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| 6. |
- Ekdahl, Christer, et al.
(författare)
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Rapid decrease of free vancomycin in dense staphylococcal cultures.
- 2005
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Ingår i: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 24:9, s. 596-602
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (10(5)-10(8) bacteria/ml) after 24 h of incubation in supplemented Mueller-Hinton broth containing vancomycin. All of the tested strains except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low inoculum (10(5) bacteria/ml), the broth MICs were 1-4 microg/ml. In a high inoculum (approximately 10(8) bacteria/ml), the broth MICs increased two- to fourfold to 4-8 microg/ml. In dense inocula ( approximately 10(9)-10(10) bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of the bioassay (
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| 9. |
- Gerogianni, Alexandra, et al.
(författare)
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Heme Interferes With Complement Factor I-Dependent Regulation by Enhancing Alternative Pathway Activation
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Hemolysis, as a result of disease or exposure to biomaterials, is characterized by excess amounts of cell-free heme intravascularly and consumption of the protective heme-scavenger proteins in plasma. The liberation of heme has been linked to the activation of inflammatory systems, including the complement system, through alternative pathway activation. Here, we investigated the impact of heme on the regulatory function of the complement system. Heme dose-dependently inhibited factor I-mediated degradation of soluble and surface-bound C3b, when incubated in plasma or buffer with complement regulatory proteins. Inhibition occurred with factor H and soluble complement receptor 1 as co-factors, and the mechanism was linked to the direct heme-interaction with factor I. The heme-scavenger protein hemopexin was the main contaminant in purified factor I preparations. This led us to identify that hemopexin formed a complex with factor I in normal human plasma. These complexes were significantly reduced during acute vasoocclusive pain crisis in patients with sickle cell disease, but the complexes were normalized at their baseline outpatient clinic visit. Hemopexin exposed a protective function of factor I activity in vitro, but only when it was present before the addition of heme. In conclusion, we present a mechanistic explanation of how heme promotes uncontrolled complement alternative pathway amplification by interfering with the regulatory capacity of factor I. Reduced levels of hemopexin and hemopexin-factor I complexes during an acute hemolytic crisis is a risk factor for heme-mediated factor I inhibition.
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| 10. |
- Hogberg, L, et al.
(författare)
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The impact of active intervention on the spread of penicillin-resistant streptococcus pneumoniae in Swedish day-care centres
- 2004
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 36:9, s. 629-635
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Tidskriftsartikel (refereegranskat)abstract
- Policies for handling cases of penicillin-non-susceptible Streptococcus pneumoniae (PNSP) in day-care groups vary between different counties in Sweden. The aim of this study was to evaluate the epidemiological effect of excluding PNSP-carriers from children's day-care centres (DCC). We followed the incidence in 14 DCC groups with ongoing PNSP-spread, by repeated group screens until no further cases could be identified. All identified carriers were excluded from DCC attendance in study area A (Skane region) while they remained in the group in study area B (Goteborg and Orebro), according to local policies. The intervention effect was evaluated by comparing the number of additional cases after the baseline screen (start of the intervention period) between the 2 study areas. All PNSP-isolates were characterized by resistance pattern, serotype and pulse-field gel electrophoresis. The relative risk for children in DCCs without active intervention was 6.4 (95% CI: 2.0-20.7). Each prevented case in area A can be estimated to have demanded the exclusion of 2 other children from day care for approximately 4 weeks each. The total cost-benefit outcome of this action has to be seen in the light of the local situation with regard to the population prevalence and the distribution of other risk factors.
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| 11. |
- Ramos, O F, et al.
(författare)
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Elevated NK-mediated lysis of Raji and Daudi cells carrying fixed iC3b fragments
- 1989
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Ingår i: Cellular Immunology. - 0008-8749 .- 1090-2163. ; 119:2, s. 459-469
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Tidskriftsartikel (refereegranskat)abstract
- Raji and Daudi cells were opsonized with C3b, iC3b and C3d fragments by using purified complement components. The sensitivity of C3-opsonized cells to lysis mediated by low density blood lymphocytes was studied. Raji and Daudi cells carrying C3b or C3d fragments were lysed with similar efficiencies as the nonopsonized cells. The presence of iC3b on the target surface imposed elevated NK sensitivity. The iC3b-mediated enhancement of NK lysis was inhibited when iC3b fragments or rabbit anti-human C3 antibodies were included into the lytic assays. These results indicate that the iC3b fragments fixed on the targets bind to the CR3 on the lymphocytes. Results obtained in immobilized conjugate-lytic assays showed that iC3b-opsonized targets interact more readily with the lymphocytes. This was reflected by the elevated proportion of lymphocytes that were bound to the iC3b-carrying targets. The proportions of conjugates in which target damage occurred were similar with the control and with the iC3b-carrying cells. It seems therefore that opsonization of targets with iC3b leads to recruitment of effector lymphocytes due to contact with their CR3. However, once the effector-target contact is established, the triggering of lytic function does not seem to be influenced by the iC3b/CR3 bridge.
