Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 415 records · Page 23Linked to original sources

PubMed1993

Prevalence and treatment of insomnia in general practice. A longitudinal study.

The aim of the study was to assess prevalence and treatment modalities of insomnia in general practice. To investigate the course of insomnia, a longitudinal study design was adopted. Two thousand five hundred and twelve patients (age 18-65 years) were investigated with a questionnaire in general practice (T1). Four months later (T2) and again 2 years later (T3) a questionnaire was sent to all patients who had complained about severe insomnia at the time of the first inquiry. To assess insomnia, operationalized diagnostic criteria were applied (DSM-III-R). Eighteen point seven percent suffered from severe, 12.2% suffered from moderate and 15% suffered from mild insomnia. In the course of 2 years insomnia appeared as a chronic health problem. A high comorbidity of severe insomnia was found with chronic somatic and psychiatric disorders, especially with depression. Of the severely insomniac patients, 23.9% used prescribed hypnotics habitually, mainly benzodiazepines. The use of prescribed hypnotics remained rather stable during the whole study period. More than half of the patients reported a daily use of the hypnotics for 1-5 years or longer, but only 22% of the severely insomniac patients reported at the time of the third inquiry a significant improvement of insomnia due to the administration of sleeping pills. Thus, the long-term administration of benzodiazepine hypnotics seems to be an inadequate treatment strategy in chronic insomnia. Whether the occurrence of rebound insomnia after benzodiazepine withdrawal may be one of the main factors for chronic hypnotic use requires discussion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

48-hour rapid cycling: results of psychopathometric, polysomnographic, PET imaging and neuro-endocrine longitudinal investigations in a single case.

We report a 64-year-old patient suffering from rapid cycling bipolar disorder who was studied by means of polysomnography, neuroendocrine tests and PET (positron emission tomography) imaging. In a manner only partly compatible with the cholinergic-aminergic imbalance model of mania and depression, a linkage of REM sleep disinhibition and depressive mood was observed, but no decisive REM sleep delay was seen on manic days. Growth hormone secretion after clonidine stimulation was blunted on depressive and hypomanic days. A series of total sleep deprivations led to a positive effect on psychopathology for about two weeks. Carbamazepine treatment normalized REM sleep variables, damped the amplitude of mood cycling of the patient, increased TSH and decreased FT4.

Bipolar Disorder↗

PubMed1993

Naps after total sleep deprivation in depressed patients: are they depressiogenic?

Total sleep deprivation (TSD) exerts beneficial but transient effects on mood in approximately 60% of patients with a major depressive disorder. The positive effects of a night of total sleep deprivation are generally reversed after the next night of sleep. Several anecdotal reports and a pilot study by our group indicated that even short naps during the period of sleep deprivation are capable of re-inducing depressive mood in responders to TSD. The present study explored whether the structure of naps at 9 a.m. was crucial for the "depressiogenic" impact of naps on mood. A negative effect on mood was replicated, but this effect was not related to any of the nap sleep variables. The effect of naps on mood was attenuated in the early afternoon. The results support the assumption of a "depressiogenic" effect of naps in patients with major depression after successful TSD.

Depressive Disorder↗

PubMed1993

Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor.

Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.

Amyloid beta-Protein Precursor↗

PubMed1993

Influence of the cholinergic agonist SDZ 210-086 on sleep in healthy subjects.

The administration of 1.0 mg SDZ 210-086, an orally acting muscarinic agonist, shortened rapid-eye movement (REM) latency, increased REM percent of sleep period time and the total duration of REM sleep, and decreased slow-wave sleep in 12 healthy male subjects. The administration of 0.5 mg SDZ 210-086 had no statistically significant effect on sleep variables. Although the tonic components of REM sleep (REM duration, the REM percent of sleep period time) were increased, REM density percent (total) was significantly decreased due to the prolongation of total REM duration (in minutes) and a parallel reduction of the total number of eye movements. This finding is in contrast to studies using other cholinomimetics (i.e., physostigmine, arecoline, and RS 86) and may implicate different generating systems of phasic and tonic REM sleep components.

