacology, 1991

In normal common marmosets administration of the D-1/D-2 agonist apomorphine or the selective D-2... more In normal common marmosets administration of the D-1/D-2 agonist apomorphine or the selective D-2 agonist quinpirole caused a dose-dependent increase in motor activity and induced stereotyped behaviour. Both the selective D-2 antagonist raclopride and the selective D-I antagonist SCH 23390 inhibited normal locomotor activity and induced catalepsy. Quinpirole-and apomorphine-induced motor activity were potently inhibited by pretreatment with raclopride. The effects of quinpirole, but not apomorphine, were weakly inhibited by SCH 23390. The selective D-1 partial agonist SKF 38393 decreased motor activity and did not induce grooming, oral movements or other behaviours. SKF 38393 inhibited motor activity induced by the administration of quinpirole but did not alter apomorphine-induced motor behaviour. Locomotor activity in normal common marmosets appears to be mediated mainly via D-2 systems. In contrast to rodents, administration of SKF 38393 does not induce behavioural activation and there does not appear to be a facilitating effect of D-1 systems on D-2 function in the normal common marmoset. However, the ability of both SKF 38393 and SCH 23390 to inhibit quinpirole locomotor activity suggests some interaction between D-1 and D-2 systems to occur in this species.

Neuropsychobiology, 1995

The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic ... more The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic zopiclone (7.5 mg) on heart rate activity was studied in 16 elderly insomniacs in a placebo-controlled, randomised, 3-fold crossover trial. After digital preprocessing of the ECG, QRS complexes were automatically recognised by a detection technique based on adaptative thresholds. Both R-R periodicity and heart rate variability were analysed as a function of sleep stages and time of night. Under placebo, heart rate decreased significantly from the first to the second half of the night. The relationship between sleep stages and heart rate remained constant under both hypnotics. Although the two substances significantly modified the distribution of sleep stages, no relevant changes in ECG activity were observed when the proportion of the different sleep stages was taken into consideration.

Neuropsychobiology, 1992

The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern perso... more The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern personal computers however, it is possible to perform signal detection within a reasonable length of time automatically. This paper presents a method for signal processing based on matched filtering. This allows the detection of sleep spindles and K-complexes in a sleep EEG recording with a high degree of accuracy. First the technique is described, and the results of a validation study based on the comparison of visual evaluations and computer analysis are presented. Thereafter, results of an application study are presented. Sleep spindle and K-complex density under the influence of lormetazepam and zopiclone were examined. Under both medications sleep spindle density increased while K-complex density decreased. Computation of Pearson's correlation coefficients demonstrated that the interindividual sleep spindle and K-complex variations under both treatments are highly correlated. The data suggest that lormetazepam and zopiclone, although chemically different, have a similar mode of action and display comparable effects on the sleep EEG.

Neuropsychobiology, 1999

In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine an... more In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine and dexnafenodone, an antidepressant drug under development, were investigated in young, healthy volunteers. In contrast to placebo, both drugs suppressed REM sleep substantially after acute and repeated administration. As a consequence, REM sleep latencies increased under active treatment to mean values which were about two to four times larger than baseline values. Since the active inhibition of the muscle tone is a distinct feature of REM sleep, we studied the influence of the two antidepressant drugs on this variable. By means of computerised EMG analysis, tonic and transient EMG activity were computed for total recording time and for the different sleep stages. While tonic EMG activity during sleep was increased with both drugs, transient EMG events remained unaffected. Computerised analysis of the microstructure of sleep is an effective tool for studying the effect of antidepressant drugs on sleep.

Neuropsychobiology, 1995

Quantitative EEG is a sensitive method for measuring pharmacological effects on the central nervo... more Quantitative EEG is a sensitive method for measuring pharmacological effects on the central nervous system. Nowadays, computers enable EEG data to be stored and spectral parameters to be computed for signals obtained from a large number of electrode locations. However, the statistical analysis of such vast amounts of EEG data is complicated due to the limited number of subjects usually involved in pharmacological studies. In the present study, data from a trial aimed at comparing diazepam and placebo were used to investigate different properties of EEG mapping data and to compare different methods of data analysis. Both the topography and the temporal changes of EEG activity were investigated using descriptive data analysis, which is based on an inspection of patterns of pd values (descriptive p values) assessed for all pair-wise tests for differences in time or treatment. An empirical measure (tri-mean) for the computation of group maps is suggested, allowing a better description of group effects with skewed data of small samples size. Finally, both the investigation of maps based on principal component analysis and the notion of distance between maps are discussed and applied to the analysis of the data collected under diazepam treatment, exemplifying the evaluation of pharmacodynamic drug effects.

