Year of publication
- Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) (2011)
- Introduction Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard of care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard of care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods Patients who received rituximab having shown an inadequate response to standard of care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2440 mg of rituximab over a median (range) of 194 (180 to 1407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies. Additional file 1: Supplemental tables. Table A1. Duration of follow-up from first rituximab infusion to last control visit by diagnosis. Table A2. Number of rituximab infusions by diagnosis.
- Mobile Air Quality Studies (MAQS) - an international project (2010)
- Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone.
- Online privacy: towards informational self-determination on the internet : report from Dagstuhl Perspectives Workshop 11061 (2011)
- The Dagstuhl Perspectives Workshop "Online Privacy: Towards Informational Self-Determination on the Internet" (11061) has been held in February 6-11, 2011 at Schloss Dagstuhl. 30 participants from academia, public sector, and industry have identified the current status-of-the-art of and challenges for online privacy as well as derived recommendations for improving online privacy. Whereas the Dagstuhl Manifesto of this workshop concludes the results of the working groups and panel discussions, this article presents the talks of this workshop by their abstracts.
- Hypoxia enhances the antiglioma cytotoxicity of b10, a glycosylated derivative of betulinic Acid (2014)
- B10 is a glycosylated derivative of betulinic acid with promising activity against glioma cells. Lysosomal cell death pathways appear to be essential for its cytotoxicity. We investigated the influence of hypoxia, nutrient deprivation and current standard therapies on B10 cytotoxicity. The human glioma cell lines LN-308 and LNT-229 were exposed to B10 alone or together with irradiation, temozolomide, nutrient deprivation or hypoxia. Cell growth and viability were evaluated by crystal violet staining, clonogenicity assays, propidium iodide uptake and LDH release assays. Cell death was examined using an inhibitor of lysosomal acidification (bafilomycin A1), a cathepsin inhibitor (CA074-Me) and a short-hairpin RNA targeting cathepsin B. Hypoxia substantially enhanced B10-induced cell death. This effect was sensitive to bafilomycin A1 and thus dependent on hypoxia-induced lysosomal acidification. Cathepsin B appeared to mediate cell death because either the inhibitor CA074-Me or cathepsin B gene silencing rescued glioma cells from B10 toxicity under hypoxia. B10 is a novel antitumor agent with substantially enhanced cytotoxicity under hypoxia conferred by increased lysosomal cell death pathway activation. Given the importance of hypoxia for therapy resistance, malignant progression, and as a result of antiangiogenic therapies, B10 might be a promising strategy for hypoxic tumors like malignant glioma.
- Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits (2013)
- Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
- Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients (2010)
- Introduction: Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods: In Germany, patients receiving protein C concentrate (Ceprotin(R), Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this National, retrospective, multi-centered study. Results: Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions: This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.
- Fir-dominated forests in Bavaria, Germany (2005)
- The map of “Regional natural forest composition by main tree species” (WALENTOWSKI et al. 2001) depicts Bavaria as a region largely predominated by the European beech (Fagus sylvatica). Analyses of climatope, hygrotope and trophotope of fir-dominated regional natural units make evident that the reasons for the preponderance of the European silver fir (Abies alba) are edaphic. In terms of regeneration vigour, growth and yield the fir particularly dominates in habitats with a combination of humus cover, acid-oligotrophic topsoils and clayey or waterlogged subsoils, where the beech usually exhibits stunted and malformed growth forms. This ecological preference has the effect that Bavarian Abies alba-forests are restricted to small patches within a matrix of potential natural vegetation formed by mixed deciduous-coniferous mountain forests. Within European Natura 2000 areas Abies- forests should be recorded carefully as special habitats. Their transitional character between temperate beech forests (habitat type 9130) and boreal spruce forests (habitat type 9410), the ecological preference of Abies alba as an endangered tree species and their sensitivity against environmental stressors, including changes in forest structure, air quality, and climate, make them important objects for nature conservation.
- Highly resolved observations of trace gases in the lowermost stratosphere and upper troposphere from the Spurt project: an overview (2006)
- During SPURT (Spurenstofftransport in der Tropopausenregion, trace gas transport in the tropopause region) we performed measurements of a wide range of trace gases with different lifetimes and sink/source characteristics in the northern hemispheric upper troposphere (UT) and lowermost stratosphere (LMS). A large number of in-situ instruments were deployed on board a Learjet 35A, flying at altitudes up to 13.7 km, at times reaching to nearly 380 K potential temperature. Eight measurement campaigns (consisting of a total of 36 flights), distributed over all seasons and typically covering latitudes between 35° N and 75° N in the European longitude sector (10° W–20° E), were performed. Here we present an overview of the project, describing the instrumentation, the encountered meteorological situations during the campaigns and the data set available from SPURT. Measurements were obtained for N2O, CH4, CO, CO2, CFC12, H2, SF6, NO, NOy, O3 and H2O. We illustrate the strength of this new data set by showing mean distributions of the mixing ratios of selected trace gases, using a potential temperature – equivalent latitude coordinate system. The observations reveal that the LMS is most stratospheric in character during spring, with the highest mixing ratios of O3 and NOy and the lowest mixing ratios of N2O and SF6. The lowest mixing ratios of NOy and O3 are observed during autumn, together with the highest mixing ratios of N2O and SF6 indicating a strong tropospheric influence. For H2O, however, the maximum concentrations in the LMS are found during summer, suggesting unique (temperature- and convection-controlled) conditions for this molecule during transport across the tropopause. The SPURT data set is presently the most accurate and complete data set for many trace species in the LMS, and its main value is the simultaneous measurement of a suite of trace gases having different lifetimes and physical-chemical histories. It is thus very well suited for studies of atmospheric transport, for model validation, and for investigations of seasonal changes in the UT/LMS, as demonstrated in accompanying and elsewhere published studies.
