Biomedical subjects

Thomas Roth

Publications and source records attributed to Thomas Roth.

24 records · Page 2Linked to original sources

PubMed2002

Tolerance to daytime sedative effects of H1 antihistamines.

Sedation is the principal side effect of first generation H1 antihistamines, and recent studies have suggested that this side effect should limit the clinical application of these drugs. The sedative effect also underlies the use of these first-generation drugs as nonprescriptive remedies for insomnia. In both cases, the potential for tolerance to the sedative effect of these drugs is an important issue for which there are few objective data. In the study reported here, 15 healthy men age 18 to 50 years received either diphenhydramine 50 mg or placebo twice a day for 4 days in a randomized, double-blind, crossover trial design. Dependent measures included objective and subjective assessments of sleepiness and computer-based tests of psychomotor performance. Both objective and subjective measures of sleepiness showed significantly higher levels on day 1 for diphenhydramine compared to placebo. By day 4, however, levels of sleepiness on diphenhydramine were indistinguishable from placebo. Similarly, diphenhydramine produced significant impairment of performance that was completely reversed by day 4. These data provide the first objective confirmation that tolerance develops to the sedative effect of a prototypical first-generation H1 antihistamine, diphenhydramine. On this dosing regimen, tolerance was complete by the end of 3 days of administration. While other antihistamines and dosing regimens may differ, these results suggest that tolerance to the sedation produced by these drugs develops with remarkable rapidity.

Adolescent↗

PubMed2001

Comparative efficacy of zolpidem and temazepam in transient insomnia.

This study compared hypnotic effects of zolpidem 10 mg, temazepam 15 mg and placebo in healthy adults. Two factors expected to promote insomnia, the 'first night effect' and a 2-hour phase advance, were combined in a single night laboratory-based double-blinded protocol. This was a multi-center study, with data collected in 13 sleep laboratories. Subjects with normal sleep histories and without prior sleep laboratory experience were randomly assigned to treatment groups. Medications were administered 15 min before lights out, with polysomnographic monitoring for 7.5 h. Subjective questionnaires and performance tests, digit symbol substitution test (DSST) and symbol copying test (SCT), were administered at study entry and after arising. 630 subjects completed the study and provided data analyzed using repeated measures ANOVAs. Neither agent significantly reduced objective sleep latency relative to placebo. Zolpidem reduced awakenings and wake after sleep onset (WASO); temazepam did not. Both agents improved sleep efficiency and most subjective sleep measures relative to placebo, with zolpidem superior for five of six subjective outcome measures compared to temazepam. SCT, morning sleepiness and morning concentration were not altered by any treatment. Zolpidem significantly reduced morning DSST performance; temazepam did not. Zolpidem 10 mg provided greater subjective hypnotic efficacy than temazepam 15 mg in this model of transient insomnia, with reduced polysomnographic awakenings and WASO. Impairment of DSST was seen with zolpidem but not temazepam. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2001

Sleep, sleepiness, sleep disorders and alcohol use and abuse.

The study of ethanol's effects on sleep has a long history dating back to the work of Nathaniel Kleitman. This paper reviews the extensive literature describing ethanol's effects on the sleep of healthy normals and alcoholics and the newer literature that describes its interactive effects on daytime sleepiness, physiological functions during sleep, and sleep disorders. Ethanol initially improves sleep in non-alcoholics at both low and high doses with disturbance in the second half of the night sleep at high doses. Tolerance develops to the initial beneficial effects. In alcoholics sleep is disturbed both while drinking and for months of abstinence and the nature of the abstinent sleep disturbance is predictive of relapse. Ethanol interacts to exacerbate daytime sleepiness and sleep-disordered breathing, even inducing apnea in persons at risk. Ethanol's effects on other physiological functions during sleep and other sleep disorders has yet to be documented. 2001 Harcourt Publishers Ltd

Journal Article↗

PubMed2000

Dose-response effects of zaleplon as compared with triazolam (0.25 mg) and placebo in chronic primary insomnia.

The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi-center, randomized, double-blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0.25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0.25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose-response effects were apparent. Triazolam 0.25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0.25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow-wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0.25 mg) produced increases in total sleep time (;25 min) and decreases in latency to persistent sleep at a dose of 0.25 mg. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

PubMedDate not supplied

Place of chronic insomnia in the course of depressive and anxiety disorders.

BACKGROUND: Insomnia is frequent in the general population and is often related to a psychiatric illness. However, little is known about how the chronicity of insomnia affects this relation and how often subjects with chronic insomnia have antecedents of psychiatric disorders. METHODS: A total of 14,915 subjects aged from 15 to 100 years representative of the general population of the United Kingdom, Germany, Italy, and Portugal were interviewed by telephone using the Sleep-EVAL system. The questionnaire assessed current psychiatric disorders according to the DSM-IV classification and a series of questions assessed the psychiatric history. Insomnia was considered as chronic when it lasted for 6 months or more. RESULTS: The prevalence for insomnia accompanied with impaired daytime functioning was 19.1% and significantly increased with age. More than 90% of these subjects had a chronic insomnia. About 28% of subjects with insomnia had a current diagnosis of mental disorders and 25.6% had a psychiatric history. A DSM-IV insomnia disorder was found in 6.6% of the sample. Presence of severe insomnia, diagnosis of primary insomnia or insomnia related to a medical condition, and insomnia that lasted more than one year were predictors of a psychiatric history. In most cases of mood disorders, insomnia appeared before (> 40%) or in the same time (> 22%) than mood disorder symptoms. When anxiety disorders were involved, insomnia appeared mostly in the same time (>38%) or after (> 34%) the anxiety disorder. CONCLUSIONS: The study shows that psychiatric history is closely related to the severity and chronicity of current insomnia. Moreover, chronic insomnia can be a residual symptom of a previous mental disorder and put these subjects to a higher risk of relapse.

Adolescent↗

PubMedDate not supplied

Comparative action of cobalt carbonyl complexes on cancer cells using human tumor xenografts.

We have previously shown that alkyne-cobalt carbonyl complexes inhibit the growth of human cancer cells. They were more active than dicobalt octacarbonyl, cobalt chloride or the free ligands. A difference in growth inhibition was observed among several cobalt complexes in two different cell lines indicating that the ligand may influence the activity of the complex. To further analyze cell type selectivity we compared the growth inhibition of two cobalt carbonyl complexes on eight different human tumor xenografts using a clonogenic assay which has been found to have a high predictive value, for further in vivo evaluation. For one compound as additional four cell lines were evaluated. Surprisingly we observed a large difference in the activity of the two complexes on cells originating from different tissues. Both compounds showed a comparable activity pattern indicating a common mechanism which seems to be different from that of the established metal-based anticancer agent cisplatin. Both complexes exceeded cisplatin in its in vitro anticancer activity.

Adenocarcinoma↗