Ophthalmological Manifestations and Tear Investigations in Systemic Sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. There are only few reports available concerning ophthalmological complications in the course of SSc, although ocular manifestations, e.g., dry eye syndrome (DES), occurs frequently and decreases the quality of life of these patients. Vascular endothelial growth factor (VEGF), the major pro-angiogenic factor, plays a key role in the pathomechanism of SSc. Although elevated levels of VEGF in sera have already been demonstrated, VEGF analysis in tears of patients with SSc has not been performed in previous studies. VEGF in the tears of patients with SSc was found to be decreased by 20%, compared to healthy controls. The reason why the VEGF levels are not elevated in the tears of patients with SSc needs further investigations, as does the sera of the same patients. The cytokine array results revealed a shift in the cytokine profile characterized by the predominance of inflammatory mediators. Our current data depict a group of cytokines and chemokines, which play a significant role in ocular pathology of SSc; furthermore, they might function as excellent candidates for future therapeutic targets in SSc with ocular manifestations

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

AIM To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients. METHODS About 458 consecutive patients [Crohn's disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-β2-Glycoprotein-I (anti-β2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed. RESULTS Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-β2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis. CONCLUSION The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course

High circulating osteoprotegerin levels are associated with non-zero blood groups

Background: Osteoprotegerin (OPG) and von Willebrand factor (VWF) form complex within endothelial cells and following secretion. The nature of blood group antigens strongly influences the levels of circulating VWF, but there is no available data concerning its ascendancy on OPG levels. We aimed to assess the relationship of AB0 blood groups with OPG, VWF levels (VWF: Ag) and collagen binding activity (VWF: CB) in peripheral arterial disease (PAD) patients. Methods: Functional and laboratory parameters of 105 PAD patients and 109 controls were examined. Results of OPG, VWF: Ag, VWF: CB (ELISA-s) were analysed by comparative statistics, together with clinical data. Results: OPG levels were higher in patients than in controls (4.64 ng/mL vs. 3.68 ng/mL, p < 0.001). Among patients elevation was marked in the presence of critical limb ischemia (5.19 ng/mL vs. 4.20 ng/mL, p = 0.011). The OPG in patients correlated positively with VWF: Ag and VWF: CB (r = 0.26, p = 0.008; r = 0.33, p = 0.001) and negatively with ankle-brachial pressure index (r = -0.22, p = 0.023). Furthermore, OPG was significantly elevated in non-0 blood groups compared to 0-groups both in patients and controls (4.95 ng/mL vs. 3.90 ng/mL, p = 0.012 and 4.09 ng/mL vs. 3.40 ng/mL, p = 0.002). Conclusions: OPG levels are associated to blood group phenotypes and higher in non-0 individuals. Increased OPG levels in PAD characterize disease severity. The significant correlation between OPG and VWF: CB might have functional importance in an atherothrombosis-prone biological environment

Experimentelle und numerische Betrachtung von Hochgeschwindigkeits-Mehrphasenströmungen

Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheIn this thesis two cases of high-speed multiphase flows were analyzed using experimental measurements techniques and computational fluid dynamics simulations. The first case considers the injection of fuel oil into the raceway of a blast furnace through a two-fluid lance. Because of the extreme ambient conditions direct measurements at the blast furnace are impossible, so a downscaled lab model is used for a high speed imaging analysis of the droplet break up. Data from the lab measurements are the basis for deriving a general correlation for the droplet size distribution. To investigate the behavior of the process, variations of the atomization settings using different model fluids like ethanol, water, paraffin oil, and different solutions of water and glycerol were used. Due to the various model fluids the investigated interval of viscosity, and other fluid properties was larger than in any other previous measurements. After the image analysis the Sauter Mean Diameter (SMD) was calculated for each distribution function and also a comparison of the functions was achieved. The data processing of the high speed video recordings was only partly successful because of the unforeseen measurement difficulties especially in the high viscosity regions. Therefore the most favorable model fluid was pure water, followed by the solutions of water and glycerol due to the lower viscosity. The investigation proved that the image analysis is an effective way to find out the SMD and the distribution functions. But for more accurate measurements, also in case of lower or higher viscosities where the values of the dimensionless numbers are closer to the real blast furnace application, the modification and improvement of the measurement system is indispensable. The further understanding of the process is needed for the improvement of the atomization process in the real blast furnace. The second case will deal with a pressurized air - water rocket. Using CFD simulation - with the open source program OpenFOAM® - a two phase high speed outflow for two different nozzle geometries was analyzed. The results of the simulations are serving for the understanding of the flow inside the rocket chamber and also to calculate the generated momentum at the nozzle exit. In this way, the functioning of a Laval and a simple nozzle (with a larger inner diameter) can be analyzed and compared. The investigation includes a one phase stationer simulation to determine the rocket-s drag coefficient. As validation the two phase outflow was calculated analytically and numerically in a simplified way. For further validation also video recordings were available to compare the behavior of the outflow. According to the preparative numerical calculations and the video recordings the simulation results were positive because they showed a strong analogy with the reality. Besides of the large amount of new information the results showed the advantages of the Laval against the simple nozzle. Irrespectively of this result using the presented initial conditions the simple nozzle achieved a better efficiency because of the larger inner diameter. The results also helped to understand the behavior of the two phase flow inside the rocket chamber.In dieser Arbeit wurden zwei komplexe Fälle von Hochgeschwindigkeits-Mehrphasenströmungen experimentell und mittels fluiddynamischer Simulation untersucht. Im ersten Fall geht es um die Bestimmung der Tropfengrößenverteilung bei einem Zweistoff-Zerstäuber in einem Hochofen, wo Schweröl als Ersatzreduktionsmittel verwendet wird. Nachdem die Möglichkeiten für direkte Messungen im Hochofen wegen der extremen Umgebung stark begrenzt sind, wurde eine Dimensionsanalyse durchgeführt, um ein verkleinertes Modell zu konstruieren. Somit ist es möglich, die Zerstäubung näher zu betrachten und Messungen durchzuführen. Die Messungen wurden mithilfe einer Hochgeschwindigkeitskamera durchgeführt. Die Aufnahmen wurden mittels Particle Image Velocimetry ausgewertet, um die Tropfengrößenverteilung zu ermitteln. Um den Vorgang zu analysieren, wurden Modellflüssigkeiten verwendet. Dabei wurde ein weiter Bereich verschiedener Fluide (mit unterschiedlicher Dichte, Viskosität, Grenzflächen-spannung) betrachtet und unterschiedliche Tropfengrößenverteilungen festgestellt. Die Qualität der Bilder und somit die Genauigkeit der Messung bei Modellfluiden war bei niedrigen Viskositäten besser. Demzufolge war die günstigste Flüssigkeit gegenüber Paraffinöl reines Wasser und wässrige Glycerin-Lösungen. Konstante und intensive Beleuchtung der Zerstäubung ist essentiell, bei höheren Geschwindigkeiten müssen kürzere Verschlusszeiten eingestellt werden. Weitere Experimente sind erforderlich um die komplexen Phänomene beim Strahlzerfall unter Hochofenbedingungen zu analysieren. Im zweiten Fall wird eine mit Druckluft und Wasser betriebene Rakete untersucht. Mit dem Opensource Programm OpenFOAM® wurde eine CFD Berechnung durchgeführt, um die zweiphasige Hochgeschwindigkeitsausströmung bei einer Lavaldüse und einer einfachen Düse (mit größerem Innendurchmesser) zu verstehen und den Impuls beim Düsenaustritt zu berechnen. Die Ergebnisse der Berechnung dienen auch dazu, die innere Strömung in dem Raketenkörper zu analysieren. Weiteres Ziel war auch die Außenströmung bei der Rakete zu betrachten und den Widerstandskoeffizienten zu berechnen. Aus Validierungsgründen wurde eine vereinfachte analytische, numerische Berechnung für den gesamten Flug durchgeführt. Neben diesen Berechnungen stehen auch Videoaufnahmen über den Abflug für die Validierung der CFD Berechnungen zur Verfügung. Die gewonnenen Ergebnisse bzw. das Geschwindigkeitsfeld zeigen eine starke Analogie mit der Realität und passen auch überwiegend mit den numerischen Berechnungen zusammen. Neben vielen neu gewonnenen Informationen und Erkenntnissen haben die Ergebnisse auch die Vorteile der Lavaldüse gezeigt. Die bessere Effizienz wurde jedoch mit den eingestellten Anfangsbedingungen gemäß der Simulationen der einfachen Düse erreicht. Die Ergebnisse der CFD Berechnungen haben es bestätigt, dass die zweiphasige Ausströmung ein sehr komplexes Phänomen ist. Die präsentierten Ziele wurden erfolgreich erfüllt, aber um den Vorgang besser zu verstehen und die optimale Düsenform zu finden sind weitere Simulationen und/oder Messungen nötig.14

