BNST and amygdala activation to threat: Effects of temporal predictability and threat mode.

Recent animal and human studies highlight the uncertainty about the onset of an aversive event as a crucial factor for the involvement of the centromedial amygdala (CM) and bed nucleus of the stria terminalis (BNST) activity. However, studies investigating temporally predictable or unpredictable threat anticipation and confrontation processes are rare. Furthermore, the few existing fMRI studies analyzing temporally predictable and unpredictable threat processes used small sample sizes or limited fMRI paradigms. Therefore, we measured functional brain activity in 109 predominantly female healthy participants during a temporally predictable-unpredictable threat paradigm, which aimed to solve limited aspects of recent studies. Results showed higher BNST activity compared to the CM during the cue indicating that the upcoming confrontation is aversive relative to the cue indicating an upcoming neutral confrontation. Both the CM and BNST showed higher activity during the confrontation with unpredictable and aversive stimuli, but the reaction to aversive confrontation relative to neutral confrontation was stronger in the CM compared to the BNST. Additional modulation analyses by NPSR1 rs324981 genotype revealed higher BNST activity relative to the CM in unpredictable anticipation relative to predictable anticipation in T-carriers compared to AA carriers. Our results indicate that during the confrontation with aversive or neutral stimuli, temporal unpredictability modulates CM and BNST activity. Further, there is a differential activity concerning threat processing, as BNST is more involved when focussing on fear-related anticipation processes and CM is more involved when focussing on threat confrontation.

Influence of reconstruction settings in electrical impedance tomography on figures of merit and physiological parameters.

OBJECTIVE: Electrical impedance tomography (EIT) is a non-invasive and relatively cheap imaging technique allowing continuous monitoring of lung function at the bedside. However, image reconstruction and processing are not yet standardized for clinical use, limiting comparability and reproducibility between studies. In addition, optimal reconstruction settings still have to be identified for different clinical applications. In this work (i) a systematic way to select 'good' EIT algorithm parameters is developed and (ii) an evaluation of these parameters in terms of correct functional imaging and consistency is performed. APPROACH: First, 19 200 reconstruction models are generated by full factorial design of experiment in 5D space. Then, in order to quantify the quality of reconstruction, known conductivity changes are introduced and figures of merit (FoM) are calculated from the response image. These measures are further used to select a subset of reconstruction models, matching certain FoM thresholds, and are then used for in vivo evaluation. For this purpose, EIT images of one piglet are reconstructed to assess changes in tidal impedance and end-expiratory lung impedance, at positive end expiratory pressure of 0 and 15 cmH2O. From ground truth spirometry measurements, physiological criteria are formulated and the subset of models is further reduced. Finally, the remaining reconstruction models are evaluated on physiological data gathered from published data in the literature to assess the generalization possibilities. MAIN RESULTS: Parametrization of EIT image reconstruction has a strong influence on the resulting FoM and the derived physiological parameter. While numerous reconstruction models showed reasonable values for a single parameter, in total only 12 matched all simulation and physiological criteria. After validation on further physiological data, only a single reconstruction model remained with a noise figure of 0.3, target size of 0.08, weight radius of 0.3, normalized voltage and strong weighting of lung and heart regions. Furthermore, the relationship between the reconstruction settings and some FoM could be partly explained by using a linear statistical model. SIGNIFICANCE: The quest for standard reconstruction settings is highly relevant for future clinical applications. Simulation measures might help to assess the quality of the reconstruction models, but further evaluation of more data and different experimental settings is required.

[Comparison of results after primary and secondary shoulder arthroplasty for proximal humeral fractures]. / Ergebnisvergleich primärer versus sekundärer Frakturprothetik am proximalen Humerus.