- Mobile air quality studies (MAQS) in inner cities: particulate matter PM10 levels related to different vehicle driving modes and integration of data into a geographical information program (2012)
- ABSTRACT: BACKGROUND: Particulate matter (PM) is assumed to exert a major burden on public health. Most studies that address levels of PM use stationary measure systems. By contrast, only few studies measure PM concentrations under mobile conditions to analyze individual exposure situations. METHODS: By combining spatial-temporal analysis with a novel vehicle-mounted sensor system, the present Mobile Air Quality Study (MAQS) aimed to analyse effects of different driving conditions in a convertible vehicle. PM10 was continuously monitored in a convertible car, driven with roof open, roof closed, but windows open, or windows closed. RESULTS: PM10 values inside the car were nearly always higher with open roof than with roof and windows closed, whereas no difference was seen with open or closed windows. During the day PM10 values varied with high values before noon, and occasional high median values or standard deviation values due to individual factors. Vehicle speed in itself did not influence the mean value of PM10; however, at traffic speed (10 -- 50 km/h) the standard deviation was large. No systematic difference was seen between PM10 values in stationary and mobile cars, nor was any PM10 difference observed between driving within or outside an environmental (low emission) zone. CONCLUSIONS: he present study has shown the feasibility of mobile PM analysis in vehicles. Individual exposure of the occupants varies depending on factors like time of day as well as ventilation of the car; other specific factors are clearly identifiably and may relate to specific PM10 sources. This system may be used to monitor individual exposure ranges and provide recommendations for preventive measurements. Although differences in PM10 levels were found under certain ventilation conditions, these differences likely are not of concern for the safety and health of passengers.
- Reference values and physiological characterization of a specific isolated pig kidney perfusion model (2007)
- BACKGROUND: Models of isolated and perfused kidneys are used to study the effects of drugs, hazardous or toxic substances on renal functions. Since physiological and morphological parameters of small laboratory animal kidneys are difficult to compare to human renal parameters, porcine kidney perfusion models have been developed to simulate closer conditions to the human situation, but exact values of renal parameters for different collection and perfusion conditions have not been reported so far. If the organs could be used out of regular slaughtering processes animal experiments may be avoided. METHODS: To assess renal perfusion quality, we analyzed different perfusion settings in a standardized model of porcine kidney hemoperfusion with organs collected in the operating theatre (OP: groups A-D) or in a public abattoir (SLA: group E) and compared the data to in vivo measurements in living animals (CON). Experimental groups had defined preservation periods (0, 2 and 24 hrs), one with additional albumin in the perfusate (C) for edema reduction. RESULTS: Varying perfusion settings resulted in different functional values (mean +/- SD): blood flow (RBF [ml/min*100 g]: (A) 339.9 +/- 61.1; (C) 244.5 +/- 53.5; (D) 92.8 +/- 25.8; (E) 153.8 +/- 41.5); glomerular filtration (GFR [ml/min*100 g]: (CON) 76.1 +/- 6.2; (A) 59.2 +/- 13.9; (C) 25.0 +/- 10.6; (D) 1.6 +/- 1.3; (E) 16.3 +/- 8.2); fractional sodium reabsorption (RFNa [%] (CON) 99.8 +/- 0.1; (A) 82.3 +/- 8.1; (C) 86.8 +/- 10.3; (D) 38.4 +/- 24.5; (E) 88.7 +/- 5.8). Additionally the tubular coupling-ratio of Na-reabsorption/O2-consumption was determined (TNa/O2-cons [mmol-Na/mmol- O2] (CON) 30.1; (A) 42.0, (C) 80.6; (D) 17.4; (E) 23.8), exhibiting OP and SLA organs with comparable results. CONCLUSION: In the present study functional values for isolated kidneys with different perfusion settings were determined to assess organ perfusion quality. It can be summarized that the hemoperfused porcine kidney can serve as a biological model with acceptable approximation to in vivo renal physiology, also if the organs originate from usual slaughtering processes.