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| 12. |
- Alfonzo, Emilia, et al.
(författare)
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No survival difference between robotic and open radical hysterectomy for women with early-stage cervical cancer: results from a nationwide population-based cohort study
- 2019
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 116, s. 169-177
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the study was to compare overall survival (OS) and disease-free survival (DFS) after open and robotic radical hysterectomy for early-stage cervical cancer. Patients and methods: This was a nationwide population-based cohort study on all women with cervical cancer stage IA1-IB of squamous, adenocarcinoma or adenosquamous histological subtypes, from January 2011 to December 2017, for whom radical hysterectomy was performed. The Swedish Quality Register of Gynaecologic Cancer was used for identification. To ensure quality and conformity of data and to disclose patients not yet registered, hospital registries were reviewed and validated. Cox and propensity score regression analysis and univariable and multivariable regression analysis were performed in regard to OS and DFS. Results: There were 864 women (236 open and 628 robotic) included in the study. The 5-year OS was 92% and 94% and DFS was 84% and 88% for the open and robotic cohorts, respectively. The recurrence pattern was similar in both groups. Using propensity score analysis and matched cohorts of 232 women in each surgical group, no significant differences were seen in survival: 5-year OS of 92% in both groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.50–2.01) and DFS of 85% vs 84% in the open and robotic cohort, respectively (HR, 1.08; 95% CI, 0.66–1.78). In univariable and multivariable analysis with OS as the end-point, no significant factors were found, and in regard to DFS, tumour size (p < 0.001) and grade 3 (p = 0.02) were found as independent significant risk factors. Conclusion: In a complete nationwide population-based cohort, where radical hysterectomy for early-stage cervical cancer is highly centralised, neither long-term survival nor pattern of recurrence differed significantly between open and robotic surgery. © 2019 The Authors
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| 13. |
- Bexborn, Fredrik, et al.
(författare)
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Hirudin versus heparin for use in whole blood in vitro biocompatibility models
- 2009
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Ingår i: Journal of Biomedical Materials Research. Part A. - Hoboken, NJ, US : John Wiley & Sons Inc. - 1549-3296 .- 1552-4965. ; 89A:4, s. 951-959
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heparin has traditionally been a widely used anticoagulant in blood research, but has been shown to be inappropriate for work with the complement system because of its complement-interacting properties. In this work, we have compared the effects of heparin with those of the specific thrombin inhibitor hirudin on complement and blood cells in vitro. Methods: Whole blood collected in the presence of hirudin (50 µg/mL) or heparin (1 IU/mL) was incubated in the slide chamber model. The plasma was analyzed for complement activation markers C3a and sC5b-9, and the polyvinylchloride test slides were stained for adhering cells. The integrity of the complement system was tested by incubating serum and hirudin-treated plasma in the presence of various activating agents.Results: In contrast to heparin, the addition of hirudin generally preserved the complement reactivity, and complement activation in hirudin plasma closely resembled that in normal serum. Importantly, immunochemical staining of surface-bound cells demonstrated the inducible expression of tissue factor on bound monocytes from hirudin-treated blood, an effect that was completely abolished in heparin-treated blood.Conclusion: Our results indicate that hirudin as an anticoagulant produces more physiological conditions than heparin, making hirudin well-suited for in vitro studies, especially those addressing the regulation of cellular processes.
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| 14. |
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| 17. |
- Denk, Stephanie, et al.
(författare)
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Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects
- 2017
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 198:12, s. 4846-4854
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Tidskriftsartikel (refereegranskat)abstract
- During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pH(i)), we propose a direct mechanistic link between complement activation and neutrophil pHi. In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by C5a increased the glucose uptake and activated glycolytic flux in neutrophils, resulting in a significant release of lactate. Furthermore, C5a induced acidification of the extracellular micromilieu. In experimental murine sepsis, pHi of blood neutrophils was analogously alkalinized, which could be normalized by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients with septic shock likewise exhibited a significantly increased pHi. These data suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate pHi balance in neutrophils resulting in profound inflammatory and metabolic changes that contribute to hyperlactatemia during sepsis.