BACKGROUND: The purpose of this retrospective cohort study was to evaluate, compare and discuss the results and complications after primary and secondary shoulder arthoplasty in proximal humeral fractures. PATIENTS AND METHODS: Thirteen consecutive patients (mean 76 years [range, 65-85] years) were at a mean of 29 (8-37) months after primary humeral head replacement (group 1), and 15 patients (mean 74 years [range, 43-80] years) at a mean of 18 (7-36) months after secondary shoulder arthoplasty (n = 8 anatomic prostheses, n = 7 reversed prostheses) due to complications/fracture sequelae (group 2) examined clinically and radiologically according to a standardised follow-up protocol. Patient satisfaction, the simple shoulder test (SST), the American shoulder elbow score (ASES) as well as the Constant score (CS) were assessed, and radiological parameters as well as complications analysed. RESULTS: 85 % of patients in group 1 and 73 % in group 2 were satisfied with the results. The SST did not show a significant difference between both groups. The adjusted ASES did not differ significantly with 70 (27-95)% in group 1 and 73 (28-100)% in group 2, as well as the adjusted CS with a mean of 53 (27-83)% in group 1 and of 49 (27-87)% in group 2. Radiological analysis resulted in a correctly centred prosthesis in 6/13 patients, and healed tuberosities in 7/13 of group 1. In group 2 4/8 anatomic prostheses were centered and 7/8 showed healed tuberosities. In the subgroup of the reversed prostheses 6/7 were centered, 3/7 patients had an inferior "notching". The rate of complications and revisions were 2/13 (15 %) in group 1 and 1/15 (7 %) in group 2. CONCLUSION: In summary, the functional results did not differ significantly between primary and secondary shoulder arthroplasty after proximal humeral fractures. The relatively low expectation of elderly patients is reflected in a high rate of patient satisfaction in spite of moderate functional results. The primary humeral head replacement showed higher rates of complications and revisions compared to secondary arthroplasty.

[Indications of HR-CT in the early postoperative phase of stapedotomy]. / Indikationen für die HR-CT nach erfolgter Stapedotomie in der frühen postoperativen Phase.

PURPOSE: This is an analysis of high-resolution computed tomography (HR-CT) performed in patients with and without symptoms after stapes surgery during the early postoperative phase. MATERIALS AND METHODS: We examined 37 patients who underwent stapes surgery between January 1995 and December 2000. HR-CT of the temporal bone was performed in axial and coronal planes with 1-mm-slice thickness and table feed. A reoperation was performed in 7 patients. CT findings were compared with clinical follow up and surgical findings. RESULTS: All patients showed postoperative opacification of the tympanic cavity and external auditory canal as well as partial opacification of the mastoid on CT scans. A dislocation of the prosthesis was found in 11 cases and air bubbles were seen in the vestibule of 5 patients. In one case, small bone fragments were detected in the vestibule. In 6 of 7 cases, CT results were confirmed by retympanotomy. CONCLUSIONS: Due to overlapping of normal and pathological findings in the early postoperative period, indications for HR-CT are limited in this period.

Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD.

This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction. A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42+/-4% predicted) received either 10 mg montelukast and 3 h later placebo via metered-dose inhaler (MDI) (M), or placebo and 3 h later 200 microg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changes versus baseline. Compared to P, S caused significant bronchodilation in FEV1 (7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1 (1.5%). The saline-induced fall in FEV1 was lower after M (-5.8%), compared with S (-10.3%) and P (-13.1%). FEV1 (11.3%) and FIV1 (7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1 (8.5 min) and FIV1 (15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1 and/or inhaled corticosteroids. Data from this study indicate beneficial effects of montelukast on hypertonic saline-induced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline.

Montelukast versus fluticasone: effects on lung function, airway responsiveness and inflammation in moderate asthma.

Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue. The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast (10 mg, once a day) or low-dose inhaled fluticasone (100 microg b.i.d.) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma. Forty patients (forced expiratory volume in one second (FEV1), 60-80% predicted) were studied in a double-blind, randomised, crossover design. Treatment periods were separated by 3-8 weeks of washout. At the beginning and end of each period, FEV1, airway responsiveness to inhaled methacholine (provocative concentration causing a 20% fall in FEV1 (PC20)), the level of exhaled nitric oxide (NO) and sputum differential cell counts were determined. Only short-acting beta2-agonists were allowed for relief of symptoms. FEV1 increased by 0.50+/-0.07 L (mean+/-SEM) after fluticasone and by 0.37+/-0.07 L after montelukast (p<0.001, each), and PC20 by 1.33+/-0.13 (p<0.001) and 0.15+/-0.17 (NS) doubling doses, respectively. Correspondingly, percentages of sputum eosinophils were reduced by factor 2.7 (p<0.01) and 1.4 (nonsignificant (NS)), and the levels of exhaled NO (at 50 mL x s(-1)) by factor 2.1 (p<0.01) and 1.1 (NS). These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma, but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods.

