Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Temporal and spatial dynamics of arthropod groups in terrestrial subsurface habitats in central Portugal.

The mesovoid shallow substratum (MSS) can act as a climatic refuge for invertebrates, as a biogeographic corridor to deeper substrates or as a permanent habitat for some species. This study characterizes the seasonal invertebrate diversity and abundance of MSS ecosystems in central Portugal focusing on Diplopoda, Diplura, Orthoptera and Coleoptera during one year. Sampling was performed with standard MSS pitfalls in scree slopes (colluvial MSS) of karst areas and environmental parameters (temperature, pH, conductivity, water content, organic carbon, nitrate, phosphate and ammonium) were quantified. Our results show that winter was the season with the highest arthropod abundance and that the MSS acts as a permanent habitat for chordeumatidan millipedes and as a climatic refuge for orthopterans and most beetles. All Diplura collected belong to a single species known previously from surface habitats in the Iberian Peninsula, which does not seem to use the Portuguese MSS as a refuge. MSS habitats in central Portugal, classified as western Mediterranean and thermophile deposits protected by the Natura 2000 network based on plant communities and geology, revealed an abundant and diverse invertebrate community that urges characterization and protection.

Elevated markers of gut leakage and inflammasome activation in COVID-19 patients with cardiac involvement.

BACKGROUND: A high proportion of COVID-19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID-19 patients. METHODS: Plasma levels of a gut leakage marker (LPS-binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL-1ß, IL-18 and their regulatory proteins) were measured at three time points (day 1, 3-5 and 7-10) in 39 hospitalized COVID-19 patients and related to cardiac involvement. RESULTS: Compared to controls, COVID-19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT-pro-BNP levels, whereas IL-18, IL-18BP and IL-1Ra were associated with higher troponin levels. CONCLUSION: Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut-heart axis in COVID-19.

Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome.

AIM: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. LOCATION: Tundra biome. TIME PERIOD: Data collected between 1964 and 2016. MAJOR TAXA STUDIED: 295 tundra vascular plant species. METHODS: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. RESULTS: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. MAIN CONCLUSIONS: Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling.

Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency.

Common variable immunodeficiency (CVID) patients have reduced gut microbial diversity compared to healthy controls. The reduced diversity is associated with gut leakage, increased systemic inflammation and ten "key" bacteria that capture the gut dysbiosis (dysbiosis index) in CVID. Rifaximin is a broad-spectrum non-absorbable antibiotic known to reduce gut leakage (lipopolysaccharides, LPS) in liver disease. In this study, we explored as a 'proof of concept' that altering gut microbial composition could reduce systemic inflammation, using CVID as a disease model. Forty adult CVID patients were randomized, (1:1) to twice-daily oral rifaximin 550 mg versus no treatment for 2 weeks in an open-label, single-centre study. Primary endpoints were reduction in plasma/serum levels of soluble (s) CD14, sCD25, sCD163, neopterin, CRP, TNF, LPS and selected cytokines measured at 0, 2 and 8 weeks. Secondary endpoint was changes in intra-individual bacterial diversity in stool samples. Rifaximin-use did not significantly change any of the inflammation or gut leakage markers, but decreased gut microbial diversity compared with no treatment (p = 0.002). Importantly, the gut bacteria in the CVID dysbiosis index were not changed by rifaximin. The results suggest that modulating gut microbiota by rifaximin is not the chosen intervention to affect systemic inflammation, at least not in CVID.

An association between YKL-40 and type 2 diabetes in psychotic disorders.