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| 18. |
- Ekdahl, Christer, 1962-
(författare)
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Infective Endocarditis : aspects of pathophysiology, epidemiology, management and prognosis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Infective endocarditis (IE) is a rare but complex disease that is fatal if untreated. With a modern combination of antimicrobial therapy and heart valve surgery, mortality is still 10-20 %. The structure of the endocarditis vegetation impedes the penetration of phagocytic cells such as monocytes and granulocytes. This leads to high bacterial counts inside the vegetation and the need for long treatment courses with a combination of intravenously administered bactericidal antibiotics.The aim of this thesis was to study the changes in epidemiology, management, and mortality at our hospital between 1980 and 2001, and to identify prognostic factors associated with mortality. To assess the issue of referral bias, differences between referred episodes and episodes from our local community were studied. Additional aims were to study the occurrence of the pro-chemotactic cytokines IL-8 and TNF-α in heart valves and vegetations during the active phase of IE, and to study the effect of the glycopeptide antibiotic vancomycin in dense staphylococcal cultures in vitro. As it is a rare and complex disease, management of IE is usually complicated for non-specialists. For this reason a computerised decision support system for IE was developed and evaluated.Between 1980 and 2001, the occurrence of Staphylococcus aureus IE and the use of early heart valve surgery increased significantly, regardless of whether the episodes were referred or of local origin. Glycopeptide antibiotics, mainly vancomycin, were used more frequently, especially among referred patients. Referred patients were younger, predominantly male, had more complications, and received surgical treatment more often than patients from our local community. The reason for the lower frequency of female patients in the referral cohort cannot be explained by more comorbidity or fewer complications. The differences between referred and local episodes seen in our study highlight the need for assessment and adjustment for referral bias in IE studies (Paper I).In six patients who needed early heart valve surgery, the largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative antimicrobial treatment courses. No such relationships were seen with respect to TNF-α-containing cells. The IL-8-containing cells and the inflammatory cells were predominantly scattered in the heart valve stroma or in the margin of the vegetation (Paper II). The primary effect of IL-8 is to stimulate chemotaxis of polymorphonuclear neutrophil granulocytes. This indicates that there is no deficiency of IL-8 in the area close to the vegetation as a cause of the localised agranulocytosis often present inside the vegetation.Our study revealed a need for computerised decision support systems (DSSs) in the field of IE, but to be used in clinical practice these DSSs need be part of knowledge bases covering larger domains (Paper IV). Some of our initial ideas described in Paper III, especially the use of Internet technology and the combination of rule-based advice and explanatory hypertext, will probably be included in these knowledge bases.In vitro, there is a rapid reduction of free vancomycin in broth containing dense staphylococcal cultures. Consequently, there is a simultaneous increase in broth MICs, particularly in high inocula, which is not caused by a development of resistance (Paper V). These findings need further evaluation in vivo, but indicate that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.Diabetes mellitus and moderate to severe heart failure were independent risk factors for 6-month mortality in left-sided, Duke definite IE episodes, regardless of referral or local origin of the episodes. Early heart valve surgery had a positive impact on the 6-month mortality in the referral cohort of episodes, which may be due to referral bias (Paper VI).
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| 20. |
- Engberg, Anna E., 1982-
(författare)
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Biomaterials and Hemocompatibility
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biomaterials are commonly used in the medical clinic today; however, artificial materials can activate the cascade systems in the blood (complement-, coagulation-, contact- and fibrinolytic systems) as well as the platelets to various degrees. When an artificial surface comes in contact with blood, plasma proteins will be adsorbed to the surface within seconds. The composition of the layer of proteins differs between materials and is crucial for the hemocompatibility of the material.This thesis includes five projects.In Paper I the anticoagulants heparin and the thrombin inhibitor hirudin were evaluated in a whole blood model. Hirudin was found to be superior to low dose heparin since it did not affect the activation of the complement system nor the leukocytes. The most interesting observation was that expression of TF was seen on surface-attached monocytes in hirudin- treated blood but not heparin blood.In Paper II peptides from the streptococcal M-protein, which has affinity for the human complement inhibitor C4BP, were attached to a polymeric surface. When being exposed to blood the endogenous complement regulator was enriched at the surface of the material, via the M-peptides. With this new approach we created a self-regulatory surface, showing significant lowered material-induced complement activation.In Paper III apyrase, an enzyme which hydrolyzes nucleoside ATP and ADP, was immobilized on a polymer surface. Lower platelet activation and platelet-induced coagulation activation was seen for the apyrase-coated surface compared to control surfaces after exposure to whole human blood, due to the enzymes capability to degrade ADP released from activated platelets.In Paper IV and V we synthesized an array of polymeric materials which were characterized regarding physical-chemical properties, adsorption of plasma proteins, and hemocompatibility. The polymers showed widely heterogeneous protein adsorption. Furthermore, when the polymers were exposed to whole blood, two of the materials showed superior hemocompatibility (monitored as complement- and coagulation activation), compared to the reference poly(vinyl chloride).