Repeated ozone exposures enhance bronchial allergen responses in subjects with rhinitis or asthma.

BACKGROUND: Single exposures to > 200 p.p.b. of ozone are capable of enhancing the early-phase lung function response to allergen. OBJECTIVE: The aim of the present study was to compare the effect of single vs. repeated exposures to ozone on early and late-phase allergen responses. METHODS: Eleven subjects with allergic asthma and 22 subjects with allergic rhinitis underwent single exposures to filtered air, 125 p.p.b. and 250 p.p.b. ozone, as well as repeated exposures to 125 p.p.b. ozone on four consecutive days. Twenty hours after the (final) exposure, subjects inhaled a single dose of allergen and a sputum induction was performed 6-7 h later. RESULTS: In the subjects with rhinitis, the mean early-phase response of FEV1 and the number of > or = 20% reductions were significantly greater after exposure to 250 or 4 x 125 p.p.b. ozone compared with filtered air. In addition, most of the > or = 15% late-phase responses in FEV1 occurred after exposure to 4 x 125 p.p.b., as well as the strongest effects on sputum parameters. The rise in the number of eosinophils was statistically significant in both groups. Regarding the number of lymphocytes and the concentrations of mast cell tryptase, histamine or LDH, significance was, however, only reached in the asthma group. CONCLUSION: Our data suggest that repeated exposure to ozone, at a peak ambient air level, can enhance both functional and inflammatory responses to inhaled allergen in subjects with pre-existing allergic airway diseases, and that these effects might reach a clinically relevant magnitude.

Effect of inhaled ciclesonide on airway responsiveness to inhaled AMP, the composition of induced sputum and exhaled nitric oxide in patients with mild asthma.

To assess the efficacy of ciclesonide, a novel corticosteroid pro-drug, we compared its effect on lung function, airway responsiveness to inhaled AMP, the composition of induced sputum, and the level of exhaled nitric oxide (NO) with the effect of budesonide in patients with asthma. Fifteen non-smoking steroid-naive patients (mean FEV(1), 94%pred) inhaled either 400 microg ciclesonide or 400 microg budesonide as a single morning dose for two weeks each separated by a > or =3 week wash-out period. The study was performed in a double-observer, randomized, cross-over design. FEV(1)increased significantly during treatment with budesonide (3.38 vs. 3.64 l P=0,003), but not after ciclesonide (3.60 vs. 3.69 l). PC(20)FEV(1)of AMP increased (P<0,001, each) after both budesonide (4.59 vs. 32.48 mg/ml, 2.8 doubling doses) and ciclesonide (3.92 vs. 20.00 mg/ml, 2.4 doubling doses). The percentage of sputum eosinophils was significantly reduced after ciclesonide (7.9 vs. 3.4% P=0.01), but not budesonide (6.0 vs. 4.3%). After both budesonide and ciclesonide, a significant (P<0.001) reduction in the level of exhaled NO occurred. In none of the parameters studied, the changes differed significantly between treatment with budesonide or ciclesonide. These data suggest that ciclesonide is equi-effective to budesonide with regard to its potency to reduce the airway responsiveness to inhaled AMP as well as airway inflammation in patients with mild asthma.

Counting of single protein molecules at interfaces and application of this technique in early-stage diagnosis.

The fluorescence-based detection and counting of single protein molecules after specific binding to antibodies at interfaces is presented. A diode laser was used as the excitation source. The unspecific binding at the interface has been reduced to a level of only 0.1% of the maximum signal level. At present, the detection limit of this molecule-counting process is in the range of 10(-17) mol/L, and the dynamic range of the signal corresponds to 7 orders of magnitude of antigen concentration, but these values are not limiting. As a preliminary application in early-stage diagnosis, we have investigated the detection of a single cardiac actin molecule in human plasma, which is of interest in myocardial infarction diagnosis.

[The management needs of the bereaved following loss of a partner]. / Die Betreuungssituation der Hinterbliebenen nach einem Partnerverlust.

A case of death results in the formation of a social group, the group consisting of the bereaved, which remains in existence for a brief spell only, but which calls for careful attention. 124 widowed persons were questioned about their reaction to their loss, and changes in their habits after bereavement. Factors of influence are indicated, important among them dependence on the deceased, the age of the bereaved person, and physical and mental health.