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51.
Jenny Bj?rkqvist Steven de Maat Urs Lewandrowski Antonio Di Gennaro Chris Oschatz Kai Sch?nig Markus M. N?then Christian Drouet Hal Braley Marc W. Nolte Albert Sickmann Con Panousis Coen Maas Thomas Renné 《The Journal of clinical investigation》2015,125(8):3132-3146
Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. 相似文献
52.
Elstein D Hollak C Aerts JM van Weely S Maas M Cox TM Lachmann RH Hrebicek M Platt FM Butters TD Dwek RA Zimran A 《Journal of inherited metabolic disease》2004,27(6):757-766
It has been shown that treatment with miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) improves key clinical features of type I Gaucher disease after 1 year of treatment. This study reports longer-term efficacy and safety data. Patients who had completed 12 months of treatment with open-label miglustat (100-300 mg three times daily) were enrolled to continue with therapy in an extension study. Data are presented up to month 36. Liver and spleen volumes measured by CT or MRI were scheduled every 6 months. Biochemical and haematological parameters, including chitotriosidase activity (a sensitive marker of Gaucher disease activity) were monitored every 3 months. Safety data were also collected every 3 months. Eighteen of 22 eligible patients at four centres entered the extension phase and 14 of these completed 36 months of treatment with miglustat. After 36 months, there were statistically significant improvements in all major efficacy endpoints. Liver and spleen organ volumes were reduced by 18% and 30%, respectively. In patients whose haemoglobin value had been below 11.5 g/dl at baseline, mean haemoglobin increased progressively from baseline by 0.55 g/dl at month 12 (NS), 1.28 g/dl at month 24 (p =0.007), and 1.30 g/dl at month 36 (p =0.013). The mean platelet count at month 36 increased from baseline by 22 x 10(9)/L. No new cases of peripheral neuropathy occurred since previously reported. Diarrhoea and weight loss, which were frequently reported during the initial 12-month study, decreased in magnitude and prevalence during the second and third years. Patients treated with miglustat for 3 years show significant improvements in organ volumes and haematological parameters. In conclusion, miglustat was increasingly effective over time and showed acceptable tolerability in patients who continued with treatment for 3 years. 相似文献
53.
Ting Gong Iurie Curosu Frank Liebold Duy M. P. Vo Konrad Zierold Hans-Gerd Maas Chokri Cherif Viktor Mechtcherine 《Materials》2020,13(24)
The paper at hand presents an investigation of the tensile behavior of high-strength, strain-hardening cement-based composites (HS-SHCC), reinforced with a single layer of continuous, two-dimensional textile made of ultra-high molecular weight polyethylene (UHMWPE). Uniaxial tension tests were performed on the bare UHMWPE textiles, on plain HS-SHCC, and on the hybrid fiber-reinforced composites. The bond properties between the textile yarns and the surrounding composite were investigated in single-yarn pullout experiments. In order to assess the influence of bond strength between the yarn and HS-SHCC on the tensile behavior of the composites with hybrid fiber reinforcement, the textile samples were analyzed both with, and without, an additional coating of epoxy resin and sand. Compared to the composites reinforced with carbon yarns in previous studies by the authors, the high elongation capacity of the UHMWPE textile established the higher strain capacity of the hybrid fiber-reinforced composites, and showed superior energy absorption capacity up to failure. The UHMWPE textile limited the average crack width in comparison with that of plain HS-SHCC, but led to slightly larger crack widths when compared to equivalent composites reinforced with carbon textile, the reason for which was traced back to the lower Young’s modulus and the higher elongation capacity of the polymer textile. 相似文献
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56.