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| 21. |
- Engberg, Anna E., et al.
(författare)
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Blood protein-polymer adsorption : Implications for understanding complement-mediated hemoincompatibility
- 2011
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1549-3296. ; 97A:1, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to create polymeric materials with known properties to study the preconditions for complement activation. Initially, 22 polymers were screened for complement activating capacity. Based on these results, six polymers (P1-P6) were characterized regarding physico-chemical parameters, for example, composition, surface area, pore size, and protein adsorption from human EDTA-plasma. P2, P4, and reference particles of polystyrene and polyvinyl chloride, were hydrophobic, bound low levels of protein and were poor complement activators. Their accessible surface was limited to protein adsorption in that they had pore diameters smaller than most plasma proteins. P1 and P3 were negatively charged and adsorbed IgG and C1q. A 10-fold difference in complement activation was attributed to the fact that P3 but not P1 bound high amounts of C1-inhibitor. The hydrophobic P5 and P6 were low complement activators. They selectively bound apolipoproteins AI and AIV (and vitronectin), which probably limited the binding of complement activators to the surface. We demonstrate the usefulness of the modus operandi to use a high-throughput procedure to synthesize a great number of novel substances, assay their physico-chemical properties with the aim to study the relationship between the initial protein coat on a surface and subsequent biological events. Data obtained from the six polymers characterized here, suggest that a complement-resistant surface should be hydrophobic, uncharged, and have a small available surface, accomplished by nanostructured topography. Additional attenuation of complement can be achieved by selective enrichment of inert proteins and inhibitors.
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| 22. |
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| 23. |
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| 24. |
- Engberg, Anna E., 1982-, et al.
(författare)
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EVALUATION OF THE HEMOCOMPATIBILITY OF NOVEL POLYMERIC MATERIALS
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- When a biomaterial surface comes in contact with blood an immediate adsorption of plasma proteins to the surface will occur, and the cascade systems in the blood, such as the complement, coagulation and contact system, will be activated to various degrees. The intensity of this reaction will determine the hemocompatibility of the materials. Here we present an evaluation of the link between the composition, the physico-chemical properties and the protein adsorption properties of six newly synthesized polymers (P1-P6) and the hemocompatibility.The hemocompatibility of the polymeric surfaces was evaluated in human blood plasma and whole blood. Commercially available polyvinylchloride (PVC) was used as reference material. The hemocompatibility of the polymeric surfaces was evaluated with regard to complement activation (C3a and sC5-9 generation) and coagulation activation (platelet loss and TAT-formation) and cytokine productions (27 analytes in multiplex assay) after contact with whole blood. Contact activation was quantified by analyses of FXIIa-C1INH, FXIa-C1INH, and kallikrein-C1INH complexes.Polymers P2 (p<0.05 for C3a), P3, P5 and P6 showed less complement activation, and polymers P1 and P4 (p<0.05 for platelet loss), as well as P5 and P6 showed less coagulation activation compared with reference PVC. Polymers P1-P3 induced activation of the contact system, P3 being the most potent. Secretion of 17 cytokines including chemokines and growth factors were differentially influenced by the polymers, P1 and P3 being significantly (p<0.05) more compatible for five of the analytes.Collectively these data demonstrate that the composition of the polymers clearly leads to different biological properties as a consequence of distinctive physico-chemical properties and protein adsorption patterns.1
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| 25. |
- Engberg, Anna E., 1982-, et al.
(författare)
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Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides
- 2009
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 30:13, s. 2653-2659
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 mu g/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma. (C) 2009 Elsevier Ltd. All rights reserved.
