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Biomedical subjects

K Wesnes

Publications and source records attributed to K Wesnes.

At least 37 records · Page 2Linked to original sources
PubMed1998

Oxygen administration selectively enhances cognitive performance in healthy young adults: a placebo-controlled double-blind crossover study.

It was recently demonstrated that oxygen administration can improve performance on a simple word recall task in healthy young adults. This study was aimed at determining the impact of various durations of oxygen administration on a wider range of cognitive measures. This was achieved using the Cognitive Drug Research computerised test battery, and employing a double-blind, placebo-controlled crossover design. Over a period of 7 weeks, 20 participants were trained and subsequently assessed on the test battery under several durations of oxygen inhalation; air administered in an identical fashion served as a control. The results provided support for our earlier work in that increases were found in both immediate and delayed word recall. In addition, oxygen administration significantly improved performance on several measures of attention and vigilance. Simple reaction time, choice reaction time, digit vigilance reaction time and picture recognition reaction time were improved in a manner which depended on the duration of oxygen inspired. With the exception of word recall, no significant improvements were found for any measure of accuracy, nor were word recognition, digit memory scanning, or spatial memory improved. These results are discussed in the context of stages of information processing and are consistent with the hypothesis that cognitive performance is "fuel-limited" and can be differentially augmented by increasing the availability of the brain's metabolic resources.

Adult↗
PubMed1998

Oxygen and cognitive performance: the temporal relationship between hyperoxia and enhanced memory.

Oxygen administration coinciding with word presentation enhances word recall in humans, suggesting that elevated levels of circulating blood oxygen may be available to neural memory consolidation processes. This double-blind experiment examined the relationship between blood oxygen levels and cognitive performance when oxygen was inspired for 2 min at different times relative to a simple word recall task, forward digit span and backward digit span. Transient hyperoxia, measured by haemoglobin-bound oxygen, was evident following oxygen inspiration. Neither forward nor backward digit span was affected by oxygen administration. Word recall (12 min following word presentation) was enhanced when oxygen was administered 5 min prior to, immediately before or immediately following word presentation; but not 10 min prior to, 5 min following nor 10 min following, word presentation. These data suggest that oxygen administration can selectively enhance aspects of cognitive performance and support a hypothesis whereby supplemental blood oxygen is sequestered by neural mechanisms involved in memory consolidation.

Adult↗
PubMed1998

Cognitive performance in recreational users of MDMA of 'ecstasy': evidence for memory deficits.

Cognitive task performance was assessed in three groups of young people: 10 regular users of 3,4-methylenedioxymethamphetamine (MDMA) who had taken 'ecstasy' 10 times or more; 10 novice MDMA users who had taken 'ecstasy' one to nine times; and 10 control subjects who had never taken MDMA. A computerized battery of cognitive tasks (Cognitive Drug Research system) was undertaken on a day when subjects were drug free. Performance on the response speed and vigilance measures (simple reaction time, choice reaction time, number vigilance), was similar across the three subgroups. However on immediate word recall and delayed word recall, both groups of MDMA users recalled significantly less words than controls. Animal research has shown that MDMA can lead to serotonergic neurodegeneration, particularly in the hippocampus and frontal cortex. Although the design of this study was far from ideal, these data are consistent with other findings of memory decrements in recreational MDMA users, possibly caused by serotonergic neurotoxicity.

Adolescent↗
PubMed1998

Tiagabine: absence of kinetic or dynamic interactions with ethanol.

Tiagabine is a new antiepileptic drug that inhibits the uptake of gamma-aminobutyric acid into neurons and glia. This double-blind, placebo-controlled study investigated the effect of multiple doses of tiagabine on the adverse cognitive effects produced by a single dose of ethanol in 20 healthy volunteers. The effects of each drug on the pharmaco-kinetics of the other were also determined. Compared with placebo, tiagabine produced no statistically significant effects on digit vigilance speed (primary assessment variable) or accuracy, choice reaction time, immediate or delayed word recall, delayed word recognition speed or sensitivity, visual tracking, body sway, or subjective measures of alertness, calmness, and contentment. There was no evidence of a pharmacodynamic interaction between tiagabine and ethanol with respect to these variables. The pharmacokinetic parameters of tiagabine and ethanol (maximum plasma concentration [Cmax], time to Cmax and area under the plasma concentration-time curve) were unchanged during concomitant administration. Adverse events, which mainly affected the central nervous system, occurred with a similar incidence during tiagabine and placebo administration and were more common after the administration of ethanol. There appears to be no need for additional caution regarding driving or operating machinery when ethanol is administered to patients taking tiagabine.

