Makrophagenrekrutierung aus Blutmonocyten bei Entzündungsreaktionen der Haut

Zusammenfassung Gesunden Probanden wurden autologe,³HDFP markierte Monocyten transfundiert und dann die Markierungsindices der Blutmonocyten und der Makrophagen im Hautfensterexsudat bestimmt. Die Ergebnisse zeigten, daß die Makrophagenbesiedlung der akut entzündlichen Hautfensterreaktion durch direkte Rekrutierung aus Blutmonocyten erfolgt. Außerdem wurden vier Patienten mit generalisierten, chronischen Ekzemen untersucht (Neurodermitis, aus bakteriellseborrhoischem Ekzem entstandene Erythrodermie, generalisierte chronische Ekzeme bei Kontaktallergie). Bei drei dieser Patienten lagen die Monocytenumsatzraten im Normbereich, bei dem vierten war sie geringfügig gesteigert. Die Makrophagenspeicher im Gebiet dieser ausgedehnten, chronischen Entzündungen setzten sich offensichtlich aus Makrophagenpopulationen zusammen, die in der Lage waren, ihren Bestand weitgehend unabhängig von der Monocytenrekrutierung zu erhalten und zu erneuern.

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Macrophage-recruitment from blood monocytes in inflammatory skin reactions

Summary Transfusion of³HDFP labeled autologous monocytes was performed in healthy probants. Subsequently labeling indices of blood monocytes and of macrophages in skin window exsudates were determined. The results demonstrated that macrophages of acute inflammatory skin reactions are directly recruited from circulating monocytes. In addition, 4 patients suffering from generalized, chronic eczematous skin diseases were examined. Monocyte turnover rates were normal in 3 of these patients and slightly increased in the fourth. Obviously the macrophage pools at the side of these wide spread chronic inflammatory reactions were composed of self-sustaining and self-renewing macrophage populations with low monocyte recruitment rates.

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Die Untersuchungen wurden durch die Deutsche Forschungsgemeinschaft unterstützt.

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Unter technischer Assistenz von B. Kasten.     

Physostigmine reverses propofol-induced unconsciousness and attenuation of the auditory steady state response and bispectral index in human volunteers

BACKGROUND: It is postulated that alteration of central cholinergic transmission plays an important role in the mechanism by which anesthetics produce unconsciousness. The authors investigated the effect of altering central cholinergic transmission, by physostigmine and scopolamine, on unconsciousness produced by propofol. METHODS: Propofol was administered to American Society of Anesthesiologists physical status 1 (n = 17) volunteers with use of a computer-controlled infusion pump at increasing concentrations until unconsciousness resulted (inability to respond to verbal commands, abolition of spontaneous movement). Central nervous system function was assessed by use of the Auditory Steady State Response (ASSR) and Bispectral Index (BIS) analysis of electrooculogram. During continuous administration of propofol, reversal of unconsciousness produced by physostigmine (28 microgram/kg) and block of this reversal by scopolamine (8.6 microgram/kg) were evaluated. RESULTS: Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 (+/- SD) microgram/ml (n = 17). Unconsciousness was associated with reductions in ASSR (0.10 +/- 0.08 microV [awake baseline 0.32 +/- 0.18 microV], P < 0.001) and BIS (55.7 +/- 8.8 [awake baseline 92.4 +/- 3.9], P < 0.001). Physostigmine restored consciousness in 9 of 11 subjects, with concomitant increases in ASSR (0.38 +/- 0.17 microV, P < 0.01) and BIS (75.3 +/- 8.3, P < 0.001). In all subjects (n = 6) scopolamine blocked the physostigmine-induced reversal of unconsciousness and the increase of the ASSR and BIS (ASSR and BIS during propofol-induced unconsciousness: 0.09 +/- 0.09 microV and 58.2 +/- 7.5, respectively; ASSR and BIS after physostigmine administration: 0.08 +/- 0.06 microV and 56.8 +/- 6.7, respectively, NS). CONCLUSIONS: These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.     