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| 26. |
- Engberg, Anna E., et al.
(författare)
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Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 36, s. 55-65
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Tidskriftsartikel (refereegranskat)abstract
- Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.
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| 27. |
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| 29. |
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| 30. |
- Gong, J, et al.
(författare)
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Tubing loops as a model for cardiopulmonary bypass circuits : both the biomaterial and the blood-gas phase interfaces induce complement activation in an in vitro model.
- 1996
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Ingår i: Journal of Clinical Immunology. - 0271-9142 .- 1573-2592. ; 16:4, s. 222-223
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Tidskriftsartikel (refereegranskat)abstract
- We describe here a model for the study of blood/surface and blood/air interaction as encountered in cardiopulmonary bypass (CPB) circuits. Polyethylene tubing was filled with serum or blood and closed end to end into loops whereby the volume of the remaining air bubble was inversely varied with respect to that of the fluid. The loops were rotated vertically in a water bath at 37 degrees C. The profiles of C3a, iC3, and TCC generation were similar to those observed at surgery, involving CPB. Soluble heparin and heparan sulfate inhibited both C3a and TCC formation, but surface-conjugated heparin had only a minor effect. Binding of C3 and/or C3 fragments to the heparin surface was much reduced compared to the amine matrix to which heparin was linked, but compared with the polyethylene surface the effect was less pronounced. These data suggest that, in addition to the biomaterial surface, the blood-gas interface seems to play an important role in the activation of complement and that this activation is inhibitable by high concentrations of soluble glucose aminoglycans.
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| 31. |
- Grahn, Birgitta E M, et al.
(författare)
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Motivated patients are more cost-effectively rehabilitated - A two-year prospective controlled study of patients with prolonged musculoskeletal disorders diagnosed in primary care
- 2000
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Ingår i: International Journal of Technology Assessment in Health Care. - 0266-4623 .- 1471-6348. ; 16:3, s. 849-863
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the cost-effectiveness of a multidisciplinary rehabilitation program with traditional treatment within primary care in terms of the health-related duality of life (HRQOL) in patients with prolonged musculoskeletal disorders (MSD) on the one hand and the costs to society on the other. Predictors of total costs, such as motivation, socio-economic level, age, pain, and working environment, were investigated. Methods: A prospective, matched, controlled 2-year follow-up study was designed. The main outcome measures were HRQOL using the Nottingham Health profile (NHP) and patient-specific total costs due to society. The cost-effectiveness was expressed as a quotient of the total costs to society/NHP global score difference value. Results: Patients with prolonged MSD generate substantial total costs to society, chiefly in the area of indirect costs. Multidisciplinary rehabilitation improved HRQOL more cost-effectively. Motivation was revealed as a predictor of total costs. The relationship in savings in terms of indirect costs between the highly-motivated and the less-motivated patients was calculated at 4:1. Conclusions: The large group of patients with prolonged MSD generate substantial total costs, and even small reductions in direct and indirect costs could be of importance to society. The multidisciplinary rehabilitation program applied here was more cost-effective as compared with conventional treatment within primary care when it came to improving the patients perceived HRQOL. Motivation could be a predictor of total costs, which has to be addressed in the process of identifying the patient as a partner in the rehabilitation process.
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| 32. |
- Grahn, B.E.M., et al.
(författare)
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Rehabilitation benefits highly motivated patients : A six-year prospective cost-effectiveness study
- 2004
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Ingår i: International Journal of Technology Assessment in Health Care. - 0266-4623 .- 1471-6348. ; 20:2, s. 214-221
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the six-year outcome of a multidisciplinary rehabilitation program with continued care within primary care in terms of health-related quality of life and cost-effectiveness. Furthermore, predictors of total costs to society were examined. Methods: A prospective, matched, controlled, six-year follow-up was designed. The study included 236 patients (42 men, 194 women) nineteen to sixty-one years of age with prolonged musculoskeletal disorders. The intervention comprised a four-week multidisciplinary rehabilitation and an active one-year follow-up based on a bio-psycho-social approach. The control group received continued care within primary care. The main outcome measures were quality of life measured using the Nottingham Health Profile, motivation identified by an interview and patient-specific total costs to society. Differences in mean costs between groups and cost-effectiveness were evaluated by applying nonparametric bootstrapping techniques. Results: Total costs per treated patient in the rehabilitation group and the control group were £43,464 (SD = 31,093) and £44,123 (SD = 33,333), respectively (p=.896). Multidisciplinary rehabilitation improved quality of life somewhat more cost-effectively. Motivation was revealed as a predictor of total costs. Conclusion: In the long-run, the evaluated multidisciplinary rehabilitation improved the highly motivated patients' quality of life most cost-effectively. The latently motivated patients may require rehabilitation, which is less intensive and with a longer duration, to improve their health in a whole-person perspective. The burden of prolonged musculoskeletal disorders to society was reaffirmed. Motivation could be a predictor of total costs, a factor which has to be taken into account in the examination procedure.
