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Biomedical subjects

G Hajak

Publications and source records attributed to G Hajak.

At least 109 records · Page 6Linked to original sources

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↗

[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↗

[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↗

[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↗

[General practice of acute inpatient treatment of mania. Retrospective comparative study of 100 patients at each of 2 psychiatric centers].

We reviewed the literature regarding acute therapy of manic patients and compared these recommendations with actual practice by reviewing 399 therapies in 100 patients each from two psychiatric care centres between 1975 und 1991. Higher age, more serious disease and a higher percentage of compulsory commitments are typical of patients treated in institutions with a mandatory admission policy as compared to university clinics, which are not compelled to admit patients. The treatment methods practised in both centres deviated greatly from recommendations in the literature. In spite of widespread therapeutic recommendations, lithium and carbamazepin are seldom employed for acute treatment; neuroleptic agents were preferred for all grades of severity. Combinations of more potent antipsychotics with more sedative neuroleptics were preferred. In contrast, the chosen substances, the preferred combinations and the application form varied considerably. The state mental hospital preferred haloperidol and levomepromazin; in the university clinic clozapin and perphenazineoenanthate were important adjuncts. Both clinics remained in the low therapeutic range of dose recommendations. There were no statistically meaningful differences with regard to either the total amount of chlorpromazine equivalents applied or the duration of inpatient care. In the first one-tenth of the total treatment period, 85% of the maximal dose reached in the second tenth is already given. A continual reduction begins thereafter, until app. 40% of the peak dose in reached. Active treatment of side effects as well as more common use of depot neuroleptics in order to minimize custodial treatment, may explain the lower number of compulsory admissions in the university hospital. Extreme interindividual differences in both dosage and length of stay help in elucidating the apparently contradictory results of comparative investigations with small patient groups. Previous treatments have little or no predictive value due to large intraindividual variations.

Adult↗

[Nightly myoclonus syndrome (NMS) and restless legs syndrome (RLS)--review and case report].

The paper gives a brief review of the existing literature concerning the nocturnal myoclonus syndrome (NMS). The clinical symptomatology, criteria for differential diagnosis and the relation to the restless legs syndrome (RLS) are discussed. Recently we investigated central dopamine receptor density with 123I-labeled 3'-iodo-6-methoxybenzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) and single photon emission tomography (SPECT) in patients with NMS and found a reduced density of dopamine D2-receptors in the striatal structures, indicating a dopaminergic dysfunction in NMS and RLS. We present a report concerning a 58-year old female with NMS-associated insomnia and present IBZM SPECTs and hypnograms before and after a 3-month treatment with L-dopa and discuss the results with regard to pathophysiological theories.

Epilepsies, Myoclonic↗

Relationship between cerebral blood flow velocities and cerebral electrical activity in sleep.

The dynamics of cerebral blood flow velocity during sleep were measured in the right and left middle cerebral artery of 12 and 10 healthy male volunteers, respectively. A computer-assisted pulsed (2-MHz) Doppler ultrasonography system was modified for continuous long-term and on-line recording of cerebral hemodynamics in combination with polysomnography. Mean flow velocity (MFV) decreased steadily during deepening nonrapid eye movement (NREM) sleep and increased suddenly during rapid eye movement sleep, corresponding to changes in brain function. However, spontaneous or provoked changes in sleep stage patterns as well as awakenings from NREM sleep were not regularly accompanied by corresponding changes in MFV. Differing values for MFV in subsequent sleep cycles could be shown for several sleep stages. Furthermore, MFV values in sleep stage II at the end of an NREM-sleep period were lower than in preceding slow-wave sleep. After application of short acoustic signals the electroencephalogram frequency rose, indicating an arousal, whereas MFV rapidly decreased for several seconds and then gradually returned to the prior level. These results imply an uncoupling between cerebral electrical activity and cerebral perfusion during sleep and support a dissociation in the activity of central regulatory mechanisms. In light of the proposal that cortical energy consumption can be accounted for by cerebral electrical activity, the concept that cerebral perfusion during sleep is regulated solely by the metabolic rate must be reconsidered.

Adult↗

Zopiclone improves sleep quality and daytime well-being in insomniac patients: comparison with triazolam, flunitrazepam and placebo.

