Lactate as clinical tumour biomarker: Optimization of lactate detection and quantification in MR spectroscopic imaging of glioblastomas.

PURPOSE: Increased lactate (Lac) level in brain tumours is in vivo detectable by 1H MR spectroscopy (MRS) but is frequently overlapped by strong lipid signals, which either leads to a weak quality of the Lac signal or even inhibit its detection. We sought to optimize the separation of Lac from lipid signals in intermediate-echo time MRS acquisitions thus allowing its applicability as clinical biomarker in glioblastomas. METHODS: Data of 27 patients with glioblastoma multiforme (GBM) were analysed using standard post-processing software as well as in-house modified technique based on the same commercially available software. The patients' Lac concentration values provided by the MRS post-processing technique were converted to realistic concentrations by using an appropriately calibrated phantom. The Cramér-Rao lower bound (%CR) was the principal criterion for estimating the quality of the MRS post-processing results. RESULTS: Based on the ex vivo calibration, the analysis of the in vivo MR spectroscopy measurements led to an improvement of the %CR(Lac) value from 18 % to 8 %. In a single case, the detection of Lac was achievable only by the modified technique, as Lac signal was contaminated with lipids using the standard analysis. The resulting in vivo Lac values from the modified analysis (median: 4.77 mmol/l, range: 1.5-9.2) were considered as a realistic order of magnitude for the metabolite concentrations, whereas no Lac was identified in the normal appearing white matter. This qualified also Lac mapping as a biomarker for regional heterogeneity in GBM. CONCLUSIONS: The proposed methodology is a promising first step for more reliable analysis of Lac signal, decontaminating it from lipid peaks in MRS, and may help to establish Lac as a biomarker for brain tumours in clinical routine.

Fluorescence based rRNA sensor systems for detection of whole cells of Saccharomonospora spp. and Thermoactinomyces spp.

Airborne thermophilic actinomycetes (TPAs) are a growing hygienic challenge in different occupational situations e.g. large scale composting. This study describes first results of a new approach for highly specific and rapid detection of organisms of this group using fluorescently labelled oligonucleotide probes as sensors for whole cells. Three genus-specific 16S rRNA-targeted probes, two for Saccharomonospora spp. and one for Thermoactinomyces spp. were developed and evaluated in a fluorescence in situ hybridisation (FISH) format with agar-grown whole cells. For optimal sensitivity and specificity of FISH, conditions for cell wall permeabilisation and hybridisation stringency were evaluated independently for both genera. Performing specified pretreatment protocols, all three probes yielded strong fluorescence signals. However, the relative fraction of detectable cells or spores clearly depended on the single bacterial species. The probes can serve as cell sensors for direct detection of TPAs in natural samples.

Dopamine reduction in the substantia nigra of Parkinson's disease patients confirmed by in vivo magnetic resonance spectroscopic imaging.

OBJECTIVES: Metabolic changes in the substantia nigra of patients with Parkinson's disease were previously investigated in different molecular-pathological examinations. The aim of our study was the in vivo measurement of these alterations using three-dimensional magnetic resonance spectroscopic imaging. METHODS: 21 patients with Parkinson's disease and 24 controls were examined using magnetic resonance spectroscopic imaging at 3 Tesla. The spectra of rostral and caudal substantia nigra regions were analyzed using LCModel. For spectral fitting, an adjusted basis data set with pathology-specific metabolites and macromolecules was used to better reproduce the in vivo spectra. To assess differences between both groups more accurately, especially in metabolites at lower concentrations, group-averaged spectra were evaluated in addition to the analysis of individual data. RESULTS: We found significantly decreased N-acetylaspartate, choline, creatine, myo-inositol, glutathione and dopamine concentrations in patients with Parkinson's disease compared to controls, whereas glutamine+glutamate, γ-aminobutyric acid, and homovanillic acid were slightly increased. According to anatomical features, clear differences in the biochemical profiles were found between rostral and caudal substantia nigra voxels in both groups. CONCLUSIONS: Reduced N-acetylaspartate and dopamine concentrations result from progressive degeneration of dopamine-producing neurons within the substantia nigra pars compacta. Decreased creatine levels can be interpreted as impaired energy metabolism due to mitochondrial dysfunction. Lower glutathione concentrations might be a cause or consequence of oxidative stress. Furthermore, slightly increased glutamine+glutamate and γ-aminobutyric acid levels are expected based on post mortem data in Parkinson's disease. To the best of our knowledge, this is the first non-invasive confirmation of these metabolic changes.

[From the Nuremberg Alliance Against Depression to a European network (EAAD)--extending community-based awareness-campaigns on national and European level]. / Vom Nürnberger Bündnis gegen Depression zur European Alliance Against Depression (EAAD)--Gemeindebasierte Awareness-Kampagnen in Deutschland und Europa.

With the aim to improve the care of depressed patients and to reduce suicidality, the Nuremberg Alliance Against Depression was initiated 2001 in the framework of the German Research Network on Depression and Suicidality (funded by the Federal Ministry of Education and Research). The Alliance's concept is based on an intervention on four levels: Co-operation with GPs, an information- and awareness-campaign for the broad public, educational training for multipliers such as teachers, priests or geriatric care-givers as well as the support and initiative of self-help-activities. After two years of intervention the number of suicidal acts, the study's main outcome criteria, was significantly reduced by 24 percent compared to the baseline and to a representative control region. Since 2002 the successful four-level-intervention, its concepts and materials have been adapted by other regions within Germany. Nearly 40 community-based local campaigns are forming the German Alliance Against Depression (GAD) and many more regions are interested. On international level the European Alliance Against Depression (EAAD) was established 2004. Funded by the European Commission the four-level-programme is implemented in 17 European countries.

[Media coverage on suicide in Nuremberg's daily papers--frequency and form of the reporting before and during media-intervention with guidelines]. / Suizidberichte in Nürnberger Printmedien--Häufigkeit und Form der Berichterstattung vor und nach der Implementierung eines Medienguides.

BACKGROUND: As one of its suicide preventive actions, the "Nuremberg Alliance Against Depression" has started cooperation with local media in 2001 by implementing a 14-item-mediaguide concerning a more sensible way of suicide-reporting to prevent copy-cat suicides. The effects of this mediaguide on the reporting are being evaluated. METHODS: A systematic recording of all suicide reports during 2000 (Baseline) and 2001 (first intervention year) was performed for three regional dailies in Nuremberg. A comparison of the reporting regarding the frequency, distribution and some qualitative aspects between baseline and intervention year as well as to a control-medium from Würzburg was carried out. RESULTS: Two out of three dailies in Nuremberg show a noticeable reduction in the numbers of articles on suicides. Compared to the baseline and control-medium one of the decreases is statistically significant. The results of the third newspaper, however, indicated an opposite direction, stating a significant increase in the number of reports. CONCLUSIONS: Crucial criterion for a mediaguide's favourable influence on the suicide-reporting is the willingness of the main editors in charge at the local dailies to be engaged and willing to cooperate. This can be achieved only through good personal contact and relationship to the project.