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| 33. |
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| 34. |
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| 35. |
- Hogberg, L, et al.
(författare)
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Penicillin-resistant pneumococci in Sweden 1997-2003: Increased multiresistance despite stable prevalence and decreased antibiotic use
- 2006
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Ingår i: Microbial Drug Resistance. - : Mary Ann Liebert Inc. - 1076-6294 .- 1931-8448. ; 12:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance patterns and capsular groups of penicillin-resistant Streptococcus pneumoniae (PRP; MIC penicillin G >= 0.5 mg/ml) in Sweden between 1997 and 2003 were described, and trends in resistance and antibiotic sales during the same period were compared. The most common serogroups were in descending order 9, 19, 14, 23, and 6. Despite a low and stable annual PRP rate (proportion of PRP out of all pneumococci) of around 2% during the study period, the proportion of PRP resistant to other antibiotics increased. Of all tested PRP isolates, 82% were also resistant to trimethoprim/sulfamethoxazole, 32% had additional resistance to tetracycline, and 26% to erythromycin. Antibiotic sales figures for all studied antibiotic subgroups decreased during the same period. Little correlation was found between antibiotic sales and PRP resistance rates, indicating that there are still other poorly defined factors contributing to the reported resistance levels in the population. However, although PRP strains in Sweden are becoming more commonly resistant to antibiotics other than beta-lactams, the low and further reduced antibiotic sales still might have delayed the development and rapid spread of PRP in the population.
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| 36. |
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| 37. |
- Horneij, E, et al.
(författare)
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Clinical tests on impairment level related to low back pain: A study of test reliability
- 2002
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1651-2081 .- 1650-1977. ; 34:4, s. 176-182
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of the study were, in a working population, to standardize and evaluate a set of clinical tests on impairment level related to the low back with reference to intra- and inter-rater reliability. The study was undertaken in two steps. In step 1, 15 tests were examined for inter-rater reliability by three pairs of physiotherapists and for intra-rater reliability by one physiotherapist. Intra-rater reliability was acceptable (kappa > 0.40) for 14 of the 15 tests. Inter-rater reliability was acceptable for 7 of the 15 tests. In step 2, the tests, indicating a non-acceptable inter-rater reliability (kappa less than or equal to 0.40) were further standardized and re-tested by two of the physiotherapists. This further standardization procedure resulted in an acceptable interrater reliability for all of these tests. Clinical tests of a working population should preferably be performed by the same rater. However, when tests are performed by different raters, it is suggested that test procedures should be regularly standardized, and in pain provocation tests, the magnitude of the applied pressure should be checked regularly and compared with co-raters, in order to improve inter-rater reliability.
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| 38. |
- Huang, Shan, et al.
(författare)
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Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.
- 2016
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 77, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.METHODS: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.RESULTS: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.CONCLUSIONS: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.
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| 39. |
- Johansson, Karin, et al.
(författare)
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A randomized study comparing manual lymph drainage with sequential pneumatic compression for treatment of postoperative arm lymphedema
- 1998
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Ingår i: Lymphology. - 0024-7766. ; 31:Jun, s. 56-64
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Tidskriftsartikel (refereegranskat)abstract
- We compared manual lymph drainage (MLD) with sequential pneumatic compression (SPC) for treatment of unilateral arm lymphedema in 28 women previously treated for breast cancer. After 2 weeks of therapy with a standard compression sleeve (Part I) with maintenance of a steady arm volume, each patient was randomly assigned to either one of two treatment regimens (Part II). MLD was performed according to the Vodder technique for 45 min/day and SPC was performed with a pressure of 40-60 mmHg for 2 hours/day. Both treatments were carried out for 2 weeks. Arm volume was measured by water displacement. Arm mobility, strength, and subjective assessments were also determined. Lymphedema was reduced by 49 ml (7% reduction) (p = 0.01) in the total group during Part I. During Part II, the MLD group decreased by 75 ml (15% reduction) (p < 0.001) and the SPC group by 28 ml (7% reduction) (p = 0.03). The total group reported a decrease of tension (p = 0.004) and heaviness (p = 0.01) during Part I. During Part II, only the MLD group reported a further decrease of tension (p = 0.01) and heaviness (p = 0.008). MLD and SPC each significantly decreased arm volume but no significant difference was detected between the two treatment methods.