Adult↗
PubMed1997

The psychological and psychiatric effects of rIL-2 therapy: a controlled clinical trial.

It has been suggested that recombinant interleukin-2 (rIL-2) may cause pyschological and psychiatric problems, although the effects of rIL-2 on its own have not been well documented. To evaluate these effects, 17 patients with advanced colorectal cancer took part in a randomised, parallel group study of rIL-2 with chemotherapy (5-fluorouracil and leucovorin) versus chemotherapy alone. Patients were assessed regularly by means of various psychometric tests including the Hospital Anxiety and Depression Scale, the Mood Rating Scale, the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Trail-Making Test and the Benton Revised Visual Retention Test. Rigorous discontinuation criteria were applied to ensure that the effect of time-related variables did not influence the results. Compared with patients who were given chemotherapy alone, patients receiving immunochemotherapy reported reduced energy, impaired confidence, higher depressed mood and more confusion. Immunochemotherapy was rated as more distressing than chemotherapy alone and patients reported a greater incidence of appetite impairment, weight loss, poor concentration and fever. Cognitive assessments indicated that brain dysfunction can be caused by rIL-2. Compared with the control group, patients receiving immunochemotherapy showed significant impairment on Trail Making Test B and the Digit Symbol Substitution Test. One patient developed repeated transient psychotic episodes associated with rIL-2 infusions and another regularly became confused. These effects were not due to sleep deprivation or pyrexia. Treatment with rIL-2 should not be discarded on psychosocial grounds, although in each case the psychological morbidity and adverse effects on quality of life need to be balanced carefully against potential therapeutic benefits.

Antimetabolites, Antineoplastic↗
PubMed1997

Moxonidine and cognitive function: interactions with moclobemide and lorazepam.

OBJECTIVE: Moxonidine represents a new generation of centrally acting antihypertensive drugs. It binds to I1-imidazoline receptors and exerts its antihypertensive activity through a reduction in systemic vascular resistance, while cardiac output remains unchanged or even increases slightly. Moxonidine is prescribed for the treatment of mild to moderate hypertension. Typical doses are 0.4 to 2.0 mg given as one dose in the morning or as divided doses in the morning and evening. METHODS: The effects of moxonidine 0.4 mg once daily in combination with moclobemide or lorazepam were investigated in two, double-blind, randomised, placebo-controlled, two-way crossover studies in a total of 48 healthy volunteers. Safety assessments were made in each study and included pre- and post-study measurement of blood pressure, heart rate, ECG, haematology, blood biochemistry, and urinalysis, and recording of adverse events. RESULTS: In the first study, moxonidine alone was found to produce small but statistically significant impairments of vigilance detection speed at 4 h and 6 h. Lowering of subjective alertness was also observed. Repeat dosing with moxonidine produced an impairment of memory scanning performance. These findings were not reproduced in the second study, in which moxonidine alone produced an improvement in immediate word recall at 4 h and 6 h. No interactions were observed when moxonidine was co-administered with moclobemide. Moxonidine, when co-administered with lorazepam, produced interactions with three tasks requiring high levels of attention: choice, simple reaction time and digit vigilance performance; memory tasks; immediate word recall, delayed word recall accuracy; and visual tracking. A total of 47 adverse events were reported in study 1. Moxonidine produced a slight decrease of systolic and diastolic blood pressure. In study 2, a total of 55 adverse events were reported. In both trials, the most frequently reported events were tiredness and dryness of mouth, the latter occurring only under the moxonidine treatment. There were no clinically relevant changes observed in blood pressure, pulse rate, and laboratory tests in either study, nor was there any evidence of any interaction between moxonidine and either moclobemide or lorazepam. CONCLUSION: Moxonidine was found to be safe and well tolerated in healthy volunteers. However, the impairments on attentional tasks were greater when moxonidine was co-administered with lorazepam 1 mg. These effects should be considered when moxonidine is codosed with lorazepam, although they were smaller than would have been produced by a single dose of lorazepam 2 mg.

Adolescent↗
PubMed1996

Incremental dosage of the new antipsychotic mazapertine induces tolerance to cardiovascular and cognitive effects in healthy men.