In a randomized, double-blind, parallel group study in private practice, zopiclone given for 28 days was compared with flunitrazepam, triazolam and placebo in its effect on quality of sleep and daytime well-being in 1507 patients suffering from insomnia. For quantitative assessment, patients were defined as responders according to either a shortening of sleep latency by at least 15 min, or prolongation of total sleep time by at least 20%, or reduction of the number of nocturnal awakenings to three or less and a fresh feeling in the morning, as well as lack of impairment in daytime well-being as a result of tiredness or anxiety. The responder rate tended to be higher with zopiclone (37.4%) than with flunitrazepam (30%) and triazolam (32.2%) and was significantly greater (p = 0.0017) than with placebo (26.8%). Daytime well-being was particularly responsive to zopiclone and most responsive in severe insomniacs. With the exception of those to triazolam, rates of response were most pronounced in patients with insomnia of a short duration (< or = 1 year) than in those with insomnia of a longer duration (> or = 1 year). Following discontinuation of treatment, all groups showed a moderate reduction in therapeutic effect, but no rebound insomnia occurred.

Azabicyclo Compounds↗

[Are there predictors for impulsive, homicidal-suicidal acts of violence].

Patient's statements or fears that they may "go crazy" and harm themselves or persons around them are rare, but extremely difficult for all participants to deal with. On the basis of the existing, unsatisfactory literature as well as an analysis of 196 incidents of homicidal-suicidal violence designated by German media as "running amok" and fulfilling defined criteria, we examined whether or not there are predictors for the degree of potential danger inherent in such threats. Impulsive, homicidal-suicidal acts of violence among patients with psychiatric disorders often occur in environments characterised by chronic psychosocial estrangement and isolation. Extremely distressing situations may trigger the course of violence, but the actual act is often planned during a seemingly peaceful interval. Personalities with a high affinity to weapons and a tendency toward acting out seem to increase the potential risks. Such events should be treated analogous to suicidal crises, with a strategy that takes the individual disorder into consideration. The parameters investigated in this paper are not sufficient, even in different combinations, to offer a satisfactory explanation or predict the occurrence of this extremely rare behaviour; further research is necessary.

Acting Out↗

Cluster arousal analysis in chronic pain-disturbed sleep.

A new cluster arousal analysis system was developed to quantify microdisturbances in the sleep architecture. The system was evaluated in 10 healthy volunteers and the sleep of 23 outpatients with chronic low back pain was investigated before and after a special rehabilitative training. The comparison of sleep parameters before and after the treatment showed a significant reduction of the cluster disturbed sleep (CDS), whereas sleep efficiency and the number of stage shifts remained unchanged. The reduction of the CDS correlated with a reduction of depression scale. This cluster arousal analysis appears to be a sensitive tool for evaluating alterations in the sleep microstructure.

Journal Article↗

Test-retest reliability and validity of the Structured Interview for Sleep Disorders According to DSM-III-R.

OBJECTIVE: The purpose of this study was to evaluate the reliability of sleep disorder diagnoses in DSM-III-R by using a newly developed interview, the Structured Interview for Sleep Disorders According to DSM-III-R (SIS-D) and to evaluate the concordance between these diagnoses and sleep laboratory data. In addition, the sources of disagreements between two interviewers in the diagnoses given to the same patient were determined. METHOD: Two different interviewers used the SIS-D to diagnose 68 patients with complaints of sleep disorders. The concordance between these interviewers' diagnoses and polysomnographic findings was investigated by using kappa statistics. RESULTS: There were excellent reliabilities for almost all current main diagnostic categories and good concordance between diagnoses made on the basis of the structured interview and polysomnographic data. The main source of disagreement between interviewers was found in the symptom information given by the patient. CONCLUSIONS: These findings provide support for the utility of DSM-III-R sleep disorder diagnoses and for their retention in DSM-IV. These findings also accord well with a recent literature review of the DSM-III-R diagnosis of primary insomnia by the DSM-IV Work Group on Sleep Disorders. The good concordance between interview diagnoses and polysomnographic data suggests that a structured interview such as the SIS-D may be a useful screening instrument. The authors discuss the implications of these findings for the polysomnographic evaluation of chronic insomnia.

Adult↗

[Blood circulation and energy metabolism of the brain in healthy sleep].

Studies on sleep-related changes of cerebral blood flow (CBF) and cerebral metabolic rate (CMR) provide important information about sleep as an active neurophysiological process. Decreases in global values of CBF and CMR during non-rapid-eye-movement sleep illustrate rate role of this sleep period as a quiescent phase for the human brain. Increases in CBF and CMR and fast alterations in cerebral perfusion during rapid-eye-movement sleep are indicative of an active state with labile regulation. Local changes in CBF and CMR characterize the heterogeneity of the underlying physiological regulation. The dynamic feature of cerebral perfusion in relation to electroencephalographic patterns obtained by new recording techniques reflects quantitative uncoupling between cerebral electrical activity and cerebral perfusion during parts of the sleep period. A critical analysis of the current literature and history of sleep research on this topic is presented.

Animals↗

The metabolic fate of infused L-tryptophan in men: possible clinical implications of the accumulation of circulating tryptophan and tryptophan metabolites.