OBJECTIVE: This study examines if YKL-40 is increased in individuals with psychotic disorders and if elevated YKL-40 levels at baseline is associated with subsequent development of type 2 diabetes. METHOD: A total of 1383 patients with a diagnosis of schizophrenia or affective psychosis and 799 healthy controls were recruited in the period 2002-2015. Plasma YKL-40 and metabolic risk factors were measured and medication was recorded. Using national registry data, association between baseline risk factors and later development of type 2 diabetes was assessed using Cox proportional hazards models. RESULTS: Plasma YKL-40 was higher in patients vs. healthy controls also after adjusting for metabolic risk factors, with no difference between the schizophrenia and affective psychosis groups. Patients were diagnosed with type 2 diabetes at a significantly younger age. Multivariate Cox regression analyses showed that elevated YKL-40 (hazard ratio (HR) = 5.6, P = 0.001), elevated glucose (HR = 3.6, P = 0.001), and schizophrenia diagnosis (HR = 3.0, P = 0.014) at baseline were associated with subsequent development of type 2 diabetes. CONCLUSIONS: Patients with psychotic disorders have at baseline increased levels of YKL-40 beyond the effect of comorbid type 2 diabetes and metabolic risk factors. Elevated YKL-40 level at baseline is associated with later development of type 2 diabetes.

Quantifying global soil carbon losses in response to warming.

The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.

Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by low immunoglobulin (Ig)G and IgA, and/or IgM. In addition to bacterial infections, a large subgroup has noninfectious inflammatory and autoimmune complications. We performed 16S ribosomal RNA-based profiling of stool samples in 44 CVID patients, 45 patients with inflammatory bowel disease (disease controls), and 263 healthy controls. We measured plasma lipopolysaccharide (LPS) and markers of immune cell activation (i.e., soluble (s) CD14 and sCD25) in an expanded cohort of 104 patients with CVID and in 30 healthy controls. We found a large shift in the microbiota of CVID patients characterized by a reduced within-individual bacterial diversity (alpha diversity, P<0.001) without obvious associations to antibiotics use. Plasma levels of both LPS (P=0.001) and sCD25 (P<0.0001) were elevated in CVID, correlating negatively with alpha diversity and positively with a dysbiosis index calculated from the taxonomic profile. Low alpha diversity and high dysbiosis index, LPS, and immune markers were most pronounced in the subgroup with inflammatory and autoimmune complications. Low level of IgA was associated with decreased alpha diversity, but not independently from sCD25 and LPS. Our findings suggest a link between immunodeficiency, systemic immune activation, LPS, and altered gut microbiota.

Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary.

Secreted Wnt antagonists during eradication of cytomegalovirus infection in solid organ transplant recipients.

We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf-1 (DKK-1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK-1 and increased secreted frizzled related protein-3 levels were predictors of poor virological outcomes during follow-up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection.

Root growth and N dynamics in response to multi-year experimental warming, summer drought and elevated CO2 in a mixed heathland-grass ecosystem.

Ecosystems exposed to elevated CO2 are often found to sequester more atmospheric carbon due to increased plant growth. We exposed a Danish heath ecosystem to elevated CO2, elevated temperature and extended summer drought alone and in all combinations in order to study whether the expected increased growth would be matched by an increase in root nutrient uptake of NH4+-N and NO3- -N. Root growth was significantly increased by elevated CO2. The roots, however, did not fully compensate for the higher growth with a similar increase in nitrogen uptake per unit of root mass. Hence the nitrogen concentration in roots was decreased in elevated CO2, whereas the biomass N pool was unchanged or even increased. The higher net root production in elevated CO2 might be a strategy for the plants to cope with increased nutrient demand leading to a long-term increase in N uptake on a whole-plant basis. Drought reduced grass root biomass and N uptake, especially when combined with warming, but CO2 was the most pronounced main factor effect. Several significant interactions of the treatments were found, which indicates that the responses were nonadditive and that changes to multiple environmental changes cannot be predicted from single-factor responses alone.

Platelet activation in patients with peripheral vascular disease: reproducibility and comparability of platelet markers.