Adult↗

PubMed1993

[Neuropathologic, immunologic and psychobiological aspects of Alzheimer's dementia].

This review attempts a consolidated overview of the results of molecular biological research on amyloid pathology in Alzheimer's disease crosslinked with other aspects of the disease that have not been so much in focus in recent years. The spotlight will be on many pointers to an immunological process as part of the Alzheimer pathology. The problem of the specificity of plaques and of neurofibrillary tangles that both are considered to be classical neuropathological markers of Alzheimer's disease is critically reviewed on the basis of existing findings in neuropathology in non-demented and demented elderly persons. The traditional unidirectional concept that interprets the neuropsychological functions inhibited in Alzheimer's dementia merely as sequels to damaged morphological structures, is questioned. Earlier and more recent experimental findings indicating that dysfunctional and deficient use of neuropsychological functions can inhibit neuronal plasticity and can be the origin of morphological changes, are placed in relation to numerous pointers to non-cognitive mental anomalies prior to the outbreak of Alzheimer's disease. In Alzheimer's dementia, pathology of synapses is preferably correlated with neuropsychological deficits. Findings on this pathology are discussed as a possible expression of a neuronal plasticity decrease that is partly conditioned by psychobiological mechanisms.

Aged↗

PubMed1993

Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with CD34+ selected autologous peripheral blood cells transduced with a human ADA gene. Amendment to clinical research project, Project 90-C-195, January 10, 1992.

Significant increases in lymphocyte adenosine deaminase activity, T cell numbers and immune function have been achieved in the two children with SCID thus far treated with autologous T cells genetically-corrected by retroviral-mediated insertion of a normal ADA gene. Although the data obtained to date demonstrate that the use of ADA gene corrected peripheral T cells appears to be an effective treatment for ADA(-)SCID, it is theoretically preferable to try to develop a treatment for these children that will result in stem cell gene correction. The genetic correction of T cell progenitors with long-term immune reconstituting ability would be more desirable because repeated infusions of genetically altered cells should not be necessary and the generation of a more complete repertoire of T cell specificities might also be possible. Furthermore, the present treatment protocol involves indefinite continuation of enzyme replacement treatment with PEG-ADA. The demonstration of ADA gene expression in the progeny of transduced stem cells may simplify the decision concerning cessation of this very costly enzyme treatment (approximately $250,000/yr./patient). Recent evidence suggests that a small fraction of bone marrow or peripheral blood mononuclear cells bearing the CD34 antigen contains hematopoietic stem cells with both lymphoid and myeloid reconstituting ability. We propose in this amendment to supplement the infusion of human ADA gene-transduced autologous T cells in children with ADA(-)SCID with autologous peripheral blood CD34+ cells transduced with a second, readily distinguishable ADA vector.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗

PubMed1993

Radical oxidation reactions of the purine moiety of 2'-deoxyribonucleosides and DNA by iron-containing minerals.

The radical oxidation capability of several classes of iron minerals, including biotite, hematite, magnetite, minette, nemalite, pyrite, vivianite and two chrysotiles (asbestos), was investigated by using a double experimental approach. One involved the electron spin resonance spin-trapping measurement of organic radicals obtained by the reaction of activated oxygen species, released upon incubation of the minerals in phosphate buffered solutions with formate used as the target molecule. In addition, the formation of mineral-mediated oxidation purine decomposition products, including 7,8-dihydro-8-oxo-2'-deoxyguanosine and 7,8-dihydro-8-oxo-2'-deoxyadenosine, was searched within nucleosides and DNA by using specific and sensitive HPLC electrochemical assays. Emphasis was placed on the mechanistic aspects of the radical oxidation reactions involved in the formation of the two C(8) hydroxylated purine decomposition products.

Adenine↗

PubMed1993

Diabetes education and insulin therapy: when will they ever learn?

