Idiopathische thrombozytopenische Purpura im Kindesalter

Zusammenfassung: Die idiopathische thrombozytopenische Purpura (ITP) ist eine Blutungskrankheit, die durch eine verkürzte Lebensdauer der Thrombozyten charakterisiert ist. Sie ist heterogen ausgeprägt und wird durch endogene und erworbene Faktoren beeinflusst. Sie ist eine Ausschlussdiagnose, deren Differenzialdiagnose stets bedacht werden muss. Die Unkenntnis der Ätiologie und der Mangel an klinischen Daten aus kontrollierten prospektiven Studien haben Kontroversen hinsichtlich Diagnose und Behandlung zur Folge. Die bisherigen prospektiven Therapiestudien haben die Beschleunigung des Thrombozytenanstiegs zum Ziel. Diese Zielsetzung wird oft in den klinischen Alltag übertragen, ohne dass bisher gezeigt werden konnte, dass ein rascher Thrombozytenanstieg von klinischem Wert ist. Bei der Behandlung des Patienten mit ITP ist meist eine Vorbeugung vor fatalen Blutungen beabsichtigt. Diese sind aber im Kindesalter sehr selten. Die Therapieziele im klinischen Alltag, aber auch in klinischen Studien müssen überdacht werden. Andere wichtige Gesichtspunkte sind Blutungen, die Lebensqualität des Patienten und seiner Angehörigen, Nebenwirkungen von Medikamenten und ökonomische Aspekt

An assessment of climate change impacts on the tropical forests of Central America using the Holdridge Life Zone (HLZ) land classification system

Ecological models have predicted shifts in forest biomes, yet there have been very few studies that have looked at the implications on carbon stocks due to these shifts. Carbon is closely correlated to biomass and constitutes an important characteristic of the forest ecosystem. It has implications for conservation and land use practices, especially for climate change mitigation strategies currently under discussion, such as REDD+. This study couples the Holdridge Life Zone (HLZ) classification with the ECHAM5 model, to evaluate the impacts of climate change using the Special Report on Emissions Scenarios (SRES) A2, A1B and B1 for the Central American region. We utilize methodologies which combine biophysical variables with model output to assess the impacts on carbon stocks for two time periods, 2000 and 2100, . Results show that overall, the tropical category of the HLZ classification gains area as a result of one type of HLZ shifting to another forest type. In many cases the shifts result in some categories of HLZ being lost in their entirety. Elevation-associated life zones are particularly vulnerable to future climatic changes. A strong point of our approach is that differences between disaggregate regional and aggregate country levels can be compared. We suggest that a critical focus of conservation and management efforts should be concentrated on where vulnerable biomes are at most risk (biomes that shift and/or reduce fall under the vulnerable category)

Enrichment of Sialylated IgG by Lectin Fractionation Does Not Enhance the Efficacy of Immunoglobulin G in a Murine Model of Immune Thrombocytopenia

Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical symptoms. For its use in immune modulating therapies such as treatment of immune thrombocytopenic purpura high doses of IVIg are required. It has been suggested that only a fraction of IVIg causes this anti immune modulating effect. Recent studies indicated that this fraction is the Fc-sialylated IgG fraction. The aim of our study was to determine the efficacy of IVIg enriched for sialylated IgG (IVIg-SA (+)) in a murine model of passive immune thrombocytopenia (PIT). We enriched IVIg for sialylated IgG by Sambucus nigra agglutinin (SNA) lectin fractionation and determined the degree of sialylation. Analysis of IVIg-SA (+) using a lectin-based ELISA revealed that we enriched predominantly for Fab-sialylated IgG, whereas we did not find an increase in Fc-sialylated IgG. Mass spectrometric analysis confirmed that Fc sialylation did not change after SNA lectin fractionation. The efficacy of sialylated IgG was measured by administering IVIg or IVIg-SA (+) 24 hours prior to an injection of a rat anti-mouse platelet mAb. We found an 85% decrease in platelet count after injection of an anti-platelet mAb, which was reduced to a 70% decrease by injecting IVIg (p<0.01). In contrast, IVIg-SA (+) had no effect on the platelet count. Serum levels of IVIg and IVIg-SA (+) were similar, ruling out enhanced IgG clearance as a possible explanation. Our results indicate that SNA lectin fractionation is not a suitable method to enrich IVIg for Fc-sialylated IgG. The use of IVIg enriched for Fab-sialylated IgG abolishes the efficacy of IVIg in the murine PIT model