BACKGROUND: Many markers of platelet activation have been described but their reproducibility and comparability in patient populations are poorly defined. OBJECTIVES: We sought to compare markers of platelet and monocyte activation with platelet-monocyte aggregates, a proposed gold standard of in vivo platelet activation, and assess their reproducibility in patients with peripheral arterial disease: a population with substantial platelet activation, inflammation and risk of thrombotic events. PATIENTS/METHODS: Thirty patients with peripheral vascular disease attended on two occasions to permit within-day and between-day comparisons. In vivo platelet and monocyte activation were determined by flow-cytometric quantification of platelet-monocyte aggregation, platelet surface expression of P-selectin and CD40L, platelet-derived microparticles, and monocyte surface expression of CD40 and CD11b. Plasma concentrations of platelet-derived microparticles, soluble P-selectin and CD40L were measured by enzyme-linked immunosorbant assays. RESULTS: Platelet-monocyte aggregation (36.7±7.86%), and platelet surface expression of P-selectin (5.8±1.65%) and CD40L (3.3±1.45%) demonstrated comparable within-day (mean difference±co-efficient of reproducibility; 0.9±15.4%, 0.21±1.65% and 0.2±2.8% respectively) and between-day reproducibility (2.0±12.4%, 0.10±2.25% and 0.9±6.4% respectively). Platelet-monocyte aggregates correlated well with other platelet (r=0.30-0.50, P<0.02) and monocyte (r=0.27-0.47, P<0.03) activation markers. Flow cytometric and assay quantified platelet-derived microparticles showed poorer reproducibility (co-efficient of reproducibility >40). CONCLUSIONS: In patients with peripheral arterial disease, measurements of platelet-monocyte aggregates have good reproducibility and consistently reflect other markers of platelet and monocyte activation.

Interactive effects of elevated CO2, warming, and drought on photosynthesis of Deschampsia flexuosa in a temperate heath ecosystem.

Global change factors affect plant carbon uptake in concert. In order to investigate the response directions and potential interactive effects, and to understand the underlying mechanisms, multifactor experiments are needed. The focus of this study was on the photosynthetic response to elevated CO(2) [CO2; free air CO(2) enrichment (FACE)], drought (D; water-excluding curtains), and night-time warming (T; infrared-reflective curtains) in a temperate heath. A/C(i) curves were measured, allowing analysis of light-saturated net photosynthesis (P(n)), light- and CO(2)-saturated net photosynthesis (P(max)), stomatal conductance (g(s)), the maximal rate of Rubisco carboxylation (V(cmax)), and the maximal rate of ribulose bisphosphate (RuBP) regeneration (J(max)) along with leaf δ(13)C, and carbon and nitrogen concentration on a monthly basis in the grass Deschampsia flexuosa. Seasonal drought reduced P(n) via g(s), but severe (experimental) drought decreased P(n) via a reduction in photosynthetic capacity (P(max), J(max), and V(cmax)). The effects were completely reversed by rewetting and stimulated P(n) via photosynthetic capacity stimulation. Warming increased early and late season P(n) via higher P(max) and J(max). Elevated CO(2) did not decrease g(s), but stimulated P(n) via increased C(i). The T×CO2 synergistically increased plant carbon uptake via photosynthetic capacity up-regulation in early season and by better access to water after rewetting. The effects of the combination of drought and elevated CO(2) depended on soil water availability, with additive effects when the soil water content was low and D×CO2 synergistic stimulation of P(n) after rewetting. The photosynthetic responses appeared to be highly influenced by growth pattern. The grass has opportunistic water consumption, and a biphasic growth pattern allowing for leaf dieback at low soil water availability followed by rapid re-growth of active leaves when rewetted and possibly a large resource allocation capability mediated by the rhizome. This growth characteristic allowed for the photosynthetic capacity up-regulations that mediated the T×CO2 and D×CO2 synergistic effects on photosynthesis. These are clearly advantageous characteristics when exposed to climate changes. In conclusion, after 1 year of experimentation, the limitations by low soil water availability and stimulation in early and late season by warming clearly structure and interact with the photosynthetic response to elevated CO(2) in this grassland species.

Effects of elevated CO2, warming and drought episodes on plant carbon uptake in a temperate heath ecosystem are controlled by soil water status.

