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Biomedical subjects

A Rodenbeck

Publications and source records attributed to A Rodenbeck.

At least 19 recordsLinked to original sources
PubMed1998

Rebound insomnia after hypnotic withdrawal in insomniac outpatients.

The effect of abrupt medication withdrawal (no-pill discontinuation) was investigated in 1507 insomniacs using the patients' self-ratings on visual analogue scales. Drug discontinuation followed a 28-day treatment period with either 7.5 mg zopiclone, 0.25 mg triazolam, 1.0 mg flunitrazepam, or placebo in a randomized, double-blind, parallel group, multicenter study in private practice. Deterioration below individual pretreatment values (no-pill baseline) in at least one of three subjective parameters of sleep quality (sleep latency, total sleep time, nocturnal awakenings) and three parameters of daytime well-being (morning freshness, daytime tiredness, anxiety) were defined as rebound. The number of patients with rebound (rebound rate) was analyzed for every day of a 2-week posttreatment period. The overall rebound rate was higher in the placebo group (p < or = 0.001) than in each group treated with active drugs. Rebound rates affecting sleep quality were higher for placebo than for zopiclone (p < or = 0.001) and for flunitrazepam (p < or = 0.05). Rebound rates were smaller for zopiclone (p < or = 0.001) and flunitrazepam (p < or = 0.01) than for triazolam. Rebound in at least one item per day appeared in 21.5% (sleep quality) and 25.5% (daytime well-being) of the patients. Rebound decreased with increasing numbers of items of sleep quality or daytime well-being. Patients who did not respond to treatment showed higher rebound rates than those who were treatment responders (p < or = 0.001). Concerning treatment nonresponders, highest rebound was seen in the placebo group, whereas rebound was lowest in placebo responders. These results show that pill discontinuation itself may worsen sleep and daytime well-being in the sense of a rebound phenomenon. Furthermore, the number of patients with rebound remained at a high and varying level during the whole posttreatment period. This result indicates that a deterioration of sleep after drug withdrawal is not apparent during a few days but may last for longer periods in some patients and is modified by marked night-to-night variations.

Adolescent↗
PubMed1998

Altered circadian melatonin secretion patterns in relation to sleep in patients with chronic sleep-wake rhythm disorders.

Human well-being depends on the entrainment of endogenous circadian rhythms of biological functions and the sleep-wake rhythm. Although the incidence of otherwise healthy subjects with chronically altered sleep-wake rhythms is rather low, the investigation of these patients provides new sights into circadian entrainment mechanisms. We therefore examined the circadian rhythm of circulating melatonin and the sleep-wake rhythm in five patients with chronic sleep-wake rhythm disorders and ten age-matched healthy controls. All patients showed altered circadian melatonin rhythm parameters in relation to their sleep-wake cycle compared to age-matched controls. These alterations were random, i.e., independent of the type, the duration, and the age of onset of the disorder. The melatonin onset to sleep onset interval varied between the patients and the melatonin acrophase to sleep offset interval was prolonged in four patients. These findings indicate individual phase relations between the circadian melatonin rhythm and the sleep-wake cycle in patients with chronic sleep-wake rhythm disorders. Since the prolonged melatonin acrophase to sleep offset interval was the most consistent finding independent of aetiological origins, this abnormality may be one possible maintaining factor in chronic sleep-wake rhythm disorders due to reduced phase-resetting properties of the circadian pacemaker. Furthermore, rather low circadian melatonin amplitudes and a subsensitivity to daylight may maintain the disorder in at least some patients.

Adult↗
PubMed1998

Tissue retention and subcellular distribution of continuously infused melatonin in rats under near physiological conditions.