Modelling the hydrological behaviour of a coffee agroforestry basin in Costa Rica

UMR LISAH, Equipe Eau et Polluants en Bassins VersantsThe profitability of hydropower in Costa Rica is affected by soil erosion and sedimentation in dam reservoirs, which are in turn influenced by land use, infiltration and aquifer interactions with surface water. In order to foster the provision and payment for Hydrological Environmental Services (HES), a quantitative assessment of the impact of specific land uses on the functioning of drainage-basins is required. The present paper aims to study the water balance partitioning in a volcanic coffee agroforestry microbasin (1 km(2), steep slopes) in Costa Rica, as a first step towards evaluating sediment or contaminant loads. The main hydrological processes were monitored during one year, using flume, eddy-covariance flux tower, soil water profiles and piezometers. A new Hydro-SVAT lumped model is proposed, that balances SVAT (Soil Vegetation Atmosphere Transfer) and basin-reservoir routines. The purpose of such a coupling was to achieve a trade-off between the expected performance of ecophysiological and hydrological models, which are often employed separately and at different spatial scales, either the plot or the basin. The calibration of the model to perform streamflow yielded a Nash-Sutcliffe (NS) coefficient equal to 0.89 for the year 2009, while the validation of the water balance partitioning was consistent with the independent measurements of actual evapotranspiration (R-2 = 0.79, energy balance closed independently), soil water content (R-2 = 0.35) and water table level (R-2 = 0.84). Eight months of data from 2010 were used to validate modelled streamflow, resulting in a NS = 0.75. An uncertainty analysis showed that the streamflow modelling was precise for nearly every time step, while a sensitivity analysis revealed which parameters mostly affected model precision, depending on the season. It was observed that 64% of the incident rainfall R flowed out of the basin as streamflow and 25% as evapotranspiration, while the remaining 11% is probably explained by deep percolation, measurement errors and/or inter-annual changes in soil and aquifer water stocks. The model indicated an interception loss equal to 4% of R, a surface runoff of 4% and an infiltration component of 92%. The modelled streamflow was constituted by 87% of baseflow originating from the aquifer, 7% of subsurface non-saturated runoff and 6% of surface runoff. Given the low surface runoff observed under the current physical conditions (andisol) and management practices (no tillage, planted trees, bare soil kept by weeding), this agroforestry system on a volcanic soil demonstrated potential to provide valuable HES, such as a reduced superficial displacement- capacity for fertilizers, pesticides and sediments, as well as a streamflow regulation function provided by the highly efficient mechanisms of aquifer recharge and discharge. The proposed combination of experimentation and modelling across ecophysiological and hydrological approaches proved to be useful to account for the behaviour of a given basin, so that it can be applied to compare HES provision for different regions or management alternatives

Analysis and Functional Consequences of Increased Fab-Sialylation of Intravenous Immunoglobulin (IVIG) after Lectin Fractionation

It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab’)2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation

Reduced Incidence of Slowly Progressive Heymann Nephritis in Rats Immunized With a Modified Vaccination Technique