The impact of elevated CO2, periodic drought and warming on photosynthesis and leaf characteristics of the evergreen dwarf shrub Calluna vulgaris in a temperate heath ecosystem was investigated. Photosynthesis was reduced by drought in midsummer and increased by elevated CO2 throughout the growing season, whereas warming only stimulated photosynthesis early in the year. At the beginning and end of the growing season, a T × CO2 interaction synergistically stimulated plant carbon uptake in the combination of warming and elevated CO2. At peak drought, the D × CO2 interaction antagonistically down-regulated photosynthesis, suggesting a limited ability of elevated CO2 to counteract the negative effect of drought. The response of photosynthesis in the full factorial combination (TDCO2) could be explained by the main effect of experimental treatments (T, D, CO2) and the two-factor interactions (D × CO2, T × CO2). The interactive responses in the experimental treatments including elevated CO2 seemed to be linked to the realized range of treatment variability, for example with negative effects following experimental drought or positive effects following the relatively higher impact of night-time warming during cold periods early and late in the year. Longer-term experiments are needed to evaluate whether photosynthetic down-regulation will dampen the stimulation of photosynthesis under prolonged exposure to elevated CO2.

Cow's milk allergy in adults is rare but severe: both casein and whey proteins are involved.

BACKGROUND: Studies on cow's milk allergy (CMA) in adults are scarce. Little is known about the clinical symptoms, eliciting doses (ED), and allergens involved. OBJECTIVE: The aim of this study was to analyse the clinical symptoms, ED and allergen recognition in adult CMA patients, compared with cow's milk (CM)-sensitized, but tolerant controls. METHODS: Adult CMA patients were evaluated by standardized questionnaires (n=30), skin prick tests (SPTs) and specific IgE for CM allergens (n=18), and a double-blind placebo-controlled food challenge (DBPCFC, n=10). A control group (n=25) of CM-sensitized, but tolerant adults was included. RESULTS: The majority of CMA patients (20/30, 67%) reported severe symptoms. In all patients participating in DBPCFC, CMA was confirmed. ED for subjective symptoms (0.3-300 mg CM protein) were significantly lower than that for objective symptoms (300-9000 mg CM protein). The severity of CMA by history and ED was not correlated with SPT or IgE. Patients had higher SPT reactivity than controls for CM, alpha-lactalbumin and beta-lactoglobulin (P=0.002, P=0.014 and P=0.004) but not for casein. Specific IgE to CM tended to be higher (P=0.068) and IgE to casein was higher in patients than that in controls (P=0.016). No difference was observed for IgE to alpha-lactalbumin and beta-lactoglobulin. CONCLUSION: Adult CMA is severe in nature. ED are low, starting from 0.3 mg CM protein. Patients with CMA recognize the same major allergens (casein and whey proteins) as controls, but display a stronger SPT and IgE reactivity.

Dialysis membrane-dependent removal of middle molecules during hemodiafiltration: the beta2-microglobulin/albumin relationship.

AIM: Current hemodialysis therapy modalities such as online hemodiafiltration (HDF) attempt to enhance solute removal over a wide molecular weight range through a combination of diffusion and convection. While the effects of variations of treatment modalities and conditions have been studied reasonably well, few studies have examined the efficacy of HDF to remove middle molecules in relation to the dialyzer and membrane characteristics. In this investigation, diverse high-flux dialyzers, covering a wide range of membrane permeabilities, were compared under identical in vivo conditions to assess their ability to eliminate larger uremic retention solutes (using beta2-microglobulin as a surrogate of middle molecules) without simultaneously causing excessive leakage of useful proteins such as albumin. PATIENTS AND METHODS: In a prospective, crossover study, 3 ESRD patients were treated with 8 different brands of high-flux dialyzers at 4 different ultrafiltration (UF)/substitution flow rates (QS: 0, 30, 60, 90 ml/min) in post-dilution HDF mode. Thus, each patient underwent 32 treatment sessions, with a total of 96 treatment sessions conducted during the entire clinical study. Albumin and beta2-microglobulin levels were measured in both, dialysate and blood. Both, albumin and beta2-microglobulin elimination was dependent upon the permeability of the dialysis membrane as well as on the ultrafiltration/substitution flow rates applied. RESULTS: At the maximum UF rate of 90 ml/min, the total albumin loss (measured in the dialysate) ranged from 300 mg/4 h (for the FLX-15 GWS dialyzers) to 7,000 mg/4 h (for the BS-1.3U dialyzers). Up to 50% reduction of albumin occurred within the first 30 minutes of the dialysis treatment, and the leakage of albumin increased exponentially with increasing UF rates as well as increasing transmembrane pressure (TMP). The various dialyzers could be classified according to their UFR-dependent beta2-m reduction rates (RR), into low (< 50%; FLX-15 GWS, CT 150G), medium (50-70%; Polyflux 14 S, BLS 814SD, H4) and high (> 70%; BS-1.3U, APS 650, FX 60) removers of middle molecules. One dialyzer type (CT 150G) showed extremely low beta2-m RR and relatively high albumin losses. Most membranes, however, showed either low albumin leakage coupled with low beta2-m removal, or high beta2-m RR but at the expense of considerable albumin leakage. Only 2 membrane types approached the desired balance between high to medium beta2-m RR while simultaneously restricting the albumin leakage especially at higher filtration/substitution rates. CONCLUSION: Our investigations demonstrate that not all dialysis membranes classified as "high-flux" are comparable in their ability to specifically and efficiently remove middle molecules, or curtail the unwanted excessive leakage of essential proteins from the patient's blood. Thus, the selection of appropriate high-flux dialyzers for specific patient requirements should be based more upon clinical evaluations and analyses rather than on product specifications alone.

