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Biomedical subjects

D Riemann

Publications and source records attributed to D Riemann.

At least 19 recordsLinked to original sources

[Diagnostics and therapy of sleep disorders in the general practice].

Sleep disorders could be the symptoms of organic or non-organic conditions. The diagnostics comprises a detailed medical history of the patient complemented by a sleep diary, as well as organic medical and psychological/psychiatric examinations. For drug therapy benzodiazepine, antidepressants, neuroleptics, antihistamines, plant-based preparations and natural sleep-inducing substances such as L-tryptophan or melatonin are used. Nondrug strategies include sleep hygiene, stimulus control, sleep restriction and cognitive techniques. For sleep disturbances due to a psychological or organic disease, the primary condition must be treated.

Diagnosis, Differential↗

Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.

INTRODUCTION: Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and trimipramine, a tricyclic antidepressant (TCA), were compared in terms of efficacy and tolerability in a six-week, parallel group, double-blind pilot study in 41 geriatric patients with major depression (61 - 85 years old). METHOD: The Hamilton Rating Scale for Depression (HAMD-17), the Montgomery-Asberg Rating Scale (MADRS), the Adjective Mood Scale (Bf-S), the Clinical Global Impression (CGI), and the Patients Global Impression (PGI) were used to measure changes in depressive symptoms. RESULTS: Improvement with treatment was found on all scales. Efficacy and tolerability were similar in both groups. No statistically significant differences were found. CONCLUSION: These findings suggest that fluoxetine and trimipramine are comparable in terms of efficacy and tolerability in the treatment of major depression in geriatric patients.

Aged↗

Impact of experimentally induced serotonin deficiency by tryptophan depletion on saliva cortisol concentrations.

BACKGROUND: Tryptophan depletion (TD) has been shown to induce a transient mood-lowering effect in psychiatric patients and susceptible healthy subjects. We investigated the effects of TD on cortisol secretion in psychiatric patients and healthy subjects based on the hypothesis that the potential mood-lowering effects may be associated with increased activity of the hypothalamic-pituitary-adrenal axis, thus leading to a rise of cortisol secretion. METHODS: After TD at 18.00 h, salivary cortisol was sampled in the evening and on the following morning. The first study was a randomized, placebo-controlled, crossover study in healthy subjects. Two further open trials in patients with obsessive-compulsive disorder (OCD) and primary insomnia compared the effects of TD on cortisol with baseline conditions. RESULTS: In healthy subjects, TD significantly diminished cortisol the next morning compared with placebo. In OCD patients and primary insomniacs, cortisol the morning after TD was lowered compared with baseline. Evening cortisol was not affected by TD in any of the groups. CONCLUSIONS: Contrary to expectation, TD led to a comparable decrease of morning cortisol in all groups investigated. However, these findings are consistent with former studies analyzing the impact of antiserotonergic drugs on cortisol secretion. The results underline that the antiserotonergic effects caused by TD may influence cortisol secretion.

Adult↗

[The importance of sleep for healthy alcohol consumers and alcohol dependent patients].

This article deals with the effects of alcohol on sleep and sleep EEG of healthy individuals and alcohol-dependent patients during different phases of alcohol dependency. Healthy individuals initially experience an improvement in sleep, although a greater quantity of alcohol can lead to problems of sleep maintenance during the second half of the night. Pre-existing sleep deprivation or sleep restriction potentiates the effects of alcohol. Alcohol-dependent patients are found to be more prone to sleep problems than healthy individuals, which can facilitate the development of alcoholism. These patients experience difficulty falling asleep and suffer from a reduced total sleep time during all phases of the disorder, often accompanied by other sleep disorders such as sleep apnea syndrome or periodic leg movements during sleep. Certain predictors for the risk of relapse in abstinent alcoholics have been identified. Neurobiological findings in sleep and alcohol dependency are discussed. The cholinergic-aminergic reciprocal interaction model of REM and non-REM sleep regulation is significant in this context. Therapeutic implications are discussed.

Alcohol-Induced Disorders↗

Polysomnography during withdrawal with clomethiazole or placebo in alcohol dependent patients--a double-blind and randomized study.