The Diabetes Education Study Group of the European Diabetes Association was founded in 1979 with its major goal to make effective patient training an integral part of any diabetes therapy. However, even today, in many places diabetes education is not an obligatory part of treatment, but is regarded as an optional service to the patient which is frequently fragmentary and haphazard. On the other hand, many physicians still subject their patients to rigid dietary instructions and obedience training, an approach which is mistaken for diabetes education. Several misconceptions about diabetes education keep counteracting the spread and hence the availability of effective treatment and teaching programmes for all Type 1 diabetic patients. One such misconception is that diabetes education could compensate for deficiencies of inappropriate insulin treatment regimens. Studies failing to demonstrate the impact of diabetes education on metabolic control, typically used an insulin treatment regimen with only one or two insulin injections per day, the predominant use of intermediate acting insulin preparations, and without (day-to-day) adjustment of insulin dosages by the patients themselves. A further reason for a lack of success of diabetes education is an unstructured approach which is frequently mistaken for individualized care. The deleterious effects of putting patients on intensified insulin therapy without offering them sufficient and systematic training have manifested themselves at various places by an excessive increase in the risk of severe hypoglycaemia, and of ketoacidosis during therapy with continuous subcutaneous insulin infusion. The effective and safe performance of insulin therapy requires both a rational system of insulin substitution and intensive training of the patients to carry it out. The injection of regular insulin before main meals and the use of intermediate or long-acting insulin preparations for the substitution of basal insulin requirements combined with daily metabolic self-monitoring and (day-to-day) adaptation of insulin dosages by the patients themselves allow a substantial improvement of glycaemic control without an increase in the risk of severe hypoglycaemia and the adoption of a more flexible life style largely freed from forcing and directive dietary and other impositions. Each diabetes centre should continuously evaluate the quality of care offered to their patients as a basis for a specific and systematic improvement of its treatment and education programmes. Such quality control measures must include a recording of the patients' degree of metabolic control and the frequencies of severe hypoglycaemia and ketoacidosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus, Type 1↗

PubMed1993

Behaviour therapy versus doctor's anti-smoking advice in diabetic patients.

OBJECTIVES: To evaluate the efficacy of a structured behaviour therapy programme on smoking cessation in diabetic patients. DESIGN: Prospective, randomized, controlled intervention study. SETTING: University out-patient diabetes clinic. SUBJECTS: A total of 794 consecutive insulin-treated smoking diabetic patients were invited to participate in a smoking cessation programme. Eighty-nine patients agreed to participate and were randomized in two groups. INTERVENTIONS: Forty-four patients were randomized to a structured extensive behaviour therapy anti-smoking intervention and 45 patients to a control group that received a single unstructured anti-smoking advice session given by a physician. MAIN OUTCOME MEASURES: After 6 months, nine patients were confirmed not to be smoking (i.e. urine cotinine concentration below 20 ng ml-1, 2 [5%] in the behaviour therapy intervention group and 7 [16%] in the control group. CONCLUSIONS: In diabetic patients an extensive behaviour therapy intervention for smoking cessation is no more successful than an unstructured physician's advice.

Adult↗

PubMed1993

Symposium: Normal and abnormal REM sleep regulation: REM sleep in depression-an overview.

Abnormalities of REM sleep, i.e. shortening of REM latency, lengthening of the duration of the first REM period and heightening of REM density, which are frequently observed in patients with a major depressive disorder (MDD), have attracted considerable interest. Initial hopes that these aberrant patterns of sleep constitute specific markers for the primary/endogenous sub-type of depression have not been fulfilled. The specificity of REM sleep disinhibition for depression in comparison with other psychopathological groups is challenged as well. Demographic variables like age and sex exert strong influences on sleep physiology and must be controlled when searching for specific markers of depressed sleep. It is still an open question whether abnormalities of sleep are state- or trait-markers of depression. Beyond baseline studies, the cholinergic REM induction test (CRIT) indicated a heightened responsitivity of the REM sleep system to cholinergic challenge in depression compared with healthy controls and other psychopathological groups, with the exception of schizophrenia. A special role for REM sleep in depression is supported by the well-known REM sleep suppressing effect of most antidepressants. The antidepressant effect of selective REM deprivation by awakenings stresses the importance of mechanisms involved in REM sleep regulation for the understanding of the pathophysiology of depressive disorders. The positive effect of total sleep deprivation on depressive mood which can be reversed by daytime naps, furthermore emphasizes relationships between sleep and depression. Experimental evidence as described above instigated several theories like the REM deprivation hypothesis, the 2-process model and the reciprocal interaction model of nonREM-REM sleep regulation to explain the deviant sleep pattern of depression. The different models will be discussed with reference to empirical data gathered in the field.

