[Recognizing and treating depression. 2: Drug therapy--psychotherapy--phased prevention].
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Biomedical subjects
Publications and source records attributed to D Riemann.
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The present study investigated the impact of the cholinesterase inhibitor tetrahydroaminoacridine (THA; tacrine) on sleep in healthy subjects. According to the reciprocal interaction model of non-rapid eye movement (NREM) and REM sleep regulation, which postulates a primary role in cholinergic neurotransmission for the initiation and maintenance of REM sleep, it was expected that THA would lead to an earlier onset of REM sleep. In 12 healthy subjects aged from 21 to 50 years two different doses (20 mg, 40 mg) were administered 1 hour prior to bed time and compared to placebo. Only the higher dose of THA significantly shortened REM latency. No other significant effects on sleep architecture were observed, although administration of 40 mg tacrine was associated with a decrease in sleep efficiency and a prolongation of sleep latency. Blood plasma levels of tacrine and its metabolite 1-hydroxytacrine measured prior to sleep and during the first 90 min of sleep were significantly correlated with the onset of REM sleep in relation to the timing of drug administration (only for the 20 mg dose). The reversible cholinesterase inhibitor THA exerts effects on REM latency comparable to those observed with other cholinomimetic agents.
Total sleep deprivation (TSD) exerts beneficial but only transient effects on mood in patients with a major depressive disorder (MDD). Though approximately 50 to 70% of depressed patients improve after sleep deprivation, the majority relapse after recovery sleep, some even after a short nap. One theoretical model postulates a critical period in the early morning hours where sleep is likely to induce a relapse, and nap studies indicate that sleep may be particularly 'depressogenic' at this time of day. A second model attributes the relapse to the release of non-REM sleep. We therefore compared the impact of an advanced sleep period (17:00-24:00 h) to a normal sleep period (23:00-06:00 h) on mood in patients who had responded to sleep deprivation. Less relapses into depression occurred after advanced sleep. Polysomnographic data showed that, as expected, normal sleep was characterized by a more pronounced improvement of sleep continuity and increased slow-wave sleep. The normal sleep group showed a stronger decrease in REM sleep density than the advanced sleep group compared with baseline. These data add to a growing body of evidence that the timing of sleep following successful sleep deprivation may be crucial for a stabilization of its antidepressant effect. Thus, avoidance of sleep during a "critical period' for more than a single night is necessary to provide a longer-lasting treatment modality.
After tumor nephrectomy, patients suffering from metastatic renal cell carcinoma (RCC) received interleukin-2 (IL-2), interferon (IFN)-alpha-2b and 5-fluorouracil (5-FU) in one to three treatment cycles over 8 weeks. Using flow cytometry, we investigated the immunophenotype of peripheral blood lymphocytes from 22 patients during therapy. In all patients, we found an increase in the absolute number of T lymphocytes, especially of the CD4 type, and in the number of HLA-DR+, CD25+ T cells and natural killer (NK) cells. The mean number of B cells did not increase during therapy. The numbers of CD4+, CD8+ and CD25+ T cells correlated significantly with the clinical response. In addition, we found that the pretherapeutic number of T lymphocytes and B cells but not of NK cells was significantly higher in patients with a therapy-induced clinical response. In conclusion, we describe the predictive value of the number of lymphocytes from peripheral blood for the efficiency of IL-2/IFN-alpha-2b therapy in combination with 5-FU in patients with metastatic renal cell carcinoma.
We tested the hypothesis that periodic breathing (PB) at high altitude is more frequent and arterial oxygen desaturation more severe during sleep in subjects developing high altitude pulmonary edema (HAPE) or acute mountain sickness (AMS) compared with subjects remaining healthy. We registered thoraco-abdominal movement, electro-encephalogram and oxygen saturation by pulse oximeter (pSao2) in 21 subjects during the first night spent at the altitude of 4,559 m. During the subsequent stay at 4,559 m, eight subjects remained well (controls), five subjects developed AMS and eight subjects developed HAPE. PB was found in all sleep stages and the percentage PB in any sleep stage was not significantly different between groups. There was a trend towards more PB in the HAPE vs. AMS and control group lasting 80 +/- 5 (mean +/- SE), 58 +/- 7, 57 +/- 9% of analyzable time, respectively (p = 0.09). The mean nocturnal decrease of pSao2 for these groups was 8.7 +/- 1.9, 5.4 +/- 2.1, 4.8 +/- 1.2%; (p = 0.36) and the median nocturnal pSao2 was 49 +/- 3, 63 +/- 3, and 63 +/- 4% (p = 0.02). Arterial blood gas analysis before and after sleep recordings indicate that the significantly lower Sao2 in the HAPE group is secondary to gas exchange rather than ventilation. The nocturnal decrease of pSao2 did not correlate with the time of PB nor the number of desaturation events > or = 4%. These findings suggest that more frequent PB in the HAPE group is a consequence of lower Sao2 due to impairment of gas exchange.