Recirculated normal platelets adhere to surfaces coated with plasma from patients with immune thrombocytopenia

Immune thrombocytopenic purpura (ITP) patients have characteristic anti-platelet antibodies in their circulation. To assess the interaction between such antibodies adhering on to a non-physiological surface and human platelets, normal anticoagulated blood was perfused over ITP patient plasma-coated surfaces in a parallel plate flow chamber. At 300 s(-1), platelet adhesion to patient plasma-coated glass coverslips (24.0 +/- 10%) was significantly higher than the adhesion to normal plasma-coated surfaces (9.8 +/- 7%). When perfused at 1300 s(-1), the adhesion to patient plasma- (5.1 +/- 1.3%) and to normal plasma- (2.5 +/- 1.2%) coated coverslips were significantly weaker. Furthermore, patient platelet binding depended on simultaneous contributions by antibodies and fibrinogen present on the plasma-coated surface, since adherence was antagonized both by normal immunoglobulins added to the perfusate, as well as by the anti-GPIIb/IIIa monoclonal antibody 16N7C2, which competes with fibrinogen for binding to its receptor on the platelet. Accordingly, platelet adhesion was only observed to coverslips coated with the plasma but not the serum of ITP patients. Hence, perfusion of normal platelets over surfaces coated with ITP patient plasma enables a functional assessment of the presence in this plasma of anti-platelet antibodies

Follow-up of thrombin generation after prostate cancer surgery: global test for increased hypercoagulability.

Recent studies provided evidence that evaluation of thrombin generation identifies patients at thrombotic risk. Thrombin generation has a central role in hemorrhage control and vascular occlusion and its measurement provides new metrics of these processes providing sufficient evaluation of an individual's hemostatic competence and response to anticoagulant therapy. The objective of the study is to assess a new measure of hypercoagulability that predisposes to venous thromboembolism in the postoperative period after radical prostatectomy. Pre- (day-1) and postoperative (hour 1, day 6, month 1 and 10) blood samples of 24 patients were tested for plasma thrombin generation (peak thrombin), routine hematology and hemostasis. Patients received low molecular weight heparin for thromboprophylaxis. Peak thrombin levels were higher in patients compared to controls at baseline (p<0.001), and elevated further in the early postoperative period (p<0.001). Longer general anesthesia and high body mass index were associated with increased thrombin generation after surgery (p = 0.024 and p = 0.040). D dimer and fibrinogen levels were higher after radical prostatectomy (p = 0.001 and p<0.001). Conventional clotting tests remained within the reference range. Our study contributed to the cognition of the hypercoagulable state in cancer patients undergoing pelvic surgery and revealed the course of thrombin generation after radical prostatectomy. Whilst it is unsurprising that thrombin generation increases after tissue trauma, further evaluation of this condition during the postoperative period would lead urologists to an international and well-supported consensus regarding thromboprophylaxis in order to provide better clinical outcome. Considering the routine evaluation of procoagulant activity and extending prophylactic anticoagulant therapy accordingly may potentially prevent late thrombotic events