OBJECTIVES: Mazapertine is a structurally novel antipsychotic compound with high affinity for D2, D3, 5-HT1a, and alpha 1 receptors. The objectives were to determine whether tolerance to orthostatic hypotension caused by this compound could be induced by slowly increasing the dose administered and to investigate its effect on cognitive and motor functions. METHODS: Thirteen healthy male subjects received incremental oral doses of mazapertine (from 5 to 50 mg over 7 days; n = 10) or placebo (n = 3) in part I and single doses in parts II (20 or 30 mg or placebo) and III (40 mg or placebo) in a double-blind fashion. Blood pressure, heart rate, cardiac hemodynamics, cognitive functions, and occurrence of acute extrapyramidal symptoms were investigated. RESULTS: Mazapertine appears to be safe and well tolerated when administered orally for 7 days to normal healthy men. No accumulation of serum prolactin occurred after multiple dosing, suggesting limited potential for inducing galactorrhea. The drug was rapidly absorbed, and kinetics appeared to be dose dependent, without accumulation. The elimination half-life was about 5 to 10 hours. No evidence of any positive or negative cognitive effects could be detected. Mild motor symptoms were observed only at high doses (not statistically significant). Mazapertine had a minimal effect on cardiac output and stroke volume. Tolerance to hypotension could be induced by slowly increasing the dose administered. CONCLUSIONS: Mazapertine is well tolerated when administered orally for seven days, and tolerance to hypotension can be induced by slowly increasing the dose administered. Therefore, nothing precludes further clinical testing on patients with schizophrenia.

Administration, Oral↗
PubMed1996

Absence of a sertraline-mediated effect on the pharmacokinetics and pharmacodynamics of carbamazepine.

UNLABELLED: A double-blind, randomized, placebo-controlled study was conducted in 14 healthy male volunteers to assess the effects of sertraline on the pharmacokinetics and pharmacodynamics of carbamazepine. METHOD: Subjects received carbamazepine 200 mg once daily for 2 days and every 12 hours thereafter. On Days 16 to 32, subjects also received either sertraline or placebo daily. The dose of sertraline was increased from 50 to 200 mg daily over 7 days; the 200-mg dose was given for 10 days. Samples for pharmacokinetic analyses were obtained on Days 15 and 32; trough plasma concentrations of carbamazepine and its principal metabolite, carbamazepine-10, 11-epoxide (CBZ-E), were determined daily beginning on Day 13. Cognitive function testing was performed on Day 1 before carbamazepine dosing (baseline), Day 15 (carbamazepine alone), and Day 32 (carbamazepine plus sertraline or placebo). RESULTS: There were no significant differences between the sertraline and placebo groups in any of the pharmacokinetic parameters for carbamazepine or CBZ-E. Carbamazepine alone impaired cognitive function. The addition of sertraline did not potentiate these effects. Side effects were reported by 2 subjects in each group, but none were severe. CONCLUSION: These findings indicate that sertraline does not affect the pharmacokinetics of carbamazepine or its principal metabolite and does not potentiate the cognitive effects of carbamazepine.

1-Naphthylamine↗
PubMed1996

Absence of effect of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin.

UNLABELLED: A double-blind, randomized, placebo-controlled study assessed the effects of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin in 30 healthy male volunteers. METHOD: All subjects received phenytoin throughout the study. The dose of phenytoin was 100 mg three times daily; steady-state trough plasma phenytoin concentrations were determined on Day 6. Concurrent treatment with sertraline (16 subjects) or placebo (13 subjects) was initiated on Day 8 and continued throughout the study in those subjects whose trough plasma phenytoin concentrations were between 5 and 20 micrograms/mL. The dose of sertraline was increased from 50 to 200 mg/day over 7 days; the 200-mg dose was then administered for 10 days. The plasma phenytoin concentration-time profile was determined on Day 7 before the start of sertraline or placebo dosing and at the end of dosing on Day 24. Psychometric testing was done before and after dosing on Days 0, 7, and 24. RESULTS: There were no significant differences between the sertraline group and the placebo group in the pharmacokinetic parameters of phenytoin. In addition, there was no indication that administration of phenytoin alone or concomitant administration of phenytoin and sertraline impaired cognitive function. Treatment-related side effects, primarily headache and nausea, were reported in 8 of 16 sertraline subjects and in 5 of 13 placebo subjects. Two subjects in the sertraline group withdrew because of side effects (rash), and 3 subjects in the placebo group withdrew because of side effects (rash and headache). CONCLUSION: High dosages of setraline did not affect the pharmacokinetics or the pharmacodynamics of phenytoin in ths study performed in healthy volunteers.

1-Naphthylamine↗
PubMed1996

Absence of effect of sertraline on time-based sensitization of cognitive impairment with haloperidol.