The fate and disposition of the melatonin released into the circulation is still poorly understood, and almost all current knowledge is derived from measurements made after a single and often a very large dose of labelled melatonin. In continuous infusion experiments in freely moving rats, we have recently demonstrated that considerable amounts of melatonin must be endogenously released in order to achieve and maintain approximately a 10-fold elevation of the low daytime plasma levels of this hormone. We have now applied this infusion paradigm to study the fate and tissue accumulation of [3H]-melatonin continuously infused under near physiological conditions into the jugular vein for a period of 2 hr. The retention of [3H]-melatonin and chloroform-insoluble [3H]-melatonin-metabolites was measured in almost all body tissues and their subcellular compartments immediately at the end of the infusion period and 6 hr later. At the end of the 2 hr infusion period, about 45% of the administered melatonin was recovered as water-soluble metabolites in the urine and about 20% in the small intestine. Some accumulation of [3H]-melatonin-derived water-soluble radioactivity was also noticed in the liver, colon, adrenals, and pituitary, as well as in the feces. The subcellular distribution of this radioactivity differed between tissues. During the period of 6 hr after the termination of infusion, a considerable amount of melatonin-derived radioactivity was found to become increasingly attached to the proteous interlayer of chloroform extracts of tissues and subcellular fractions, from where it could only be liberated by protease treatment.

Adrenal Glands↗
PubMed1998

Effect of continuous melatonin infusions on steady-state plasma melatonin levels in rats under near physiological conditions.

It was the aim of this study to measure the actual amount of melatonin required for elevating the circulating hormone from low daytime levels to the 10-fold higher nocturnal steady-state concentrations in rats. For this purpose, escalating doses of melatonin were continuously infused into the right jugular vein and blood samples were repeatedly drawn from the left jugular vein for a period of 2 hr in freely moving catheterized rats. In order to achieve an about 10-fold elevation of the plasma melatonin concentration, 500 ng melatonin/hr had to be infused, i.e., about 300 times the normal nocturnal melatonin content of the pineal. Infusions of up to 61 ng melatonin/hr (equivalent to the melatonin content of 40 pineals at darkness) failed to cause a significant rise of the low daytime steady-state concentrations in the blood. If the dose of 500 ng melatonin/h was infused at night, a less-pronounced rise of the blood levels was observed, as compared to that caused by the infusion of the same dose during daytime. No differences were found in the rate of metabolism between daytime and nighttime. The results of this study indicate 1) that the low basal concentrations of melatonin in the blood are not affected by an increased melatonin supply up to a certain critical threshold, 2) that the rat pineal gland would have to release all its melatonin content almost every 10 sec in order to sustain the elevated steady-state level of melatonin in the circulation during the dark period, and 3) that significant day/night differences exist in the disposition of circulating melatonin if administered in near physiological amounts and under near physiological conditions.

Animals↗
PubMed1997

No evidence for a physiological coupling between melatonin and glucocorticoids.

Much has been speculated about the existence of a physiological coupling between melatonin and glucocorticoid secretion and about a possible anti-stress action of melatonin. We examined the relationship between melatonin and glucocorticoid secretion under close-to-physiological conditions, when the plasma concentration of either melatonin or glucocorticoids was elevated acutely or chronically in both rats and humans. Tryptophan administration caused a massive rise of plasma melatonin, but had no effect on corticosterone levels in rats or on cortisol levels in humans. The acute and long-lasting exposure of rats to uncontrollable stress resulted in a significant rise of adrenal corticosterone secretion, but had no effect on circulating melatonin levels. Orchectomy caused an initial increase in circulating corticosterone (when melatonin was unaffected) and a delayed rise in circulating melatonin (when corticosterone levels were normalized). In humans, no correlation was found between the nocturnal urinary excretion of melatonin and cortisol, either among healthy subjects, or among patients suffering from panic disorder (with an increased urinary excretion of cortisol) or among insomnia patients (with a high incidence of low melatonin secretion). Furthermore, no evidence was found for a suppressive action of melatonin on dexamethasone-mediated thymus regression in rats and on dexamethasone-mediated suppression of lymphocyte proliferation in vitro. Taken together, the results of this study provide no evidence for the existence of mutual influences between melatonin and glucocorticoid secretion, nor do they support the proposed attenuation of glucocorticoid-mediated effects on target cells or tissues by melatonin under physiological conditions.

Adult↗
PubMed1996

[123I]IBZM SPET analysis of dopamine D2 receptor occupancy in narcoleptic patients in the course of treatment.