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| 40. |
- Klinth, J. E., et al.
(författare)
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A novel application of multi-wavelength TIRF spectroscopy for real time monitoring of antithrombin interactions with immobilized heparin
- 2006
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 21:10, s. 1973-80
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Tidskriftsartikel (refereegranskat)abstract
- Real time interactions of antithrombin (AT) with Corline Heparin Surfaces (CHS) with one and two layers of heparin conjugate have been examined using a multi-wavelength TIRF spectroscopy technique with continuous flow. Fluorescently labeled AT, adsorbed from citrated human blood plasma, showed significantly higher signals on CHS compared to the cationic surface used to attach the heparin conjugate. The AT binding to CHS was very stable, also after exposure to soluble heparin at a concentration of 1.5 IU/mL. Only a few percent of the bound AT were displaced from the surfaces by AT present in plasma after long-term exposure to plasma. In contrast, larger amounts of the freshly added AT had adsorbed to the surfaces, especially to the surface with two layers of heparin conjugate, indicating the presence of unsaturated AT binding sites. The amount of AT bound to the different surfaces was quantified after elution using an enzyme immunoassay (EIA). Characteristic emission spectra of proteins and fluorophores of labeled proteins, obtained at the surfaces after a long-term exposure to plasma, confirmed their presence at the surfaces. The multi-wavelength TIRF technique proved to be a useful tool when combined with other techniques to study the time course of interactions of fluorescently labeled proteins with biomaterials, even in a complex environment such as plasma.
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| 41. |
- Kokelj, Spela, 1992, et al.
(författare)
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Activation of the Complement and Coagulation Systems in the Small Airways in Asthma
- 2023
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Ingår i: Respiration. - : S. Karger. - 0025-7931 .- 1423-0356. ; 102:8, s. 621-631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma. Objectives: We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control. Method: Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry. Results: 53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways. Conclusions: The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system.
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| 42. |
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| 43. |
- Kuraya, M, et al.
(författare)
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C3d-mediated negative and positive signals on the proliferation of human B cells separated from blood
- 1990
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Ingår i: Immunology Letters. - 0165-2478 .- 1879-0542. ; 26:1, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Soluble C3d applied to human blood-derived B lymphocytes inhibited anti-μ, T cell-produced growth factor, and EBV-induced DNA synthesis in serum-free culture. C3d added to the B cell cultures 1 and 2 days after the stimulus, still exerted inhibition, though with gradually diminishing efficiency.C3d, fixed on zymosan or attached to the culture wells, induced [3H]thymidine incorporation of the B cells in serum-free medium. The concentration of C3d used to coat the wells was critical, with optimal stimulatory effect of 8.3 μg/ml. These C3d molecules were shown to be denatured.Our results are in line with earlier data on B cells derived from mouse spleen and human tonsils showing that depending on the way of presentation and its amounts, the natural ligand of CR2 can exert negative or positive signals. Moreover, we demonstrate that C3d can inhibit even the proliferative stimulus of EBV.
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| 44. |
- Kuraya, M, et al.
(författare)
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C3d-mediated negative and positive signals on the proliferation of human B cells separated from blood.
- 1990
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Ingår i: Immunology Letters. - 0165-2478 .- 1879-0542. ; 26:1, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Soluble C3d applied to human blood-derived B lymphocytes inhibited anti-mu, T cell-produced growth factor, and EBV-induced DNA synthesis in serum-free culture. C3d added to the B cell cultures 1 and 2 days after the stimulus, still exerted inhibition, though with gradually diminishing efficiency. C3d, fixed on zymosan or attached to the culture wells, induced [3H]thymidine incorporation of the B cells in serum-free medium. The concentration of C3d used to coat the wells was critical, with optimal stimulatory effect of 8.3 micrograms/ml. These C3d molecules were shown to be denatured. Our results are in line with earlier data on B cells derived from mouse spleen and human tonsils showing that depending on the way of presentation and its amounts, the natural ligand of CR2 can exert negative or positive signals. Moreover, we demonstrate that C3d can inhibit even the proliferative stimulus of EBV.