Neuropsychobiology, 1995

Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances o... more Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances on the central nervous system (CNS) activity. A standard technique is to measure the EEG under vigilance-controlled and resting conditions for a short duration, for example 5 min. The aim of the present study was to investigate the stability of 5-min EEG recordings. While the time course of the EEG was fairly stable during the recording session under the vigilance-controlled condition, systematic trends became apparent under the resting condition. Pharmaco-sensitivity of the EEG and its reliability increased with the recording duration. Five minutes of EEG recording seem to be sufficient and well chosen to evaluate the influence of drugs on the EEG.

Journal of Neural Transmission - Parkinsons Disease and Dementia Section, 1991

Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactiv... more Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPAantagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease.

European Journal of Pharmacology, 1993

The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8... more The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8 months), young adult (2-4 years) and aged (8-10 years) common marmosets were compared. Juvenile marmosets were more resistant to the actions of MPTP and required a greater cumulative dose over a longer period to induce the same degree of motor disability observed in older animals. Young adult and aged marmosets showed an equivalent motor recovery in the 4-5 weeks following cessation of MPTP treatment, but juvenile animals were less able to compensate for the motor impairments. Losses of putamen [3H]dopamine uptake and caudate nucleus dopamine content were equivalent in young adult and aged animals. However, juvenile animals showed a more marked degree of dopamine depletion and reduction in [3H]dopamine uptake. Histological analysis showed cell loss in the substantia nigra to be most prominent in juvenile animals although it was evident in all groups. No loss of cells in the locus coeruleus was apparent in any of the groups studied, and no intraneuronal eosinophilic inclusions were seen. Greater nigral cell loss and dopamine depletion were required in juvenile animals to impair motor function. The degree of behavioural recovery was less in juvenile animals than in young adult and aged marmosets. The extent of behavioural recovery appeared linked to the severity of cell loss and was not reduced in old age.

Vaccine, 2015

Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictabi... more Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictability of production to meet global demand. This study compared the safety and tolerability of TIVc with an egg-derived trivalent influenza vaccine (TIVf) in 4-17 year-olds. A Phase 3 observer blind, multicentre study enrolled 2055 healthy participants randomized 2:1 to receive either TIVc or TIVf, respectively (1372 TIVc and 683 TIVf evaluable subjects). Participants received one dose each on Days 1 and 28 (4-8 year-olds not previously vaccinated [NPV]) or one dose on Day 1 (4-8 and 9-17 year-olds previously vaccinated [PV]). Solicited adverse events (AEs) occurring within 7 days after each vaccination were assessed; participants were followed up for 6 months after their last dose for safety. Most solicited and unsolicited AEs were mild to moderate with <1% in the severe category. No withdrawals due to AEs, deaths or vaccine related SAEs were reported. TIVc and TIVf were similar in percentages of participants reporting solicited reactions in 4-8 years NPV group after the 1st dose: local reactions, TIVc: 48%, TIVf: 43%; systemic reactions, TIVc: 34%, TIVf: 32%; percentages were lower following the 2nd dose in TIVc; local reactions: TIVc: 40%; TIVf: 43%; systemic reactions: TIVc: 21%; TIVf: 22%. In 4-17 years PV group, solicited reactions were lower following TIVf, local reactions: TIVc: 53%; TIVf: 43%; systemic reactions: TIVc: 37%, TIVf: 30%. Injection site pain was the most common solicited reaction, and was similar following TIVc and TIVf in 4-8 year-olds (TIVc: 56%; TIVf: 55%), and lower following TIVf in 9-17 years group (TIVc: 52%; TIVf: 42%). Reporting of unsolicited AEs was similar for TIVc and TIVf across the two age groups. TIVc was well tolerated and had a safety and reactogenicity profile similar to that of TIVf in healthy 4-17 year-olds (NCT01857206).

Neuropsychobiology, 1995

The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic ... more The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic zopiclone (7.5 mg) on heart rate activity was studied in 16 elderly insomniacs in a placebo-controlled, randomised, 3-fold crossover trial. After digital preprocessing of the ECG, QRS complexes were automatically recognised by a detection technique based on adaptative thresholds. Both R-R periodicity and heart rate variability were analysed as a function of sleep stages and time of night. Under placebo, heart rate decreased significantly from the first to the second half of the night. The relationship between sleep stages and heart rate remained constant under both hypnotics. Although the two substances significantly modified the distribution of sleep stages, no relevant changes in ECG activity were observed when the proportion of the different sleep stages was taken into consideration.

