| 1. |
- Smailhodzic, Dzenita, et al.
(författare)
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Zinc supplementation inhibits complement activation in age-related macular degeneration.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression.
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| 2. |
- van Krieken, J. H., et al.
(författare)
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Guideline on the requirements of external quality assessment programs in molecular pathology
- 2013
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 462:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. For these reasons, analyses in molecular pathology must be highly reliable and hence external quality assessment (EQA) programs are called for. Several EQA programs exist to which laboratories can subscribe, but they vary in scope, number of subscribers, and execution. The guideline presented in this paper has been developed with the purpose to harmonize EQA in molecular pathology. It presents recommendations on how an EQA program should be organized, provides criteria for a reference laboratory, proposes requirements for EQA test samples, and defines the number of samples needed for an EQA program. Furthermore, a system for scoring of the results is proposed as well as measures to be taken for poorly performing laboratories. Proposals are made regarding the content requirements of an EQA report and how its results should be communicated. Finally, the need for an EQA database and a participant manual are elaborated. It is the intention of this guideline to improve EQA for molecular pathology in order to provide more reliable molecular analyses as well as optimal information regarding patient selection for treatment.
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| 4. |
- Funck-Brentano, Christian, et al.
(författare)
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Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial
- 2011
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 13:7, s. 765-772
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Tidskriftsartikel (refereegranskat)abstract
- Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. Methods and results In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at >= 50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P < 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P < 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. Conclusion The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.
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| 5. |
- Van de Ven, Louis L. M., et al.
(författare)
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The effect of treatment with bisoprolol-first versus enalapril-first on cardiac structure and function in heart failure
- 2010
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 144:1, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- Background: In CIBIS III, initiating chronic heart failure (CHF) treatment with bisoprolol (target dose 10 mg q.d.) followed by combination therapy with enalapril (target dose 10 mg b.i.d.), compared to the opposite order, showed similar effects on survival and hospitalization. By echocardiography, we evaluated the effects of these treatment strategies on cardiac structure and function. Methods: In a single-centre substudy, we compared the impact on left ventricular (LV) dimensions and ejection fraction (EF) of treatment with bisoprolol-first (n = 21) and enalapril-first (n = 19) in 40 beta-blocker and angiotensin-converting-enzyme-inhibitor naive patients, with stable, mild or moderate CHF (NYHA II-III) and LVEF <= 35%. Echocardiography was performed at baseline, after the 6-month monotherapy phase and after 12 months, i.e. after 6 months combination therapy. Results: Baseline characteristics were similar across treatment groups. After 6 months LVEF increased by 5.1 +/- 4.0 EF-% (P<0.0001) with Bisoprolol and 4.0 +/- 4.0 EF-% (P = 0.0005), with enalapril (between-group P = 0.47). LV end-diastolic volume (LVEDV) decreased by 8.1 +/- 4.7 ml (P<0.0001) with bisoprolol and by 4.6 +/- 8.2 ml (P = 0.03) with enalapril (between-group P = 0.16). Mean wall thickness (WT) decreased by 0.31 +/- 0.43 mm (P = 0.004) with bisoprolol and by 0.18 +/- 0.48 mm (P = 0.11) with enalapril (between-group P = 0.29). From baseline to 12 months, LVEF increased by 7.5 +/- 4.0 EF-% (P<0.0001) in Bisoprolol first group and 6.0 +/- 4.6 EF-% (P<0.0001), in the enalapril first group (between-group P = 0.31). LVEDV decreased by 12.9 +/- 6.3 ml (P<0.0001) with bisoprolol-first and by 7.9 +/- 7.7 ml (P = 0.0006) with enalapril-first (between-group P = 0.16) and WT decreased by 0.38 +/- 0.44 mm (P = 0.0008) and 0.59 +/- 0.54 mm (P = 0.0004), respectively (between-group P = 0.10). Conclusion: During both monotherapy and combined therapy, bisoprolol-first and enalapril-first similarly reversed cardiac remodelling and improved LVEF. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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| 7. |
- Zackrisson, Sophia, et al.
(författare)
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Light in and sound out: emerging translational strategies for photoacoustic imaging.
- 2014
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Ingår i: Cancer Research. - 1538-7445. ; 74:4, s. 979-1004
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Forskningsöversikt (refereegranskat)abstract
- Photoacoustic imaging (PAI) has the potential for real-time molecular imaging at high resolution and deep inside the tissue, using nonionizing radiation and not necessarily depending on exogenous imaging agents, making this technique very promising for a range of clinical applications. The fact that PAI systems can be made portable and compatible with existing imaging technologies favors clinical translation even more. The breadth of clinical applications in which photoacoustics could play a valuable role include: noninvasive imaging of the breast, sentinel lymph nodes, skin, thyroid, eye, prostate (transrectal), and ovaries (transvaginal); minimally invasive endoscopic imaging of gastrointestinal tract, bladder, and circulating tumor cells (in vivo flow cytometry); and intraoperative imaging for assessment of tumor margins and (lymph node) metastases. In this review, we describe the basics of PAI and its recent advances in biomedical research, followed by a discussion of strategies for clinical translation of the technique. Cancer Res; 74(4); 979-1004. ©2014 AACR.
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