A slowly progressive Heymann nephritis (SPHN) was induced in three groups of rats by weekly injections of a chemically modified renal tubular antigen in an aqueous medium. A control group of rats received the chemically unmodified version of the antigen in an aqueous solution. One group of SPHN rats were pre- and post-treated with weekly injections of IC made up of rKF3 and rarKF3 IgM antibody at antigen excess (MIC) (immune complexes [ICs] containing sonicated ultracentrifuged [u/c] rat kidney fraction 3 [rKF3] antigen and IgM antibodies specific against the antigen, at slight antigen excess). One group of SPHN rats were post-treated with MIC 3 weeks after the induction of the disease and one group of SPHN animals received no treatment. The control group of rats received pre- and post-treatment with sonicated u/c rKF3

EEG for good outcome prediction after cardiac arrest: a multicentre cohort study.

AIM Assess the prognostic ability of a non-highly malignant and reactive EEG to predict good outcome after cardiac arrest (CA). METHODS Prospective observational multicentre substudy of the "Targeted Hypothermia versus Targeted Normothermia after Out-of-hospital Cardiac Arrest Trial", also known as the TTM2-trial. Presence or absence of highly malignant EEG patterns and EEG reactivity to external stimuli were prospectively assessed and reported by the trial sites. Highly malignant patterns were defined as burst-suppression or suppression with or without superimposed periodic discharges. Multimodal prognostication was performed 96 hours after CA. Good outcome at 6 months was defined as a modified Rankin Scale score of 0-3. RESULTS 873 comatose patients at 59 sites had an EEG assessment during the hospital stay. Of these, 283 (32%) had good outcome. EEG was recorded at a median of 69 hours (IQR 47-91) after CA. Absence of highly malignant EEG patterns was seen in 543 patients of whom 255 (29% of the cohort) had preserved EEG reactivity. A non-highly malignant and reactive EEG had 56% (CI 50-61) sensitivity and 83% (CI 80-86) specificity to predict good outcome. Presence of EEG reactivity contributed (p<0.001) to the specificity of EEG to predict good outcome compared to only assessing background pattern without taking reactivity into account. CONCLUSION Nearly one-third of comatose patients resuscitated after CA had a non-highly malignant and reactive EEG that was associated with a good long-term outcome. Reactivity testing should be routinely performed since preserved EEG reactivity contributed to prognostic performance

Expression of the 60 kDa and 71 kDa heat shock proteins and presence of antibodies against the 71 kDa heat shock protein in pediatric patients with immune thrombocytopenic purpura

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against platelet proteins, particularly platelet glycoprotein IIb/IIIa. Heat shock proteins (Hsp) have been shown to be major antigenic determinants in some autoimmune diseases. Antibodies to Hsps have also been reported to be associated with a number of pathological states. METHODS: Using western blot, we measured the levels of the 60 kDa heat shock protein (Hsp60) and of the inducible 71 kDa member of the Hsp70 family (Hsp71) in lymphocytes and the presence of antibodies against these hsps in plasma of 29 pediatric patients with ITP before the treatment and in 6 other patients before and after treatment. RESULTS: Interestingly only one out of 29 patients showed detectable Hsp60 in lymphocytes while this heat shock protein was detected in the 30 control children. Hsp71 levels were slightly lower in lymphocytes of patients with ITP than in controls (1567.8 ± 753.2 via 1763.2 ± 641.8 integrated optical density (IOD) units). There was a small increase of Hsp71 after recovery from ITP. The titers of plasma antibodies against Hsp60 and Hsp71 were also examined. Antibodies against Hsp71 were more common in ITP patients (15/29) than in control children (5/30). The titer of anti-Hsp71 was also higher in children patients with ITP. The prevalence of ITP children with antibodies against Hsp71 (51.7%) was as high as those with antibodies against platelet membrane glycoproteins (58.3%). CONCLUSIONS: In summary, pediatric patients with ITP showed no detectable expression of Hsp60 in lymphocytes and a high prevalence of antibody against Hsp71 in plasma. These changes add to our understanding of the pathogenesis of ITP and may be important for the diagnosis, prognosis and treatment of ITP