Journal Article↗

PubMed1993

Treatment of narcolepsy-cataplexy syndrome with the new selective and reversible MAO-A inhibitor brofaromine-a pilot study.

Eighteen narcoleptic patients were treated in a single-blind study with brofaromine, a new selective and reversible MAO-A-inhibitor. After a drug-free period of seven days, brofaromine was administered for two weeks. Patients were treated with 75 mg brofaromine for the first week and with 150 mg brofaromine for the second week of the study. After an adaptation night nocturnal sleep EEGs were recorded under placebo before brofaromine was given, one week later under 75 mg, and another week later under 150 mg brofaromine. Excessive daytime sleepiness (EDS) was evaluated under placebo at the beginning of the study, under 75 mg at the end of the first week, and under 150 mg brofaromine at the end of the second week by means of the Multiple Sleep Latency Test (MSLT) and the Maintenance of Wakefulness Test (MWT). The number of cataplexies was protocolled by the patients. Compared to placebo the administration of 150 mg brofaromine led to a significant increase of sleep latency in the MLST as well as in the MWT. REM sleep was significantly suppressed in the nocturnal sleep EEG, in the MSLT and in the MWT. The number of cataplexies protocolled by the patient was significantly decreased under 150 mg of brofaromine compared to placebo. Improvement of vigilance and cataplexy occurred in dose-dependent manner. No serious side effects were observed. The results of the present single-blind study indicate that brofaromine seems to be a well-tolerated and effective drug for the treatment of excessive daytime sleepiness and cataplexy in narcoleptic patients.

Journal Article↗

PubMed1993

The influence of total sleep deprivation on urinary excretion of catecholamine metabolites in major depression.

To elucidate the influence of total sleep deprivation (TSD) on catecholaminergic neurotransmission, which is assumed to be disturbed in depression, 9 depressive patients collected consecutive 24-h urine samples prior to (baseline), during (TSD) and following total sleep deprivation (post-TSD). Urine samples were analysed for total MHPG (3-methoxy-4-hydroxyphenylglycol), conjugates of MHPG (glucuronide and sulfate), excretion of HVA (homovanillic acid) and VMA (3-methoxy-4-hydroxymandelic acid). TSD increased the urinary excretion of MHPG-sulfate as a marker of the central norepinephrine metabolism and the excretion rates of VMA and HVA as indices of the peripheral catecholamine metabolism. Patients with higher VMA values prior to TSD reacted worse, and the VMA increase due to TSD was positively correlated with the response. The results demonstrate that TSD, besides acting as a stimulus on the peripheral sympathetic nervous system, influences central nervous noradrenergic neurotransmission, as reflected by the increase of MHPG-sulfate.

Adult↗

PubMed1993

The effect of carbamazepine on endocrine and sleep EEG variables in a patient with 48-hour rapid cycling, and healthy controls.