INTRODUCTION: The present study was designed to assess if the routine application of clomethiazole to ameliorate withdrawal symptoms in chronic alcohol dependent patients perpetuates sleep disturbances. METHODS: Twenty inpatients with alcohol dependence according to DSM-IV criteria received clomethiazole or placebo in a double-blind, randomized design upon admission. 11 patients were randomized to the clomethiazole group and 9 patients to the placebo group. During the first 5 days of treatment the patients received either clomethiazole (1st day: 3 x 384 mg, 2nd day: 4 x 384 mg, 3rd day: 3 x 384 mg, 4th day: 2 x 384 mg and 5th day: 1 x 384 mg) or placebo capsules at constant intervals. The patients spent two consecutive nights in the sleep laboratory at each of three assessment times: the first time at the beginning of abstinence (night 1 and 2, T0), the second time 6 days later (i. e. after 5 days of treatment and one day of discontinuation of clomethiazole or placebo: nights 6 and 7, T1) and the third time after 13 days (nights 13 and 14, T2). The first night at each of the three assessment times was an adaptation night. RESULTS: During the first two weeks of abstinence, the analysis of variance demonstrated a significant variation of Rapid Eye Movement (REM) sleep variables in the clomethiazole group. The placebo group showed no such variation. Clomethiazole evidently had a pronounced REM sleep suppressing effect, whereas the discontinuation of clomethiazole led to a REM sleep rebound. Furthermore, analysis of sleep continuity and sleep architecture variables showed that the clomethiazole group had significantly disturbed sleep at T1 in comparison to the placebo group. Simultaneous statistical testing with alcohol intake as covariate reduced the test power so that contrasts between the groups became nonsignificant. CONCLUSIONS: The REM sleep results are in line with earlier findings that REM sleep disinhibition in primary alcohol dependency is partly due to a REM sleep rebound after withdrawal from medication. Differences in the polysomnographic variables of sleep continuitiy and sleep architecture at T0 and T1 found between the clomethiazole and the placebo patients correspond to rebound insomnia following discontinuation of clomethiazole. Our findings indicate that drugs enforcing GABAergic neurotransmission may perpetuate the neuroadaptative effects caused by chronic alcohol consumption.

Adult↗

IL-10 and TGF-beta differ in their regulation of aminopeptidase N/CD13 expression in monocytes.

Human monocytic cells express considerable amounts of aminopeptidase N (APN)/CD13, a transmembrane protein proposed to play a role in the modulation of kinins, neuropeptides and chemotactic mediators as well as in adhesion and cell-cell interactions. Previous studies have shown that APN/CD13 participates in antigen processing and presentation, trimming peptides protruding out of MHC class II molecules. In several inflammatory processes, macrophages have been shown to express especially high amounts of MHC class II molecules and of this peptidase. To learn more about the regulation of APN/CD13 on monocytes we investigated its expression under the influence of cytokines. Here, we report a dose- and time-dependent up-regulation of APN/CD13 mRNA and protein expression by transforming growth factor (TGF)-beta on human monocytes. To the contrary, we found IL-10 down-regulating the expression of APN/CD13 mRNA and protein. Both the regulation of the APN/CD13 protein assessed by immunofluorescence and the gene expression assessed by real-time PCR were highly correlated. Using the Dual-Luciferase reporter assay, we demonstrate that TGF-beta treatment of monocytes results in a higher activity of the APN/CD13 myeloid promoter. Our results implicate differences in the expression of the membrane peptidase APN/CD13 and therefore in the peptide-modulating ability of monocytes after exposure to these two immunosuppressive cytokines, TGF-beta and IL-10.

CD13 Antigens↗

[Algorithms for diagnosis and therapy of sleep disorders in general practice].

Complaints of insomnia, i.e. problems to fall asleep or maintain asleep and/or non-restorative sleep are very common in general practice. This article presents the clinical algorithm non-restorative sleep which was devised by the German Society for Sleep Research and Sleep Medicine. This algorithm presents a guideline for the diagnosis and the treatment of insomnia.

Age Factors↗

[Non-restorative sleep and insomnia. Diagnostic and therapeutic options for psychiatry and psychotherapy].