Neuropsychobiology, 1992

The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern perso... more The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern personal computers however, it is possible to perform signal detection within a reasonable length of time automatically. This paper presents a method for signal processing based on matched filtering. This allows the detection of sleep spindles and K-complexes in a sleep EEG recording with a high degree of accuracy. First the technique is described, and the results of a validation study based on the comparison of visual evaluations and computer analysis are presented. Thereafter, results of an application study are presented. Sleep spindle and K-complex density under the influence of lormetazepam and zopiclone were examined. Under both medications sleep spindle density increased while K-complex density decreased. Computation of Pearson's correlation coefficients demonstrated that the interindividual sleep spindle and K-complex variations under both treatments are highly correlated. The data suggest that lormetazepam and zopiclone, although chemically different, have a similar mode of action and display comparable effects on the sleep EEG.

Neuropsychobiology, 1999

In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine an... more In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine and dexnafenodone, an antidepressant drug under development, were investigated in young, healthy volunteers. In contrast to placebo, both drugs suppressed REM sleep substantially after acute and repeated administration. As a consequence, REM sleep latencies increased under active treatment to mean values which were about two to four times larger than baseline values. Since the active inhibition of the muscle tone is a distinct feature of REM sleep, we studied the influence of the two antidepressant drugs on this variable. By means of computerised EMG analysis, tonic and transient EMG activity were computed for total recording time and for the different sleep stages. While tonic EMG activity during sleep was increased with both drugs, transient EMG events remained unaffected. Computerised analysis of the microstructure of sleep is an effective tool for studying the effect of antidepressant drugs on sleep.

Neuropsychobiology, 1995

Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances o... more Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances on the central nervous system (CNS) activity. A standard technique is to measure the EEG under vigilance-controlled and resting conditions for a short duration, for example 5 min. The aim of the present study was to investigate the stability of 5-min EEG recordings. While the time course of the EEG was fairly stable during the recording session under the vigilance-controlled condition, systematic trends became apparent under the resting condition. Pharmaco-sensitivity of the EEG and its reliability increased with the recording duration. Five minutes of EEG recording seem to be sufficient and well chosen to evaluate the influence of drugs on the EEG.

Clinical Pharmacology & Therapeutics, 2003

Sleep

Sleep onset latency (SOL) is frequently defined as the time between lights-out and the first epoc... more Sleep onset latency (SOL) is frequently defined as the time between lights-out and the first epoch of sleep stage 2. In practice, SOL can be quantified easily on the basis of visual examination. We have developed a computer algorithm allowing an automatic estimation of this parameter. The agreement between both strategies, visual and computer analysis, was tested using data from a pharmacological sleep study with 16 elderly insomniacs, which was aimed at comparing the effects of lormetazepam and zopiclone on polysomnography. A high correlation was found between the visual and the computer-based determination of SOL. Drug-related differences in SOL could be shown with both approaches.

Sleep

A method for the automatic detection of episodes of wakefulness during sleep is presented. The al... more A method for the automatic detection of episodes of wakefulness during sleep is presented. The algorithm is based on the evaluation of the alpha slow-wave index (ASI), a measure that has been developed to detect fluctuations of vigilance in daytime pharmaco-electroencephalogram studies. Its application to sleep data was validated with polysomnographic recordings from 16 elderly insomniacs and 16 young healthy subjects. The rate of agreement between the computerized procedure and the visual scoring of wakefulness was 94.0% for the insomniacs and 96.9% for the healthy subjects. The decision criterion used by the computer allowed the definition of a subject-adapted threshold for the detection of wake episodes. The method opens new perspectives for the automatic analysis of continuous 24-hour sleep-wake recordings.

Journal of Infectious Diseases, 2014

Background: A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an avai... more Background: A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.

