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- Glassman, A. H., et al.
(författare)
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Sertraline treatment of major depression in patients with acute MI or unstable angina
- 2002
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Ingår i: JAMA. - 0098-7484. ; 288:6, s. 701-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease. OBJECTIVE: To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001. PATIENTS: A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%). INTERVENTION: After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks. MAIN OUTCOME MEASURES: The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD. RESULTS: Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P> or = .05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P =.049), but not the HAM-D (P =.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P =.01), in the group with at least 1 prior episode of depression (72% vs 51%; P =.003), and in the more severe MDD group (78% vs 45%; P =.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline. CONCLUSION: Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.
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| 2. |
- Berntorp, Erik, et al.
(författare)
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Consensus perspectives on prophylactic therapy for haemophilia: summary statement.
- 2003
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 9:Suppl 1, s. 41278-41278
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Tidskriftsartikel (refereegranskat)abstract
- Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.
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| 3. |
- Boyadjiev, SA, et al.
(författare)
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Physical map of the chromosome 6q22 region containing the oculodentodigital dysplasia locus: analysis of thirteen candidate genes and identification of novel ESTs and DNA polymorphisms
- 2002
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Ingår i: Cytogenetic and genome research. - : S. Karger AG. - 1424-8581 .- 1424-859X. ; 98:1, s. 29-37
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Tidskriftsartikel (refereegranskat)abstract
- Oculodentodigital dysplasia (ODDD) is an autosomal dominant condition with congenital anomalies of the craniofacial and limb regions and neurodegeneration. Genetic anticipation for the dysmorphic and neurologic features has been inferred in a few families. Our previous linkage studies have refined the ODDD candidate region to chromosome 6q22→q23. In an attempt to clone the ODDD gene, we created a yeast artificial chromosome contig with 31 redundant clones spanning the region and identified and ordered candidate genes and markers. Fluorescent <i>in situ</i> hybridization mapped two of these YAC clones to chromosome 6q22.2 telomeric to a known 6q21 fragile site, excluding it as a possible cause of the suggested anticipation. We performed mutation analysis on thirteen candidate genes – GRIK2, HDAC2, COL10A1, PTD013, KPNA5, PIST, ROS1, BRD7, PLN, HSF2, PKIB, FABP7, and HEY2. Although no mutations were found, we identified 44 polymorphisms, including 28 single nucleotide polymorphisms. Direct cDNA selection was performed and fifty-five clones were found to contain sequences that were not previously reported as known genes or ESTs. These clones and polymorphisms will assist in the further characterization of this region and identification of disease genes.
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| 4. |
- Perez-Torres, M. A., et al.
(författare)
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High-resolution radio imaging of young supernovae
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The high resolution obtained through the use of VLBI gives an unique opportunity to directly observe the interaction of an expanding radio supernova with its surrounding medium. We present here results from our VLBI observations of the young supernovae SN 1979C, SN 1986J, and SN 2001gd.
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| 5. |
- Dollery, Clare M., et al.
(författare)
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Neutrophil elastase in human atherosclerotic plaques : production by macrophages
- 2003
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 107:22, s. 2829-2836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Catabolism of the extracellular matrix (ECM) contributes to vascular remodeling in health and disease. Although metalloenzymes and cysteinyl proteinases have garnered much attention in this regard, the role of serine-dependent proteinases in vascular ECM degradation during atherogenesis remains unknown. We recently discovered the presence of the metalloproteinase MMP-8, traditionally associated only with neutrophils, in atheroma-related cells. Human neutrophil elastase (NE) plays a critical role in lung disease, but the paucity of neutrophils in the atheromatous plaque has led to neglect of its potential role in vascular biology. NE can digest elastin, fibrillar and nonfibrillar collagens, and other ECM components in addition to its ability to modify lipoproteins and modulate cytokine and MMP activity.METHODS AND RESULTS: Fibrous and atheromatous plaques but not normal arteries contained NE. In particular, NE abounded in the macrophage-rich shoulders of atheromatous plaques with histological features of vulnerability. Neutrophil elastase and macrophages colocalized in such vulnerable plaques (n=7). In situ hybridization revealed NE mRNA in macrophage-rich areas, indicating local production of this enzyme. Freshly isolated blood monocytes, monocyte-derived macrophages, and vascular endothelial cells in culture produced active NE and contained NE mRNA. Monocytes produced NE constitutively, with little regulation by cytokines IL-1beta, TNF-alpha, or IFN-gamma but released it when stimulated by CD40 ligand, a cytokine found in atheroma.CONCLUSIONS: These findings point to a novel role for the serine protease, neutrophil elastase, in matrix breakdown by macrophages, a critical process in adaptive remodeling of vessels and in the pathogenesis of arterial diseases.
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| 7. |
- Gustafsson, Björn, et al.
(författare)
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Restriction operators, balayage and doubly orthogonal systems of analytic functions
- 2003
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Ingår i: Journal of Functional Analysis. - 0022-1236 .- 1096-0783. ; 199:2, s. 332-378
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Tidskriftsartikel (refereegranskat)abstract
- Systems of analytic functions which are simultaneously orthogonal over each of two domains were apparently first studied in particular cases by Walsh and Szego, and in full generality by Bergman. In principle, these are very interesting objects, allowing application to analytic continuation that is not restricted (as Weierstrassian continuation via power series) either by circular geometry or considerations of locality. However, few explicit examples are known, and in general one does not know even gross qualitative features of such systems. The main contribution of the present paper is to prove qualitative results in a quite general situation. It is by now very well known that the phenomenon of double orthogonality is not restricted to Bergman spaces of analytic functions, nor even indeed has it any intrinsic relation to analyticity; its essence is an eigenvalue problem arising whenever one considers the operator of restriction on a Hilbert space of functions on some set, to a subset thereof, provided this restriction is injective and compact. However, in this paper only Hilbert spaces of analytic functions are considered, especially Bergman spaces. In the case of the Hardy spaces Fisher and Micchelli discovered remarkable qualitative features of doubly orthogonal systems, and we have shown how, based on the classical potential-theoretic notion of balayage, and its modern generalizations, one can deduce analogous results in the Bergman space set-up, but with restrictions imposed on the geometry of the considered domains and measures; these were not needed in the Fisher-Micchelli analysis, but are necessary here as shown by examples. From a more constructive point of view we study the Bergman restriction operator between the unit disk and a compactly contained quadrature domain and show that the representing kernel of this operator is rational and it is expressible (as an inversion followed by a logarithmic derivative) in terms of the polynomial equation of the boundary of the inner domain.
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