UNLABELLED: This double-blind, randomized, placebo-controlled study evaluated the effects of haloperidol alone and haloperidol plus sertraline on cognitive and psychomotor function in 24 healthy male subjects. METHOD: All subjects received placebo on Day 1 and haloperidol 2 mg on Days 2 and 25. From Days 9 to 25, subjects were randomly assigned to either sertraline (12 subjects) or placebo (12 subjects); the sertraline dose was titrated from 50 to 200 mg/day from Days 9 to 16, and remained at 200 mg/day for the final 10 days of the drug administration period. Cognitive function testing was performed before dosing and over a 24-hour period after dosing on Days 1, 2, and 25. RESULTS: Impairment of cognitive function was observed 6 to 8 hours after administration of haloperidol on Day 2 but was not evident 23 hours after dosing. When single-dose haloperidol was given again 25 days later, greater impairment with earlier onset was noted in several tests in both treatment groups, suggesting enhancement of this effect. There was no indication that sertraline exacerbated the impairment produced by haloperidol since an equivalent effect also occurred in the placebo group. Three subjects (2 on sertraline and 1 on placebo) withdrew from the study because of side effects. Ten subjects in each group reported side effects related to treatment. The side effect profiles of sertraline and of placebo were similar. CONCLUSION: Haloperidol produced a clear profile of cognitive impairment that was not worsened by concomitant sertraline administration.

1-Naphthylamine↗
PubMed1995

The cognitive and psychomotor effects of opioid analgesics. I. A randomized controlled trial of single doses of dextropropoxyphene, lorazepam and placebo in healthy subjects.

Twelve subjects (3 male) took part in a randomised double-blind four way crossover study designed to examine the cognitive and psychomotor effects of single doses of dextroproxyphene. On four study days one week apart each subject received each study product (i) dextropropoxyphene napsylate 100 mg, (ii) dextropropoxyphene napsylate 200 mg, (iii) lorazepam 2 mg and (iv) placebo. Performance measures were simple reaction time, choice reaction time, number vigilance, memory scanning, word recall (immediate and delayed), word recognition, picture recognition, critical flicker fusion threshold (CFFT) and visual analogue scales of alertness, calmness and contentment. Lorazepam had a marked effect on the range of tests used illustrating the sensitivity of the best battery. This was in contrast to the effects of dextropropoxyphene. A dose related effect in CFFT was detected, the 200 mg dose producing a significant decrease in CFFT throughout the testing period. Dextropropoxyphene also showed a tendency to improve scores on the verbal memory tasks. These data indicate that dextropropoxyphene in the usual doses does not produce significant impairment of cognitive and psychomotor function.

Adult↗
PubMed1995

The cognitive and psychomotor effects of opioid analgesics. II. A randomized controlled trial of single doses of morphine, lorazepam and placebo in healthy subjects.

Twelve subjects (8 male) took part in a randomised double blind four way crossover design study comparing four treatments: (i) morphine sulphate 10 mg, (ii) morphine sulphate 15 mg, (iii) lorazepam 1 mg (positive control) and (iv) placebo. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam produced a marked impairment in the tests of attention and memory. CFFT was reduced from 1-4 h but this only reached significance at 4 hours. The subjective measures suggested impaired alertness but this did not reach significance. The effects of morphine were less dramatic; both doses of morphine produced significant impairment at 1 hour on tests of secondary memory retrieval (delayed word recall and picture recognition sensitivity). CFFT was reduced for the whole observation period (6 h) achieving statistical significance at 4 hours. Morphine 15 mg produced a significant improvement in accuracy on the choice reaction time test at the 2, 4 and 6 h assessments. These results show minimal impairment of cognitive and psychomotor function after single oral doses of morphine and with possible improvement in one test. Further studies are required to examine the effect of repeated doses.

Adult↗
PubMed1995

Cognitive and quantified electroencephalographic correlates of cycloserine treatment in Alzheimer's disease.

Cycloserine acts as a potent and selective modulator of the N-methyl-D- aspartate (NMDA) receptor-associated glycine recognition site, which may be a possible mechanism for this compound's positive effects on memory formation and retrieval processes in animals. Studies in normal human volunteers have shown that cycloserine can have significant positive effects on cognitive processing in the elderly and can ameliorate memory deficits induced by subcutaneously administered scopolamine. Based on this profile, a double-blind, placebo controlled, parallel group (three drug dosages) study was conducted as part of a larger study to assess the efficacy and safety, as well as the cognitive and central nervous system (CNS) impact, of 6 months of cycloserine treatment in patients (N = 40) with probable dementia of the Alzheimer type (DAT). The Cognitive Drug Research Computerize Assessment System (CDR System) served as the primary outcome measure of efficacy. CNS activity was assessed using quantified electroencephalography (QEEG). Safety measures included adverse effects documentation and analysis of blood chemistry/hematology. Cycloserine proved to be a safe agent in this population at the doses given but failed to show any statistically significant effects in the areas of cognition and global clinical ratings and did not indicate significant CNS activity on QEEG. These findings suggest that cycloserine has no measurable therapeutic effect on Alzheimer's disease at the doses given.