Klinische Neurophysiologie, 1993

Vaccine, 2004

This study investigated the immune response and safety in 430 adults, when boosted more than 3 ye... more This study investigated the immune response and safety in 430 adults, when boosted more than 3 years after primary or booster TBE immunisation as measured by neutralization test (NT) and ELISA. Tested by NT, the post-booster day 21 geometric mean titer (GMT) was 331 and 142 for the 18-49 and ≥50 years old, respectively. The post-/pre-booster geometric mean titer ratio (GMR) was 2.29 for the 18-49 years old and 3.21 for the ≥50 years old. An at least four-fold increase of neutralizing TBE antibodies was observed in only 26 and 38% of subjects aged 18-49 and ≥50 years, respectively. The booster effect in subjects with only the primary vaccination course prior to study entry clearly depended on the time elapsed since last TBE vaccination with an estimated annual decline rate of 15%. In subjects with at least one additional booster vaccination virtually no antibody decline was observed. This study clearly indicates that (1) adults may be effectively and safely boosted with a different TBE vaccine and (2) following four immunisations protective antibodies can be detected far beyond a period of 3 years, thus, strongly supporting the reconsideration of currently recommended booster intervals.

Vaccine, 2004

A descriptive evaluation of protective immunity was performed on subjects with a complete primary... more A descriptive evaluation of protective immunity was performed on subjects with a complete primary tick-borne encephalitis (TBE) immunization (and additional regular boosters) more than 3 years after primary or booster TBE immunization, as measured by neutralization test and two different ELISA systems. The study population (n = 430) was stratified for age (i.e., 18-49 or 50 years of age) and for the number of years since last TBE vaccination. GMTs (NT) of all subgroups (at the time of the present evaluation) were above detection limit: 144 and 44 for the 18-49-and 50-year-old subjects, respectively. One percent of subjects aged 18-49 years, and 6% of subjects aged 50 years were ELISA-negative. A detailed sub analysis revealed that subjects with either low NT and/or negative to borderline ELISA test results are usually older and constitute a higher number of subjects without any TBE booster vaccination compared to the respective test-positive subject group. From the fourth year (exceeding 3 years after last vaccination) titers show a decline rate of 6-7%. This study indicates that after multiple TBE (booster) immunizations protection surpasses the currently advised TBE booster interval of 3 years, thus supporting reconsideration of the recommendations for booster intervals.

Psychopharmacology, 1991

In normal common marmosets administration of the D-1/D-2 agonist apomorphine or the selective D-2... more In normal common marmosets administration of the D-1/D-2 agonist apomorphine or the selective D-2 agonist quinpirole caused a dose-dependent increase in motor activity and induced stereotyped behaviour. Both the selective D-2 antagonist raclopride and the selective D-I antagonist SCH 23390 inhibited normal locomotor activity and induced catalepsy. Quinpirole-and apomorphine-induced motor activity were potently inhibited by pretreatment with raclopride. The effects of quinpirole, but not apomorphine, were weakly inhibited by SCH 23390. The selective D-1 partial agonist SKF 38393 decreased motor activity and did not induce grooming, oral movements or other behaviours. SKF 38393 inhibited motor activity induced by the administration of quinpirole but did not alter apomorphine-induced motor behaviour. Locomotor activity in normal common marmosets appears to be mediated mainly via D-2 systems. In contrast to rodents, administration of SKF 38393 does not induce behavioural activation and there does not appear to be a facilitating effect of D-1 systems on D-2 function in the normal common marmoset. However, the ability of both SKF 38393 and SCH 23390 to inhibit quinpirole locomotor activity suggests some interaction between D-1 and D-2 systems to occur in this species.

Neuropsychobiology, 1995

The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic ... more The influence of the benzodiazepine hypnotic lormetazepam (1 mg) and the cyclopyrrolone hypnotic zopiclone (7.5 mg) on heart rate activity was studied in 16 elderly insomniacs in a placebo-controlled, randomised, 3-fold crossover trial. After digital preprocessing of the ECG, QRS complexes were automatically recognised by a detection technique based on adaptative thresholds. Both R-R periodicity and heart rate variability were analysed as a function of sleep stages and time of night. Under placebo, heart rate decreased significantly from the first to the second half of the night. The relationship between sleep stages and heart rate remained constant under both hypnotics. Although the two substances significantly modified the distribution of sleep stages, no relevant changes in ECG activity were observed when the proportion of the different sleep stages was taken into consideration.