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Growth hormone (GH) responses to the alpha 2-adrenoceptor agonist clonidine and to GH-releasing hormone (GHRH) were measured in 12 patients fulfilling DSM-III-R criteria for major depressive disorder and in 12 age- and sex-matched controls. GH responses to clonidine correlated significantly with the GH responses to GHRH in the depressed patients as well as in the controls. Neither the responses to clonidine nor the responses to GHRH were significantly lower in depressed patients than in controls. Similarly, somatomedin-C (Sm-C) plasma concentrations and baseline GH concentrations were not different between the two groups. The data do not suggest that blunted GH responses to clonidine and/or GHRH represent specific features of depression.
BACKGROUND: Pulmonary type II pneumocytes have been examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and morphometry in numerous mammals. Until now, the fine structure of the human type II pneumocyte has not been studied by means of morphometry. METHODS: Eleven human donor lungs, which could not be made available for a suitable recipient, were preserved with Euro Collins solution (ECS) according to clinical organ preservation techniques. The lungs were fixed via the airways. Systematic random samples were analyzed by SEM, TEM, and classical stereological methods. RESULTS: Type II pneumocytes showed normal fine structural characteristics. Morphometry revealed that although inter-individual variation due to some oedematous swelling was present, the cells were in a normal size range as indicated by an estimated mean volume of 763 +/- 64 microns 3. The volume densities were: nucleus 21.9 +/- 2.2%, mitochondria 5.8 +/- 0.9%, lamellar bodies 9.8 +/- 3.6%, and remaining cytoplasmic components 62.4 +/- 2.9% of the cell volume. Since the inter-individual variations in the volume densities referred to the cell may, to variable degrees, reflect the variation in the reference space, the volume densities referred to the constant test point system and the respective volume-to-surface ratios were used for inter-individual comparisons. These parameters indicate that lamellar bodies were independent of cellular swelling, while mitochondria < nucleus < remaining cytoplasmic components increased in size with increasing cell size. CONCLUSIONS: Two to 7.5 hours of cold ischemia following ECS preservation do not deteriorate the fine structure of type II pneumocytes of human donor lungs. For reliable assessment of fine structural variations, morphometric parameters are required that are independent of variations in cell size.
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The interpretation of data from continuous monitoring of intracranial pressure (ICP) in patients with suspected normal pressure hydrocephalus (NPH) is the subject of controversy. Despite the fact that overnight ICP monitoring is widely used for the diagnosis of NPH, normative criteria are poorly defined. The present study demonstrates that there is a relationship between the relative frequency, the absolute amplitude, the wavelength and the morphology of B-waves and different sleep stages. Intraventricular intracranial pressure was recorded continuously overnight in 16 patients with suspected normal pressure hydrocephalus. Simultaneous polysomnography was performed to investigate the relation of spontaneous ICP oscillations to different sleep stages. A correlative analysis was done with the data of 13 patients. Three patients were excluded, one who was awake throughout the night and two in whom polysomnography was incomplete due to technical reasons. The mean resting cerebrospinal fluid (CSF) pressure was 12.87 cm CSF. B-waves were observed in the ICP recordings of all patients. They were present for a mean of 72% of the total recording time. The relative frequency of B-waves was higher during REM sleep and sleep stage 2 as compared to wakefulness (87.8% and 83.2% vs. 56. p < 0.05). The absolute amplitude was higher during REM sleep than in wakefulness (9.56 vs. 3.44 cm CSF, p < 0.05). Wavelengths were longer in REM sleep than in wakefulness and stages 1 and 2 (62.4 vs. 42, 40.7 and 44.8 sec, p < 0.05). The morphology of B-waves was also related to different sleep stages. Ramp-type B-waves were associated with REM sleep in six patients, however, were also present in sleep stage 2 in three of them. Knowledge of the relation of spontaneous ICP oscillations to different sleep stages may help to establish physiological foundations and alterations. Furthermore, polysomnography may be useful to avoid erroneous interpretation of ICP recordings due to sleep stage related variability.