Carbamazepine treatment of a patient with 48-hour rapid cycling led to a dampening of mood cycling, and prolonged rapid eye movement (REM) sleep latency. No effect on central alpha-receptors as measured by growth hormone (GH) secretion after clonidine stimulation or on spontaneous 48-hour GH secretion was observed. In 12 healthy subjects given 400 mg carbamazepine daily for a period of 5 days, improved sleep continuity and increased slow-wave sleep occurred with treatment. REM sleep percentage and REM latency remained uninfluenced, whereas REM density decreased. GH secretion after clonidine stimulation was not altered. Data from the single-case longitudinal study emphasize that carbamazepine is effective in treating rapid-cycling affective psychosis. Furthermore, neuroendocrine and sleep EEG data from the study in healthy subjects indicate a different profile of action for carbamazepine compared to most other antidepressants or antimanic drugs.

Adult↗

PubMed1993

Increased sensitivity to agonist stimulation of the Ca2+ response in neutrophils of manic-depressive patients: effect of lithium therapy.

The agonist-stimulated increase of intracellular free-Ca2+ concentration, an indicator of the sensitivity of the inositol phospholipid second-messenger generating system, was measured in neutrophils from patients with manic-depressive disorder, and controls. Dose-response curves of the calcium response were determined by measuring the fluorescence of neutrophils loaded with fura-2 and stimulated with various concentrations of the chemotactic tripeptide formylmethionylleucylphenylalanine. EC50 values were obtained for 14 medication-free patients (5 acutely depressive, and 9 symptom free remitted patients with a history of manic-depression or recurrent major depression), 9 lithium-treated, euthymic manic-depressive patients and 10 drug-free healthy controls. The EC50 values of the untreated patients were significantly lower than in the controls. Lithium-treated patients had EC50 values significantly higher than controls. These results suggest that manic-depressive disorder is associated with an increased sensitivity of the inositol phospholipid second-messenger generating system, which is counteracted by lithium treatment.

Adult↗

PubMed1993

Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans.

A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved in the regulation of sleep and wakefulness. The aim of the present pilot study was to investigate the relationship between interleukin-1 beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation of sleep and wakefulness. Four healthy male volunteers were investigated. After one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by means of a mobile long-term EEG and blood samples were drawn every 45 min for the analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of cytokines whole blood cultures were established. After 48 h of incubation in the presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were measured in the culture supernatants using specific immunodetection assays. Methods of stochastic time series analysis were adopted to evaluate the biochemical data. Our results show the capability of cultured blood cells to produce cytokines upon endotoxin challenge to be at a maximum around the time of sleep onset and during the first hours of sleep, declining during the night to a minimum level in the morning hours. The opposite was observed for cortisol. The analysis of autocorrelation functions gives evidence of a 24-hour rhythm of cortisol and cytokines. The results indicate that the cytokines IL-1 beta and gamma-IFN may play a role in sleep regulation.

Adult↗

PubMed1993

Effects of single and repeated clonidine administration on the properties of central and peripheral alpha 2-adrenoceptors in man.

The centrally acting alpha 2-adrenoceptor agonist clonidine was used to assess the sensitivity of alpha 2-adrenergic neurotransmission in man, using receptor-binding studies and clonidine-induced growth hormone response. Neither acute (2 micrograms/kg body weight) nor subchronic (3 days, 2 x 150 micrograms/kg body weight) administration of clonidine affected platelet alpha 2-adrenoceptor number in humans as judged by 3H-yohimbine and 3H-UK-14,304 binding. The same treatment also did not modify central postsynaptic alpha 2-adrenoceptor function in the same individuals as assessed by clonidine-induced growth hormone responses. Similarly, subchronic (3 days, 500 micrograms/kg body weight, i.p.) or chronic (14 days, 500 micrograms/kg, i.p.) administration of clonidine to mice failed to change 3H-yohimbine or 3H-UK-14,304 binding sites in membranes prepared from frontal cortex. On the other hand, in vitro experiments using mouse frontal cortex or human platelet membranes showed pronounced reduction of 3H-UK-14,304 but not of 3H-yohimbine binding sites after incubation with several adrenoceptor agonists. The data indicate that acute and subchronic clonidine treatment may not change alpha 2-adrenoceptor sensitivity in humans or mice as assessed both at the functional and receptor level.

Adaptation, Physiological↗

PubMed1993

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↗