Neuropsychobiology, 1992

The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern perso... more The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern personal computers however, it is possible to perform signal detection within a reasonable length of time automatically. This paper presents a method for signal processing based on matched filtering. This allows the detection of sleep spindles and K-complexes in a sleep EEG recording with a high degree of accuracy. First the technique is described, and the results of a validation study based on the comparison of visual evaluations and computer analysis are presented. Thereafter, results of an application study are presented. Sleep spindle and K-complex density under the influence of lormetazepam and zopiclone were examined. Under both medications sleep spindle density increased while K-complex density decreased. Computation of Pearson's correlation coefficients demonstrated that the interindividual sleep spindle and K-complex variations under both treatments are highly correlated. The data suggest that lormetazepam and zopiclone, although chemically different, have a similar mode of action and display comparable effects on the sleep EEG.

Neuropsychobiology, 1999

In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine an... more In a placebo-controlled study, the effects on sleep of single and repeated doses of imipramine and dexnafenodone, an antidepressant drug under development, were investigated in young, healthy volunteers. In contrast to placebo, both drugs suppressed REM sleep substantially after acute and repeated administration. As a consequence, REM sleep latencies increased under active treatment to mean values which were about two to four times larger than baseline values. Since the active inhibition of the muscle tone is a distinct feature of REM sleep, we studied the influence of the two antidepressant drugs on this variable. By means of computerised EMG analysis, tonic and transient EMG activity were computed for total recording time and for the different sleep stages. While tonic EMG activity during sleep was increased with both drugs, transient EMG events remained unaffected. Computerised analysis of the microstructure of sleep is an effective tool for studying the effect of antidepressant drugs on sleep.

Neuropsychobiology, 1995

Quantitative EEG is a sensitive method for measuring pharmacological effects on the central nervo... more Quantitative EEG is a sensitive method for measuring pharmacological effects on the central nervous system. Nowadays, computers enable EEG data to be stored and spectral parameters to be computed for signals obtained from a large number of electrode locations. However, the statistical analysis of such vast amounts of EEG data is complicated due to the limited number of subjects usually involved in pharmacological studies. In the present study, data from a trial aimed at comparing diazepam and placebo were used to investigate different properties of EEG mapping data and to compare different methods of data analysis. Both the topography and the temporal changes of EEG activity were investigated using descriptive data analysis, which is based on an inspection of patterns of pd values (descriptive p values) assessed for all pair-wise tests for differences in time or treatment. An empirical measure (tri-mean) for the computation of group maps is suggested, allowing a better description of group effects with skewed data of small samples size. Finally, both the investigation of maps based on principal component analysis and the notion of distance between maps are discussed and applied to the analysis of the data collected under diazepam treatment, exemplifying the evaluation of pharmacodynamic drug effects.

Neuropsychobiology, 1995

Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances o... more Quantitative EEG is a sensitive method used to assess the effects of pharmacological substances on the central nervous system (CNS) activity. A standard technique is to measure the EEG under vigilance-controlled and resting conditions for a short duration, for example 5 min. The aim of the present study was to investigate the stability of 5-min EEG recordings. While the time course of the EEG was fairly stable during the recording session under the vigilance-controlled condition, systematic trends became apparent under the resting condition. Pharmaco-sensitivity of the EEG and its reliability increased with the recording duration. Five minutes of EEG recording seem to be sufficient and well chosen to evaluate the influence of drugs on the EEG.

Journal of Neural Transmission - Parkinsons Disease and Dementia Section, 1991

Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactiv... more Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPAantagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease.

European Journal of Pharmacology, 1993

The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8... more The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8 months), young adult (2-4 years) and aged (8-10 years) common marmosets were compared. Juvenile marmosets were more resistant to the actions of MPTP and required a greater cumulative dose over a longer period to induce the same degree of motor disability observed in older animals. Young adult and aged marmosets showed an equivalent motor recovery in the 4-5 weeks following cessation of MPTP treatment, but juvenile animals were less able to compensate for the motor impairments. Losses of putamen [3H]dopamine uptake and caudate nucleus dopamine content were equivalent in young adult and aged animals. However, juvenile animals showed a more marked degree of dopamine depletion and reduction in [3H]dopamine uptake. Histological analysis showed cell loss in the substantia nigra to be most prominent in juvenile animals although it was evident in all groups. No loss of cells in the locus coeruleus was apparent in any of the groups studied, and no intraneuronal eosinophilic inclusions were seen. Greater nigral cell loss and dopamine depletion were required in juvenile animals to impair motor function. The degree of behavioural recovery was less in juvenile animals than in young adult and aged marmosets. The extent of behavioural recovery appeared linked to the severity of cell loss and was not reduced in old age.