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- Karlsson, Johanna, 1973, et al.
(författare)
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Pneumococcal vaccine responses in elderly patients with multiple myeloma, Waldenstrom’s macroglobulinemia, and monoclonal gammopathy of undetermined significance
- 2013
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Ingår i: Trials in vaccinology. - : Elsevier BV. - 1879-4378. ; 2, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) has been recommended for elderly patients with B cell malignancies and dysfunctions because of their enhanced susceptibility to pneumococcal infections. More recent recommendations advocate the use of conjugate pneumococcal vaccines. Methods We compared responses to single dose vaccination with either PPV or the 7-valent pneumococcal conjugate vaccine (PCV7) in fifty-six patients ⩾60 years with a diagnosis of multiple myeloma (n = 24), Waldenstrom’s macroglobulinemia (n = 15) and the non-malignant B cell disorder monoclonal gammopathy of undetermined significance (MGUS) (n = 17), and 20 age-matched controls. Serum was collected prior to vaccination and 4–8 weeks later, and analyzed for IgG antibody levels to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F by ELISA. Functional antibody activity towards pneumococcal serotypes 4 and 14 was measured using an opsonophagocytic killing assay (OPA). Results All patient groups had lower pre-vaccination IgG antibody and OPA titers to the investigated serotypes compared to the healthy controls. Following vaccination, myeloma patients responded with significant IgG titer increases to 1/7 serotypes and OPA titer increases to 1/2 serotypes. Corresponding IgG and OPA vaccine responses were 3/7 and 0/2 for Waldenstrom patients, 4/7 and 1/2 for MGUS patients, and 4/7 and 2/2 for the healthy controls, respectively. Notably high antibody levels without corresponding OPA titers were seen among a few myeloma patients indicating the presence of non-functional antibodies. Neither of the two vaccines elicited significantly higher serotype-specific IgG concentrations, OPA titers or antibody fold increases in any of the study groups. Hypogammaglobulinemia and ongoing chemotherapy were associated with poor vaccine responses in a multivariate analysis. Conclusion Our findings confirm that B cell malignancies and disorders among elderly patients are associated with suboptimal responses to pneumococcal vaccination. Single-dose PCV7 was not shown to be superior to PPV.
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| 2. |
- Aygül, Mustafa, 1970, et al.
(författare)
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Investigation of distortion-induced fatigue cracked welded details using 3D crack propagation analysis
- 2014
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Ingår i: International Journal of Fatigue. - : Elsevier BV. - 0142-1123 .- 1879-3452. ; 64, s. 54-66
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Tidskriftsartikel (refereegranskat)abstract
- The behaviour of distortion-induced fatigue cracks in welded details in an existing bridge was studied analytically by performing crack propagation analysis based on linear elastic fracture mechanics. The real load history of the bridge was obtained from strain measurements. These loads were utilised to examine the crack growth rate and the residual service life of the cracked detail. Moreover, the effectiveness, accuracy and applicability of the crack propagation analysis on bridge structures were investigated by simulating a complex case of fatigue cracking using several crack propagation analyses. The results of the analyses revealed that the fatigue crack in the studied details had significantly different crack growth characteristics in different directions. In the thickness direction, for instance, the crack was seen to propagate at a certain rate, which increased with the propagated crack from the beginning and, as expected, the crack propagation rate decreased when the crack grew longer. The crack was subsequently arrested half way through the thickness of the plate. In the longitudinal direction, the crack was not, however, arrested in the same way as in the thickness direction and it continued to propagate at a reduced yet constant crack growth rate. The results also revealed that, even though distortion-induced fatigue cracking was usually caused by a mixed-mode condition (i.e. a combination of modes I, II and III), the governing propagation mode is still mode I. Furthermore, it was also observed that the contribution of modes II and III to crack propagation was very little and dependent on the location of the propagated crack front, as well as the geometrical configuration of the cross-beam. (C) 2014 Elsevier Ltd. All rights reserved.
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| 3. |
- Schiopu, Alexandru, et al.
(författare)
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Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
- 2012
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 223:2, s. 291-298
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Transplant arteriosclerosis (TA) restricts long-term survival of heart transplant recipients. Although the role of monocyte/macrophages is well established in native atherosclerosis, it has been studied to a much lesser extent in TA. Plasma cholesterol is the most important non-immunologic risk factor for development of TA but the underlying mechanisms are largely unknown. We hypothesized that monocyte/macrophages might play an important role in the pathogenesis of TA under hyperlipidemic conditions. Methods: We studied TA in fully mismatched arterial allografts transplanted into hyperlipidemic ApoE(-/-) recipients compared to wild-type controls. The recruitment of distinct monocyte populations into the grafts was tracked by in vivo labelling with fluorescent microspheres. We used antibody-mediated depletion protocols to dissect the relative contribution of T lymphocytes and monocytes to disease development. Results: In the hyperlipidemic environment the progression of TA was highly exacerbated and the inflammatory CD11b(+)CD115(+)Ly-6C(hi) monocytes were preferentially recruited into the neointima. The number of macrophage-derived foam cells present in the grafts strongly correlated with plasma cholesterol and disease severity. Depletion of Ly-6C(hi) monocytes and neutrophils significantly inhibited macrophage accumulation and disease progression. The accelerated monocyte recruitment occurs through a T cell-independent mechanism, as T cell depletion did not influence macrophage accumulation into the grafts. Conclusions: Our study identifies for the first time the involvement of inflammatory Ly-6C(hi) monocytes into the pathogenesis of TA, particularly in conditions of hyperlipidemia. Targeted therapies modulating the recruitment and activation of these cells could potentially delay coronary allograft vasculopathy and improve long-term survival of heart transplant recipients. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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