586 research outputs found

    Conflict Prevention in the Pacific

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    AusAI

    Continuous registration of thrombin generation in plasma:Its use for the determination of the thrombin potential

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    A method is described by which the time-course of thrombin generation in plasma can be obtained from a continuous optical density recording of p-nitroaniline (pNA) production in a 2:3 diluted plasma. A chromogenic substrate, methylmalonyl-methylanalyl-arginyl-pNA (SQ 68), is used that is specifically split by thrombin but at a low rate. The thrombin that appears and disappears in the plasma does not split more than 5% of the substrate added, so the rate of substrate conversion is in good approximation proportional to the amidolytic activity in the plasma over the entire period of thrombin generation. The course of the enzyme concentration can be calculated from the amidolytic activity curve. It is shown that the thrombin generation curves obtained in this way are essentially identical to those obtained via the classical subsampling method.The presence of SO 68 influences the amount of free thrombin that appears in plasma because it competitively inhibits the inactivation of thrombin by AT III and alpha2 macroglobulin. The inhibition of the thrombin peak by heparin, relative to an uninhibited control, remains unaltered by the presence of the substrate.From the course of thrombin activity and the prevailing decay constants, the course of prothrombin conversion velocity can be calculated. Prothrombin conversion was seen to be inhibited at high (>500 muM) substrate concentrations only, and experimental conditions are found under which the inhibition of the clotting process by the substrate is negligible.The amidolytic activity is the sum of the activities of free thrombin and of the alpha2 macroglobulin-thrombin complex formed. Via a mathematical procedure the amount of SQ 68 that has been split by thrombin alone and not by the alpha2 macroglobulin-thrombin complex, can be derived from the course of the optical density.The total amount of SQ 68 eventually split by thrombin alone is proportional to the surface under the thrombin generation curve, i. e. to the time-integral of free thrombin. This value, that we call the thrombin potential (TP), directly indicates how much of any physiological substrate can potentially be split by the thrombin being generated in the plasma

    Prevention and treatment of cystoid macular edema after cataract surgery

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    Cataracts are one of the most common cause of blindness and visual impairment worldwide. However, very few people in Europe will go blind due to cataracts. In order to prevent blindness and visual impairment, more than 550 patients undergo cataract surgery every weekday in the Netherlands. Of these patients, 3.4% experience impaired recovery due to an accumulation of fluid in the retina, called pseudo-cystoid macular oedema. In a European multi-centre study among 1,100 patients, we researched the most effective treatment method for preventing macular oedema after cataract surgery. The most important results of this ESCRS PREMED study are described in this dissertation

    Kinetics of antibody response to Coxiella burnetii infection (Q fever): Estimation of the seroresponse onset from antibody levels

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    AbstractBackgroundFrom 2007 to 2009, the Netherlands experienced a major Q fever epidemic. Long-term serological follow-up of acute Q fever patients enabled the investigation of longitudinal antibody responses and estimating the onset of the seroresponse in individual patients.MethodsAll available IgG and IgM phase I and II antibody measurements determined by immunofluorescence assay at month 3, 6, 12, and 48 from 2321 acute Q fever patients were retrospectively analyzed. Characteristic features of the antibody response were calculated. To model the seroresponse onset, serological data from patients diagnosed with a positive C. burnetii PCR test (n=364), and therefore with a known time of infection, were used as reference.ResultsIn 9083 IgG samples and 3260 IgM samples large heterogeneity in shape and magnitude of antibody responses was observed. Phase II reached higher levels than phase I, and IgG antibodies were more persistent than IgM. The estimated seroresponse latency allowed for determining the time since start of the seroresponse from the concentrations of the different antibodies against C. burnetii.ConclusionsThe extraordinary large serological dataset provides new insight into the kinetics of the immunoglobulins against C. burnetii antigens. This knowledge is useful for seroprevalence studies and helps to better understand infection dynamics

    The dissemination among Staphylococcus aureus of the Staphylococcal Chromosome Cassette mec (SCCmec) which confers multiresistance

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    Staphylococci are gram-positive bacteria present on the skin of most healthy humans. Although majority of coagulase-negative staphylococci (CNS) are commensals that generally do not cause severe clinical problems, some, including Staphylococcus epidermidis and Staphylococcus haemolyticus, may cause clinically relevant infections and bactereamia related to indwelling devices. In addition, one third of healthy humans carry Staphylococcus aureus, which may cause severe invasive disease. S. aureus accounts for the majority of nosocomial infections around the world, causing high mortality when untreated. Several types of antibiotics, directed to different targets in bacterial metabolism, were employed to fight infections caused by S. aureus. However, S. aureus has acquired resistance to most extant antibiotics, including vancomycin, and evolved to be one of the most difficult-to-treat pathogens in hospitals. This thesis describes the essential role of horizontal gene transfer between the chromosomes of different staphylococci in the dissemination of resistance genes
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