The outcome in myasthenia gravis patients--an eight-year follow-up after finishing immunoabsorption therapy.

Eight years ago four patients suffering from myasthenia gravis (MG) type C and E according to Compston with failed drug therapy were treated three times (one patient 11 times) by protein A immunoabsorption (Immunosorba, Excorim, Fresenius Hemocare GmbH, StWendel, Germany). No further immunoabsorption treatments have been carried out. In addition, three patients were given a thymectomy. The present status of the patients was checked six and eight years thereafter. We could see a beneficial effect in all MG patients. The patients are fit for work; all have an improved Besinger index. The patients were used as their own controls. A higher anti-AChR-ab level six years after protein A immunoabsorption than at the beginning was seen in all patients combined with a less serious MG. In addition, their immunomodulation could be induced as seen in lymphocyte and inflammatory protein changes during the first 36 days after beginning immunoabsorption treatment. A larger population has to be investigated to verify these results.

Two cases of refractory endocrine ophthalmopathy successfully treated with extracorporeal immunoadsorption.

Endocrine ophthalmopathy (EO) is a severe disease entity that is characterized by retrobulbar swelling due to accumulation of glycosaminoglycans on an autoimmune basis. This disorder can lead to the loss of vision and often is resistant to conventional therapy. There is a relation to Graves' hyperthyroidism, but probably no close association. Two patients with severe EO that was resistant to usual therapeutic approaches including steroids and radiological and surgical measures underwent a 20 session course of intensive immunoadsorption therapy (Plasmaselect/Therasorb Anti-IgG) with a mean 2- to 3-fold plasma volume treated. After the first sessions, both patients voiced an impressive relief of their major symptoms, which was confirmed by ophthalmological investigation. Throughout the time of therapy until present, these patients have remained at their respective levels of improvement. We consider immunoadsorption an effective therapeutic opportunity in severe EO resistant to conventional treatment.

Three cases of C-ANCA-positive vasculitis treated with immunoadsorption: possible benefit in early treatment.

Wegener's granulomatosis is a vasculitic disease predominantly affecting the upper respiratory tract, lungs, and kidneys. Three patients with Wegener's granulomatosis and rapidly progressive glomerulonephritis were treated with an intensified regimen of immunoadsorption (IA) (Excorim or Therasorb) in addition to cyclophosphamide (CYC) and methylprednisolone (PRE). Patient A had been in remission under oral CYC/PRE. The first exacerbation was treated successfully with 4 IA treatments without changing medication. Patient B experienced 3 flares within 1 year, which were treated with 28 IA (3-7 IAs/course), intravenous CYC after each course, and PRE. A fall of creatinine levels from 120 to 190 micromol/L to 100 micromol/L was noted after IA and before administration of CYC. Patient C presented in uremia. Autoantibodies were eliminated by 11 IA treatments parallel to CYC/PRE therapy. They remained within a normal range for >1 year's follow-up; however, kidney function did not return. In conclusion, the observations in Patients A and B suggest a beneficial therapeutic effect of early IA in WG.