Propofol anesthesia and cerebral blood flow changes elicited by vibrotactile stimulation: a positron emission tomography study

We investigated the effects of the general anesthetic agent propofol on cerebral structures involved in the processing of vibrotactile information. Using positron emission tomography (PET) and the H(2)(15)O bolus technique, we measured regional distribution of cerebral blood flow (CBF) in eight healthy human volunteers. They were scanned under five different levels of propofol anesthesia. Using a computer-controlled infusion, the following plasma levels of propofol were targeted: Level W (Waking, 0 microg/ml), Level 1 (0.5 microg/ml), Level 2 (1.5 microg/ml), Level 3 (3.5 microg/ml), and Level R (Recovery). At each level of anesthesia, two 3-min scans were acquired with vibrotactile stimulation of the right forearm either on or off. The level of consciousness was evaluated before each scan by the response of the subject to a verbal command. At Level W, all volunteers were fully awake. They reported being slightly drowsy at Level 1, they had a slurred speech and slow response at Level 2, and they were not responding at all at Level 3. The following variations in regional CBF (rCBF) were observed. During the waking state (Level W), vibrotactile stimulation induced a significant rCBF increase in the left thalamus and in several cortical regions, including the left primary somatosensory cortex and the left and right secondary somatosensory cortex. During anesthesia, propofol reduced in a dose-dependent manner rCBF in the thalamus as well as in a number of visual, parietal, and prefrontal cortical regions. At Level 1 through 3, propofol also suppressed vibration-induced increases in rCBF in the primary and secondary somatosensory cortex, whereas the thalamic rCBF response was abolished only at Level 3, when volunteers lost consciousness. We conclude that propofol interferes with the processing of vibrotactile information first at the level of the cortex before attenuating its transfer through the thalamus.     

Preliminary evidence for cognitive mediation during cognitive-behavioral therapy of panic disorder

Cognitive-behavioral therapy (CBT) and pharmacotherapy are similarly effective for treating panic disorder with mild or no agoraphobia, but little is known about the mechanism through which these treatments work. The present study examined some of the criteria for cognitive mediation of treatment change in CBT alone, imipramine alone, CBT plus imipramine, and CBT plus placebo. Ninety-one individuals who received 1 of these interventions were assessed before and after acute treatment, and after a 6-month maintenance period. Multilevel moderated mediation analyses provided preliminary support for the notion that changes in panic-related cognitions mediate changes in panic severity only in treatments that include CBT.     

The effects of acute exercise on CO(2) challenge reactivity

The present study examined the effects of acute exercise on anxiogenic responding to 65% O₂/35% CO₂ challenge. Participants (N = 92) were 51 female and 41 male volunteers ranging in age from 17 to 24 (M = 19.43, SD = 1.31). Participants had no history of panic attacks and were randomized to moderate treadmill exercise (i.e., 70% of HR_max) or quiet rest prior to taking a single vital capacity inhalation of 35% CO₂/65% O₂. Gender and measures of negative affectivity and anxiety sensitivity were included in the design as control variables. Results indicated participants who exercised prior to challenge showed significantly reduced reactivity compared to their counterparts who rested prior to challenge. Importantly, the effect sizes for the advantage of exercise over rest remained in the medium to large range (i.e., partial η² > .07) after controlling for the effects of gender, anxiety sensitivity, and negative affectivity. These findings are the first to demonstrate that the anti-panic effects of exercise are unique from, and cannot be better explained by, established risk factors of CO₂ challenge reactivity.     

Changes in respiration mediate changes in fear of bodily sensations in panic disorder

The purpose of the study was to examine whether changes in pCO(2) mediate changes in fear of bodily sensation (as indexed by anxiety sensitivity) in a bio-behavioral treatment for panic disorder that targets changes in end-tidal pCO(2). Thirty-five panic patients underwent 4 weeks of capnometry-assisted breathing training targeting respiratory dysregulation. Longitudinal mediation analyses of the changes in fear of bodily symptoms over time demonstrated that pCO(2), but not respiration rate, was a partial mediator of the changes in anxiety sensitivity. Results were supported by cross lag panel analyses, which indicated that earlier pCO(2) levels predicted later levels of anxiety sensitivity, but not vice versa. PCO(2) changes also led to changes in respiration rate, questioning the importance of respiration rate in breathing training. The results provide little support for changes in fear of bodily sensations leading to changes in respiration, but rather suggest that breathing training targeting pCO(2) reduced fear of bodily sensations in panic disorder.     

Treatments for blood-injury-injection phobia: A critical review of current evidence

Blood-injury-injection (BII) phobia presents with a unique anxiety response that often involves blood pressure drops and pronounced bradycardia, which can culminate in fainting. The current recommended treatment for BII phobia is Applied Tension (AT), a tension technique that includes in vivo exposure. However, surprisingly little empirical evidence is available on the additive efficacy of tension beyond exposure alone. Our literature search yielded five controlled treatment studies for BII phobia, all from one research group. Beyond AT, these studies also tested Exposure only (E), Tension only, Applied Relaxation (AR), or a combination of AR and AT. Based on self-reported levels of anxiety, in-session avoidance and fainting, AT was superior over other conditions; however, when considering pre- to post-treatment effect sizes on BII-related questionnaires, E outperformed all other treatments. In addition, AT did not yield better results on physiological measures, and individuals with BII fears improved similarly within studies across treatment groups, regardless of fainting status. Heterogeneity in patient populations (e.g. extent of fainting-proneness), differential targeting of BII phobia manifestations, and small sample sizes may explain some of the variability in findings. Further research is needed to determine the efficacy of treatment techniques for BII phobia patients with and without fainting history.     