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| 45. |
- Lanner, M, et al.
(författare)
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Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists
- 2021
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Ingår i: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. - : BMJ. - 1525-1438. ; 31:4, s. 575-584
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Tidskriftsartikel (refereegranskat)abstract
- ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees.MethodologyNational representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher’s exact test, were used.ResultsNational representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system.ConclusionSince the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.
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| 46. |
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| 47. |
- Matsson, Elin M., et al.
(författare)
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Combined in Vitro-in Vivo Approach To Assess the Hepatobiliary Disposition of a Novel Oral Thrombin Inhibitor
- 2013
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 10:11, s. 4252-4262
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Tidskriftsartikel (refereegranskat)abstract
- Two clinical trials and a large set of in vitro transporter experiments were performed to investigate if the hepatobiliary disposition of the direct thrombin inhibitor prodrug AZD0837 is the mechanism for the drug-drug interaction with ketoconazole observed in a previous clinical study. In Study 1, [H-3]AZD0837 was administered to healthy male volunteers (n = 8) to quantify and identify the metabolites excreted in bile. Bile was sampled directly from the jejunum by duodenal aspiration via an oro-enteric tube. In Study 2, the effect of ketoconazole on the plasma and bile pharmacokinetics of AZD0837, the intermediate metabolite (AR-H069927), and the active form (AR-H067637) was investigated (n = 17). Co-administration with ketoconazole elevated the plasma exposure to AZD0837 and the active form approximately 2-fold compared to placebo, which may be explained by inhibited CYP3A4 metabolism and reduced biliary clearance, respectively. High concentrations of the active form was measured in bile with a bile-to-plasma AUC ratio of approximately 75, indicating involvement of transporter-mediated excretion of the compound. AZD0837 and its metabolites were further investigated as substrates of hepatic uptake and efflux transporters in vitro. Studies in MDCK-MDRI cell monolayers and P-glycoprotein (P-gp) expressing membrane vesicles identified AZD0837, the intermediate, and the active form as substrates of P-gp. The active form was also identified as a substrate of the multidrug and toxin extrusion 1 (MATE!) transporter and the organic cation transporter 1 (OCT1), in HEK cells transfected with the respective transporter. Ketoconazole was shown to inhibit all of these three transporters; in particular, inhibition of P-gp and MATE1 occurred in a clinically relevant concentration range. In conclusion, the hepatobiliary transport pathways of AZD0837 and its metabolites were identified in vitro and in vivo. Inhibition of the canalicular transporters P-gp and MATE1 may lead to enhanced plasma exposure to the active form, which could, at least in part, explain the clinical interaction with ketoconazole.
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| 48. |
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| 49. |
- Nilsson, Bo, et al.
(författare)
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Distinctive expression of neoantigenic C3(D) epitopes on bound C3 following activation and binding to different target surfaces in normal and pathological human sera
- 1989
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 26:4, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Binding of C3 to sheep erythrocytes in a serum-free milieu (EAC14oxy2, EAC142) has previously been shown to mimic the antigenic change that occurs upon denaturation of C3 in sodium dodecyl sulphate (SDS), whereby neoantigenic C3(D) epitopes are exposed. The present paper deals with C3 bound to various target surfaces which are known to modulate the functional properties of C3 in different ways. Bound C3 fragments on serum-treated human aggregated gammaglobulin, zymosan, rabbit and sheep erythrocytes, and on circulating immune complexes isolated from sera of patients with rheumatoid arthritis and systemic lupus erythematosus, were shown to be mainly in the iC3b form. By RIAs, employing polyclonal antibodies, the range of C3(D) antigenic epitopes of 125I-labelled SDS denatured C3 expressed by the particle-bound iC3b was monitored. The physiologically bound iC3b on all tested particles expressed wide ranges of C3(D) epitopes and each type of particle-bound C3 exposed its individual range. By competition ELISA specific C3(D)α epitopes were monitored, employing monoclonal antibodies. A distinct difference in the expression of these epitopes was observed in iC3b bound to various test particles in the presence of normal serum and in iC3b present on circulating immune complexes from pathological sera. Considering that the neoantigenic C3(D) epitopes have been shown to be associated with different functions of C3, the distinctive antigenic expression of each type of serum-treated particle might reflect different functional forms of the protein.
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| 50. |
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