Aged↗
PubMed1995

A pilot study of the effect of low level exposure to mercury on the health of dental surgeons.

OBJECTIVES: This project was conducted to examine whether the computerised analysis of psychomotor responses available from Cognitive Drug Research is appropriate for measuring an effect of low level exposure to mercury in dentists. METHODS: A computerised battery of psychomotor tests was given to two groups of dentists (older dentists and trainees) and to two age matched control groups. As well as the psychomotor tests, volunteers were required to complete a questionnaire to identify potential influences on psychomotor performance and to provide a sample for analysis of urinary mercury. RESULTS: Statistical analysis of the results showed that the older dentists had slightly higher concentrations of urinary mercury although most were around background levels and they were all within occupational limits. Five of the psychomotor tests showed no differences between the performance of the four groups. The older dentists showed significantly better performance on the simple reaction time test and significantly poorer performance in the immediate word recall and delayed word recall tests. CONCLUSIONS: Poorer performance in memory recall tests confirms previously reported studies. This together with the confirmation that this test system is a practical tool in the occupational setting suggests that a larger study of the effects of mercury exposure on dentists would be appropriate.

Adult↗
PubMed1994

Single dose human pharmacology of umespirone.

We have compared the cognitive, EEG, and neuroendocrine effects of single doses of umespirone (20 mg and 80 mg) with those of buspirone (30 mg) and placebo in double-blind, cross-over studies in 44 healthy men. The pattern and time-course of the cognitive effects with umespirone and buspirone were dissimilar. Peak effects of buspirone were seen shortly after dosing and then receded, whilst the effects of umespirone persisted for up to 23 h. Although both drugs objectively impaired attention, buspirone reduced subjective alertness, calmness, and contentedness, whilst umespirone increased subjective alertness and contentedness and showed potential to improve secondary verbal memory. The EEG effects of umespirone were different from those seen with buspirone; they included a decrease of power in the alpha 1 band and the beta bands in the frontocentral area and an increase in the delta and theta bands in the occipitotemporal area. Umespirone had a later onset of action than buspirone but its effects lasted longer. Similar transient increases in serum prolactin and growth hormone concentrations were seen with buspirone and 80 mg umespirone; umespirone 20 mg had no effect. Plasma concentrations of ACTH and adrenaline and serum concentrations of cortisol were unaffected by either dose of umespirone. There was some evidence that buspirone increased ACTH and cortisol concentrations in some cases, and that umespirone increased noradrenaline concentrations. The frequency of adverse events was higher with buspirone than with 80 mg of umespirone. At the lower dose of umespirone, the frequency was similar to that with placebo.

Adult↗
PubMed1992

Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function.

OBJECTIVE: To assess whether fluvoxamine alters the pharmacokinetics of alcohol or potentiates alcohol-related impairment of cognitive function. METHODS: The study design required partially "blinded" balanced crossover studies, each involving 12 healthy male volunteers who each received a 40 gm dose of intravenous or oral alcohol after single and multiple doses of 50 mg fluvoxamine. Main outcome measures for pharmacokinetics were venous blood alcohol and plasma fluvoxamine. Main outcome measures for pharmacodynamics were word recall, simple and choice reaction time, number vigilance, memory scanning, and word recognition. RESULTS: The pharmacokinetics of intravenous alcohol were not affected by concomitant administration of fluvoxamine. Compared with placebo-alcohol, alcohol slightly increased the rate of fluvoxamine absorption, but the area under the plasma concentration-time curve from 0 to 12 hours at steady state was unchanged. As expected, alcohol significantly impaired cognitive function in volunteers. However, fluvoxamine did not potentiate the effects of alcohol and in some instances appeared to reverse the effects or reduce their duration. Fluvoxamine was well tolerated: only mild adverse effects were reported, and none of those required intervention. CONCLUSION: Fluvoxamine does not interact significantly with alcohol or potentiate alcohol-related impairment of cognitive function.

Administration, Oral↗