Over the last few years, a shift in paradigm has taken place in the diagnosis and therapy of insomnia. Traditionally, treatment focused on improving night sleep, i.e. shortening sleep latency and prolonging total sleep time. Modern approaches aim at improving or restoring the recuperative value of sleep and ensuring daytime functioning on a social, psychological and professional level. Based on the guidelines "Non-restorative Sleep" of the German Society of Sleep Research and Sleep Medicine, this article presents a clinical algorithm for the diagnosis and therapy of non-restorative sleep with predominant insomnia. The term "non-restorative sleep" permits us to view the restorative value of sleep and the resulting daytime functioning of the individual afflicted with insomnia as the focus for the diagnosis of and therapy for insomnia. This algorithm is suitable for the clinical practice of outpatient psychiatric and psychotherapeutic services as well as for psychiatric inpatients. The main features for psychiatrists and psychotherapists in the diagnosis and therapy of non-restorative sleep are underlying psychiatric-psychological factors or secondary psychiatric sequelae of chronic primary insomnias. For primary, organic and psychiatric insomnias, a broad spectrum of psychopharmacological and cognitive behavioral methods can be applied either alone or in combination.

Algorithms↗

Is the antidepressive effect of sleep deprivation stabilized by a three day phase advance of the sleep period? A pilot study.

Sleep deprivation (SD) induces a rapid amelioration of mood in about 60 % of depressed patients. After the next night of sleep, however, most patients experience a relapse. Previous studies demonstrated that a six day sleep-phase advance protocol prevents relapses in about 60 % of patients who responded positively to SD. We investigated whether also a three day phase advance of the sleep period might be able to maintain the antidepressant effects of SD. Twenty-eight medicated depressed inpatients, who had a significant improvement after a SD in one night were recruited for this study. The phase advance protocol began on the first day after SD with a bed time from 5:00 p. m. to 12:00 p. m. on the first, from 7:00 p. m. to 2:00 a. m. on the second and 9:00 p. m. to 4:00 a. m. on the third day after SD. Three patients dropped out because of protocol violations. Only ten of the remaining 25 SD responders had a relapse during the three days of phase advance treatment or during the two days after it. Two of the relapsers improved again until day 6, i. e. 68 % showed an improvement of at least 30 % six days after the beginning of the treatment. This study indicates that even a three day phase advance protocol may help to prevent relapses after successful SD.

Circadian Rhythm↗

Sleep and manipulations of the sleep-wake rhythm in depression.

OBJECTIVE: Disturbed sleep is typical for most depressed patients and complaints about disordered sleep are the hallmarks of the disorder. Polysomnographic sleep research has demonstrated that besides impaired sleep continuity, sleep in depression is characterized by a reduction of slow wave sleep and a disinhibition of random eye movement (REM) sleep, with a shortening of REM latency, a prolongation of the first REM period and increased REM density. METHOD: Our own experimental work has focused on the reciprocal interaction hypothesis of non-REM and REM sleep regulation as a model to explain the characteristic features of depressed sleep. RESULTS: In agreement with the major tenet of this model, administration of cholinomimetics provoked shortened REM latency in healthy subjects and led to an even stronger REM sleep disinhibition in depressed patients. Manipulations of the sleep-wake cycle, such as sleep deprivation or a phase advance of the sleep period, alleviate depressive symptoms. CONCLUSION: These data indicate a strong bidirectional relationship between sleep, sleep alterations and depression.

Cholinergic Agents↗

Changes in monocytic expression of aminopeptidase N/CD13 after major trauma.

HLA-DR expression on monocytes as marker for monocytic function is severely depressed after major trauma. The membrane enzyme aminopeptidase N/CD13 can trigger help in antigen processing by MHC class II molecules of antigen-presenting cells. We determined the simultaneous expression of HLA-DR and CD13 on peripheral blood monocytes of patients with major trauma (injury severity score of > or =16). 1 : 1 conjugates of phycoerythrin (PE)-to-monoclonal antibody were used in combination with QuantiBRITE PE beads for a standardized quantification in terms of antibodies bound per cell (ABC). The very low expression of HLA-DR antigen on monocytes of patients at day 1 after major trauma confirmed previous results in the literature. Monocytic HLA-DR expression increased slowly to reach values in the lower range of healthy volunteers at day 14. Monocytic CD13 expression at day 1 showed values in the range of healthy volunteers, and a strong rise afterwards. Fourteen days after trauma, the monocytic expression of CD13 was still much higher than in the control group. Because lipopolysaccharide (LPS) and the anti-inflammatory cytokine interleukin (IL)-10 have been shown to be involved in the depressed HLA-DR expression on monocytes in trauma patients, we studied the in vitro effects of LPS and interleukin (IL)-10 on the expression of CD13 on monocytes prepared from the peripheral blood of healthy volunteers. Whereas a 3-day IL-10 treatment resulted in a down-regulation of both HLA-DR and CD13 expression on monocytes, LPS caused a down-regulation of HLA-DR but a rapid up-regulation of CD13 levels. Therefore we suggest that, with respect to monocytic CD13 expression, LPS rather than IL-10 could well be the explanation for monocytic surface molecules after severe injury, although other mediators with a CD13 regulating function have to be considered.