Elevated levels of central D2 dopamine receptors were found on postmortem examination in cases of human narcolepsy. In vivo investigations using positron emission tomography (PET) and single photon emission tomography (SPET) found no changes of D2 binding in the striatal structures. To investigate whether the elevated D2 receptors in postmortem investigations are due to long-term treatment effects, we applied 123I-labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) ([123I]IBZM, a highly selective CNS D2 dopamine receptor ligand) and SPET in narcoleptic patients in the course of treatment with stimulants and/or antidepressants. Before treatment we found no changes in D2 binding in 10 patients (in comparison to 10 normal controls). After treatment (performed in five patients for 3 months) we found changes in D2 binding in four of them, indicating that the results of the postmortem studies could have been influenced by long-term medications. Human narcolepsy seems not to be related to a striatal D2 dopaminergic disturbance.

Adolescent↗
PubMed1996

Effects of chronic treatment with methadone and naltrexone on sleep in addicts.

Previous studies have described sleep disturbance secondary to chronic opiate use and abuse. Drug-dependency insomnia is of interest because chronic sleep disturbances can promote depressive symptoms which could lead to a drug relapse. For the first time we compared the polysomnographic parameters of 10 methadone-substituted outpatients and 10 naltrexone-treated outpatients. Methadone (mu-opioid agonist) produced a marked fragmentation of the sleep architecture with frequent awakenings and a decrease in EEG arousals. In comparison with methadone and controls, the naltrexone (mu-opioid antagonist) group showed the shortest sleep latency and the longest total sleep time. These data indicate that mu-agonists and mu-antagonists have different effects on sleep. The implications, especially the involvement of opioid-dopamine interactions on sleep and movements during sleep, are discussed.

Adult↗
PubMed1996

[Ambulatory, comprehensive, behavior therapy-oriented weight reduction program (Optifast Program). An alternative therapy in obstructive sleep apnea].

We investigated the therapeutic effect of marked body weight reduction on the predominantly obstructive sleep apnea syndrome by the application of an out-patient, behaviour therapy based body weight reduction program (Optifast-program) in five of our obese apnea patients (mean overweight by Broca 53.6 +/- 24.8 kg). Mean body weight reduction was 32.7 +/- 15.8 kg after six months. The mean apnea-index of 34.5 +/- 23.1/h prior to the weight reduction dropped to 7.8 +/- 6.1/h after therapy. The mean apnea-hypopnea-index (so called "respiratory disturbance index", RDI) could be reduced from 45,7 +/- 26.0/h to 14.0 +/- 11.4/h. The best therapeutic effect on the sleep related respiratory parameters was seen in patients who reached their normal weight whereas the absolute weight reduction itself seems to be less important. Our results should encourage this causal therapy in appropriate patients.

Adult↗
PubMed1996

Nocturnal plasma melatonin levels after flunitrazepam administration in healthy subjects.

Polysomnographic sleep patterns and melatonin secretion were investigated in 5 young (age 25.6 +/- 1.1 years) and 5 middle-aged (age 49.4 +/- 5.4 years) healthy male subjects after intravenous administration of 1 mg flunitrazepam and placebo in a randomized, double-blind and cross-over setting. The area under the curve (AUC) of total nocturnal melatonin plasma concentration decreased 23.3 +/- 11.5% in young subjects (P < or = 0.05) and 39.3 +/- 5.2% in middle-aged subjects (P < or = 0.05) after flunitrazepam infusion compared with placebo infusion. Differences in nocturnal peak values of melatonin were 5.4 +/- 22.0% in young subjects (not significant) and 34.0 +/- 14.7% in middle-aged subjects (p < or = 0.05). Flunitrazepam significantly (P < or = 0.05) improved sleep latency and the number of sleep stage changes in the group of all subjects. These results show that, although the benzodiazepine flunitrazepam improves sleep, it reduces the nocturnal secretion of melatonin, and therefore alters the circadian rhythm of a hormone which is supposed to play a special role in circadian sleep-wake rhythmicity.

Adult↗
PubMed1996

Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia.