Bart F. E. Feyen Dries Coenen Philippe G. Jorens Kristien Wouters Andrew I. R. Maas Viviane Van Hoof Walter Verbrugghe 《Neurocritical care》2013,18(1):64-69
Introduction
Thiopental is a cornerstone in the treatment of refractory status epilepticus and intractable intracranial hypertension. In our center we observed that thiopental might cause falsely elevated serum sodium levels.Methods
Triggered by a recent case experience of extremely elevated serum sodium levels during thiopental treatment, we retrospectively identified 53 patients treated with thiopental in our intensive care unit between 2007 and 2011 and evaluated electrolyte changes. We differentiated the analysis before and after introduction of a new device for sodium assays (Dimension Vista, Siemens) in the central laboratory in April 2010. Standardized in vitro laboratory tests were performed to study the effect of thiopental on sodium analysis.Results
Before April 2010, serum sodium levels determined in the central laboratory showed a good agreement with the bedside point-of-care (POC) device during thiopental therapy with [sodium]laboratory ? [sodium]POC of only 1.08 mmol/L (P = .0517). After April 2010, a strong discrepancy between laboratory values and POC values was observed with [sodium]laboratory ? [sodium]POC = 11.57 mmol/L (P < .0001). Standardized in vitro testing confirmed that thiopental induced a dose-dependent false hypernatremia (P = .002).Conclusions
Thiopental treatment can result in falsely elevated serum sodium. This is a critical finding since high sodium levels preclude administrating mannitol or hypertonic saline for the treatment of elevated intracranial pressure. Moreover, a false high sodium level might lead to the inappropriate administration of hypotonic fluids potentially resulting in increased brain edema and even higher intracranial pressure. To our knowledge, this is the first paper describing this clinically relevant phenomenon. 相似文献57.
Matthew B. Maas Neil F. Rosenberg Adam R. Kosteva Shyam Prabhakaran Andrew M. Naidech 《Neurocritical care》2013,18(2):166-169
Background
Anticoagulation increases the risk of intracerebral hemorrhage (ICH), yet whether different underlying disease processes are equally affected is unknown. We tested the hypothesis that coagulopathy, measured by admission international normalized ratio (INR), disproportionately increases the risk for lobar hemorrhages.Methods
Patients with primary ICH were enrolled into a registry between December 2006 and February 2012 with prospective data acquisition and systematic follow up. Logistic regression was used to test whether lobar versus deep ICH location was independently associated with INR, and then whether INR had an influence on mortality. Spearman’s correlation coefficient was used to test for an association between INR and hematoma volume separately in the lobar and deep ICH groups.Results
221 patients were studied. Patients with lobar ICH were older (71 vs. 62 years old, p < 0.001) and more likely to have prior ICH (10 vs. 0 %, p < 0.001). INR >1.4 was observed on admission more frequently in lobar versus deep ICH (19 vs. 8 %, p = 0.02). Lobar ICH location was independently associated with INR >1.4 (OR: 2.51, 95 % CI: 1.03–6.14, p = 0.043). ICH volume correlated with INR in lobar ICH (p = 0.009), but not deep ICH (p = 0.8). Death at 1 month was independently associated with INR >1.4 (OR: 7.6, 95 % CI: 2.4–24.1, p = 0.001) after correction for the ICH Score.Conclusions
Abnormal coagulation occurs disproportionally in lobar versus deep ICH, and is associated with larger ICH volumes and higher mortality. These findings suggest a unique risk interaction between coagulopathy and underlying brain pathology due to cerebral amyloid angiopathy. 相似文献58.
PD Dr. O. Grottke PhD MPH T. Frietsch M. Maas H. Lier R. Rossaint 《Der Anaesthesist》2013,62(3):213-224
Massive bleeding with coagulopathy and hemorrhagic shock poses a potential threat to life in numerous clinical settings. Optimal treatment including the prevention of exsanguination necessitates a standardized and interdisciplinary approach. Several studies have shown the importance of massive transfusion protocols and standardized coagulation algorithms to improve survival of severely bleeding patients and to avoid secondary complications. Thus, the Helsinki declaration for patient safety in anesthesiology demands the implementation of clinical practice guidelines for the treatment of patients requiring massive transfusion. This paper introduces a standardized algorithm for the treatment of patients with massive bleeding which was developed in consensus with the German Society of Anaesthesiology and Intensive Care Medicine (DGAI). 相似文献
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