L-Tryptophan (Trp) was widely used as a natural tool for the support of serotonin-mediated brain functions and as a challenge probe for the assessment of serotonin-mediated neuroendocrine responses. The metabolic fate of the administered Trp and the kinetics of the accumulation of Trp metabolites in the circulation, however, have never thoroughly been investigated. This study describes the time- and dose-dependent alterations in the plasma levels of various Trp metabolites and large neutral amino acids after the infusion of Trp to healthy young men (1, 3 and 5 g; placebo-controlled, double-blind, cross-over study during day- and night-time). The major Trp metabolites (kynurenine, indole acetic acid and indole lactic acid) in plasma increased dose-dependently but rather slowly after Trp administration to reach their maximal plasma levels (up to 10-fold after the 5 g dose) at about 3 h p.i., and remained at an elevated level (about 5-fold) for up to 8 h. N-acetyl-Trp and 5-hydroxy-Trp rose rapidly and massively after Trp infusions, at the 5 g dose more than 200- and 20-fold, respectively, and declined rapidly to about 5-fold baseline levels within 2 h. Whole blood serotonin levels were almost unaffected by the Trp infusions. A rather slow increase of 5-hydroxyindole acetic acid was seen, reaching maximum values (3-fold at the 5 g dose) at about 2 h after the infusion of Trp. Additionally, a dose-dependent rise of circulating melatonin was observed after L-Trp infusions. The administration of L-Trp caused a depletion of the concentrations of the other large neutral amino acids and a dose dependent decrease of the ratio between plasma tyrosine and the sum of the plasma concentrations of the other large neutral amino acids. Apparently, none of the existing pathways of peripheral Trp metabolism is saturated by its substrate, Trp in men. At least some of the central effects reported after L-Trp administration may be mediated by the Trp-stimulated formation of neuroactive metabolites or by the decreased availability of tyrosine for catecholamine synthesis.

Adult↗

Assessment of intracranial hemodynamics in sleep apnea syndrome.

BACKGROUND AND PURPOSE: Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. METHODS: A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. RESULTS: Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). CONCLUSIONS: The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.

Adult↗

[Somnambulism and pavor nocturnus--review and case report].

A case of night terror with sleepwalking in an adult patient is described. Sleep polygraphic data are presented. The literature related to sleepwalking, night terror and its treatment is reviewed. The psychopathologic patterns of sleepwalking and night terror are illustrated and the differentiations of parasomnias and epileptic seizures discussed. The clinical applications of these findings are described and practical recommendations made for the management of NON-REM parasomnia.

Arousal↗

Problems in performing a double-blind multicenter study using a hypnotic in private practice.

1. The procedure described--the immediate data transfer and entry system (ITES)--is suitable to improve the quality of data collected in multicentre studies in private practice. 2. The results of the study show that regarding influence on sleep quality and daytime well-being the non-benzodiazepine Z is significantly superior to placebo and slightly superior to the benzodiazepines F and T. 3. The advantage of Z treatment is the better daytime well-being after taking the hypnotic for sleep induction the night before. 4. This study shows that a quality standard equal to that in clinical practice may be achieved in private practice.

Adolescent↗

Changes in heart rate during obstructive sleep apnoea.

The mechanisms behind the decrease in heart rate during apnoeas in patients with obstructive sleep apnoea (OSA) are little known. Recent findings in animal experiments indicate that stimulation of the upper airway activates postinspiratory and cardiac vagal neurones in the medullary respiratory centre, causing alterations in heart rate and respiratory rhythm. Since OSA leads to a collapse of the airway and consequent stimulation of upper airway receptors, we studied the interrelations between heart rate and respiratory rhythm during apnoea and during negative intrathoracic pressure generated by the Mueller manoeuvre (MM). Fifteen patients with OSA (apnoea hypopnoea index (AHI) 45 +/- 28.h-1) were studied by polysomnography, during a MM and a Valsalva manoeuvre, each of 15 s duration. The heart rate decrease (delta HRA) and the increase in total respiratory cycle duration (TOT) were evaluated during apnoea in non-rapid eye movement (REM) sleep. Patients with OSA demonstrated a decrease in heart rate during apnoea (-14.4 +/- 9.0 beats.min-1), and during MM (-11.5 +/- 13.5 in OSA vs 3.1 +/- 7.8 beats.min-1 in a control group). TOT increased during apnoea (4.6 +/- 3.1 s). There was a significant correlation between delta HRA and AHI (r = -0.64) as well as between delta HRA and increase in TOT (r = 0.62). These findings indicate that upper airway obstruction may cause an activation of receptors at the site of airway collapse or distortion leading to changes in heart rate and respiratory rhythm.

Female↗