Nocturnal melatonin secretion and polysomnographic sleep patterns were investigated in ten patients with chronic primary insomnia (age 41.3 +/- 9.5 years) and in five healthy subject, (age 27.2 +/- 0.7 years) after either a single intravenous administration of 25 mg doxepin or placebo in a randomized, double blind, and cross-over setting. In the patient group a third session was performed after a three-week open oral treatment with 25 mg doxepin daily. The single-dose administration of doxepin did not affect plasma melatonin concentrations in either the patients on the healthy subjects. After three weeks of oral doxepin intake by the patients, the area under the curve of total nocturnal plasma melatonin concentration was significantly increased by 26% and the peak values were increased by 30%. Both after the single i.v. treatment as well as after long-term oral administration, doxepin also significantly improved sleep latency, total sleep time, and sleep efficiency in the insomniacs as well as the healthy subjects, whereas the nocturnal wake time was decreased. These findings indicate that this tricyclic antidepressant not only improves sleep and but also preserves the secretion of a hormone which is believed to play a special role in the circadian sleep-wake rhythm. Long-term doxepin treatment of chronic insomniac patients not only improves sleep but also restores nocturnal melatonin secretion in these patients.

Adult↗
PubMed1996

Clinical management of patients with insomnia. The role of zopiclone.

Insomnia, especially when chronic, is associated with disturbances in daytime well-being and performance, resulting in a poor quality of life for those affected. Zopiclone has been proven as a drug that favourably balances sleep induction and maintenance as well as an improvement in daytime well-being (efficacy) with a low potential for adverse effects (safety) in the symptomatic treatment of insomnia. Management of chronic insomnia with zopiclone needs a multidimensional approach involving the proper diagnosis of possible underlying causes, and combined use of causal treatment, general sleep hygiene measures, basic elements of psychological treatment and adjunctive medication. It is recommended that therapy with the nonbenzodiazepine hypnotic zopiclone should conform to the guidelines for the use of hypnotics, which are valid for all benzodiazepine receptor agonists.

Azabicyclo Compounds↗
PubMed1996

[Sleep complaints and hypnotic use by the elderly--results of a representative survey in West Germany].

For the first time, a country-wide group of West-Germans were interviewed regarding their sleep complaints and hypnotic intake. Therefore 344 persons who were older than 65 years and 1653 subjects between the age of 14 and 65 years were representatively selected by a random route system. Around the age of 45 the prevalence of sleep-disturbances starts rising continuously and dramatically. Over the age of 65 nearly half of the West-Germans (43%) suffer from difficulties in initiating and/or maintaining sleep (DIMS) at least sometimes, 15% suffer frequently or always from these complaints. 79% of the sleep disturbed elderly (over the age of 65) are chronically ill, having sleep-complaints for more than 2 years or since childhood. The hypnotika intake increases with age as well. Around 45 years of age the irregular hypnotika intake (several times the year or month), and after 55 years of age, regular hypnotic intake (daily or several times the week) rapidly rises. After 65 years of age hypnotic intake increases much more than the sleep complaints do. So, every third elderly person (34%) takes hypnotics at least irregularly. The results of this study indicate that sleep complaints in the elderly are three times more common and more severe than in younger persons, and that they tend to chronify while treated with hypnotics.

Adolescent↗
PubMed1996

[Functional palatoraphy and modified genioplasty in obstructive sleep apnea].

10 patients with obstructive sleep apnea syndrome (OSAS) have been treated with the new surgical procedure functional palatoraphy and modified genioplasty. 5 months after surgery 7 patients with an apnea hypopnea index under 10 were cured. Three therapy refractory patients were all overweight with a body mass index of more than 29 kg/m2. Excessively overweight patients should therefore not be operated. Following the selection criteria we introduced an effective new treatment method for OSAS.

Adult↗
PubMed1995

Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia.