Adult↗

Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis.

Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared to patients with osteoarthritis. In contrast to the restricted expression of IL-17, the IL-17 receptor (IL-17R/CDw217) is expressed ubiquitously. Using a real-time RT-PCR assay, we detected similar absolute levels of IL-17R mRNA expression in fibroblast-like synoviocytes (SFC) from patients with RA (mean 9 pg/microg total RNA; ranged from 0.1 pg to 96 pg IL-17R mRNA/microg total RNA) compared to synoviocytes of non-RA patients. Analysis of the IL-17R surface expression confirmed the results obtained for IL-17R mRNA expression. Exposure of SFC to IL-17 led to a mRNA induction of CXC chemokines IL-8, GRO-alpha and GRO-beta. An anti-IL-17 antibody blocked these effects of IL-17. The MAPK p38 appears necessary for the regulation of IL-8, GRO-alpha and GRO-beta expression as shown by inhibition with SB203580. The inhibitors genistein (tyrosine kinase inhibitor) and calphostin C (inhibitor of protein kinase C) reduced significantly the IL-17-stimulated mRNA expression of IL-8, GRO-alpha and GRO-beta in SFC, whereas PD98059 (inhibitor of MEK-1/2) was without effect. Pharmacological drugs used in therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase of IL-17R mRNA expression and augmented the IL-17-stimulated IL-8 expression. Our results support the hypothesis that IL-17/IL-17R may play a significant role in the pathogenesis of RA contributing to an unbalanced production of cytokines as well as participating in connective tissue remodelling.

Antirheumatic Agents↗

Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.

In recent years, sedating antidepressants have been increasingly used to treat primary insomnia. Up to now, only one open pilot study with trimipramine and one double-blind placebo-controlled study with doxepin have provided scientific support for this approach in treating primary insomnia. In order to test the hypothesis that sedating antidepressants are useful in the treatment of primary insomnia, the effect of trimipramine on objectively and subjectively measured parameters of sleep was investigated in a double-blind placebo- and lormetazepam-controlled study in a sample of 55 patients with primary insomnia attending outpatient sleep-disorder clinics. Trimipramine was selected since it has shown positive effects on sleep continuity with a lack of REM sleep suppression in studies on depressed patients and in one pilot study on patients with primary insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks significantly enhanced sleep efficiency, but not total sleep time (which had been the primary target variable) compared to placebo as measured by polysomnography. Changes in objective sleep parameters were paralleled by changes in subjective sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased wake time and sleep stage 3 and increased REM sleep compared to placebo. After switching trimipramine to placebo, sleep parameters returned to baseline. There was no evidence of any rebound effect from trimipramine. Side effects from trimipramine were only marginal. This first double-blind placebo-controlled study with trimipramine suggests its efficacy in the treatment of primary insomnia. However, due to the large intra- and interindividual variance in the parameters of interest before and during treatment a larger sample size would have been necessary to strengthen the validity of our findings.