Classical analysis of the spontaneous sleep EEG has revealed alterations of REM sleep in psychiatric diseases and under the influence of drugs. In order to elucidate possible functional differences between different REM episodes even in healthy subjects we investigated in 10 volunteers the transfer properties of the brain by measuring auditory (AEP) and visual evoked potentials (VEP) from scalp positions Fz, Cz and Pz during the night. According to linear system theory we computed the so-called amplitude-frequency characteristics (AFC) from averaged AEPs and VEPs during the first and each of the following 3 REM episodes. These functions describe the relationship between the input and output of the investigated system. A 3-factorial analysis of variances with the independent factors frequency band, REM episode and electrode position revealed a statistically significant main effect for the factor REM episode under auditory stimulation (P = 0.05), whereas no significant main effect for REM episode was found under visual stimulation (P = 0.88). Applying a 2-factorial analysis of variance with the independent factors REM episode and electrode position in the case of auditory stimulation we could demonstrate a statistically significant main effect (P = 0.029) for the factor REM episode in the beta range (12.5-20 Hz). A subsequent analysis of contrasts revealed that the first REM episodes could be differentiated from each other. For auditory stimulation the beta resonance during the first REM episode appears enhanced compared to each of the later REM episodes. These findings point to a functional difference of the brain's transfer functions between the first and the 3 following REM episodes, indicating different information processing during consecutive paradoxical sleep.
Growth-hormone (GH) responses to the alpha 2-adrenoceptor agonist clonidine were measured in 9 panic disorder patients, in 9 patients fulfilling DSM-III-R criteria for major depressive episode, and in 9 age- and sex-matched controls. GH responses to clonidine were not significantly different between the groups. The data do not agree with the assumption that blunted GH responses to clonidine represent a general feature of panic disorder or major depression.
Total sleep deprivation (TSD) exerts beneficial but only transient effects on mood in approximately 60% of the patients with a major depressive disorder (MDD). The positive effect of TSD is generally reversed after the next night of sleep. A pilot study of our group indicated that a consecutive one week phase advance of the sleep phase stabilized mood in more than half of the patients who responded to TSD. However, the majority of patients in our pilot study had been treated concomitantly with antidepressive medication. To exclude a possible synergistic effect of simultaneous antidepressive medication and the sleep-wake manipulation in the present study eleven medicated and sixteen drug-free depressed patients were investigated. In two thirds of the patients relapse into depression after successful TSD could be prevented. This effect seemed to be independent of adjunct antidepressant pharmacotherapy. Ten of these patients were studied polysomnographically prior to and during the treatment. Data analysis revealed that during the advance of the sleep phase no prolonged partial sleep deprivation took place. At the end of the study REM % had even increased and REM latency was still short in spite of clinical improvement, thus contradicting the assumption that REM sleep suppression is a necessary prerequisite for antidepressive therapy. The results support the hypothesis of a "critical phase" in the morning hours during which sleep can reinduce depressive mood and, vice versa, prevention of sleep during this time may act antidepressively.
Aminopeptidase N (APN) and dipeptidylpeptidase IV (DPIV) are transmembrane type II molecules widely distributed in mammalian tissues. In recent years, the interest in cell surface peptidases has increased considerably because, among other things, several reports indicate roles of ectopeptidases in tumour cell metastasis. Investigations into the regulation of APN and DPIV on tumour cells are rare. We report, for the first time, that IL-4 and IL-13 can up-regulate protein expression as well as enzymatic activity of both the peptidases on renal carcinoma cells and renal tubular epithelial cells in culture. The analysis of mRNA by competitive polymerase chain reaction (PCR) confirmed our results with respect to the APN increase at the level of gene expression. IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) augmented the IL-4-induced effect with respect to APN but not to DPIV. A 5-day incubation with interferon-gamma (IFN-gamma) increased protein expression, especially of APN and, to a lesser extent, also of DPIV, whereas no significant increase in enzymatic activity could be observed. Small concentrations of transforming growth factor-beta 1 (TGF-beta 1) inhibit the expression and enzyme activity of DPIV. IL-6, IL-7, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been found to be without any effect on APN and DPIV. For a prospective therapeutic regimen with T cell-derived cytokines it has to be considered that--besides their effect on tumour cell growth--cytokines might affect surface ectopeptidases involved in tumour cell adhesion processes. The inhibition of APN and DPIV could be a new approach to suppression of cancer spread.
The present study aimed at investigating the question whether abnormalities of sleep, especially disinhibition of rapid eye movement (REM) sleep, are already present in adolescents with primary major depressive disorder (MDD). Ten healthy controls assessed at home, 10 inpatients with MDD and 10 inpatients with schizophrenia (age range: 13-19 years) were investigated polysomnographically. REM latency was significantly shortened in MDD compared with the two other groups. Adolescents with MDD did not display disturbances of sleep continuity as typically observed in adults with major depression. The most pronounced impairment of sleep continuity was noted in schizophrenic patients. The results stress that shortened REM latency may already occur in adolescent depression.