| 11. |
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| 12. |
- Jayne, David R W, et al.
(author)
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Glomerulonephritides.
- 2014
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In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3, s. 27-29
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Conference paper (peer-reviewed)
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| 13. |
- Legendre, C. M., et al.
(author)
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Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome
- 2013
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 368:23, s. 2169-2181
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Journal article (peer-reviewed)abstract
- Background Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. Methods We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). Results A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. Conclusions Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome.
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| 14. |
- Motoba, T., et al.
(author)
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In situ evidence for interplanetary magnetic field induced tail twisting associated with relative displacement of conjugate auroral features
- 2011
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 116, s. A04209-
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Journal article (peer-reviewed)abstract
- We provide in situ evidence for a twisted near-Earth tail configuration that is responsible for the time sequence of conjugate auroral features associated with relative interhemispheric displacement during a weak substorm, as reported by Motoba et al. (2010). We analyzed the magnetic field data observed using four Cluster satellites in the vicinity of 11-14 R-E central downtail, in close conjunction with the Iceland-Syowa conjugate optical auroral features. Interestingly, we found that the variations in the magnetic field y component (B-y) at all satellites correlated moderately well with the variations in the time-shifted interplanetary magnetic field (IMF) clock angle (theta(CA)). The correlation coefficients (0.56 similar to 0.61) between the B-y field at Cluster and IMF theta(CA) peaked at a time delay of 52 +/- 1 min from the dayside magnetopause, probably corresponding to the time scale for the reconfiguration of the IMF theta(CA) related B-y field in the near-Earth tail. The IMF theta(CA) related B-y variation at Cluster, regarded as a manifestation of the twisting magnetotail configuration, also roughly coincided with the relative magnetic local time displacement of nightside conjugate auroral forms. These results provide strong evidence that the reconfiguration (twisting) process of the near-Earth tail on a relatively longer time scale controls the nightside conjugate auroral locations in both ionospheres.
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| 15. |
- Ogawa, Y., et al.
(author)
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Relationship between auroral substorm and ion upflow in the nightside polar ionosphere
- 2013
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In: J GEOPHYS RES-SPACE. - 2169-9380. ; 118:11, s. 7426-7437
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Journal article (peer-reviewed)abstract
- We investigated ionospheric ion upflow during an auroral substorm using simultaneous European Incoherent Scatter radar and IMAGE satellite data. Approximately 6 min after an initial brightening identified with data from the IMAGE wideband imaging camera instrument, ion upflow was seen and the electron temperature became enhanced, too. The ion upflow, with a velocity of about 150 m/s, and the electron temperature enhancement lasted for about 25 min. During the poleward expansion phase, surges of large upward ion velocity and flux, and high ion and electron temperatures occurred over Longyearbyen. The upward ion flux reached 2x10(14) m(-2)s(-1). Naturally enhanced ion-acoustic lines (NEIALs) were seen near the poleward edge of the expanded auroral oval both near the end of expansion phase 17 min after onset and also later in the recovery phase. The NEIALs seemed to be accompanied by another type of enhanced echoes, obliquely to the local geomagnetic field. Data from the Low Energy Neutral Atom instrument on the IMAGE satellite show that energetic neutral oxygen reaches the IMAGE satellite about 40 min after the initial brightening, and oxygen continues to get detected during the recovery phase. We propose that ion upflow at the poleward edge of the auroral oval during the expansion phase is related to ion/neutral outflow with energy below 18-27 eV, whereas during the recovery phase of a substorm upward ions are accelerated up to about 60 eV and flow out in the entire polar region.
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| 16. |
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| 17. |
- Tricoci, Pierluigi, et al.
(author)
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Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
- 2012
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 366:1, s. 20-33
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Journal article (peer-reviewed)abstract
- BACKGROUND:Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.METHODS:In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.RESULTS:Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.CONCLUSIONS:In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
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