Adult↗

Expression of cathepsin B, D and L protein in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common childhood autoimmune rheumatic disease and like rheumatoid arthritis (RA), it is characterized by inflammation and the progressive destruction of joints. In RA, cathepsins as proteinases play a major role in destroying synovial tissue and cartilage matrix. So far no data on cathepsin expression in pannus tissue of HA patients exist. The aim of this study was to characterize the expression levels of cathepsins B, D, H, and L in HA and to compare them with those in RA. Synovectomy tissue from 16 HA and 12 RA patients was investigated for cathepsin expression levels by Western blot analysis. Expression of cathepsins B, D and L was on comparable levels in the synovectomy tissue of HA and RA patients. The following graduation of expression was determined: cathepsin D > cathepsin L > cathepsin B. Cathepsin H was neither found to be expressed in HA nor in RA patients. The expression levels of cathepsins in pannus tissue showed no clear difference between patients with systemic JIA and patients with monoarticular JIA. In summary, the comparable expression of cathepsins B, D and L in RA and JIA synovectomy tissue suggests that they may play a similarly important role in destroying synovial tissue and cartilage matrix in the course of HA and RA.

Adolescent↗

[Sleep disorders. Differential diagnosis and therapy in general practice].

Sleep Disorders are one of the most common complaints of patients seen by general practitioners. Prevalences vary considerably--depending on the kind of research and the definition of sleep disorders--between 4 and 40%. In 2000 the first grand nationwide survey was carried out in primary care settings [1]. 12.3% of the 17,928 questioned stated sleep disorders as the main reason for their consultation, the prevalence of all kinds of sleep disorders being 29%. Like seen in other studies sleep complaints increased with age and predominated significantly in women. In one-third of the sample the differential diagnosis was primary or non-organic insomnia [1] while treatment was mainly conducted by the general practitioner. In two-thirds of the patients sleep disorders existed for more than 12 months while 41%--by their own account--took sleep agents at least once a week. This article gives an overview of the causes and treatment of sleep disorders, particularly therapy of non-organic insomnia.

Central Nervous System Agents↗

Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation.

We have established an immunomagnetic separation procedure for the detection of circulating tumor cells in the peripheral blood based on the magnetic cell sorting (MACS) technique. In previous in vitro experiments, renal-cell carcinoma (RCC) cells were mixed with peripheral blood. In dilutions of 1:200 to 1:107 tumor cells per mononuclear blood cells, an average recovery rate of 84% of tumor cells was determined. In our study, 104 peripheral blood samples from 59 renal carcinoma patients were analyzed. MACS resulted in significant depletion of leukocytes, permitting a search for tumor cells on just 1 slide. Analyzing 8 ml of peripheral blood per patient, 19/59 RCC patients carried disseminated tumor cells (32%) in the range of 1 to 38 cells (median 8). Interestingly, for the cytokeratin-positive (CK+) patient group, we found a correlation between tumor cell number and grading (G2 vs. G3) and an increased number of CK+ patients with advanced tumor stage. MACS appears to be an efficient technique to detect disseminated tumor cells in peripheral blood.

Adult↗

Caveolae/lipid rafts in fibroblast-like synoviocytes: ectopeptidase-rich membrane microdomains.

Membrane peptidases play important roles in cell activation, proliferation and communication. Human fibroblast-like synoviocytes express considerable amounts of aminopeptidase N/CD13, dipeptidyl peptidase IV/CD26, and neprilysin/CD10, transmembrane proteins previously proposed to be involved in the regulation of intra-articular levels of neuropeptides and chemotactic mediators as well as in adhesion and cell-cell interactions. Here, we report these peptidases in synoviocytes to be localized predominantly in glycolipid- and cholesterol-rich membrane microdomains known as 'rafts'. At the ultrastructural level, aminopeptidase N/CD13 and dipeptidyl peptidase IV/CD26 were found in caveolae, in particular in intracellular yet surface-connected vesicle-like structures and 'rosettes' made up of several caveolae. In addition, clusters of peptidases were seen at the cell surface in flat patches ranging in size from about 60 to 160 nm. Cholesterol depletion of synoviocytes by methyl-beta-cyclodextrin disrupted >90% of the caveolae and reduced the raft localization of aminopeptidase N/CD13 without affecting Ala-p-nitroanilide-cleaving activity of confluent cell cultures. In co-culture experiments with T-lymphocytes, cholesterol depletion of synoviocytes greatly reduced their capability to induce an early lymphocytic expression of aminopeptidase N/CD13. We propose caveolae/rafts to be peptidase-rich 'hot-spot' regions of the synoviocyte plasma membrane required for functional cell-cell interactions with lymphocytes. The peptidases may act in concert with other types of proteins such as receptors and signal transducers localized in these specialized membrane domains.

Blotting, Western↗