Polysomnographic sleep patterns and melatonin secretion were investigated in 10 patients (age: 41.3 +/- 9.5 years) who suffered from chronic primary insomnia and complained predominantly about difficulties in maintaining sleep and in five healthy controls (age 27.2 +/- 0.7 years). Nocturnal plasma melatonin concentrations were obtained hourly, measured by direct radioimmunoassay and statistically compared between insomniacs and controls with age as a covariate. Plasma melatonin levels in the patient group tended to begin increasing earlier in the evening and were significantly (P < or = 0.01) lower during the middle of the night (peak value 82.5 +/- 26.5 pg/ml) than in the healthy controls (peak value 116.8 +/- 13.5 pg/ml). Among the patients, the most severely reduced nocturnal plasma melatonin levels were found in those patients with a history of sleep disturbance lasting for longer than five years (N = 6; age 41.8 +/- 11.7 years; duration 15.3 +/- 5.9 years; peak value 72.1 +/- 25.0 pg/ml); whereas those chronic insomniacs affected for fewer than five years had relatively higher nocturnal levels (N = 4; age 40.6 +/- 6.5 years; duration 3.8 +/- 1.5 years; peak value 98.2 +/- 23.9 pg/ml). These results show that the circadian rhythm of melatonin secretion is disturbed in patients with chronic primary insomnia, and that the nocturnal plasma melatonin secretion is increasingly more affected the longer the patients are unable to maintain a regular sleep pattern.

Adult↗
PubMed1995

[Chronification of sleep disorders. Results of a representative survey in West Germany].

In a representative selection of German citizens who were older than 13 years of age, 1,997 were asked about their sleep complaints. They were also asked how frequently a physician was consulted and how often sleeping pills were taken. According to our results sleep disturbances are an important health problem in Germany. Every fourth person suffers at least sometimes from difficulties in falling asleep and/or staying asleep, problems which are not due to external influences. Seven percent suffer frequently or always from these complaints; 15% report that they are frequently tired or that they are always tired during the day. Ten percent of all persons suffering from sleep complaints take sleeping pills daily or at least sometimes during the week. Forty-five percent of all persons who take hypnotics daily still frequently or always suffer from difficulties in falling asleep and/or staying asleep. Furthermore, sleep complaints tend to become chronic: 75% of the sleep-disturbed population are chronically ill, having had complaints for more than 2 years of since childhood. They suffer from sleep disturbances and from reduced performance during the following day. Nevertheless, it appears as though neither patients nor physicians take insomnia seriously. This might answer the question of why only 17% of the persons who do not suffer more than 2 years from sleep disturbances and only 49% of the chronically ill population consult a doctor because of their sleep disturbances. The results of this study indicate the importance of informing patients and physicians about insomnia and different ways of treating it.

Adolescent↗
PubMed1995

[Disorders of the circadian sleep-wake rhythm--diagnostic and therapeutic principles].

The most important circadian rhythm disorders are presented excluding jet lag syndrome and shift work. Clinical and psychological findings, pathophysiological principles and social consequences are discussed with reference to recent literature. The ICSD classification is reviewed critically and proposals for operationalisation of new diagnostic procedures are offered. The current therapeutic principles are described and it is attempted to develop a more systematic documentation of therapy aiming at the possibility of future outcome-comparison between the presently very heterogenic principles.

Biological Clocks↗
PubMed1995

[Treatment of obstructive sleep apnea syndrome by ambulatory, comprehensive, behavior therapy oriented weight reduction (Optifast program)].

We investigated the therapeutic effect of marked body weight reduction on the predominantly obstructive sleep apnea syndrome by the application of an out-patient, behaviour therapy based body weight reduction program (Optifast-program) in 5 of our obese apnea patients. Mean body weight reduction was 32.7 +/- 15.8 kg after 6 months. The mean apnea-index of 34.5 +/- 23.1/h prior to the weight reduction dropped to 7.8 +/- 6.1/h after therapy. The mean apnea-hypopnea-index could be reduced from 45.7 +/- 25.9/h to 14.0 +/- 11.4/h. The best therapeutic effect on the sleep related respiratory parameters, was seen in patients who reached their normal weight. Our results shows that even severe, predominantly obstructive sleep apnea syndromes could be treated successfully with a marked body weight reduction.

Adult↗