Augmentation of exposure therapy with D-cycloserine for social anxiety disorder

CONTEXT: Social anxiety disorder (SAD) is common and debilitating. Although exposure therapy is one of the most effective forms of psychotherapy for this disorder, many patients remain symptomatic. Fear reduction in exposure therapy is similar to extinction learning, and early clinical data with specific phobias suggest that the treatment effects of exposure therapy for SAD may be enhanced with d-cycloserine, an agonist at the glutamatergic N-methyl-d-aspartate receptor. OBJECTIVE: To determine whether short-term treatment with 50 mg of d-cycloserine enhances the efficacy of exposure therapy for SAD. DESIGN: Randomized, double-blind, placebo-controlled augmentation trial examining the combination of d-cycloserine or pill placebo with exposure therapy for SAD. SETTING: Patients were self-referred from the general community to 1 of 3 research clinics. PARTICIPANTS: Twenty-seven participants meeting DSM-IV criteria for SAD with significant public speaking anxiety. INTERVENTIONS: Following a diagnostic interview and pretreatment assessment, participants received 5 therapy sessions delivered in either an individual or group therapy format. The first session provided an introduction to the treatment model and was followed by 4 sessions emphasizing exposure to increasingly challenging public speech situations with videotaped feedback of performances. One hour prior to each session, participants received single doses of d-cycloserine or placebo. MAIN OUTCOME MEASURES: Symptoms were assessed by patient self-report and by clinicians blind to the randomization condition before treatment, after treatment, and 1 month after the last session. RESULTS: Participants receiving d-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo. Controlled effect sizes were in the medium to large range. CONCLUSION: The pilot data provide preliminary support for the use of short-term dosing of d-cycloserine as an adjunctive intervention to exposure therapy for SAD.     

Treatment for Anhedonia: A Neuroscience Driven Approach

Anhedonia, or loss of interest or pleasure in usual activities, is characteristic of depression, some types of anxiety, as well as substance abuse and schizophrenia. Anhedonia is a predictor of poor long-term outcomes, including suicide, and poor treatment response. Because extant psychological and pharmacological treatments are relatively ineffective for anhedonia, there is an unmet therapeutic need for this high-risk symptom. Current psychological and drug treatments for anxiety and depression focus largely on reducing excesses in negative affect rather than improving deficits in positive affect. Recent advances in affective neuroscience posit that anhedonia is associated with deficits in the appetitive reward system, specifically the anticipation, consumption, and learning of reward. In this paper, we review the evidence for positive affect as a symptom cluster, and its neural underpinnings, and introduce a novel psychological treatment for anxiety and depression that targets appetitive responding. First, we review anhedonia in relation to positive and negative valence systems and current treatment approaches. Second, we discuss the evidence linking anhedonia to biological, experiential, and behavioral deficits in the reward subsystems. Third, we describe the therapeutic approach for Positive Affect Treatment (PAT), an intervention designed to specifically target deficits in reward sensitivity.     

Universelles Neugeborenen-Hörscreening

Background

Since 2009, all newborns in Germany have been entitled to universal neonatal hearing screening (UNHS). UNHS with tracking of test results leads to earlier detection of hearing disorders. The Association of German Hearing Screening Centers (Verband Deutscher Hörscreening-Zentralen, VDHZ) was founded to promote nationwide tracking, validity and quality control of UNHS results.

Objectives

A comparable data structure in the different screening centers, with uniform definitions of primary parameters is essential for the nationwide evaluation of UNHS results. To address the question of whether a data structure with comparable definitions already exists or still has to be created, the existing structures and primary parameter definitions in the hearing screening centers should be investigated and compared.

Methods

A survey was conducted in all hearing screening centers to assess how data on the primary UNHS parameters defined in pediatric guidelines was gathered. In the case of discrepancies, uniform definitions were created. Finally, the practicability of these definitions was evaluated.

Results

Due to differing definitions of primary parameters, some of the data were not comparable between the individual centers. Therefore, uniform definitions were created in a consensus process. In the centers, the screening method, the two-step first screening and the result of the first screening now correspond to these uniform definitions. Other parameters, e.g. the total number of newborns, still vary widely, rendering the comparison of screening rates almost impossible.

Conclusion

Valid evaluation of UNHS not only requires nationwide establishment of hearing screening centers, but also unified data structures and parameter definitions.